Issue

volume fourteen • number seven

September 2008

Peer-Reviewed Journal of the

Academy of Managed Care Pharmacy

Page

626

Sources and Types of Discrepancies Between

Electronic Medical Records and Actual Outpatient

Medication Use

632 Prevalence and Humanistic Impact of

Potential Misdiagnosis of Bipolar Disorder

Among Patients With Major Depressive Disorder in a Commercially Insured Population

643 2008: A Tipping Point for Disease Management?

650 New Agents in the Management of Type 2 Diabetes:

Do They Provide an Opportunity for a Shift in the

Treatment Paradigm?

655

The Benefits and Risks of New Therapies for

Type 2 Diabetes

658

Diabetes Drug Therapy—First Do No Harm

661

Rethinking the “Whodunnit” Approach to Assessing the

Quality of Health Care Research—A Call to Focus on the Evidence in Evidence-Based Practice

675

Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference

697 Managed Care Pharmacy Residencies, Fellowships, and Other Programs

volume 14, no. 7

C o n t e n t s

■ reseArCH

626 Sources and Types of Discrepancies Between Electronic Medical Records and Actual Outpatient Medication Use

Kathleen B. Orrico, PharmD, BCPS

632 Prevalence and Humanistic Impact of Potential Misdiagnosis of Bipolar Disorder Among Patients With Major Depressive Disorder in a Commercially Insured Population

Siddhesh A. Kamat, MS; Krithika Rajagopalan, PhD; Ned Pethick, PharmD, MBA,

Vincent Willey, PharmD; Michael Bullano, PharmD; and Mariam Hassan, PhD

■ dePArtMents

584 Cover Impressions

The Scout Sculpture Overlooking Kansas City (2005)

Richard Cummins

Sheila Macho, Cover Editor

643 Commentary

2008: A Tipping Point for Disease Management?

Brenda R. Motheral, BPharm, MBA, PhD

650 Commentary

New Agents in the Management of Type 2 Diabetes:

Do They Provide an Opportunity for a Shift in the Treatment Paradigm?

Connie A. Valdez, PharmD, MSEd

655 Commentary

The Benefits and Risks of New Therapies for Type 2 Diabetes

Carl V. Asche, PhD, and Richard E. Nelson, PhD

658 Editorial

Diabetes Drug Therapy—First Do No Harm

Frederic R. Curtiss, PhD, RPh, CEBS, and Kathleen A. Fairman, MA

661 Editorial

Rethinking the “Whodunnit” Approach to Assessing the Quality of Health Care

Research—A Call to Focus on the Evidence in Evidence-Based Practice

Kathleen A. Fairman, MA, and Frederic R. Curtiss, PhD, RPh, CEBS

675 Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference

697 Managed Care Pharmacy Residencies, Fellowships, and Other Programs

576 Journal of Managed Care Pharmacy JMCP September 2008 Vol. 14, No. 7 www.amcp.org

AMCP HeAdquArters

100 North Pitt St., Suite 400

Alexandria, VA 22314

Tel: 703.683.8416 • Fax: 703.683.8417

BoArd of direCtors

President: Cathryn A. Carroll, PhD, MBA, BSPharm,

Comprehensive Pharmacy Services, Smithville,

MO

President-Elect: Shawn Burke, RPh, FAMCP,

Coventry Health Care, Inc., Kansas City, MO

Past President: Richard A. Zabinski, PharmD,

OptumHealth; a division of UnitedHealth Group,

Golden Valley, MN

Treasurer: C.E. (Gene) Reeder, RPh, PhD, FAMCP,

Xcenda-AmerisourceBergen Specialty Group,

Columbia, SC ( JMCP liaison)

Secretary: Judith A. Cahill, CEBS,

Academy of Managed Care Pharmacy,

Alexandria, VA (Executive Director, AMCP)

Director: Jean Brown, RPh, PharmD ,

Coventry Health Care, Flagstaff, AZ

Director: William K. Fleming, PharmD, RPh,

Humana, Inc., Prospect, KY

Director: Robert S. Gregory, RPh, MS, MBA,

Aetna, Inc., Hartford, CT

Director: Robert McMahan, PharmD, MBA,

Fidelis Care, Rego Park, NY

Director: Pete Penna, PharmD,

Formulary Resources, LLC, Mercer Island, WA

Advertising

Advertising for Journal of Managed Care

Pharmacy is accepted in accordance with the advertising policy of the Academy of Managed

Care Pharmacy.

For advertising information, contact:

Peter Palmer

Professional Media Group, Inc., 52 Berlin Rd.,

Suite 4000, Cherry Hill, NJ 08034

Tel.: 856.

795.5777,

Fax: 856.795.6777

ext. 13

E-mail: peter@promedgroup.net

editoriAl

Questions related to editorial content should be directed to JMCP Editor-in-Chief Frederic R. Curtiss: fcurtiss@amcp.org.

Manuscripts should be submitted electronically at jmcp.msubmit.net. For questions about submission, contact Peer Review Administrator

Jennifer A. Booker: jmcpreview@amcp.org;

703.317.0725.

suBsCriPtions

Annual subscription rates: USA, individuals, institutions–$90; other countries–$110. Single copies cost $15. Missing issues are replaced free of charge up to 6 months after date of issue.

Send requests to AMCP headquarters.

rePrints

For article reprints and Eprints, contact Theresa

Caprinolo at Sheridan Reprints, 800.352.2210, ext. 8219; tcaprinolo@tsp.sheridan.com. Microfilm and microfiche editions of Journal of Managed Care

Pharmacy are available from University Microfilms,

300 N. Zeeb Rd., Ann Arbor, MI 48106. Reprint

Guidelines are available at www.amcp.org.

All articles published represent the opinions of the authors and do not reflect the official policy or views of the Academy of Managed Care Pharmacy or the authors’ institutions unless so specified. Copyright © 2008,

Academy of Managed Care Pharmacy. All rights reserved. No part of this publication maybe reproduced or transmitted in any form or by any means, electronic or mechanical, without written permission from the Academy of Managed Care Pharmacy.

Editorial Mission

JMCP publishes peer-reviewed original research manuscripts, subject reviews, and other content intended to advance the use of the scientific method, including the interpretation of research findings in managed care pharmacy. JMCP is dedicated to improving the quality of care delivered to patients served by managed care pharmacy by providing its readers with the results of scientific investigation and evaluation of clinical, health, service, and economic outcomes of pharmacy services and pharmaceutical interventions, including formulary management. JMCP strives to engage and serve professionals in pharmacy, medicine, nursing, and related fields to optimize the value of pharmaceutical products and pharmacy services delivered to patients. JMCP employs extensive bias-management procedures intended to ensure the integrity and reliability of published work.

Editorial staff

Editor-in-Chief

Frederic R. Curtiss, PhD, RPh, CEBS

830.935.4319, fcurtiss@amcp.org

associate Editor, Kathleen A. Fairman, MA, 602.867.1343, kathleenfairman@qwest.net

Cover Editor, Sheila Macho , 952.431.5993, jmcpcoverart@amcp.org

Peer review administrator, jmcpreview@amcp.org

Jennifer A. Booker, 703.317.0725,

Graphic designers, Leslie Goodwin, Margie Hunter

Publisher

Judith A. Cahill, CEBS, Executive Director, Academy of Managed Care Pharmacy

Editorial advisory board

The JMCP Editorial Advisory Board is chaired by Marvin D. Shepherd, PhD , Center for Pharmacoeconomic Studies,

College of Pharmacy, University of Texas at Austin; Thomas Delate, PhD, Kaiser Permanente of Colorado, Aurora, serves as vice chair.

They and the other advisers review manuscripts and assist in the determination of the value and accuracy of information provided to readers of JMCP.

Carl Victor Asche, PhD, MBA,

Salt Lake City

John P. Barbuto, MD,

Jingdong Chao, PhD,

Edina, MN

East Hanover, NJ

College of Pharmacy, University of Utah,

HealthSouth Rehabilitation Hospital, Sandy, UT

Chris F. Bell, MS, Global Health Outcomes, GlaxoSmithKline Research

& Development, Research Triangle Park, NC

Joshua Benner, PharmD, ScD, Brookings Institution, Washington, DC

Eliot Brinton, MD, School of Medicine, University of Utah, Salt Lake City

Leslee J. Budge, MBA, Kaiser Permanente, Oakland, CA

Scott A. Bull, PharmD, ALZA Corporation, Mt. View, CA

Norman V. Carroll, PhD, School of Pharmacy, Virginia Commonwealth

University, Richmond, VA

Abbott Laboratories, Abbott Park, IL

Eric J. Culley, PharmD, MBA, Highmark Blue Shield, Pittsburgh, PA

Gregory W. Daniel, RPh, MPH, PhD, HealthCore, Inc., Wilmington, DE

Quan V. Doan, PharmD, MSHS, Outcomes Insights, Inc., Orange, CA

Lida R. Etemad, PharmD, MS, UnitedHealth Pharmaceutical Solutions,

Patrick R. Finley, PharmD, BCPP, University of California at San Francisco

Feride Frech-Tamas, MPH, Novartis Pharmaceuticals Corp.,

Patrick P. Gleason, PharmD, BCPS, Prime Therapeutics, LLC, Eagan, MN

Charnelda Gray, PharmD, BCPS, Kaiser Permanente, Atlanta, GA

Ann S. M. Harada, PhD, MPH, Prescription Solutions, Irvine, CA

Noelle Hasson, PharmD, Veterans Affairs Palo Alto Health Care System,

Palo Alto, CA

Lillian Hsieh, MHS, PharmD candidate, School of Pharmacy, University of California, San Francisco

Mark Jackson, BScPharm, BComm, RPh, Green Shield Canada,

Windsor, Ontario

Richard A. Kipp, MAAA, Milliman USA, Wayne, PA

Stephen J. Kogut, PhD, MBA, College of Pharmacy, University of

Rhode Island, Kingston

Joanne LaFleur, PharmD, MSPH, College of Pharmacy, University of Utah,

Salt Lake City

Daniel C. Malone, PhD, RPh, College of Pharmacy, University of Arizona,

Tucson

Bradley C. Martin, PharmD, PhD, College of Pharmacy, University of

Arkansas, Little Rock

Lynda Nguyen, PharmD candidate, School of Pharmacy, University of

California, San Francisco

Robert L. Ohsfeldt, PhD, School of Rural Public Health, Texas A&M

Health Science Center, College Station

Steven Pepin, PharmD, BCPS, PharmWorks, LLC, Arden Hills, MN

Mary Jo V. Pugh, PhD, South Texas Veterans Healthcare System,

San Antonio, TX

Brian J. Quilliam, PhD, RPh, College of Pharmacy, University of Rhode

Island, Kingston

Gene Reeder, RPh, PhD, Xcenda, Columbia, SC (AMCP Board Liaison)

Elan Rubinstein, PharmD, MPH, EB Rubinstein Associates, Oak Park, CA

Fadia T. Shaya, PhD, MPH, School of Pharmacy, University of Maryland,

Baltimore

Denise Sokos, PharmD, BCPS, School of Pharmacy, University of

Pittsburgh, PA

Brent Solseng, PharmD, BlueCross BlueShield of North Dakota, Fargo

Joshua Spooner, PharmD, MS, Advanced Concepts Institute, Philadelphia, PA

Marilyn Stebbins, PharmD, CHW Medical Foundation, Rancho Cordova,

CA; University of California, San Francisco

Kent H. Summers, RPh, PhD, School of Pharmacy, Purdue University,

West Lafayette, IN

Connie A. Valdez, PharmD, MSEd, Health Sciences Center, University of

Colorado, Denver

Robert J. Valuck, RPh, PhD, School of Pharmacy, University of Colorado

Health Sciences Center, Denver

Peter Whittaker, PhD, School of Medicine, Wayne State University,

Detroit, MI

Journal of Managed Care Pharmacy (ISSN 1083–4087) is published 9 times per year and is the official publication of the Academy of Managed Care Pharmacy (AMCP),

100 North Pitt St., Suite 400, Alexandria, VA 22314; 703.683.8416; 800.TAP.AMCP; 703.683.8417 (fax). The paper used by the Journal of Managed Care Pharmacy meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper) effective with Volume 7, Issue 5, 2001; prior to that issue, all paper was acid-free. Annual membership dues for AMCP include $60 allocated for the Journal of Managed Care Pharmacy.

POSTMASTER: Send address changes to JMCP , 100 North Pitt St., Suite 400, Alexandria, VA 22314.


c o v e r i m p r e s s i o n s

A b o u t o u r c o v e r a r t i s t

The Scout Sculpture Overlooking Kansas City

(2005) n

Richard Cummins

L ighthouses ultimately led the way to 2 different careers for Richard

Cummins. Growing up in the city of Cork, Ireland, he worked on a fishing boat during the summers while he was in high school, and often passed by some of

Ireland’s majestic lighthouses. Cummins was fascinated by the towering structures and decided that he wanted to become a lighthouse keeper someday. To achieve his goal, he studied at the Commissioners of

Irish Lights maritime school in Dublin.

After graduation, Cummins served 10 years in the Irish Lighthouse Service, working at most of the nation’s lighthouses.

“I love shooting cities—trying to extract details to show the individuality of a city.”

“I first got into photography to show my family and friends the

Irish lighthouses and the spectacular scenery surrounding them,” he explains. “I eventually had several images published in books in Ireland. When my wife and I emigrated to Southern California in 1989, I continued to pursue photography, but only as a hobby.

After a few years, I won the Sierra Club national photography contest and the National Geographic Traveler photo contest, and headquarters in San Francisco. Many of his stunning photographs can be seen on his

Web site (richardcumminsphotos.com).

In addition to his own stock photography agency (with more than 100,000 photos on file), he contributes images to quite a few of the major stock photo companies.

Cummins, who has taken photos in urban and rural areas all over the world, finds cities particularly intriguing. “I love shooting cities—trying to extract details to show the individuality of a city,” he says.

In 2005, he accepted an assignment to take pictures for various Kansas City, Missouri, tourism books. One of the most compelling images from that photo shoot is The Scout

Sculpture Overlooking Kansas City.

Cummins used a Canon ELAN film camera equipped with a Canon EF 100-300mm zoom lens to capture The Scout gazing upon downtown Kansas City.

A famous icon in Kansas City, The Scout statue stands more than 10 feet tall and depicts a Sioux Indian on horseback as he returns from hunting. Cyrus E. Dallin of Arlington, Massachusetts, sculpted The Scout in 1914 for the Panama-Pacific International this led to other images being published.” Before Cummins knew it, he was making a living as a professional photographer. In 1996,

Cummins and his wife Catherine launched the Richard Cummins

Stock Photography agency, which has proven to be very successful. They became naturalized U.S. citizens in 2000.

As a self-taught photographer, Cummins learned his craft by reading photography books and carefully studying the images of other photographers. His work is best described as graphic with bold splashes of color. “My favorite style of photography is ‘Light

Painting,’ an old turn-of-the-century photographic technique in which you light the subject during long exposures,” he says.

“I spend many hours in the California desert at night lighting the landscape with huge spotlights covered with colored filters.

Creating one shot can last from a few minutes to several hours.”

Cummins specializes in travel and landscape photography and has received many awards, including 2 from the United

Nations Photographic Council. His photos and accompanying articles have appeared in numerous magazines and newspapers, including Time, U.S. News & World Report, Popular Photography , the

Los Angeles Times , and The Observer . Cummins has also written and photographed a children’s book about Ireland and recently completed a book for the National Park Service featuring the

Cabrillo National Monument in San Diego. Other publishers that have used his images include Houghton Mifflin, Time-Life Books,

Macmillan, Frommer’s, and AAA Publications.

Cummins’ fine-art photographic prints have been exhibited in several galleries in California and Ireland, as well as New York’s

Rockefeller Center, the City of Palm Springs, and the Sierra Club

Exposition (1915 World’s Fair) held in San Francisco, where it won a gold medal. On its way back east, the sculpture was exhibited in Kansas City’s Penn Valley Park. The Scout was so popular, the citizens wanted it to stay. Dallin agreed to a price of $15,000, which was raised in nickels and dimes by local children who called themselves “The Kids of Kansas City.” The Scout statue was permanently installed in Penn Valley Park and dedicated as a memorial to indigenous Indian tribes. Several area attractions have been named after the bronze work of art, most notably

“Kansas City Scout,” Kansas City’s traffic management system.

Also of interest is a nearly identical sculpture located in Seville,

Spain—Kansas City’s sister city. The 2 statues point toward each other across the globe.

If you are attending AMCP’s 2008 Educational Conference in Kansas City October 15-18 and would like to see the scene depicted in Cummins’ beautiful photograph, Penn Valley Park is located just south of the Liberty Memorial in downtown Kansas

City.

Sheila Macho

COVER CREDIT

Richard Cummins, The Scout Sculpture Overlooking Kansas City , analog photograph. Kansas City, Missouri, 2005.

Copyright© Richard Cummins/Lonely Planet Images.

SOURCE

Interview with the artist.

Cover Editor


Jmcp

Editorial Policy

■■ Editorial Content and Peer Review

All articles, editorials, and commentary in JMCP undergo peer review; articles undergo blinded peer review. Letters may be peer reviewed to ensure accuracy. The funda mental departments for manuscript submission are:

• Research

• Subject Reviews

• Formulary Management

• Contemporary Subjects

• Brief Communications

• Commentary/Editorials

• Letters

All submissions other than Editorials,

Commentary, and Letters should include an abstract and inform the reader at the end of the manuscript of what is already known about the subject and what the article adds to our knowledge of the subject.

For manuscript preparation requirements, see “ or at

JMCP Author Guidelines”

www.amcp.org.

in this Journal editori a l M ission a nd pol icies

JMCP publishes peer-reviewed original research manuscripts, subject reviews, and other content intended to advance the use of the scientific method, including the interpretation of research findings in managed care pharmacy. JMCP is dedicated to improving the quality of care delivered to patients served by managed care pharmacy by providing its readers with the results of scientific investigation and evaluation of clinical, health, service, and economic outcomes of pharmacy services and pharmaceutical interventions, including formulary management. JMCP strives to engage and serve professionals in pharmacy, medicine, nursing, and related fields to optimize the value of pharmaceu tical products and pharmacy services delivered to patients.

JMCP employs extensive bias-management procedures that include (a) full disclosure of all sources of potential bias and conflicts of interest, nonfinancial as well as financial; (b) full disclosure of potential conflicts of interest by reviewers as well as authors; and (c) accurate attribution of each author’s contribution to the article. aggressive bias-management methods are necessary to ensure the integrity and reliability of published work.

editorial content is determined by the editor-in-chief with suggestions from the editorial advisory Board. the views and opinions expressed in JMCP do not necessarily reflect or represent official policy of the academy of Managed care pharmacy or the authors’ institutions unless specifically stated.

■■ Research

These are well-referenced articles based on original research that has not been published elsewhere and reflect use of the scientific method. The research is guided by explicit hypotheses that are stated clearly by the authors.

■■ Subject Reviews

These are well-referenced, comprehensive reviews of subjects relevant to managed care pharmacy. The Methods section in the abstract and in the body of the manuscript should make clear to the reader the source of the material used in the review, including the criteria used for inclusion and exclusion of information.

■■ Formulary Management

These are well-referenced, comprehensive reviews of subjects relevant to formulary management methods or procedures in the conduct of pharmacy and therapeutics (P&T) committees and may include description and interpretation of clinical evidence.

■■ Contemporary Subjects

These are well-referenced submissions that are particularly timely or describe research conducted in pilot projects. Contemporary

Subjects, like all articles in JMCP , must describe the hypothesis or hypotheses that guided the research, the principal methods, and results.

■■ Brief Communications

The results of a small study or a descriptive analysis that does not fit in other JMCP departments may be submitted as a Brief

Communication.

■■ Editorials/Commentary

These submissions should be relevant to managed care pharmacy and address a topic of contemporary interest: they do not require an abstract but should include references to support statements.

■■ Letters

If the letter addresses a previously published article, an author response may be appropriate. (See “Letter to the Editor” instruc tions at www.amcp.org.)

■■ Advertising/Disclosure Policy

A copy of the full advertising policy for JMCP is available from AMCP headquarters and the

Advertising Account Manager. All aspects of the advertising sales and solicitation process are completely independent of the editorial process. Advertising is positioned either at the front or back of the Journal ; it is not accepted for placement opposite or near subjectrelated editorial copy.

Employees of advertisers may submit articles for publication in the editorial sections of JMCP , subject to the usual peerreview process. Financial disclosure, conflict-of-interest statements, and author attestations are required when manuscripts are submitted, and these disclosures generally accompany the article in abstracted form if the article is published.

See “Advertising Opportunities” at www.amcp.org. Contact the Advertising

Representative to receive a Media Kit.

Editorial Office

Academy of Managed Care

Pharmacy

100 North Pitt St., Suite 400

Alexandria, VA 22314

Tel.: 703.683.8416

Fax: 703.683.8417

Email: jmcpreview@amcp.org

Advertising Sales Office

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52 Berlin Rd., Suite 4000

Cherry Hill, NJ 08034

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Fax: 856.795.6777

Email: peter@promedgroup.net


JMCP

Author Guidelines

JMCP accepts for consideration manuscripts prepared

according to the Uniform Requirements for Manu scripts Submitted to Biomedical Journals.

1

■■ Manuscript Preparation

Manuscripts should include, in this order: title page, abstract, text, references, tables, and figures (see Submis sion Checklist for details).

JMCP abstracts should be carefully written narratives that contain all of the principal quantitative and qualita tive findings, with the outcomes of statistical tests of comparisons where appropriate. Abstracts are required for all articles in Research, Subject Reviews, Formulary

Management, Contemporary Subjects, and Brief Commu nications. The format for the abstract is Background,

Objective, Methods, Results, Conclusion. Editorials and Commentary do not require an abstract but should include references. Letters do not require an abstract.

For descriptions of editorial content, see “ JMCP

Editorial Policy” in this Journal or at ww.amcp.org.

Please note:

• The JMCP Peer Review Checklist is the best guide for authors to improve the likelihood of success in the

JMCP peerreview process. It is available at: www.

amcp.org (Peer Reviewers tab).

• A subsection in the Discussion labeled “Limitations” is generally appropriate for all articles except Editorials,

Commentaries, and Letters.

• Most articles, particularly Subject Reviews, should incorporate or at least acknowledge the relevant work of others published previously in JMCP (see “Article

Index by Subject Category” at www.amcp.org).

• For most articles in JMCP , a flowchart is recom mended for making the effects of the inclusion and exclusion criteria clear to readers (see JMCP examples in 2007; 13(3):237 (Figure 1), or 2007; 13(1):22 (Figure

1), or 2006; 12(3):234 (Table 3).

• Product trade names may be used only once for the purpose of providing clarity for readers, generally at the first citation of the generic name in the article but not in the abstract.

• Many articles involve research that may pose a threat to either patient safety or privacy. It is the responsibil ity of the principal author to ensure that the manu script is submitted with either the result of review by the appropriate institutional review board (IRB) or a statement of why the research is exempt from IRB review (see JMCP Policy for Protecting Patient Safety and Privacy at www.amcp.org).

■■ Reference Style

References should be prepared following modified

AMA style. All reference numbers in the manuscript should be superscript (e.g., 1 ). Each unique reference should have only one reference number. If that refer ence is cited more than once in the manuscript, the same number should be used. Do not use ibid or op cit for JMCP references. Please provide Web addresses for references whenever possible. See the following exam ples of common types of references:

1.

Journal articles (list up to 6 authors; if more, list only the first 3 and add et al.)—Kastelein JJP, Akdim F,

Stroes ESG, et al., for the ENHANCE Investigators.

Simvastatin with or without ezetimibe in familial hyper cholesterolemia. N Engl J Med . 2008;358(14):143143.

2.

No author given — Anonymous. Top 25 U.S. hospitals, ranked by admissions, 1992. Manag Healthcare . 1994;

4(9):64.

3.

Journal paginated by issue— Gregory DW,

Malone DC. Characteristics of older adults who meet

The Journal of Managed Care Pharmacy, including supplements, is indexed by MEDLINE/PubMed, the International Pharmaceutical Abstracts (IPA),

Science Citation Index Expanded (SCIE), Current

Contents/Clinical Medicine (CC/CM), and Scopus.

the annual prescription drug expenditure threshold for

Medicare medication therapy management programs.

J Manag Care Pharm . 2007;13(2):14254. Available at: www.amcp.org/data/jmcp/p14254.pdf.

4.

Book or monograph by authors— Tootelian DH,

Gaedeke RM. Essentials of Pharmacy Management .

St. Louis, MO: C.V. Mosby; 1993.

5.

Book or monograph with editor, compiler, or chairperson as author— Chernow B, ed. Critical Care Pharma cotherapy . Baltimore, MD: Williams & Wilkins; 1995.

6.

Chapter in a book— Kreter B, Michael KA, DiPiro JT.

Antimicrobial pro phyl axis in surgery. In: DiPiro JT,

Talbert RL, Hayes PE, Yee GC, Matzke GR, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach .

Norwalk, CT: Appleton & Lange; 1992:1811-12.

7.

Government agency publication— Akutsu T. Total heart replacement device. Bethesda, MD: National

Institutes of Health, National Heart, Blood, and Lung

Institute; April 1974. Report no.: NIHNHLI692185 4.

8.

Dissertation or thesis— Youssef NM. School adjust ment of children with congenital heart disease [disserta tion]. Pittsburgh, PA: University of Pittsburgh; 1988.

9.

Drug Label —BristolMyers Squibb Company. Gluco phage (metformin hydrochloride tablets); Glucophage XR

(metformin hydrochloride extendedrelease tablets)

[prescribing information]. June 2006.

10.

Letter or editorial

Markson, LE, Bukstein, DA, Luskin AT. Health care uti lization determined from administrative claims analysis for patients who received inhaled corticosteroids with either montelukast or salmeterol [letter]. J Manag Care

Pharm . 2006;12(6):48687. Available at: www.amcp.org/ data/jmcp/letter_486487.pdf.

11.

Paper (or Poster) presented at a meeting Reagan

ME. Workers’ compensation, managed care, and reform.

Poster presented at: 1995 AMCRA Midyear Managed

Care Summit; March 13, 1995; San Diego, CA.

12.

Newspaper article— Lee G. Hospitalizations tied to ozone pollution: study estimates 50,000 admissions annually. Wash Post . June 21, 1996;A:3.

13.

Web site— National Heart, Lung, and Blood Insti tute. Expert panel report 3: guidelines for the diagnosis and management of asthma. Full report 2007 (EPR3: full report 2007). Available at: www.nhlbi.nih.gov/guide lines/asthma/asthgdln.pdf. Accessed August 29, 2007.

14.

Supplement— AMCP Task Force on Drug Payment

Methodologies: AMCP guide to pharmaceutical payment methods [suppl]. J Manag Care Pharm . 2007;13(8, Sc):

S1S40. Available at: www.amcp.org/data/jmcp/

JMCPSUPPC_OCT07.pdf.

■■ Manuscript Submission

Please submit manuscripts electronically at jmcp. msubmit.net.

All text should be submitted in Microsoft

Word, prepared in 12point type, 1.5 line spacing. Tables must be prepared in either Microsoft Word or Excel and may use a smaller text (e.g., 10point). Figures should be submitted in their original native format, preferably

Adobe Illustrator or Photoshop. Figures may also be pre pared in Microsoft Word, but please send original native files rather than embedded images (tables or figures) to permit editing by the JMCP graphic designer. The JMCP graphic designer has permission to recreate any figures.

Please identify each file submitted with the following information: format (PC or MAC), software application, and file name.

Note: Please do not include author identification in the electronic manuscript document.

Technical style: P values should be expressed to no more than 3 decimal points in the format 0.xxx, to 3 decimal places.

Cover letter: the corresponding (lead) author should include a cover letter with the manuscript, which

• briefly describes the importance and scope of the manuscript, and

• certifies that the paper has not been accepted for publication or published previously and that it is not under consideration by any other publication.

Disclosures and conflicts of interest: Manuscript submissions should include a statement that identifies the nature and extent of any financial interest or affilia tion that any author has with any company, product, or service discussed in the manuscript and clearly indi cates the source(s) of funding and financial support and be accompanied by completed and signed author attesta tion forms for the principal author and each coauthor.

All manuscripts are reviewed prior to peer review.

Manuscripts may be returned to authors prior to peer review for clarification or other revisions. Peer review generally requires 4 weeks but may extend as long as

12 weeks in unusual cases. Solicited manuscripts are subject to the same peerreview standards and editorial policy as unsolicited manuscripts.

■■ Submission Checklist

Before submitting the paper copy of your manuscript to the Journal of Managed Care Pharmacy , please check to see that your package includes the following:

❑ Cover letter

❑ Manuscript: prepared in 12point type, 1.5 line spacing, including

• abstract: no more than 650 words

• references: cited in numerical order as they appear

in the text (use superscript numbers) and prepared

following modified AMA style; do not include

footnotes in the manuscript

• tables and figures (generally no more than a total

of 6). Submit referenced tables and figures on separate

pages with titles (and captions, as necessary) at the

end of the manuscript; match symbols in tables and

figures to explanatory notes, if included. May use

10point type.

• information indicating what is known about the

subject and what your article adds.

❑ Disclosures and conflict-of-interest forms: completed and signed author attestation forms (available at www.

amcp.org); clearly indicate source(s) of funding and financial support.

Note: Please do not include author identification in the electronic manuscript document.

For “Manuscript Submission Checklist” and “Peer Review

Checklist,” see www.amcp.org.

RefeReNCe

1. International Committee of Medical Journal Editors.

Uniform requirements for manuscripts submitted to biomedical journals: writing and editing for biomedical publication. Updated July 27, 2008. Available at: www.

icmje.org/. Accessed April 14, 2007.


R E S E A R C H

Sources and Types of Discrepancies Between Electronic Medical

Records and Actual Outpatient Medication Use

Kathleen B. Orrico, PharmD, BCPS

ABSTRACT

BACKGROUND: Accuracy and transportability of the recorded outpatient medication list are important in the continuum of patient care. Classifying discrepancies between the electronic medical record (EMR) and actual drug use by the root cause of discrepancy (either system generated or patient generated) would guide quality improvement initiatives.

OBJECTIVES: To quantify and categorize the number and type of medication discrepancies that exist between the medication lists recorded in EMRs and the comprehensive medication histories obtained through telephone interviews conducted by a team of nurses providing advice to health plan members at the Palo Alto Medical Foundation in Palo Alto, California.

METHODS: The study was conducted as a retrospective comparison of EMR medication lists with information obtained by patient interview. Interview data were obtained by a review of telephone calls made to a nurse advice line by health plan members seeking information about sinusitis, urinary tract infection, acute conjunctivitis, pharyngitis, emergency contraception, or mastitis. As part of the advice protocol, a medication reconciliation process was conducted between July 1 and December 31, 2006. Changes to the medication list made during the telephone visit were extracted, categorized, and evaluated by the study’s principal investigator. Data extraction included the number and type of identified medication discrepancies, patient age, gender, and condition that prompted the telephone contact.

A modified version of the Medication Discrepancy Tool (MDT) was used to categorize medication discrepancies as either system generated (e.g., failure of the provider to update a medication list) or patient generated (e.g., failure of the patient to report use of an over-the-counter product).

RESULTS: A total of 233 discrepancies were identified from 85 medication reconciliation phone visits, averaging 2.7 per medication list. The most common type of discrepancy was a medication recorded in the EMR but no longer being used by the patient (n=164, 70.4%), followed by omission from the EMR of a medication being taken by the patient (n=36, 15.5%).

79.8% (n=186) of the discrepancies were attributed to system-generated factors, whereas 20.2% (n=47) were patient generated. Approximately half (n=118, 50.6%) of the discrepancies fell into 4 broad American

Hospital Formulary System therapeutic classifications: anti-infective agents (14.2%), anti-inflammatory agents (14.2%), analgesics (12.4%), and vitamins (9.9%). The most common patient-generated discrepancy was omission of a multivitamin (n=13, 27.7%), and the most common systemgenerated prescription drug discrepancy was expired entry for the intranasal corticosteroid mometasone furoate (n=12, 6.5%).

CONCLUSION: Discrepancies in the outpatient setting were common and predominantly system generated. The most common discrepancy was the presence in the EMR of a medication no longer being taken by the patient.

Adding foreseeable end dates to prescription drug orders at computerized order entry might be considered in an effort to improve the accuracy of the outpatient medication list. Reliable systems to involve patients in routinely reconciling EMRs with actual medication use may also warrant examination. The MDT methodology served as a useful qualitative guide for evaluating discrepancies and developing targeted means for resolution.

J Manag Care Pharm. 2008;14(7):626-631

Copyright © 2008, Academy of Managed Care Pharmacy. All rights reserved

What is already known about this subject

• At hospital admission, an estimated 60%–67% of medication histories contain at least 1 error, either omission of a medication being taken, or reporting of a medication not being used. An estimated 11%–59% of these errors are clinically important.

• A comparison of hospital discharge orders and a comprehensive medication assessment conducted after discharge identified medication discrepancies in 14.1% of patients aged 65 years and older and with at least 1 chronic condition. Of these discrep ancies, 50.8% were patient generated and 49.2% were system generated.

What this study adds

• For 85 outpatients contacting a health plan medical advice line for assistance with relatively minor medical conditions, a total of 407 medication entries in an electronic medical record (EMR) were identified. Of those, 233 (57.2%) did not match to infor mation obtained using a comprehensive medication assessment conducted telephonically by a nurse.

• In the majority (70.4%) of discrepancies between EMR entries and medication assessments, a medication recorded in the EMR was no longer being taken by the patient.

• 79.8% of the discrepancies were system generated, whereas

20.2% were patient generated.


Sources and Types of Discrepancies Between Electronic

Medical Records and Actual Outpatient Medication Use

M any studies evaluating medication reconciliation have focused on activities occurring at times of transi tion during or immediately following hospital care.

1–6

Cornish et al. reported that upon hospital admission, few patients could produce an accurate account of their current medication regimens, and that the most common error identified in the medication use history was the omission of a regularly used medication (46.4%).

1 Because the genesis of most prescription drug orders occurs in the physician office setting, improving the accuracy and transportability of the recorded outpatient medica tion list would extend a measure of quality throughout the con tinuum of patient care.

People are particularly vulnerable for experiencing medica tion mishaps during care transitions such as hospital discharge.

Coleman et al.’s study of 375 elderly patients assessed 1 week post-hospitalization showed that 14.1% had experienced 1 or more medication discrepancies, defined as a lack of agreement between prescribed drug therapy indicated on the hospital dis charge record and the therapy actually received by the patient.

2

The study used the Medication Discrepancy Tool (MDT), a meth odology developed and tested for reliability by Smith et.al, to cat egorize these transition-related discrepancies as being generated at either the system level (i.e., under the control of providers) or the patient level (i.e., under the control of patients).

3 Of the 124 discrepancies identified in the Coleman et al. study, 49.2% were categorized as system generated and 50.8% were categorized as patient generated.

2 A systematic review of studies of medication errors at hospital admission indicated that 60%–67% of prescrip tion medication histories contained at least 1 error, either the omission of a medication being taken by the patient or the report ing of a medication not being taken. An estimated 11%–59% of these errors were deemed clinically important.

6

The objective of this study was to determine the state of accu racy of the outpatient medication list by quantifying and catego rizing medication discrepancies between the recorded medica tion list contained in the EMR and a comprehensive medication history obtained through telephone interview by an advice nurse at the Palo Alto Medical Clinic (PAMC). The intended use of a modified MDT to classify the root cause of each discrepancy as either system or patient generated was to allow quality improve ment activities to be appropriately devised and directed.

■■ Methods

Study Setting and Patient Population

The study was conducted at the PAMC, a division of the Palo Alto

Medical Foundation for Health Care, Research, and Education located in Northern California, and was approved by the Palo

Alto Medical Foundation Institutional Review Board. The foun dation is an affiliate of Sutter Health, a system of not-for-profit hospitals and physician organizations. PAMC, a multispecialty medical group with approximately 250 physicians and 900 other professionals at its main facility and 4 satellite clinics, is respon sible for approximately 190,000 covered enrollees.

In 2002, PAMC implemented a full-featured EMR, allow ing electronic documentation of all clinician activity, including computerized medication order entry and the generation of a medication list. Because prescription order entry is a universally used feature, the medication list contains all prescription orders generated at PAMC, including scheduled medications (i.e., con trolled substances). Prescription orders are entered into the sys tem and sent by fax to any retail pharmacy. The physician also can generate printed copies of prescriptions, including scheduled medications, which are routed to secure printers containing tam per-proof forms as required by California law. The system allows for entry of over-the-counter (OTC) items, herbal medications, and nutraceuticals. As a standard practice at PAMC, medications prescribed by providers outside of PAMC but reported as being actively received by the patient are recorded on the medication list and given the system designation of “historical medication,” indicating that the information is patient reported.

The study was conducted as a retrospective, encounter-based

EMR review of telephone calls made to a nurse advice line in the PAMC Department of Family Medicine from July through

December 2006. Registered nurses are authorized to enact stan dardized procedures and telephone treatment protocols for the following complaints: acute conjunctivitis, emergency contracep tion, mastitis in breast feeding women, pharyngitis, sinusitis, and urinary tract infection in women. To qualify to enact these protocols, a nurse must have at least 2 years of prior experience as a registered nurse, have a current California nursing license, and have passed an initial and annual competency evaluation. Only patients who received their primary care at PAMC and who met specific symptom criteria for 1 of the 6 conditions listed above were eligible for telephone treatment and received medication reconciliation. A sample was identified for review by randomly selecting 10 clinic log sheets from approximately 150 clinic log sheets recorded during the 6-month data collection time period.

Each log sheet listed the date of service and medical record num ber of the patient receiving medication reconciliation. No other restrictions were placed on the group of patients included in the study.

Beginning in July 2006, the 8 advice-line nurses began to incorporate a medication reconciliation process into their usual workflow. During the telephone visit (encounter), patients were asked to verify their current medication regimen and to include medications prescribed by physicians outside of PAMC, OTC medications, and herbal preparations. The nurse first verified the medication list by naming each recorded medication using both the generic and brand name, if applicable, and then asking the patients whether they were actively taking that medication. The dose, frequency, and route of administration were also verified with the patient. For medications prescribed on an as-needed basis, such as medications for pain or allergies, patients were asked whether they had used the drug within the past year. The www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 627


Medical Records and Actual Outpatient Medication Use medication was left on the medication list if the patient reported use within the past year or if the patient requested that it remain listed. Next, the patient was asked to report any active use of OTC items, herbal supplements, nutraceuticals, vitamins, and any other prescription medication not recorded on the medication list, including medications prescribed by providers not affiliated with PAMC. At the end of the interview, the nurse updated the medication list. Electronic notification was sent to the primary care physician for review and approval of all changes made including additions and deletions.

Medication Discrepancy Classification

Changes and updates to the medication list enacted during the

85 telephone visits were extracted, quantified, and classified using a retrospective comparison with the EMR. Data extraction was conducted by the principal investigator, and each alteration made to the medication list during the nurse visit was trans ferred to Microsoft Excel worksheets for categorization. The medical record number was the only patient identifier extracted.

Additional data points extracted included patient age, sex, date of visit, and which of the 6 medical conditions prompted the call to the advice line.

For the purpose of this evaluation a “discrepancy” was defined as any lack of agreement between the medication list in the EMR and the patient-reported medication regimen. Discrepancies included any incongruity in medication, dose, frequency, or route, as well as any omission, duplication of the same medi cation in the EMR list, or drug no longer being taken by the patient remaining current on the EMR list. Each discrepancy was assigned to a therapeutic classification based on the American

Hospital Formulary Service (AHFS) standard.

7 The AHFS thera peutic classification categories are extremely broad and can include oral, ophthalmic, topical, nasal, inhaled, and oral agents.

For example, the classification of anti-inflammatory drugs would include oral methylprednisolone tablets, montelukast tablets, mometasone nasal spray, fluticasone inhalation, desonide topical, and hydrocortisone suppositories.

Discrepancies also were assigned to categories based on the

MDT methodology developed by Smith et al.

3 The MDT was created to identify health care facility transition-related medica tion discrepancies and assign them to actionable categories. A main element of the MDT is the classification of each discrep ancy as being either system generated or patient generated. This initial assignment allows for the analysis of the root cause of a discrepancy. A system-generated discrepancy occurred if the physician or a health system process was deemed to have control or responsibility for the medication list inaccuracy. An example of a system-generated discrepancy in the outpatient record was the current listing on the medication list of an antibiotic, such as ciprofloxacin for the treatment of a urinary tract infection, long after the course of therapy had been completed. A discrepancy was classified as patient generated if it occurred because of a fac tor under the patient’s control. An example of a patient-generated discrepancy was the omission from the medication list of a daily multivitamin that the patient initiated; this discrepancy is consid ered patient generated, because the only means for inclusion of this product in the EMR is through patient report.

In accordance with the MDT methodology, discrepancies were further classified into subcategories based on contributing fac tors. The intent of this action is to explore the frequency, causes, and contributing factors to the generation of medication discrep ancies. Adaptations of the original tool were made to make the subcategorization more applicable to the study. For example,

MDT subcategories such as “Did not fill prescription” and “No caregiver” did not apply to this study setting. For the purpose of this study, subcategories included duplicate entry of the same generic entity, omission from the EMR of a medication that the patient reported receiving, erroneous entry of either the dose or directions, and inclusion on the EMR of a medication that the patient reported no longer receiving.

To identify causal factors and provide guidance for corrective action planning, a third categorization scheme that was not part of the original MDT was added to the analysis. Each systemgenerated discrepancy was categorized as caused by (a) an end date not entered at the time of prescribing when it was foresee able to determine length of therapy or (b) failure to update the medication list. Patient-generated discrepancies were categorized as caused by (a) OTC medication/product being taken by the patient but not listed in the EMR, (b) prescription medication prescribed by a non-PAMC provider, or (c) reported intentional nonadherence. Discrepancies involving OTC medications and those prescribed by non-PAMC physicians (historical medica tions) are classified as patient generated because the patient has firsthand knowledge of current use; thus, strategies to resolve the discrepancy depend on updates provided by the patient.

■■ Results

Population Characteristics

The 85 evaluated medication reconciliation telephone calls were associated with 85 unique patients who were all assigned to a primary care provider at PAMC. Because the study included only patients who met specific symptom criteria for 1 of the 6 condi tions managed by telephone treatment protocol, the study popu lation was skewed towards women (female n=69 [81.2%]), with a mean (SD) age of 42 (14) years (Table 1). Medical conditions reported by callers included: sinusitis (n=38, 44.7%), urinary tract infection in adult women (n=26, 30.6%), acute conjunctivitis

(n=9, 10.6%), pharyngitis (n=7, 8.2%), emergency contraception

(n=4, 4.7%), and mastitis in breastfeeding women (n=1, 1.2%).

Types of Medication Discrepancies

The 85 recorded medication lists contained a total of 407 current medication entries, an average of 4.8 entries per list. A total of

233 discrepancies were identified (average of 2.7 per list) and cat -



Medical Records and Actual Outpatient Medication Use egorized as resulting from duplicate entries (n=27, 11.6%), active medications omitted from the profile (n=36, 15.5%), medications recorded in the EMR but no longer being taken (n=164, 70.4%), and differences in dosage or directions (n=6, 2.6%; Table 2).

Each discrepancy was further classified as being either system-generated (n=186, 79.8%) or patient-generated (n=47,

20.2%; Table 2). The majority (n=155, 83.3%) of the 186 systemgenerated discrepancies resulted from discontinued or expired medications that had been left active on the medication list. The most frequently occurring patient-generated discrepancies (n=36,

76.6%) resulted from omission from the EMR of OTC medica tions and those prescribed by providers outside of PAMC.

Categorization of discrepancies based on causal factors is sum marized in Table 3. An actionable causation factor for approxi mately half (48.4%) of the system-generated discrepancies was the lack of the entry of an end date for medications with known lengths of therapy. A causal factor for more than half (61.7%) of the patient-generated discrepancies was the lack of documenta tion for active OTC medication or product use.

-

TABLE 1 Characteristics of Outpatients Telephoning a Health Plan Nurse Advice Line

Number of unique patients

Age (years) mean (SD)

Variable

Age range (years), by age category

18–89

18–39

40–59

60–89

Male

Female

Medical Condition Reported by Patient

Sinusitis

Urinary tract infection in women

Acute conjunctivitis

Pharyngitis

Emergency contraception

Mastitis in breastfeeding women

85

42 (14)

N (%)

34 (40.0)

45 (52.9)

6 (7.1)

16 (18.8)

69 (81.2)

38 (44.7)

26 (30.6)

9 (10.6)

7 (8.2)

4 (4.7)

1 (1.2) Medication Classes

Half of the 233 identified discrepancies (n=118, 50.6%) fell into

4 broad AHFS medication classes: anti-infective agents (14.2%), anti-inflammatory agents (14.2%), analgesics (12.4%), and vita mins (9.9%; Table 4). The first 3 categories contained medications that typically have a finite or seasonal course of use (antibiotics, analgesics, nasal corticosteroids). The omission of a multivitamin from the EMR list was the most commonly occurring patientgenerated discrepancy (n=13, 27.7%, data not shown). An entry for the intranasal corticosteroid mometasone furoate, a seasonal anti-inflammatory agent, was the prescription drug most com monly occurring as a system-generated discrepancy because it remained on the medication list after active use had stopped

(n=12, 6.5%, data not shown).

■■ Discussion

The results of the study showed that the EMR medication list contained many discrepancies, the majority of which were attrib utable to system-generated factors. True inaccuracies, such as the entry into the EMR of an incorrect dose or frequency or the entry of a duplicate order entry, were rare. Because the majority of discrepancies were the result of discontinued medications being allowed to remain on the list long after the course of therapy had been completed, it follows that discrepancies fell into therapeutic classifications that have a finite or seasonal, rather than chronic, treatment course.

TABLE 2 Categorization of Medication Discrepancies by System-Generated and Patient-Generated Factors

Factors Definition

Duplicate entry Generic entity listed more than once

Omission from EMR Patient reports currently receiving a medi cation that is not listed

Patient not receiving—current on EMR Medication present on EMR, but patient reports not currently receiving

Erroneous entry—dose Medication entry on EMR shows different dose than what patient reports receiving

Erroneous entry—directions Medication entry on EMR shows differ ent directions than what patient reports receiving

EMR=electronic medical record

System Generated n (%)

186 (79.8)

27 (14.5)

0

155 (83.3)

3 (1.6)

1 (0.5)

Patient Generated n (%)

47 (20.2)

0

36 (76.6)

9 (19.1)

1 (2.1)

1 (2.1)

Total n (%)

233 (100)

27 (11.6)

36 (15.5)

164 (70.4)

4 (1.7)

2 (0.9) www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 629


Medical Records and Actual Outpatient Medication Use

TABLE 3 Medication Discrepancies:

Causal Factors

System-Generated Factors n=186

Medication list not updated

End date not entered

Patient-Generated Factors n=47

Omission of OTC medication or product

Prescribed by outside physician

Intentional nonadherence

OTC=over-the-counter n (%)

96 (51.6)

90 (48.4) n (%)

29 (61.7)

9 (19.1)

9 (19.1)

Although anti-infective and anti-inflammatory agents were the classes of medications found to be most often involved in discrepancies in this outpatient setting, medication discrepan cies reported in previous studies conducted in hospital settings involved different categories of medications. Coleman et al.’s study of post-hospital discharge discrepancies found that antico agulants (13%), diuretics (10%), angiotensin-converting enzyme inhibitors (10%), and lipid-lowering agents (10%), were the 4 most commonly occurring medication classes involved in dis crepancies.

2 Cornish et al.’s evaluation of discrepancies upon hos pital admission found cardiovascular agents (26.6%) and central nervous system agents (25.9%) to be most commonly identified .1

The variation in identified medication classes may be the result of the differences in the populations studied. Both pre- and posthospitalization studies evaluated senior patients with high acuity, whereas our outpatient population represented a younger, less medically complicated group. A study that evaluated predictors of discrepancies in outpatient practice found through multivariate analysis that older age was strongly associated with the occur rence of medication discrepancies .8

Results of the present study show that discrepancies are evident in younger age groups as well, suggesting the importance of process improvement activi ties directed at building reliable systems that affect the accuracy of medication lists for all patients.

Classifying the causes of patient-generated discrepancies was a useful approach and highlighted the need to partner with the patient in order to arrive at medication list accuracy. OTC prod ucts initiated by the patient accounted for 61.7% of the patientgenerated discrepancies. A prospective study of 104 primary care outpatients conducted at the Mayo Clinic, that evaluated the prevalence of medication discrepancies in the EMR, also found that omission of OTC drugs from the recorded medica tion list was a common discrepancy.

9 In that study, a program of mailed letters reminding patients to bring medication informa tion to appointments, coupled with verification and correction of medication lists, was associated with a decrease in discrepancies from 89% to 66% of visits. Phase I of the Mayo Clinic study com pared the medication list recorded in the EMR with a reconciled medication list produced by a nurse telephone interview with the patient. Of the 147 OTC and herbal products reported as being taken by the patients, 87 (76%) were omitted from the EMR medication list.

9 Developing similar strategies for capturing this information from the patient would be valuable in addressing patient-generated discrepancies.

TABLE 4 Top 10 Discrepancies Categorized by

AHFS Therapeutic Class a (n=233)

Therapeutic Class

Anti-infective agents b

Anti-inflammatory agents c

Analgesics d

Vitamins

Anxiolytics, sedatives, and hypnotics

Contraceptives

Antidepressants

Beta-adrenergic agonists

Supplements n (%)

33 (14.2)

33 (14.2)

29 (12.4)

23 (9.9)

15 (6.4)

15 (6.4)

13 (5.6)

9 (3.9)

9 (3.9)

Antiemetic

Total number of discrepancies in top 10 categories

5 (2.1)

184 (79.0) a Therapeutic categories are broad and include all dosage forms.

b Anti-infective agents include antibiotics, antifungals, and antiviral agents (e.g., azithroc mycin tablets, ketoconazole tablets, and clindamycin topical).

Anti-inflammatory agents is a broad therapeutic category that includes oral, nasal, topical, and rectal drugs (e.g., oral methylprednisolone tablets, montelukast tablets, mometasone nasal spray, fluticasone inhalation, desonide topical, and hydrocortisone suppositories).

d Analgesics include nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, and opiate analgesics (e.g., ibuprofen tablets, celecoxib capsules, and acetaminophen/ codeine tablets).

AHFS=American Hospital Formulary Service

Process Improvement

The MDT methodology served as a useful qualitative guide for evaluating discrepancies and developing targeted means for reso lution. The finding that the greatest number of system-generated discrepancies resulted from expired medications being left active on the medication lists permitted the development of a targeted, systematic corrective action plan. An examination of the top 3

AHFS therapeutic classes showed the presence of many medica tions for which the length of therapy is known at prescribing; the simple addition of an order end date to the EMR would automate removal from the EMR medication list.

To aid this effort, an educational campaign was launched at

PAMC to encourage physicians to enter an appropriate end date to prescription orders when the length of therapy was predictable upon order entry. Chronic medications, which were rarely identi fied as discrepancies in our evaluation, were not to be given an end date. The information was presented to the Family Medicine physicians at a department meeting. As a process check, the



Medical Records and Actual Outpatient Medication Use percent of short-course azithromycin orders written with an end date was measured 30 days pre- and post-presentation. Before the presentation, 7 of 25 (28%) total orders of azithromycin con tained an end date. After the presentation the percentage rose to

16 of 23 (70%). Plans are under way to automatically populate the end date field for many medications.

As part of its “5 Million Lives Campaign,” the Institute for

Healthcare Improvement recommends encouraging patients to play a major role in ensuring that the medication list is kept up to date as they visit multiple providers in the outpatient setting.

10

Strategies for reducing patient-generated discrepancies have been explored by other medical groups.

Harvard Pilgrim Health Care conducts a comprehensive medi cation reconciliation program that involves direct pharmacist intervention with high-risk patients.

11 A similar program that uses pharmacists to conduct a comprehensive medication recon ciliation while a patient undergoes dialysis has been successful at the Dialysis Clinic Inc. in Kansas City, Missouri.

12

Limitations

First, our study was limited to a small sample of outpatients who telephoned an advice-line nurse to request assistance with relatively minor medical conditions. Thus, our results may not be generalizable to a broader outpatient population. Second, the nurse interview process relied on patient self-report as a “gold standard” against which the EMR was compared. Errors made by patients in reporting drug, duration, or dose, or by nurses using the protocol could have overstated the rate of discrepancy between the EMR and the patient-reported information. Lastly, because data extraction was conducted by one person, errors or biases could have affected the data collection process.

■■ Conclusions

Discrepancies in the outpatient setting were common and pre dominantly system generated. Establishing appropriate medica tion order end dates at the point of prescription order entry could eliminate 50% of the system-generated discrepancies in this study setting. Effective methods to improve medication list accu racy should address both system- and patient-generated discrep ancies. A “stretch goal” for all outpatient office settings should be to supply every patient with an accurate list of active medications that would improve patient safety throughout the continuum of patient care. The MDT methodology served as a useful qualitative guide for evaluating discrepancies and developing targeted means for resolution.

DISCLOSURES

The author reported no funding for this study and no conflicts of interest related to the subject of this article.

REFERENCES

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Pharmacother. 2004;2(2):141–48.

4. Kripalani S, LeFevre F, Phillips CO, Williams MV, Basaviah P, Baker DW.

Deficits in communication and information transfer between hospital-based and primary care physicians: implications for patient safety and continuity of care. JAMA . 2007; 297(8):831–41.

5. Kripalani S, Jackson AT, Schnipper JL, Coleman EA. Promoting effective transitions of care at hospital discharge: a review of key issues for hospital ists. J Hosp Med.

2007; 2(5):314–23.

6. Tam VC, Knowles SR, Cornish PL, Fine N, Marchesano R, Etchells EE.

Frequency, type, and clinical importance of medication history errors at admission to hospital: a systematic review. CMAJ . 2005;173(5):510–15.

7. McEvoy GK, ed. AHFS Drug Information 2005.

Bethesda, MD: American

Society of Health-System Pharmacists; 2005.

8. Bedell SE, Jabbour S, Goldberg R, Glaser H, Gobble S, Young-Xu Y, et.al. Discrepancies in the use of medications. Arch Intern Med.

2000;160

(14):2129–34.

9. Varkey P, Cunningham J, Bisping S. Improving medication reconciliation in the outpatient setting . Jt Comm J Qual Patient Saf.

2007;33(5):286–92.

10. Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academy Press; 2001.

11. Bernstein L, Frampton J, Minkoff NB, et al. Medication reconciliation:

Harvard Pilgrim Health Care’s approach to improving outpatient medication safety. J Healthc Qual.

2007;29(4):40–45

12. Manley HJ, Drayer DK, McClaran M, Bender W, Muther RS. Drug record discrepancies in an outpatient electronic medical record: frequen cy, type, and potential impact on patient care at a hemodialysis center.

Pharmacotherapy . 2003:23(2):231–39.

Author

KATHLEEN B. ORRICO, PharmD, BCPS, is Health Sciences Assistant

Clinical Professor of Pharmacy, University of California, San Francisco,

School of Pharmacy; and Clinical Pharmacist, Palo Alto Medical

Foundation, Palo Alto, California.

AUTHOR CORRESPONDENCE: Kathleen B. Orrico, PharmD, BCPS,

Palo Alto Medical Foundation, 795 El Camino Real, Pharmacy Level A, Palo

Alto, CA 94301. Tel.: 650.614.3217; E-mail: orricok@pamf.org.

www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 631

R E S E A R C H

Prevalence and Humanistic Impact of Potential Misdiagnosis of

Bipolar Disorder Among Patients With Major Depressive Disorder in a Commercially Insured Population

Siddhesh A. Kamat, MS; Krithika Rajagopalan, PhD; Ned Pethick, PharmD, MBA;

Vincent Willey, PharmD; Michael Bullano, PharmD; and Mariam Hassan, PhD

ABSTRACT

BACKGROUND: Patients with bipolar disorder typically present to physicians in the depressed rather than the manic or hypomanic phase of illness.

Because the depressive episodes in bipolar disorder may be indistinguishable from those in major depressive disorder (MDD), misdiagnosis may occur.

OBJECTIVES: To estimate from administrative claims data and a telephone survey the prevalence of potential misdiagnosis of bipolar disorder among patients with MDD and the humanistic (health-related quality of life

[HRQOL] and disability) effects associated with misdiagnosis in a managed care setting.

METHODS: Administrative claims data were used to identify patients with medical claims for MDD from a database of 9 million members of commercial health plans from 3 U.S. regions. The inclusion criteria were as follows:

(a) adults aged 18 years or older; (b) at least 2 medical claims, including a primary or secondary diagnosis of MDD: ICD-9-CM codes 296.2x (MDD, single episode), 296.3x (MDD, recurrent episode), or 311 (depressive disorder, not classified elsewhere) during an identification period from

January 1, 2000, through March 31, 2004 (study intake period); (c) at least

12 months of pre-index and 12 months of post-index plan eligibility; and

(d) active enrollment through March 31, 2005. The index date was defined as the date of the first claim for MDD during the identification period.

Patients with ICD-9-CM codes for bipolar disorder at any time throughout the study period (January 1, 2000, through March 31, 2005) were excluded from this cohort. This cohort was targeted for a telephone survey that was conducted from August 1 through October 30, 2006. From the telephone survey sampling frame of 5,777, a total of 1,360 interviews were completed for a response rate of 23.5%. Respondents were screened for potential bipolar disorder using the Mood Disorder Questionnaire (MDQ). The Medical

Outcomes 12-Item Short Form Survey (SF-12), Version 2, a widely used and validated instrument that assesses health-related functioning, and the Sheehan Disability Scale (SDS), which measures depression-related disability, were administered to a convenience subsample of 112 survey respondents to collect HRQOL and disability information, respectively.

RESULTS: Of 1,360 adult patients aged 18 years or older with a diagnosis of

MDD but without a medical claim for diagnosis of bipolar disorder,

94 (6.9%) screened positive for bipolar disorder on the MDQ. More patients with a positive screen for bipolar disorder reported lifetime histories of obsessive compulsive disorder (24.5% vs. 8.2%, P < 0.001), psychotic disorders or hallucinations (9.6% vs. 2.4%, P < 0.001), suicidal ideation

(61.7% vs. 29.4%, P < 0.001), and drug abuse (34.0% vs. 11.1%, P < 0.001) than did patients with a negative screen for bipolar disorder. In the subgroup of patients who completed the SF-12 and SDS, patients with a positive screen for bipolar disorder (n = 33) had lower scores (i.e., greater impairment) on the social functioning, role emotional, and overall mental component summary scales of the SF-12 than did patients with a negative screen for bipolar disorder (n = 79, P < 0.001), but did not significantly differ on the physical component summary scale. Patients with a positive screen for bipolar disorder on the MDQ were more likely than patients who screened MDQ-negative to report severe depression-related impairment

(scores of 7 and higher on the SDS scale) with work life (54.5% vs. 24.1%, respectively, P = 0.002), social life (66.7% vs. 39.2%, P = 0.008), and family life (66.7% vs. 34.2%, P = 0.002) on the SDS.

CONCLUSIONS: In this study of patients carrying medical claims for a diagnosis of MDD in their administrative claims data, approximately 7% screened positive for bipolar disorder on a validated self-report assessment instrument. Patients with MDD who screened positive for bipolar disorder reported poorer HRQOL and disability scores than did patients with MDD who screened MDQ-negative. These findings may encourage interventions for appropriate screening, diagnosis, and management of potentially misdiagnosed bipolar disorder patients.

J Manag Care Pharm. 2008;14(7):632-642

Copyright © 2008, Academy of Managed Care Pharmacy. All rights reserved.

What is already known about this subject

• Misdiagnosis of bipolar disorder is common. In a survey of support group participants diagnosed with bipolar disorder,

69% reported initial misdiagnosis by the first physician from whom they sought treatment, and misdiagnosed patients reported seeing a mean of 4 physicians before being diagnosed with bipolar disorder.

• Previous studies of the misdiagnosis of bipolar disorder were conducted in the clinical/outpatient setting. However, the rate of misdiagnosis among commercially insured patients, who may be “healthier” than patients recruited from clinical/outpatient service centers, is unknown.


Prevalence and Humanistic Impact of Potential Misdiagnosis of Bipolar Disorder

Among Patients With Major Depressive Disorder in a Commercially Insured Population

B ipolar disorder, a chronic psychiatric illness with a variable course, affects between 1% and 4.4% of the U.S. popula tion 1,2 and costs more than $7 billion in direct medical costs and $38 billion in indirect costs (1991 values).

3 According to the World Health Organization, bipolar disorder was among the top 10 causes of disability in the world in 2000 4 and was asso ciated with significant impairment of a patient’s health-related quality of life (HRQOL) even after symptomatic recovery.

5,6

Patients with bipolar disorder suffer high rates of unemployment 7

(up to 60%) or occupational difficulties 8,9 (up to 88%), and twothirds of patients report difficult family relationships.

9 Moreover, misdiagnosis of bipolar disorder is common.

7,10 In Hirschfeld et al.’s survey of support group participants diagnosed with bipolar disorder, 69% reported initial misdiagnosis by the first physician from whom they sought treatment, and misdiagnosed patients reported seeing a mean of 4 physicians before being diagnosed with bipolar disorder.

7

Without proper treatment, the symptoms of bipolar disorder

(including suicide attempts) tend to increase in frequency and severity 11 and are less easy to manage with pharmacological intervention.

12 Accurate diagnosis necessitates a medical history from the patient and family or friends, 7 and the patient-rated

Mood Disorder Questionnaire (MDQ) has been shown to be a useful screening tool for bipolar disorder.

13-15 In particular, differentiation of bipolar disorder from major depressive disor der (MDD) is essential for the appropriate management of the patient’s condition, 16 and an analysis of administrative claims data found an association between undiagnosed bipolar disorder and higher total all-cause medical costs.

17

This study was undertaken to document the rate of positive screens for bipolar disorder among an MDD population in a managed care setting. The impact of misdiagnosis on HRQOL and depression-related disability was evaluated. Quantifying potential bipolar disorder misdiagnosis among the MDD popu lation may help to optimize the identification and therapeutic management of these patients and may result in better patient outcomes.

■■ Methods

This study was a retrospective analysis of administrative claims, with cross-sectional diagnostic and HRQOL evaluations per formed on a subset of patients. The study used data from 3 geo graphically dispersed health plans located in the southeastern, western, and midwestern regions of the United States, consisting of approximately 9 million commercially insured members.

Patients enrolled in Medicare or Medicaid were not included in the study. The claims dataset included medical (inpatient, outpatient, and emergency room [ER] visits) and pharmacy encounters, as well as eligibility files. The study protocol and the survey instrument were sent to Quorum Review Inc., an independent institutional review board (IRB), for approval and to receive a Partial Waiver of Authorization under the terms of

What this study adds

• Using the Mood Disorder Questionnaire (MDQ), 6.9% of patients diagnosed with major depressive disorder (MDD) screened positive for bipolar disorder.

• Patients who screened positive for bipolar disorder were less likely than MDQ-negative patients to be married (48.9% vs.

60.7%, respectively), and reported higher lifetime rates of highrisk behaviors, including suicidal ideation (61.7% vs. 29.4%), drug abuse (34.0% vs. 11.1%), and psychiatric symptoms, including obsessive-compulsive disorder (24.5% vs. 8.2%) and psychotic disorders or hallucinations (9.6% vs. 2.4%).

• Compared with patients with MDD who screened MDQnegative, those who screened positive for bipolar disorder were more likely to indicate depression-related impairment on the

Sheehan Disability Scale (SDS) and had greater impairment in

3 SF-12 measures, including social functioning, role emotional, and the mental component summary scale.

the Health Insurance Portability and Accountability Act (HIPAA) to use patient-level data for purposes of contacting patients for the survey. The study protocol included involvement of an external vendor to conduct the survey, which was approved by the IRB. All researchers handling protected health information were autho rized to do so per company guideline and policies, and all study materials were treated with confidentiality.

Patient Identification

The study population was identified in 2 phases—first through examination of data from administrative claims, and then by telephone survey, conducted in a subset of patients (Figure 1).

Identification of Survey Sample

Adults aged 18 years or older with (a) at least 2 medical claims, including a primary or secondary diagnosis of MDD with dates of service between January 1, 2000, and March 31, 2004 (study identification period); (b) at least 12 months of pre-index and

12 months of post-index plan eligibility; and (c) active enrollment through March 31, 2005, were selected for the claims analysis.

The index date was defined as the date of the first claim for MDD during the identification period. Patients were required to have at least 2 medical claims for MDD because we wanted to select a patient population that had a chronic form of depression. MDD diagnostic codes were based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM;

Table 1). Patients with ICD-9-CM codes for bipolar disorder at any time during the entire study period (January 1, 2000, through March 31, 2005) were excluded from this cohort.




Telephone Survey: Bipolar Disorder Screening,

Health Functioning, and Impairment Assessment

A minimum sample of approximately 1,300 completed surveys was needed to assess the screen positive rate for bipolar disorder using the MDQ. Using a standard confidence interval formula, the sample size required to estimate the prevalence of misdiag nosis within ± 2.75% around the true population misdiagnosis rate was approximately 1,300 completed surveys.

18 The research question was to assess the unknown screen positive rate in the general population by conducting the survey on a sample of patients with MDD.

The surveys were initiated in August 2005 and were con ducted by telephone survey interviewers who were experienced in health services research and trained extensively on the survey script. Because we wanted the survey sample to have the same age, gender, and regional distribution as that of the master calling list, we interviewed patients after categorizing them into different strata based on age, gender, and regions, then randomly selected patients from each stratum for completing the survey. The struc tured telephone survey was administered by placing calls at vari ous times throughout the week. To confirm the MDD diagnoses that had been used to select the sample, prospective respondents were asked during the screening process whether they had ever been told by a physician that they had depression.

Demographics (age, gender, employment status, and marital status), self-reported lifetime history of mental health conditions,



Among Patients With Major Depressive Disorder in a Commercially Insured Population such as suicidal ideation (“thoughts about suicide”); obsessive compulsive disorder; psychotic symptoms (“psychotic disorder, hallucinations, or delusions”); and lifetime history of lifestyle characteristics, such as alcohol use and substance abuse, were collected from the entire group of 1,360 patients through this survey. Respondents who completed this portion of the survey were paid $25 for their time. A convenience sample subset of patients (n = 112) was selected from among the 1,360 patients who completed the MDQ screening portion of the survey and

2 additional self-report instruments were administered to the subsample during the same interview: the Medical Outcomes

Study 12-Item Short Form Health Survey (SF-12), Version 2, 19,20 a widely used and validated instrument that assesses health-related functioning, and the Sheehan Disability Scale (SDS), a measure of depression-related disability.

21,22 Patients who were selected and agreed to complete the SF-12 and the SDS were compensated with an additional $10.

MDQ

The MDQ, a self-report screening instrument for bipolar I and II disorder, has been validated in adults across a wide array of settings.

14-16 The questionnaire consists of 13 Yes/No items assessing lifetime history of disturbances in mood, selfconfidence, mental functioning, energy, social functioning, inter est in sex, and risk behavior. The MDQ also assesses the impact of these symptoms on functioning (e.g., “like being unable to work; having family, legal, or money troubles; getting into argu ments or fights”) on a 4-point scale (no problem, minor problem, moderate problem, or serious problem). A positive MDQ screen is defined as a positive response for greater than or equal to 7 of the 13 symptom items, co-occurrence of “several” symptoms, and moderate or serious symptom impact.

13

SF-12

The SF-12 is a validated, reliable screening tool for assessing

HRQOL on a 5-point scale.

19,20 The SF-12 measures the domains of physical functioning, role physical, bodily pain, and general health, and vitality, which constitute the physical component scale (PCS). The SF-12 also measures social functioning, role emotional, and mental health domains that constitute the mental component scale (MCS).

TABLE 1 ICD-9-CM Codes for Major

Depressive Disorder

ICD-9-CM

Code ICD-9-CM Description

296.20

296.21

296.22

296.23

296.24

296.25

296.26

296.30

296.31

296.32

296.33

296.34

296.35

296.36

311

Major Depressive Disorder Codes

Major depressive affective disorder single episode unspecified degree

Major depressive affective disorder single episode mild degree

Major depressive affective disorder single episode moderate degree

Major depressive affective disorder single episode severe degree without psychotic behavior

Major depressive affective disorder single episode severe degree specified as with psychotic behavior

Major depressive affective disorder single episode in partial or unspecified remission

Major depressive affective disorder single episode in full remission

Major depressive affective disorder recurrent episode unspecified degree

Major depressive affective disorder recurrent episode mild degree

Major depressive affective disorder recurrent episode moderate degree

Major depressive affective disorder recurrent episode severe degree without psychotic behavior

Major depressive affective disorder recurrent episode severe degree specified as with psychotic behavior

Major depressive affective disorder recurrent episode in partial or unspecified remission

Major depressive affective disorder recurrent episode in full remission

Depressive disorder not elsewhere classified

296.0x

296.1x

296.4x

296.5x

296.6x

296.7x

296.8x

Bipolar Disorder Codes

Bipolar I disorder, single manic episode

Manic affective disorder, recurrent episode

Bipolar I, most recent episode manic

Bipolar I, most recent episode depressed

Bipolar I, most recent episode mixed

Bipolar I, most recent episode unspecified

Other and unspecified bipolar disorders

ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical

Modification.

SDS

The SDS is a 10-point self-rated assessment tool with demon strated validity and reliability in psychiatric populations.

21,22 SDS items measure depression-related impairments in work, social, and family life (reported as item scores and summary scores), as well as depression-related absenteeism and reduced efficiency.

the proportion of patients who screened positive for bipolar dis order on the MDQ and dividing by the total number of patients with MDD who completed the survey.

Prevalence Outcomes

The prevalence of potentially misdiagnosed bipolar disorder among patients diagnosed with MDD was derived by calculating

Burden of Disease: Humanistic Outcomes

HRQOL and disability/impairment were evaluated using summary scale and domain scores from the SF-12 and SDS item and composite scores and compared for those patients screening positive and negative for bipolar disorder using the MDQ. The www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 635



TABLE 2 Responses of Survey Participants to Items on the Mood Disorder Questionnaire

MDQ Items

The MDQ consists of 13 yes/no questions on lifetime history of patients’ experiences: Has there ever been a period of time when you were NOT your usual self AND

MDQ 1: you felt so good or so hyper that other people thought you were not your normal self, or you were so hyper that you got into trouble?

MDQ 2: you were so irritable that you shouted at people or started fights or arguments?

MDQ 3: you felt much more self-confident than usual?

MDQ 4: you got much less sleep than usual and found that you didn’t really miss it?

MDQ 5: you were much more talkative or spoke faster than usual?

MDQ 6: thoughts raced through your head or you couldn’t slow your mind down?

MDQ 7: you were so easily distracted by things around you that you had trouble concentrating or staying on track?

Percentage of Patients

Answering YES

Screen positive, n = 94

56.4% (53)

87.2% (82)

71.3% (67)

68.1% (64)

81.9% (77)

86.2% (81)

92.6% (87)

Screen negative, n = 1,266

7.9% (100)

41.2% (522)

24.7% (313)

23.3% (295)

20.6% (261)

40.2% (509)

45.2% (572)

MDQ 8: you had much more energy than usual?

83.0% (78)

MDQ 9: you were much more active or did many more things than usual?

83.0% (78)

MDQ 10: you were much more social or outgoing than usual; for example, you telephone friends in the middle of the night?

60.6% (57)

22.2% (281)

26.9% (341)

8.9% (113)

MDQ 11: you were much more interested in sex than usual?

64.9% (61)

MDQ 12: you did things that were unusual for you or that other people might have thought as excessive, foolish, or risky? 76.6% (72)

15.2% (192)

14.5% (184)

MDQ 13: spending money got you or your family into trouble?

Mean [SD] number of positive responses

57.4% (54)

9.7 [2.1]

11.5% (145)

3.0 [2.7]

Note: Comparisons of proportions of MDQ-positive vs. MDQ-negative respondents indicating “yes” are statistically significant for all items using Pearson chi-square test ( P < 0.001).

MD Q = Mood Disorder Q uestionnaire.

13-15

Items in italics represent exact quotations from the MD Q portion of the survey instrument.

SDS item and summary scale scores were reported as the propor tion of patients with “marked impairment” (score of 7-10 on a scale of 0-10).

Statistical Analysis

Demographic data and self-reported history were presented sepa rately for the cohorts of patients who screened positive (MDQpositive) and negative (MDQ-negative) for bipolar disorder.

Descriptive statistics were used to report continuous data and fre quencies, and percentages were reported for categorical variables.

SF-12 summary and item scores and productivity and absentee ism data from the SDS were compared using independent sample t -tests, and the percentages of patients with “marked impairment” in family, work, or social functioning domains as reported on the

SDS were compared using Pearson chi-square tests. For all analy ses, an a priori 2-tailed level of significance (alpha value) was set at the 0.05 level. Analyses were performed using STATA software version 8.2 (STATACorp., College Station, Texas).

■■ Results

-

A total of 41,738 patients from the claims database were iden tified as having MDD without bipolar disorder (Figure 1).

Among the MDD-only patients with contact information, 5,777 patients (13.8%) were contacted for participation in the telephone survey; 4,417 (76.5%) of those (a) could not be reached due to no response to phone calls placed by survey interviewers, (b) did not reply to voicemail messages, or (c) refused participation. All patients who were asked in the screening process whether they had been told by a physician that they had depression answered affirmatively.

The mean age for the 1,360 patients responding to the survey was 42.8 years (68.5% female); for nonrespondents, the mean age was 43.5 years (63.9% female) (data not shown). The age and gender distribution of the 1,360 patients completing the survey was similar to that of the overall 41,738 MDD patient popula tion (mean age 43.1 years, 68.2% female) in our original study sample.

Prevalence of Bipolar Disorder

Of the 1,360 patients with MDD and no current diagnosis of bipolar disorder in medical claims, 6.9% (n = 94) screened posi tive for bipolar disorder based on the MDQ. As expected, poten tially misdiagnosed (MDQ-positive) patients had significantly more positive responses on the 13 items of the MDQ than did

MDQ-negative patients (mean [SD] score: 9.7 [2.1] vs. 3.0 [2.7],

P < 0.001; median score: 9.5 vs. 2.0, respectively; Table 2). Patients



Among Patients With Major Depressive Disorder in a Commercially Insured Population who screened positive for bipolar disorder were much more likely than patients who screened negative to report symptoms of distraction, trouble concentrating, or trouble staying on track

(92.6% vs. 45.2% of respondents, respectively, P < 0.001) and racing thoughts (86.2% vs. 40.2%, respectively, P < 0.001). The greatest differences between MDQ-positive and MDQ-negative patients in the proportion of patients responding positively were for the symptoms of feeling “hyper” (56.4% vs. 7.9%, respectively,

P < 0.001) and “much more social or outgoing than usual” (60.6% vs. 8.9%, respectively, P < 0.001).

The prevalence of a MDQ-positive screen trended higher for men than for women (8.6% vs. 6.1%), but the difference was not statistically significant ( P = 0.091). Prevalence was higher in patients aged between 18 and 45 years of age (8.5%) than in patients aged 46 years or older (4.8%, P = 0.007; Figure 2; Table 3).

Disease Burden: Humanistic Outcomes

As shown in Table 4, patients with a positive MDQ screen were less likely to be married than were MDQ-negative patients (48.9%

TABLE 3 Age Category and Gender Stratification of Results From the Mood Disorder

Questionnaire

Number of Patients in Each Category

(by Age and Gender)

Male

Positive screen for BD on MDQ

Negative screen for BD on MDQ

Total

Female

Positive screen for BD on MDQ

Negative screen for BD on MDQ

Total

Prevalence of positive

MDQ screen by age groups

Age

18-35

13

93

106

18

236

254

8.6%

Age

36-45

13

112

125

22

266

288

8.4%

Age

46-55

9

128

137

14

239

253

5.9%

BD = bipolar disorder; MD Q = Mood Disorder Q uestionnaire.

13-15

Age 56 and Older

2

59

61

3

133

136

2.5% www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 637



TABLE 4 Comparisons of Characteristics of MDQ-Positive and MDQ-Negative Patients (n = 1,360)

Variable, Proportion of Patients

Male, % (n)

Age, % (n)

≤ 35 years

36-45 years

46-55 years

≥ 56 years

Work Status, % (n)

Unemployed/looking for work

High school or some college

Annual income ≤$15,000, % (n)

Marital Status, % (n)

Married vs. single or divorced

MDQ-Positive Cohort

(n = 94)

39.4 (37)

33.0 (31)

37.2 (35)

24.5 (23)

5.3 (5)

11.7 (11)

68.1 (64)

30.9 (29)

MDQ-Negative Cohort

(n = 1,266)

31.0 (392)

26.0 (329)

29.9 (378)

29.0 (367)

15.2 (192)

5.2 (66)

48.3 (612)

21.4 (271)

Univariate

Odds Ratio

1.44

REF

0.98

0.66

0.27

2.40

2.27

1.63

P Value

0.092

–

0.956

0.153

0.009

0.011

a

0.000

b

0.035

48.9 (46) 60.7 (768) 0.62

0.025

Risk Behaviors and Symptoms, % (n)

Cigarette or tobacco use during the past week

Suicidal ideation (lifetime) c

Dependence on or abuse of street drugs or prescription drugs

(lifetime)c

Dependence on alcohol (lifetime) c,d

41.5 (39)

61.7 (58)

34.0 (32)

9.6 (9)

22.5 (285)

29.4 (372)

11.1 (141)

2.9 (37)

2.44

3.87

4.11

3.51

< 0.001

< 0.001

< 0.001

< 0.001

Other Self-Reported Measures and Diagnoses % (n)

Psychotic disorders or hallucinations (lifetime diagnosis) e

OCD (lifetime diagnosis) e

Family history of mania (lifetime) f

Nervousness or anxiety (current) g

9.6 (9)

24.5 (23)

36.2 (34)

64.9 (61)

2.4 (31)

8.2 (104)

14.6 (185)

41.4 (524)

4.21

3.61

3.31

2.61

< 0.001

< 0.001

< 0.001

< 0.001

a Alternative category: employed.

b Alternative category: bachelor’s degree or higher.

c Preface to item asked: “For each item I read, please tell me whether it has ever applied to you.” d Item was skipped and coded “No” for respondents who indicated that they had not consumed any alcoholic beverages in the past 4 weeks.

e Preface to item asked “Has a doctor ever mentioned that you have or have had …?” f Preface to item asked “Has any of the following ever applied to any of your family members, that is, your parents, brothers, sisters, aunts, uncles, or grandparents?” g Item asked “Would you describe yourself as frequently nervous, worried or anxious?”

MD Q -positive = screened positive for bipolar disorder on Mood Disorder Q uestionnaire; 13-15 OCD = Obsessive-compulsive disorder.

vs. 60.7%, P = 0.025). Self-reported annual income of less than or equal to $15,000 was also significantly more common among

MDQ-positive than MDQ-negative patients (30.9% vs. 21.4%,

P = 0.035). Additionally, more patients with a positive screen for bipolar disorder reported lifetime histories of obsessive compul sive disorder (24.5% vs. 8.2%, P < 0.001), psychotic disorders or hallucinations (9.6% vs. 2.4%, P < 0.001), suicidal ideation (61.7% vs. 29.4%, P < 0.001), and drug abuse (34.0% vs. 11.1%, P < 0.001) than did patients with a negative screen for bipolar disorder.

SF-12

Thirty-three of 94 MDQ-positive respondents (35.1%) and 79 of

1,266 MDQ-negative respondents (6.2%) completed the SF-12 and SDS questionnaires. PCS and MCS scores (range 0-100, with higher scores representing better health) were compared between

MDQ-positive and MDQ-negative cohorts (Figure 3). This analysis represented a point estimate of disease burden in terms of health status, with a recall period of the past 4 weeks. The

2 groups did not significantly differ on the PCS; however, patients with a positive screen for bipolar disorder had significantly lower mental health functioning as measured by the MCS (mean

[SD] = 34.7 [11.7]) than did those with a negative screen (48.9

[10.8], P < 0.001). Among the individual domains or items, MDQpositive patients reported significantly worse performance on the social functioning and role emotional scales than did MDQnegative patients.




SDS

A significantly greater proportion of MDQ-positive patients reported marked impairment (score of 7 or higher on 10) in the

3 areas assessed than did MDQ-negative patients: work life

(54.5% vs. 24.1%, respectively, P = 0.002), social life (66.7% vs.

39.2%, P = 0.008), and family life (66.7% vs. 34.2%, P = 0.002;

Table 5) Additionally, in the 4 weeks before assessment, patients in the MDQ-positive cohort missed more than 6 times as many days of work (mean [SD] = 2.0 [2.4]) as the MDQ-negative cohort

(0.3 [1.0], P = 0.001). Reported days of reduced efficiency for

MDQ-positive and MDQ-negative patients did not significantly differ (1.0 [1.8] vs. 0.5 [1.2], respectively, P = 0.085).

■■ Discussion

This study evaluates the prevalence of potentially misdiagnosed bipolar disorder among a sample of patients with medical claims for MDD and the humanistic impact associated with misdiag nosis. Additionally, the study identified self-reported patient characteristics that were associated with potential misdiagnosis of bipolar disorder. Using the MDQ screening tool developed by

Hirschfeld et al., 13-15 the overall proportion of patients screening positive for bipolar disorder was approximately 7%. This rate is similar to that reported in a study of 1,157 patients seeking primary care at an urban medicine clinic serving a low-income population, in which 10% screened positive on the MDQ for a lifetime history of bipolar disorder.

23 However, it is significantly lower than other prevalence reports in the literature, which range from 19% to 37%.

24,25 Calabrese et al. (2006) reported a MDQ screen positive prevalence rate of 18.6% using the traditional scor ing method.

25 A recent study by Hirschfeld et al. (2005) 15 using the MDQ showed evidence of bipolarity in 21% of patients with

MDD in primary care settings. Ghaemi et al. (2000) 24 found a

37% rate of misdiagnosis in an outpatient psychiatric population.

Prevalence estimates in primary care populations may yield lower rates than those in psychiatric populations.

25 Other causes of differences between the rates found in this study and other reported estimates include the use of a telephone survey rather than face-to-face diagnostic interviews, and the use of the MDQ screening tool as opposed to Structured Clinical Interview for

DSM-IV (SCID).

It is well recognized that patients with bipolar disorder have diminished quality of life.

5,6,26,27 In this analysis, patients with potentially misdiagnosed bipolar disorder as assessed by the MDQ had significantly lower performance on the social functioning, www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 639



TABLE 5 Sheehan Disability Scale Results

Sheehan Disability Scale

On a scale from 0 to 10, with 0 equal to not at all and 10 equal to severe, how much has depression disrupted:

Your work life (% with marked impairment) b

Your social life (% with marked impairment) b

Your family life (% with marked impairment) b

Number of days missed or unable to do responsibilities in the past week: mean [SD]

Number of days of reduced efficiency even though you went to school/work in the past week: mean [SD]

MDQ-

Positive

(n = 33)

MDQ-

Negative

(n = 79)

54.5% (18) 24.1% (19)

66.7% (22) 39.2% (31)

66.7% (22) 34.2% (27)

2.0 [2.4] 0.3 [1.0]

1.0 [1.8] 0.5 [1.2]

P

Value

0.002

0.008

0.002

0.001

0.085

MD Q -positive = screened positive for bipolar disorder on Mood Disorder

Q uestionnaire.

13-15 a P value for Pearson chi-square for percentages and t-test for number of days.

b Patients with scores ≥ 7 on a scale of 0 to 10 were considered to have marked impairment.

a bipolar disorder.

30 Several published reports assessing costs of bipolar disorder and the economics of misdiagnosis suggest that misdiagnosis is associated with an increased direct and indirect cost burden.

11,17,30-33

Although the patients screening positive on the MDQ in this study may encompass both bipolar I and bipolar II patients, it is noteworthy that a previous study found that mean 1-year allcause health care costs were nearly 4 times as high for patients with bipolar I disorder as for a comparison group of age- and sex-matched health plan members without a diagnosis of bipolar disorder ($7,663 vs. $1,962, respectively).

34 Rajagopalan et al.

(2006) found significantly higher all-cause annual health care service costs in employees with bipolar disorder compared with employees with other mental disorders and estimated the annual all-cause health care costs for employees with bipolar disorder at

$9,983, compared with $3,147 for a matched comparison group without bipolar disorder.

outcomes.

33

The poor humanistic outcomes in MDQ-positive patients in this study and the burden of illness associated with bipolar disorder reported in previous studies suggest that accurate and early diagnosis of bipolar disorder may result in improved patient role emotional, and mental health scales of the SF-12, compared with MDQ-negative patients. In terms of personal interactions, our study findings indicate that a positive screen on the MDQ is associated with marked impairment in work, family, and social function. Results also suggest that patients screening positive for bipolar disorder on the MDQ are less likely to be married than

MDQ-negative patients with MDD, and more likely to engage in high-risk behaviors.

The findings of this study are consistent with the findings reported by Calabrese et al., in that patients screening positive on the MDQ have more difficulties with work-related performance, social/leisure activities, and social/family interactions, compared with MDQ-negative patients.

28 Das et al.

23 reported that, in an urban clinic setting, patients screening positive on the MDQ had significantly lower mental health functioning as evaluated by the

SF-12 and higher rates of marked depression-related impairment

(a score greater than or equal to 7 on the subscales of the SDS) in their social and family life than did MDQ-negative patients. Our findings further strengthen the data presented in the literature on poor HRQOL and social functioning for patients screening posi tive on the MDQ.

Although this study did not evaluate burden of illness in terms of indirect costs, previous studies have documented the loss of productivity associated with bipolar disorder.

3,29 Gardner et al. found that employees with bipolar disorder missed 18.9 work days annually, compared with 7.4 days for employees without

Limitations

Although the combination of a claims-based analysis coupled with personal interviews of a large sample of MDD and bipolar disorder patients provides a unique source of data, this study has several limitations. First, the MDQ was used as the sole screen ing instrument for bipolar disorder, and the positive MDQ cases were not validated by the SCID diagnostic interview. The MDQ has been reported to have a sensitivity of 73% and a specificity of 90% in an outpatient clinical setting, 13 which suggests the occurrence of some false-positive screens in our study sample.

Second, the 23.5% response rate to the telephone survey may raise concerns about nonresponse bias. However, a comparison of age and gender between respondents and nonrespondents indicated no meaningful differences between the groups on these characteristics. Third, the study design was retrospective, and the MDQ-positive cohort was populated using a quota sampling methodology. Causality cannot be ascribed in a study with a cross-sectional design, and the possibility exists that a factor other than bipolar disorder symptoms was the cause of the differences in outcomes.

Fourth, the use of administrative data also raises issues of coding accuracy and completeness, which may affect the results, and statistical differences in retrospective reviews reflect the quality of the data entered and abstracted from the database. Data updated through March 31, 2005, were used to conduct the sur vey in August 2005. During this time frame, patients with MDD may have been diagnosed with bipolar disorder, but due to a lag in claims processing, these patients may have been included in the MDD-only cohort of patients that were surveyed.




Finally, the study excluded patients younger than 18 years of age, and bipolar disorder symptoms may appear in a large proportion of patients before age 15.

7 Despite the limitations, the present study provides evidence of the humanistic impact associ ated with potential misdiagnosis of bipolar disorder.

ACKNOWLEDGEMENTS

The authors would like to acknowledge the editorial assistance of Eleanor

Bull, PhD, and Anusah Bolonna, PhD, (PAREXEL MMS) in manuscript review and revisions. Financial support for this assistance was provided by

AstraZeneca Pharmaceuticals LP.

■■ Conclusion

The bipolar disorder misdiagnosis rate was 7% among managed care patients diagnosed with MDD. Patients with MDD who screened positive for undiagnosed bipolar disorder reported poorer scores on measures of mental health, role functioning, and depression-related disability scores than did patients who screened negative. Single marital status; lower self-reported income; a higher rate of high-risk behaviors; and poor social, family, and work functioning also were associated with an MDQpositive screen for bipolar disorder. Future research should focus on the development of clinically relevant predictors of bipolar disorder misdiagnoses that can help to identify high-risk patients.

Authors

SIDDHESH A. KAMAT, MS, is Research Operations Director at

HealthCore, Wilmington, Delaware. KRITHIKA RAJAGOPALAN,

PhD, is currently Director of Health Economics and Outcomes

Research at Biogen-Idec, Cambridge, Massachusetts. At the time of this study, Dr. Rajagopalan was Director of Health Economics and

Outcomes Research at AstraZeneca Pharmaceuticals LP, Wilmington,

Delaware. VINCENT WILLEY, PharmD, is Associate Professor of

Pharmacy, University of the Sciences in Philadelphia. At the time of the study, Vincent Willey was Vice President, Research Operations, at

HealthCore. NED PETHICK, PharmD, MBA, is Director of Managed

Markets; MARIAM HASSAN, PhD, is Manager of Health Economics and Outcomes Research; and MICHAEL BULLANO, PharmD, is

Director of Health Economics and Outcomes Research at AstraZeneca

Pharmaceuticals LP. At the time of this study, Michael Bullano was

Director of Analytics at HealthCore.

AUTHOR CORRESPONDENCE: Siddhesh A. Kamat, MS.

HealthCore Inc., 800 Delaware Ave., 5th Floor, Wilmington, DE

19801. Tel.: 302.230.2177; E-mail: skamat@healthcore.com

DISCLOSURES

This study was supported by a research grant from AstraZeneca

Pharmaceuticals LP, Wilmington, Delaware. Three of the authors—Ned

Pethick, Mariam Hassan, and Michael Bullano—are current employees of AstraZeneca Pharmaceuticals LP, and Krithika Rajagopalan is a former employee of that company.

Study concept and design were contributed primarily by Kamat,

Rajagopalan, and Pethick. Bullano and Kamat collected the data. Data inter pretation was performed primarily by Bullano, Hassan, and Willey. The man uscript was written primarily by Kamat, Hassan, and Willey. The manuscript was revised primarily by Kamat and Hassan.

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Mood Disorder Questionnaire. Am J Psychiatry . 2000;157:1873-75.

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Disord . 2002;4:398-405.


C O M M E N TA R Y

2008: A Tipping Point for Disease Management?

Brenda R. Motheral, BPharm, MBA, PhD

G iven recent events, 2008 has certainly been a year of discontent for the commercial disease management industry 1 and ultimately may turn out to be its tipping point. The year kicked off with continuing questions about the effectiveness of disease management, precipitated by Mattke et al.’s highly publicized study from late 2007, “Evidence for the effect of disease management: Is $1 billion a year a good investment?” Based on a review of the literature, the authors concluded that the savings from population-based programs are uncertain, warning plan sponsors to be “skeptical about vendor claims.” 2

In early January, The Centers for Medicare & Medicaid

Services (CMS) announced that it had lowered the savings target for the Medicare Health Support (MHS) Program from 5% net savings to budget neutrality at the request of the MHS vendor organizations.

3 This news was quickly followed by a CMS announcement that it would terminate the MHS demonstrations for failure to meet the statutory requirements, including cost savings that matched vendor fees.

4

At about the same time, Inverness Medical Innovations publicized its intention to purchase Matria, one of the largest disease management companies in the United States.

5 With Inverness’ previous purchases of Alere and Paradigm and the late 2007 acquisition of Health Dialogue by British United Provident

Association, only the largest of the 3 disease management companies remained independent. On top of the CMS announcement, the industry’s largest vendor was further challenged by unexpected reductions in demand for its services.

6

Concerns about disease management resurfaced again in June when a peer-reviewed study found that disease management had no significant impact on adherence to pharmacologic treatment after myocardial infarction.

7 In an editorial accompanying the study, Mattke asked whether a disease management backlash exists.

8 Increasingly, the answer appears to be yes. Once the darling of employers and benefits consultants, disease management is now the object of considerable dissatisfaction and growing doubts.

9,10 Industry observation suggests multiple reasons for this disaffection. Five of the most important include a desire for (a) better alignment of vendor and client interests, (b) greater transparency in business arrangements, (c) improved plausibility in reports of financial and clinical outcomes, (d) more rigorous evaluation methodology, and (e) more convincing evidence of outcomes improvement.

1. Misalignment of Vendor and Client Interests

The most common form of disease management enrollment is the opt-out model, which means that members are enrolled in the program unless they explicitly opt out.

11 The industry shift to an opt-out model was consistent with the belief that continual efforts were needed to engage members and, conveniently, allowed use of return on investment (ROI) methodologies without casematching, which adds complexity. The opt-out model has been positive for revenue and gross margin. Members who cannot be reached are still enrolled, with an accompanying revenue stream from the plan sponsor, yet accrue little cost to the disease management vendor. Furthermore, members infrequently “graduate” from the program, thus providing a perpetual revenue stream for the disease management vendor until the member leaves the health plan or employer.

Although good for vendor revenue, the opt-out model has resulted in a lack of alignment between vendor and plan sponsor. The disease management vendor has limited incentive to aggressively reach out to members for 2 reasons: Outreach efforts incur incremental costs without raising incremental revenue; and there is a risk that, once reached, the member will opt out of the program. In its extreme, the opt-out model encourages disease management vendors to cut costs in time of pricing pressure by reducing call center staff. Although one might expect that the competitive need to demonstrate ROI would provide an incentive to enroll members into services, it is not clear that the link between staffing levels and outcomes (which appear to be more methodology driven than intervention driven) is strong enough, from the vendor’s perspective, to overcome the disincentive to incur higher operational costs. Accordingly, a disease management vendor can titrate its operational expenses to meet its profit goal in times of pricing pressure. Equally important, the opt-in model has left plan sponsors paying a monthly fee for an entire population of diseased members when only 25% may actually participate in the program at least once, and far fewer engage on an ongoing basis.

12

The largest plan sponsors are increasingly addressing the lack of alignment through 2 approaches. The first approach is to have contractual requirements for minimum staffing levels or administrative performance metrics, but these arrangements require precise contractual language. For example, if staffing levels are calculated at the end of the month (per the contract), a vendor can wait until the last week of the month to hire and begin training www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 643

2008: A Tipping Point for Disease Management?

new staff for open positions, thus effectively operating at a lower than required staffing levels during most of the month.

The second approach has been to move to an engagement model, meaning that the vendor is paid the full fee for only those members who are reached, typically by telephone. A stricter version of the engagement model is the opt-in model, which requires members to agree to participate in the program before they are enrolled and before the plan sponsor pays any fee. Neither option provides a complete solution to the problem of misaligned incentives, but both options represent a better-aligned relationship than the opt-out model in the face of questionable improvement in clinical and financial outcomes.

2. Insufficient Transparency

Closely related to concern over misalignment of vendor and client interests in disease management is a growing frustration with insufficient transparency, particularly in the areas of engagement, intervention, and reporting. Perhaps the biggest transparency concern revolves around levels of engagement, which means knowing how many members are contacted, typically by telephone. Plan sponsors desire transparency because engagement levels can serve as an early indicator of ultimate success, a plausibility indicator when reviewing outcomes results (i.e., patients with higher engagement levels should have better outcomes), and as one comparative process measure of vendor effectiveness (i.e., better vendors are expected to contact more patients).

Despite its obvious importance, engagement is commonly a

“black box” to plan sponsors because of limited vendor reporting.

Even when engagement levels are reported, there are options for defining engagement and vendors use different methodologies, adding to the transparency challenge. For example, one vendor might exclude members with invalid telephone numbers from the denominator when calculating engagement levels, whereas another may not. Given that members with invalid telephone numbers can represent 10%–20% of the membership, the exclusion of these individuals from the calculation can make a material difference in the overall reported engagement level.

For larger and more sophisticated plan sponsors, the desire for transparency around engagement extends beyond aggregate reporting to identifying exactly which members are engaged by which channel (telephone, mail, etc.). Such information allows plan sponsors to conduct independent assessments of program effectiveness and understand interactive effects between the disease management and other vendors’ programs on both participation and outcomes.

Greater transparency is desired around not only the level of engagement, but also the intervention itself. Plan sponsors have no reliable, routine, and cost-effective way to assess the quality of the intervention. Neither call recording (i.e., recording of the actual phone conversation) nor intervention notes (i.e., detailed notes of the call that are taken by the nurse/coach) are standards in the industry.

13

In addition to enhanced reporting on engagement, greater transparency is desired on evaluation methodology and clinical results through timelier, more detailed, and more readily accessible reporting. For example, MacStravic suggests that vendors should better develop their “paper trail” of metrics that should be linked to outcomes improvement.

14 Examples could include motivation, self-management knowledge, behavior changes, and self-efficacy. By seeing real changes in these leading indicators, plan sponsors could have more confidence that the outcome improvements are actually a result of the disease management intervention. Finally, it is important to keep in mind that the transparency challenges go beyond the 3 issues mentioned here and extend to other aspects of operations, such as transparency in referral fees paid to consultants, quality of data on enrollment, etc.

As plan sponsors and consultants push for greater transparency, some vendors have yet to embrace the transparency movement given the potential business implications and the capital required to make the necessary system changes. Will disease management vendors hold up under the scrutiny that comes with greater transparency? The push for greater transparency in pharma funding in the pharmacy benefit management (PBM) industry resulted in one PBM discontinuing any ancillary funding from pharmaceutical manufacturers, 15 led to the development of client pledges that outlined specific behaviors around alignment and transparency, 16 and opened the door for new, smaller

PBMs that claimed to offer aligned and fully transparent business models.

17,18 If other industries are any indication, expect the demand for transparency to drive widespread changes in business practices and perhaps even the competitive landscape.

3. Improved Plausibility Is Needed

Surprisingly, concerns about plausibility have been a more recent phenomenon as plan sponsors are increasingly questioning the size and timing of the ROI and researchers continue to challenge the scientific underpinnings of the disease management model.

Although many vendors produce ROIs that range from 1.5 to 3.0, larger ROIs are sometimes still claimed for the core chronic conditions, such as diabetes and heart failure. In the case of noncore conditions (e.g., arthritis), vendors have been known to claim

ROIs that are 10- or even 20-fold. Obviously, the 10- and 20-fold

ROIs raise red flags and strongly suggest that the statistical phenomenon of regression to the mean (the tendency for utilization of high-cost members to decline over time, with or without intervention), rather than the intervention, is the more plausible explanation for the findings.

In the case of the less extreme ROIs, plan sponsors will still question the ROI, particularly when it does not align with other relevant data points, such as engagement levels. For example, a plan sponsor would question a vendor who showed an ROI that increased over time while engagement decreased over time.

Similarly, a health plan would question a vendor that claimed a



higher ROI for Employer A than for Employer B, even though

Employer A had significantly lower engagement levels, all else being similar. Another simple and powerful plausibility test is a comparison of the ROI for engaged versus nonengaged members because one would expect the ROI to be higher for engaged members.

Although the examples above are good screeners for plausibility, they are no guarantee that the ROI is legitimate. The plausibility of the results can be further assessed by comparison to utilization changes. Lewis and Linden have led adoption of this approach. They provide an example of the utilization plausibility test for asthma based on the disease management model of reducing emergency room (ER) visits and hospitalizations for asthma through better daily management.

19

For this example, assume that the program fee is 5% of total expenditure and that asthma-related ER visits and hospitalizations represent 25% of total expenditure (Table 1). Under these assumptions, a 40% reduction in ER and hospitalization expenditure for asthma is needed to achieve a 2:1 ROI. Obviously, a

40% reduction in ER/hospital costs for asthma is a high bar and beyond the effect seen in published studies of disease management.

On a related note, CMS questioned the plausibility of costsavings for the MHS pilots given the relatively low level of disease-related admissions observed across vendors. Specifically,

CMS reported that the MHS vendors had 3 nondisease-related admissions for every 1 disease-related admission, in the case of both heart failure and diabetes, and expressed concern that vendors have “overestimated the impact of their intervention on their ability to reduce the stream of beneficiary utilization.” 20

It is important to keep in mind that, in the above example, a 40% reduction is conservative because it assumes no increase in drug expenditure or other services that would have to be offset through additional savings and does not reflect real-world engagement levels. Continuing the previous example, if one half of the asthmatics targeted by the program are actually engaged, an

80% reduction in asthma-related ER/hospital costs for those asthmatics engaged in the program is needed to achieve a 2:1 ROI.

The formal analysis for this approach is number needed to decrease (NND), which allows plan sponsors to determine whether the claimed ROI is even possible.

21 The Disease

Management Association of American (DMAA) adopted the NND plausibility test as part of its outcomes guidelines.

22 However, use of this test is just beginning to take hold in the industry—the ability of disease management vendors to “pass” the plausibility test remains to be seen.

Although the plausibility test focuses on a retrospective assessment, there is growing evidence that challenges the epidemiologic foundation of the outcomes expected from disease management programs. Again, an example best illustrates the issue. Suppose that a program serves a 50-year-old, 250-pound male diabetic with a hemoglobin A1c of 9 and low-density lipoprotein cho-

TABLE 1 Lewis and Linden Plausibility

Example a

Total Expenditure

ER/hospital expenditure—all reasons

ER/hospital expenditure—asthma-related

Program fee

Expenditure Per

Asthmatic Per

Year

$2,000

$1,000

$500

$100

Percent of Total

Expenditure

–

50%

25%

5%

2:1 ROI = $100 (program fee) × 2 = $200

Asthma-related ER/hospital expenditure reduction needed = $200/$500 or 40% a

ER=emergency room; ROI=return on investment

From Lewis A and Linden A. The ultimate guide to outcomes measurement for disease management and wellness.

19 lesterol (LDL-C) of 228. A well-validated epidemiologic model shows that aggressive management to lower the A1c from 9 to 7 will reduce the 3-year risk of myocardial infarction from 12.9% to 11.3%, the risk of stroke from 1.7% to 1.4%, the risk of retinopathy from 0.23% to 0.12%, and the risk of foot problems from

0.5% to nearly zero.

23

Although clinically meaningful, these reductions seem insufficient to drive a short-term positive ROI given the small absolute risk reduction and incremental cost to manage. Accordingly, a plan sponsor must be willing to believe that short-term savings will be generated from reductions in ER visits (and hospitalizations) for short-term complications, primarily hypoglycemic events requiring emergency care, which average 3.4 per 100 person-years among diabetics.

24 Research suggests otherwise.

More than a decade ago, researchers using a Monte Carlo simulation of the Diabetes Control and Complications (DCCT) Trial found that intensive management of blood glucose in patients with diabetes did not provide either short- or long-term net direct medical savings.

25 Recently, researchers from the American

Diabetes Association and American Heart Association, using a well-validated epidemiologic model, found that neither blood glucose control nor blood pressure control in patients with diabetes produced cost savings even over 30 years.

26 The question of value is compounded by the recent outpouring of evidence that chasing biomarkers is also not associated with expected nonfinancial end-point outcomes.

27

Against this backdrop, disease management vendors have been conspicuous in the lack of provision of epidemiologic and economic underpinnings for program intervention effects.

Given the large datasets at their disposal, vendors could provide population-based modeling, based on evidence in the literature that shows the causal pathway and the corresponding effect on process measures to produce the desired results. In addition, many vendors should have sufficient experience at this point to factor in the cost of medications and other services that generate a cost increase. Of course, vendors run the risk that a priori identification of the outcomes drivers will suggest that the program is not a good investment for a particular plan sponsor given its www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 645


underlying utilization patterns. This question was raised more than a decade ago, when clinical researchers challenged the economic and clinical benefit of an asthma disease management program for a health plan with a high ratio of drug costs and a low ratio of ER and inpatient hospitalization costs (relative to total expenditure).

28

4. More Rigorous Evaluation Methodology

The need to conduct plausibility tests is partially a symptom of the historic weakness of the methodologies used to evaluate disease management programs. The most common approach to calculating an ROI has been to compare the actual observed trend for the diseased members to an expected trend based on actuarial forecasting techniques and other adjustments developed specifically for disease management (e.g., using the trend of nondiseased members as the expected trend). Major challenges with this approach are that trends for whole programs are subject to random variation and that trend estimates can vary dramatically depending on reimbursement rates, claims run-out patterns, and numerous other wild cards. These externalities and methodological decisions can have a dramatic impact on the ROI calculation even when they affect expected or actual trend by only a few percentage points.

From a design perspective, the ROI methodology has been inadequate to establish a causal link between the program and the outcomes because the threats to validity, including regression to the mean and selection bias (i.e., a comparison to a nonequivalent group), are not sufficiently addressed.

11 Absent a randomized trial, which was used in the MHS demonstrations but is clearly not practical on a routine basis, the strongest evaluation approach for disease management interventions is the quasi-experimental, pre-post with comparison group design, adjusting for known differences. The use of a comparator group is essential to control for many potential confounders, one of the most concerning of which is regression to the mean. Vendors have developed numerous methodologies, short of control groups, in an attempt to address this limitation (e.g., adjust for nondiseased trend), but none has been shown empirically to be adequate.

More recently, DMAA has advocated the use of control groups as best practice when practical, but their use in the market has been limited to date. If disease management vendors provide a comparison group, they frequently use nonparticipants as the comparator.

29 Although convenient, this approach is problematic because the reasons why an individual chooses to participate in a program (e.g., motivation, trust of provider, or general inclination toward adherence with medical treatments) are likely related to their ultimate outcomes, yet cannot be controlled empirically through variables that are measurable using medical claims data.

In terms of the preferred approach of using comparison groups from other populations (e.g., a group of members who meet the same diagnostic criteria as disease management participants but to whom no disease management program is available), some argue that the use of comparison groups is too costly, takes too much time, or is simply not possible because no comparison group exists. In other words, they argue that there is a trade-off between rigor and practicality. Typically, these barriers are the exception rather than the rule. Many health plans sell disease management services as an add-on to the medical benefit for their administrative service only (ASO) groups (i.e., employers who self-fund). This sales strategy provides multiple employer groups for comparison because purchase of disease management services among ASO groups is rarely 100%. Similarly, in the case of an employer who purchases directly from a disease management vendor, the disease management vendor can often provide an adequate comparison group from its health plan’s ASO customers who have not yet purchased the program 30 or, if desired, through staggered implementation across the employer’s sites.

Although vendors cannot provide a comparison group in every case, they can usually do so for larger clients. For smaller clients, providing relevant benchmarks of expected outcomes improvement over time (for employers with and without disease management) would be a positive step forward, even though no direct statistical comparisons can be made. Increasingly, more sophisticated plan sponsors do not rely on the disease management vendors to provide comparison group results. Instead, they are producing their own analyses in-house or with third-party assistance.

Finally, as evidenced by DMAA changing its name to DMAA:

The Care Continuum Alliance, 31 disease management vendors have expanded rapidly into the health and wellness arena, which is fraught with numerous new methodological issues that warrant close attention. For example, the measurement of productivity savings is currently as much art as it is science, offering degrees of freedom in terms of methodological options and making it susceptible to exaggeration.

32 A vendor might apply productivity savings from a member survey that had only a 20% response rate to the entire population to generate an ROI for the program.

This approach will overstate health-related productivity loss if the individuals who responded to the survey are significantly sicker and incur greater health-related productivity loss than the overall population, as is frequently the case. Determining the value of improvements in biometrics scores is another area of relatively uncharted territory where extraordinary claims of value are being made, but the rigor of methodologies to validate those claims is not keeping pace. On these new issues, it will be important to proactively identify rigorous and practical solutions to assessing the value of these programs.

5. Evidence of Improvement in Outcomes

Ultimately, most of the issues identified above are symptoms of the fundamental question surrounding disease management: Does it work? By “work,” decision makers usually mean “save money,” with a secondary interest in improved clinical outcomes.

A meta-analysis of studies from 1995 to 2003 found a small to moderate effect of disease management on medical costs.

However, the statistical analysis combined multiple models of



disease management from numerous countries, making it difficult to reach any conclusions about the sparsely represented commercial, population-based, telephonic programs in the U.S.

33 As mentioned earlier, Mattke et al.’s review (December 2007) 2 found just 3 studies of population-based disease management from

1990 to 2005, only 1 of which used a quasi-experimental design but had other limitations, 34 leading the authors to conclude that plan sponsors should take a hard look at vendor assertions of success.

2 Since that time, Chan and Cooke found that disease management had no impact on pharmacotherapy after myocardial infarction.

7 Finally, CMS found no evidence of cost savings from the MHS demonstrations; 20 and although the design and implementation of the pilot have been criticized, 35,36 CMS has not waivered.

Interestingly, of all this work, Chan and Cooke received the least attention, although the study was quite important due to its use of a contemporary comparison group to examine medication compliance, a critical indicator of program success. To date, there is no strong evidence that disease management has improved the well-known compliance problem that exists for chronic diseases such as diabetes and cardiovascular disease. This is somewhat ironic given that first-generation disease management programs were frequently funded by pharmaceutical manufacturers and focused on increasing patient compliance with chronic medications.

Given little rigorous evidence suggesting that telephone-based disease management programs save money, how do many of the disease management vendors make claims of value? They do so by citing their own analyses that are lower in the hierarchy of evidence (e.g., case reports and case controls) and/or studies that do not address effectiveness directly. After 10 years and tens of millions of enrolled members, one would expect a richer body of literature. Although some might claim that rigorous studies are not feasible for all the reasons mentioned earlier, pre-post, comparison group studies are a viable approach. Accordingly, the lack of literature is more likely explained by a lack of effectiveness combined with publication bias. Absent a countervailing force, one would expect disease management vendors in a competitive marketplace to selectively publish results that put them in the most favorable light. Evidence of this publication bias was found in a meta-analysis published in 2005.

37

It is important to keep in mind that a lack of evidence and potential for publication bias are hardly unique to the disease management industry. Publication bias is a systemic problem that has been documented most extensively in the pharmaceutical industry.

38,39 If we look to that industry for guidance, several partial solutions have been suggested and a few implemented, including Guidelines for Good Publication Practice, 40 as well as calls for more government or other independent funding, independent statistical assessment of results before publication, and a trials database that requires companies to register their clinical trials at the outset.

41 All represent only partial solutions but as a whole, provide some checks and balances for the industry.

Clearly, pharma has come under the most scrutiny because pharmaceuticals can do real harm when ingested. Accordingly, although it would be useful to implement many of the solutions above in disease management, it would be unrealistic to expect such an implementation to materialize. Even the government is not likely to fund additional pilots until 2010 or beyond. Thus, the responsibility lies with plan sponsors, both health plans and employers, to conduct these evaluations (or share their data with third-party researchers) for dissemination. MacStravic advocates that employers and health plans expand and/or coordinate their efforts, perhaps even financially sponsor a national body to conduct systematic analyses of disease management programs.

42 As

MacStravic notes, the criteria for disease management interventions are already established and generally agreed upon, so the incremental time and cost should be modest. MacStravic argues that “if payers demand comparative information from all HDM

[health and disease management] providers, in some standard format and understandable mode of reporting, providers will have little choice but to deliver it… No provider will want to be shut out of consideration for having failed to provide the information called for by their prospects and current clients.” 42

Finally, research continues to suggest that the fundamental question of what defines the value proposition for disease management should be revisited. Although disease management had its roots in improving the quality of care, it quickly evolved to a net savings requirement, even though literature suggests that less than 20% of treatments for existing conditions are cost-saving.

43

A net savings requirement may simply be too high a hurdle given the findings to date. Kahn et al. found that smoking cessation was the only prevention intervention that produced cost savings over

30 years in the U.S. population given current market prices.

26

However, when measured on a cost per quality-adjusted life-year saved (QALY), some disease management interventions may, in fact, provide a good value. Kahn et al. found that glucose control in patients with diabetes costs $48,759 per QALY (not including the cost of a disease management program) and using aspirin in high-risk individuals costs only $2,779 per QALY. In contrast, lowering of LDL-C in those at high-risk for coronary heart disease costs $83,327 per QALY, which exceeds the well-known but arbitrary threshold of $50,000 per QALY.

26

■■ Conclusions

Although enthusiasm for disease management was once a matter of philosophical belief, the tolerance of plan sponsors for weak evidence of the value of disease management is dissipating. Current evidence does not suggest that commercial disease management saves money in any of its current variations. As to whether disease management can produce beneficial outcomes, the answer will likely depend, in part, on the criteria for effectiveness—net savings, clinical improvement, or a reasonable cost per QALY. That said, the business challenge is that deciwww.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 647


TABLE 2 Disease Management Purchasers’

Challenges and Opportunities

Challenges

Misalignment of vendor and client interests

Strategies to Drive Greater Value from Disease Management

• Move to a revenue model that aligns incentives between vendor and client.

Insufficient transparency • Require greater transparency on engagement, interventions, and reporting.

Improved plausibility needed

• Conduct plausibility tests, both prospective and retrospective.

More rigorous evaluation methodology

Evidence of improvement in outcomes

• Require comparison groups from nonparticipat ing groups, rather than from nonparticipating individuals.

• Expand outcomes assessment and contract requirements to include key clinical indicators

(e.g., medication compliance).

• Share findings with other purchasers.

-

Author

BRENDA R. MOTHERAL, BPharm, MBA, PhD, is President,

CareScientific LLC, Brentwood, Tennessee.

AUTHOR CORRESPONDENCE: Brenda R. Motheral, PhD,

CareScientific LLC, 5115 Maryland Way, Brentwood, TN 37027. Tel:

615.915.1357; E-mail: bmotheral@carescientific.com

DISCLOSURES

The author is a former employee of a disease management company and provides consulting services in the design, management, and evaluation of disease management interventions.

sions to fund disease management become much more difficult under a cost per QALY framework than when claiming net cost savings, particularly in economic downturns. Regardless of the success measure, to overcome the current hurdles to establishing value, future disease management programs may require a more targeted approach that includes more selective enrollment, more focused interventions, and greater customization to the specific gaps and cost drivers of an individual plan sponsor.

Plan sponsors also bear responsibility for the current situation.

As long as they demand a short-term ROI in the current model and inconsistently require comparison groups, they are more likely to promote methodological creativity than they are to inspire true innovation. They must consistently challenge vendors, look for the evidence beyond the marketing, and share their experience.

The same holds true for those benefits consultants who have bought into the ROI concept so much that their requests for proposals demand a methodologically unsound ROI calculation. That demand puts pressure on the disease management companies to have an ROI option even when they know it makes no sense— they risk losing the contract to another company that promises an exaggerated ROI. Table 2 summarizes the 5 challenges and accompanying actions that plan sponsors and consultants can take immediately to mitigate the issues outlined here.

Although some people question whether disease management will meet a fate similar to that of the HMOs in the late 1990s, 8 the continued experimentation in the retail- and employer-based model and optimism among some stakeholders for the medical home model will keep the disease management industry on the radar for the near future. During this time, marketplace entry by new vendors with notably innovative solutions is likely. If plan sponsors and consultants work collaboratively to set a higher bar, the next generation of vendors will be required to put more emphasis on the epidemiologic and economic science of disease management than has been seen previously.

REfEREnCES

1. Referring specifically to the telephonic-focused, nurse-based, for-profit sector of the disease management industry

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2007;13:670-76.

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2008. Available at: www.cms.hhs.gov/CCIP/downloads/QAforPublic.pdf.

Accessed August 13, 2008.

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28, 2008. Available at: www.cms.hhs.gov/CCIP/downloads/EOP_Fact_

Sheet_FINAL_012808.pdf. Accessed August 13, 2008.

5. Inverness Medical Innovations enters into a definitive agreement to acquire Matria Healthcare Inc. January 28, 2008. Available at: www.

invernessmedical.com/news.cfm. Accessed August 13, 2008.

6. Healthways Confirms Second Quarter Guidance and Lowers Fiscal 2008

Guidance, February 26, 2008. Available at: www.investors.healthways.

com/phoenix.zhtml?c=91592&p=irol-newsArticle&ID=1112213&highlight.


7. Chan V, Cooke CE. Pharmacotherapy after myocardial infarction: disease management versus usual care. Am J Managed Care.

2008;14(6):352-58.

8. Mattke S. Is there a disease management backlash? Am J Manag Care.

2008;14(6):349-50.

9. Boehm EW. EBN /Forrester study: Disease management, wellness programs mark steady progress…yet challenges remain. January 1, 2008.

Available at: www.ebn.benefitnews.com/asset/article/522211/ebnforresterstudy-disease-management-wellness-programs.html. Accessed August 13,

2008.

10. Geyman J. Disease management: panacea, another false hope, or something in between? Ann Fam Med.

2007;5:257-60.

11. Foote SM. Population-based disease management under fee-for-service

Medicare.

Health Aff (Millwood).

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12. MacStravic S. The challenge of participation in disease management. Dis

Manag. 2007;10(5):247-51.

13. Programs would be required to follow Health Insurance Portability and

Accountability Act (HIPAA) guidelines.

14. MacStravic S. Adapting Einstein’s Formula to Health Management.

October 20, 2007. World Congress World Health Care Blog.

Available at: www.

worldhealthcareblog.org/2007/08/20/adapting-einstein’s-formula-to-healthmanagement. Accessed August 25, 2008.

15. Express Scripts reports record third quarter earnings: strong cash flow from operations of $161 million. October 29, 2003. Available at: www.phx.corporate-ir.net/phoenix.zhtml?c=69641&p=irolnewsArticle&ID=464566&highlight. Accessed August 13, 2008.



16. Express Scripts issues client pledge and publicizes pharmacy benefit management business principles. March 17, 2003. Available at: www.phx.corporate-ir.net/phoenix.zhtml?c=69641&p=irolnewsArticle&ID=391360&highlight. Accessed August 12, 2008.

17. Cohen P. New breed of PBMs are poised to address transparency in healthcare. Manag Healthcare Exec.

February 2006. Available at: www.medinitiatives.com/pdf/PBM_Article_by_PC_030606.pdf. Accessed August 24,

2008. Accessed August 24, 2008.

18. Bridgeford L. Transparency matters: Employers rate PBM services.

Employee Benefit News. February 1, 2008. Available at: www.ebn.benefitnews.

com/asset/article/536781/transparency-matters-employers-rate-pbm-services.html.

19. Lewis A, Linden A. The Ultimate Guide to Outcomes Measurement for

Disease Management and Wellness.

2007. Wellesley, MA: Disease Management

Purchasing Consortium International; 2007. Available for purchase at: www.

dismgmt.com/roi.htm.

20. McCall N, Cromwell J, Bernard S. Evaluation of Phase I of Medicare

Health Support (Formerly Voluntary Chronic Care Improvement) Pilot

Program Under Traditional Fee-for-Service Medicare: Report to Congress.

June 2007. Available at: www.cms.hhs.gov/Reports/Downloads/McCall.pdf.

Accessed July 31, 2008.

21. Linden A. What will it take for disease management to demonstrate a return on investment? New perspectives on an old theme. Am J Manag Care.

2006;12(4):217-22.

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DC:DMAA;2007. Available for purchase at: www.dmaa.org/pubs_guide.asp.

23. Available at: www.diabetes.org/phd. Accessed July 31, 2008.

24. Ginde AA, Espinola JA, Camargo CA Jr. Trends and disparities in U.S. emergency department visits for hypoglycemia, 1993-2005.

Diabetes Care.

2008;31(3):511-13.

25. Lifetime benefits and costs of intensive therapy as practiced in the diabetes control and complications trial. The Diabetes Control and Complications

Trial Research Group. JAMA.

1996;276(17):1409-15.

26. Kahn R, Robertson RM, Smith R. Eddy D. The impact of prevention on reducing the burden of cardiovascular disease. Circulation.

2008:118(5):576-85.

27. Curtiss FR, Fairman KA. Looking for the outcomes we love in all the wrong places: the questionable value of biomarkers and investments in chronic care disease management interventions.

J Manag Care Pharm.

14(6):563-70. Available at: www.amcp.org/data/jmcp/JMCPMaga_563-570.

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1997;54:2217-29

29. Sidorov J, Shull R, Tomcavage J, Girolami S, Lawton N, Harris S. Does diabetes disease management save money and improve outcomes? A report of simultaneous short-term savings and quality improvement associated with a health maintenance organization-sponsored disease management program among patients fulfilling health employer data and information set criteria.

Diabetes Care.

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30. With permission from the health plan.

31. DMAA: The Continuum Care Alliance Announces New Name, Expanded

Scope, September 16, 2007. Available at: www.dmaa.org/news_releases/2007/pressrelease_091607b.asp. Accessed August 22, 2008.

32. MacStravic S. The Heisenberg Uncertainty Principle in EHM. World

Congress World Health Care Blog.

December 6, 2007. Available at: www.worldhealthcareblog.org/2007/12/06/the-heisenberg-uncertainty-principle-inehm/. Accessed August 12, 2008.

33. Krause DS. Economic effectiveness of disease management programs: a meta-analysis. Dis Manag.

2005;8(2):114-34.

34. Wilson T, Linden A. Measuring diabetes management.

Health Aff

(Millwood). 2004;23:277-78.

35. Healthways Questions CMS’ Conclusions with Regard to

Company’s MHS Phase I Pilot, February 13, 2008. Available at: www.investors.healthways.com/phoenix.zhtml?c=91592&p=irolnewsArticle&ID=1107809&highlight. Accessed August 13, 2008.

36. Kuraitis V. Disease management and the Medicare Health Support (MHS) project: “Houston, we have a problem.” eCareManagement blog.

Sept 6, 2007.

Available at: www.e-caremanagement.com/disease-management-and-themedicare-health-support-mhs-project-houston-we-have-a-problem. Accessed

August 13, 2008.

37. Tsai AC, Morton SC, Mangione CM, Keeler EB. A meta-analysis of interventions to improve care for chronic illnesses. Am J Manag Care.

2005;11(8):478-88.

38. Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ.

2003:326(7400):1167-70.

39. Liss H. Publication bias in the pulmonary/allergy literature: effect of pharmaceutical company sponsorship.

Isr Med Assoc J.

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40. Wager E, Field EA, Grossman L. Good publication practice for pharmaceutical companies. Curr Med Res Opin.

2003;19(3):149–54.

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2008:358(7):661-63.



New Agents in the Management of Type 2 Diabetes: Do They Provide an Opportunity for a Shift in the Treatment Paradigm?

Connie A. Valdez, PharmD, MSEd

A ccording to the Centers for Disease Control and

Prevention (CDC), approximately 20.8 million

Americans were living with diagnosed (14.6 million) or undiagnosed (6.2 million) diabetes in 2005, and 41 million were considered to be in a prediabetic state and at high risk of developing diabetes.

1 Worldwide, the International Diabetes

Federation estimates that 246 million people currently have diabetes, and by 2025, this number is expected to increase to 380 million.

2 Even with access to medical counseling and various treatment modalities, only about 50% of patients reach the glycosylated hemoglobin (A1c) target set by the American

Diabetes Association (ADA) of less than 7%.

3 In an attempt to manage type 2 diabetes more rigorously and successfully, the ADA has provided recommendations using a treatment algorithm. Based on this treatment algorithm, metformin, sulfonylureas, thiazolidinediones, and insulin are recommended as preferred agents.

4 Newer agents in 3 therapeutic classes known as glucagon-like peptide-1 (GLP-1) analogs (e.g., exenatide), amylin analogs (e.g., pramlintide), and dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin) do not have a clear place in therapy and are only briefly mentioned or not addressed at all in the guidelines.

In the May 2008 issue of JMCP , VanDeKoppel et al. reviewed the pathophysiology of type 2 diabetes and summarized the existing data for 3 new agents “to help the clinician identify clinical situations in which the new agents should be considered in the treatment algorithm.” 5 This review provides valuable information for clinicians, and VanDeKoppel et al. should be congratulated on their efforts. VanDeKoppel et al.’s assertion of weak or absent treatment recommendations for exenatide, pramlintide, and sitagliptin is supported by the discussion of these agents in the ADA Standard of Medical Care in Diabetes (2008): “Other medications such as pramlintide, exenatide, alpha-glucosidase inhibitors, the glinides, and dipeptidyl peptidase IV inhibitors were not included in the consensus algorithm, owing to less glucose-lowering effectiveness, limited clinical data, and/or relative expense. However, they may be appropriate choices in individual patients to achieve glycemic goals.” 6 The American Association of

Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus have yet to define a place in therapy for these new agents.

7 Yet, there is rapid uptake of the

3 new agents, as demonstrated by sitagliptin’s market share of

14% of new prescriptions for diabetes treatment during the first

6 weeks following its approval.

5 This discrepancy highlights how the market uptake of new agents for diabetes can diverge from the clinical guidelines of respected organizations.

Within their review of diabetes treatment and pathophysiology, VanDeKoppel et al. did recognize that these 3 new agents may have a positive or neutral effect on weight loss but added that only a modest reduction in A1c is achieved when compared with other agents recommended by the ADA (metformin, sulfonylureas, insulin, etc.). While weight loss may occur with exenatide and pramlintide, clinical trials have not demonstrated that this weight loss is clinically relevant or results in improved health outcomes. In addition, evidence related to the safety and efficacy of these 2 agents for weight reduction is lacking.

8,9

The authors also note that decline in beta-cell function is common in individuals with type 2 diabetes. When beta-cell apoptosis exceeds the rate of replication, beta-cell failure ensues, resulting in worsened diabetes. Excessive apoptosis is thought to be secondary to glucotoxicity, lipotoxicity, and pro-inflammatory cytokines and leptin.

10 This hypothesized causal relationship is important to consider when linking the pathophysiology with possible treatment options, since type 2 diabetes is associated with hyperglycemia and dyslipidemia characterized by elevated triglycerides and free fatty acids. As diabetes worsens, this related glucotoxicity and lipotoxicity promotes further decline of beta-cell function. This cycle of worsening diabetes and loss of beta- cell function continues until beta-cell exhaustion occurs. At recent meetings of the Metropolitan Diabetes Society (2007) and the ADA (2008), diabetes researcher Ralph DeFronzo advanced the idea that appropriate treatment would include not only reversing insulin resistance but also improving beta-cell function. Bloomgarden’s summary of the presentations suggested the implications of DeFronzo’s idea: The ideal agent would additionally “correct the pathophysiologic disturbances responsible for type 2 diabetes.” 11 While VanDeKoppel et al. note that exenatide may promote beta-cell proliferation and synthesis, and that sitagliptin may improve beta-cell function, the importance of this concept may have been overlooked by these authors when considering the potential role of these agents.

Wang et al. demonstrated in an animal model that glucose intolerance, secondary to age-dependent beta-cell function decline, was reversed with a constant infusion of GLP-1.

12 In another animal model, Fineman et al. demonstrated that betacell function was increased by 50%-100% at days 14 and 28 for all GLP-1 agonist arms compared with no change with placebo.

Specifically, the homeostasis model assessment of B-cell function


New Agents in the Management of Type 2 Diabetes:

Do They Provide an Opportunity for a Shift in the Treatment Paradigm?

(HOMA-B) cell index was used to measure beta-cell function, with a higher number representative of more beta-cell function.

The HOMA-B was approximately 43 on day 1, 68 on day 14, and

92 on day 28 for the twice daily (breakfast/dinner) GLP-1 agonist arm; approximately 43 on day 1, 78 on day 14, and 68 on day 28 for the twice daily (breakfast/bedtime) GLP-1 agonist arm; and approximately 55 on day 1, 96 on day 14, and 90 on day 28 for the thrice daily (breakfast/dinner/bedtime) GLP-1 agonist arm, compared with the placebo arm which decreased from day 1 to day 28 (approximately 58 on day 1, 57 on day 14, and 51 on day

28).

13 The practical implication of using HOMA-B as a measurement of beta-cell function in humans was demonstrated with the

United Kingdom Prospective Diabetes Study (UKPDS) findings.

Sixty-two percent of patients receiving a sulfonylurea as monotherapy with HOMA-B below 27% required additional therapy to maintain glycemic goals compared with 28% of patients with

HOMA-B above 55% who required additional treatment.

14 Salehi et al. reviewed 14 studies using animal models and concluded that incretin-based drugs (GLP-1 agonists and DPP-4 inhibitors) have the potential to improve glucose tolerance by a favorable effect on beta-cell physiology and maintaining or possibly expanding beta-cell mass.

15 Additional animal model studies support that these agents preserve beta-cell function and mass, providing a basis to evaluate their effects on beta-cell function, mass, and preservation in humans.

16-37

There are few studies of the effects of GLP-1 agonists and

DPP-4 inhibitors in human cells. Farilla et al. found that within

5 days, GLP-1 preserved beta-cells through inhibiting apoptosis, preserving morphology and potentiating glucose-dependent insulin secretion in human islet cells. Specifically, at day 5, (a) approximately 45% of the control islet cells lost morphology compared with 15% in the GLP-1 treated islets; (b) apoptosis occurred in 18.9% of the control islet cells compared with 8.9% in the GLP-1 treated islets; and (c) the glucose-dependent secretion of insulin was greater in the GLP-1 treated islets.

29 Buteau et al. also evaluated GLP-1 in human islet cells and found that

GLP-1 prevented apoptosis.

30 Although these data do not represent clinical practice, and the practical value of these effects has not yet been demonstrated, there seems to be sufficient basis for conducting further research to evaluate the effects of using these agents in an attempt to preserve beta-cell function in a clinical practice setting.

The results of several studies have led to the hypothesis that these agents may alter the course of diabetes or possibly prevent diabetes. Mu et al. concluded that these agents may offer “longlasting efficacy in the treatment of type 2 diabetes by modifying the courses of the disease.” 26 Farilla et al. stated that “because

GLP-1 is being considered for the treatment of type 2 diabetes, the identification of its antiapoptotic properties may better define the indication for its use in subjects at early stages of the disease when restoration of a normal islet mass delays or perhaps prevents the onset of diabetes.” 29 Tourrel et al. concluded that “GLP-1 represents a unique tool because of its beta-cell replenishing effect” and that GLP-1 “may prove to be an invaluable agent for the prevention of human type 2 diabetes.” 37 Although these results appear promising, a test of the clinical significance of medications on beta-cell function in humans is needed. Unfortunately, in clinical practice, no method exists to directly measure beta-cell function. However, results of the ADOPT (A Diabetes Outcome

Progression Trial) study suggest that it may be possible to evaluate preservation of beta-cell function from GLP-1 agonists and

DPP-4 antagonists in a clinical practice setting.

38

The ADOPT study enrolled and randomized drug-naive patients who had been diagnosed with type 2 diabetes for less than 3 years to glyburide, metformin, or rosiglitazone (dose titrated to achieve ADA goals) for 4 years. The primary outcome was the time to monotherapy failure (defined as “fasting plasma glucose level, >180 mg per deciliter on consecutive testing after at least 6 weeks of treatment at the maximum-dictated or maximum-tolerated dose of the study drug”) with secondary outcomes of change in glycemic control, insulin sensitivity and beta-cell function from baseline. Rosiglitazone had the slowest decline in glycemic control (15% failure rate and annual beta-cell function decline of 2.0%), a finding consistent with the theory (based on small trials) that glitazones may have beta-cell preservation properties. Glyburide, which does not preserve beta-cell function or mass, had the most rapid decline in glycemic control (34% failure rate and annual beta-cell function decline of 6.1%). For decline of both glycemic control and beta-cell function, comparisons of rosiglitazone with glyburide were statistically significant

( P <0.001).

38

Since the completion of the ADOPT trial, 2 clinical studies have evaluated the effect of the DPP-4 inhibitor sitagliptin on beta-cell function using HOMA-B measurements, but these studies were 24 weeks in duration. Aschner et al. performed a double-blind, placebo controlled study of 741 patients who were not on an oral antiglycemic agent for at least 8 weeks. The patients were randomized to sitagliptin 100 mg daily, sitagliptin 200 mg daily, or placebo for 24 weeks. The authors found that HOMA-B increased significantly from approximately 58 to 71 and 55 to

68, respectively, with sitagliptin 100 mg daily and 200 mg daily compared with no change (56 to 56) with placebo from baseline to 24 weeks.

39 Charbonnel et al. performed a randomized, placebo-controlled study of 701 patients with mild to moderate hyperglycemia (mean A1c 8.0%) receiving ongoing metformin

(>1,500 mg per day). The patients were randomized to additionally receive sitagliptin 100 mg once-daily in a 1:2 ratio or placebo for 24 weeks. The authors found that HOMA-B increased significantly from approximately 46 to 65 with sitagliptin 100 mg daily compared with 45 to 48 with placebo.

40 Longer-term studies similar to ADOPT for both GLP-1 agonists and DPP-4 antagonists are needed. However, the available data suggest that if researchers look beyond A1c reduction as described by VanDeKoppel et al., and towards the opportunity of these 2 agents to preserve betawww.amcp.org Vol. 14, No. 57 September 2008 JMCP Journal of Managed Care Pharmacy 651



cell function and mass, perhaps they will be encouraged to obtain funding in order to conduct clinical studies similar to ADOPT.

These studies could evaluate whether using these agents in early stages of diabetes, including the prediabetes stage, will slow down and possibly prevent diabetes progression.

To further understand the possible role of exenatide and sitagliptin in treating type 2 diabetes, it is important to recognize that the initial phase of the diabetes continuum (the prediabetes phase) is when patients begin to present with impaired glucose homeostasis in the form of hyperglycemia, thus reflecting the initial decline in beta-cell function. Beta-cell function continues to decline as the disease progresses.

41 In fact, based on the UKPDS findings, patients diagnosed with type 2 diabetes had already lost approximately 50% of their beta-cell function at the time of diagnosis followed by a linear reduction in beta-cell function.

Specifically, subjects treated with diet therapy had lost 49% of their beta-cell function at the time of diagnosis and continued to lose beta-cell function during the study period, resulting in a 72% loss of beta-cell function after 6 years.

14 As suggested by Farilla et al., if beta-cell preservation medications are introduced early in the disease course, then perhaps the evolution of diabetes can be altered.

29 Admittedly, this proposed mechanism is only speculative, and rigorous clinical trials are required to substantiate it and to establish a place in therapy for these medications. However, the hypothesized mechanism does set forth a reasonable therapeutic theory. Of course, any use of these new agents in the management of prediabetes would be considered experimental and currently off-label. Long-term efficacy and safety data are not available for the new agents, and this information is necessary to permit evaluation of their possible role in preservation of beta-cell function and not just A1c reduction.

Pharmacoeconomic analyses of these new agents and their contribution to the costs of diabetes management are also needed.

VanDeKoppel et al. provided information related to the direct drug cost of the new agents which ranged from $171 per month for sitagliptin to approximately $230 per month for exenatide.

5

The authors note that these agents carry a higher financial burden in direct drug cost than conventional agents, and that cost should be a consideration prior to determining appropriate therapy.

However, VanDeKoppel et al. did not consider the possible costsavings that could result by changing the treatment paradigm, and using GLP-1 agonists or DPP-4 antagonists early in disease progression, which could ultimately lead to fewer cases of severe diabetes in the United States. Although Watkins et al. performed a pharmacoeconomic analysis of exenatide to estimate the incremental effect of exenatide over other available therapies, the authors did not assess the pharmacoeconomic impact of initiating exenatide early in treatment, as patients in the Watkins et al. analysis had an average duration of type 2 diabetes for 8 years.

42

Without clinical data to support the number needed to treat and/or harm, possible cost savings associated with early use of sitagliptin or exenatide cannot be determined. However, we do know that the total direct and indirect costs of diabetes in the

United States were estimated to be $174 billion in 2007.

43 This figure included direct costs related to medical expenditures of $116 billion ($27 billion for diabetes care, $58 billion for complications related to diabetes, $31 billion for excess general medical expenses) and indirect costs of $58 billion. The indirect costs were determined based on disease-related unemployment disability, reduced productivity, absenteeism, and loss of productive capacity from early mortality. Medical expenditures are approximately 2.3 times higher for patients with diabetes than for those without diabetes. Furthermore, the CDC estimates that 54 million Americans have prediabetes.

1 Most of these individuals will likely develop diabetes if the disease process is not altered.

Imagine the economic impact of halting or at least slowing down the progression of prediabetes to diabetes with lifestyle modifications and drug therapy.

As concluded by VanDeKoppel et al., based on the current high direct drug cost and lack of long-term safety and efficacy data, these new agents should be reserved for individuals with either a contraindication or evidence of inadequate response to other recommended agents.

5 These conclusions are consistent with the

Cochrane Systematic Review, which reviewed 25 DPP-4 inhibitor studies of “good quality” and concluded that “DPP-4 inhibitors have some theoretical advantages over existing therapies with oral antidiabetic compounds but should currently be restricted to individual patients. Long-term data especially on cardiovascular outcomes and safety are urgently needed before widespread use of these new agents. More information on the benefit-risk ratio of DPP-4 inhibitor treatment is necessary especially analysing adverse effects on parameters of immune function. Also, longterm data are needed investigating patient-oriented parameters like health-related quality of life, diabetic complications and all-cause mortality.” 44 These conclusions are also consistent with some managed care organizations, such as the Regence Group, that have explicit clinical guidelines for the use of exenatide and sitagliptin.

8,45 However, as suggested by Farilla et al., Mu et al., and Tourrel et al., further studies are needed to determine if use of exenatide and sitagliptin early in the course of diabetes and/or during the prediabetes phase would preserve beta-cells (while the patient still has adequate numbers) to the extent that the clinical course of diabetes could be altered.

26,29,37

Author

CONNIE A. VALDEZ is Assistant Professor, Department of Clinical

Pharmacy, School of Pharmacy, University of Colorado Denver.

AUTHOR CORRESPONDENCE: Connie A Valdez, PharmD, MSEd,

University of Colorado Denver, School of Pharmacy C238-L15,

Academic Office 1, 12631 E. 17th Ave., Room L15-1221 P.O. Box

6511, Aurora, CO 80045. Tel.: 303.724.2630; Fax: 303.724.2627;

Email: connie.valdez@uchsc.edu




DISCLOSURE

The author reports no conflicts of interests related to consulting fees, paid expert testimony, employment, grants, honoraria, patents, royalties, stocks, or other financial or material gain that may involve the subject matter of the manuscript. There was no external funding to support the development of this manuscript.

REfEREnCES

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2005. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2005. Available at: www.ndep.nih.gov/ diabetes/pubs/2005_National_Diabetes_Fact_Sheet.pdf. Accessed June 30,

2008.

2. International Diabetes Federation. Diabetes prevalence. Available at: www.idf.org/home/index.cfm?node=264. Accessed August 24, 2008.

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10.1002/14651858.CD006739.pub2.





The Benefits and Risks of New Therapies for Type 2 Diabetes

Carl V. Asche, PhD, and Richard E. Nelson, PhD

A pproximately 7.8% of the U.S. population has either diagnosed (5.9%) or undiagnosed (1.9%) diabetes, and 90%-95% of cases of diabetes in adults are type

2.

1 Because of the disease and related complications, diabetes places a significant financial burden on the health care system; the total cost of diabetes in the United States in 2007 was an estimated $174 billion, of which $116 billion were for treatment of the disorder and $58 billion were attributable to reduced productivity.

2 In 2007, 1.6 million people aged 20 or older were newly diagnosed with diabetes in the United

States.

1 Current guidelines issued by the American Diabetes

Association (ADA) recommend a combination of lifestyle change and treatment with metformin, if not contraindicated, at the time of diagnosis, and an established treatment goal of attaining and maintaining hemoglobin A1c (A1c) less than

7.0%.

3

Recent figures indicate that more patients with type 2 diabetes are able to achieve glycemic control than in the past. In

1999-2000, 37.0% of patients with type 2 diabetes achieved glycemic control as defined by A1c level less than 7%. This number rose to 55.7% in 2003-2004.

4 However, although treatment with metformin will initially reduce A1c and result in significant weight reduction, Riedel et al. found that nearly one third of patients will experience “treatment failure,” which they defined as at least 1 A1c value of 7% or greater, on metformin monotherapy with the average time to treatment failure approximately one and one half years.

5 Thus, it is not surprising that over one third of new type 2 diabetic patients who remain on antidiabetic pharmacotherapy for at least 12 months have at least 1 change in their treatment regimen during that time.

6 Treatment strategies are intended to delay or prevent failure to maintain desirable A1c in the hope of preventing complications.

As with all new agents, determining place in therapy is important for payers and providers, and in the case of type 2 diabetes, predicting treatment success or failure with initial therapy will factor into immediate and long-term treatment strategies.

In the June 2008 issue of JMCP , VanDeKoppel et al. presented a review of the safety and efficacy of 3 new agents (exenatide, pramlintide and sitagliptin) used to treat type 2 diabetes, as well as an effort to define their place in therapy.

7 The authors performed their review via a MEDLINE search (1950 to June 2007, including systematic reviews and meta-analyses through December 2007) for English-language articles of studies of human subjects using search terms that included type 2 diabetes and generic names of the 3 drugs. VanDeKoppel et al. reported that all 3 agents have demonstrated a modest effect on reducing A1c, and 2 of the 3 agents have modest positive effect on weight loss; sitagliptin was the agent that has not been associated with weight loss.

VanDeKoppel noted that the long-term safety and efficacy of these agents are unknown and that these agents are more costly than the first-line agents, metformin and sulfonylureas, both available in generic form. The authors concluded that the newer agents should be reserved for patients who are not adequately managed by older agents that have known long-term efficacy and safety and are usually available at much lower cost.

VanDeKoppel et al.’s review puts the value of these 3 agents into context by providing a comprehensive literature review of these new agents and presenting the current (2008) real world prices of all of the drugs in the treatment guidelines to help determine their place in therapy. Overall, VanDeKoppel et al. have made important and valid points addressing the best way to determine the relative value of these 3 new agents.

Patients often do not possess the knowledge necessary to make choices between new and established therapies. Efforts to increase public awareness of the relative value of new drug therapies are often underpowered compared with the influence of drug companies over physicians’ and patients’ assessments of the benefits and risks associated with new agents. The influence that drug companies have over the perception of their products has markedly increased since the 1997 regulatory shift on the part of the U.S. Food and Drug Administration (FDA) that led to the increasing use of direct-to-consumer (DTC) pharmaceutical advertising in the United States. The introduction and growth of this form of advertising make it evident that the news media might play an important role in offsetting the DTC advertising phenomenon. However, a study by Hartley and Coleman, in which the authors analyzed print news coverage from August

1997 to July 2003, found that the pharmaceutical industry is given more prominence, as measured by the number of times mentioned and the number of times quoted, than are other stakeholders (providers, consumers, corporate purchasers, state, or DTC critics).

8

VanDeKoppel et al.’s article in JMCP is neutral and factual in examining the findings from the short-term studies available to date including the reports of adverse effects, such as the potential for severe allergic and dermatologic reactions with sitagliptin.

They urge caution on the part of patients and providers because of the lack of long-term effectiveness and safety information for www.amcp.org Vol. 14, No. 57 September 2008 JMCP Journal of Managed Care Pharmacy 655

The Benefits and Risks of New Therapies for Type 2 Diabetes these new agents. Although it is true that these new agents have not benefited from the attention that conventional treatments have received, this relative lack of attention has occurred primarily because the new agents have not been marketed long enough for the accumulation of long-term efficacy and safety data. Yet, for each of these agents, VanDeKoppel et al. present encouraging preliminary short-term research information about their efficacy, mechanisms of action, and safety. Specifically, the authors report on the A1c-lowering effects (by 0.5% to 1% for exenatide and pramlintide, and by 0.5% to 0.7% for sitagliptin). However, the authors also report notable side effects for these agents (nausea in exenatide and pramlintide, severe hypoglycemia in pramlintide, and severe allergic and dermatologic reactions with sitagliptin).

Additional studies with longer time frames for each of these

3 drugs have shown results consistent with those presented by

VanDeKoppel et al. For example, in an open-ended, open-label extension of 3 clinical trials, exenatide was shown to reduce A1c

(mean [SE] —1.1% [0.1%] P < 0.001) from baseline to 12 weeks and maintain this reduction for 3 years in patients on metformin and/or a sulfonylurea; 46% of patients achieved A1c of 7% or less.

9 In the same clinical trials, patients lost weight (—5.3 [0.4] kg, P < 0.001) over the 3-year period. Those patients with serum lipid laboratory values experienced decreases in triglycerides

(by 12%, P < 0.001), total cholesterol (by 5%, P < 0.001), and lowdensity lipoprotein cholesterol (by 6%, P < 0.001), and increases in high-density lipoprotein cholesterol (by 24%, P < 0.001).

9 In two 52-week trials, type 2 diabetes patients on pramlintide experienced A1c reductions of 0.60%-0.62% and body weight reductions of 1.3-1.4 kg.

10 In a subsequent placebo-controlled study, patients on pramlintide experienced weight loss (mean [SE] —1.6

[0.3] kg for pramlintide vs. +0.7 [0.3] kg for placebo, P < 0.001) and decreases in high-sensitivity C-reactive protein (—0.8 [0.2] mg per liter for pramlintide vs. 0.1 [0.2] mg per liter for placebo,

P < 0.01).

11 Individuals at high cardiovascular risk (baseline triglycerides at least 150 mg per dL) experienced decreases in triglycerides (—43 [14] mg per dL P < 0.05).

11 Finally, although no evidence is available for a cardiovascular benefit for sitagliptin, in a 52-week active-comparator study (Sitagliptin Study 024

Group) in which patients with inadequate glycemic control with metformin were randomized to receive either sitagliptin or glipizide as adjunctive therapy, both drugs reduced A1c by —0.67% from a mean baseline of 7.5%, showing that sitagliptin was not inferior to glipizide.

12 In the Sitagliptin Study 024 Group, patients taking sitagliptin experienced mean weight loss of —1.5 kg compared with mean weight gain of +1.1 kg for glipizide, yielding a between-group difference of —2.5 kg (95% CI=–3.1 to –2.0,

P < 0.001), and the proportion reporting hypoglycemic events was lower for sitagliptin-treated patients (5%) than for glipizidetreated patients (32%, P < 0.001).

12

While glycemic control is clearly the intermediate and primary outcome of these short-term studies, the apparent weight loss and favorable changes in serum lipids suggest possible future value that may be manifest in end point outcomes. While weight loss in diabetic patients has been shown to improve glycemic control, 13 it remains to be determined if the modest weight loss observed with exenatide, pramlintide, and perhaps an absence of weight gain with sitagliptin will persist long term and be associated with end point outcomes.

In a recent editorial, Nathan criticized the decision by the FDA to approve sitagliptin, “one of the less effective glycemia-lowering drugs introduced in recent years,” despite little evidence of its long-term efficacy and safety.

14 In his opinion, a major barrier to good diabetes care is the failure of clinicians and their patients to effectively implement currently available interventions, in part because clinicians receive most of their information directly from drug company representatives and promotional material from drug companies.

14 For this reason, more peer-reviewed studies on the long-term risks and benefits of these newer diabetes medications are crucial in determining their therapeutic niches. A recent (2008) Cochrane Systematic Review of 25 studies of dipeptidyl peptidase-4 (DPP-4) inhibitors, the class of drugs to which sitagliptin belongs, concluded that the DPP-4 inhibitors have

“theoretical advantages” over conventional therapies, but longterm data are unavailable to determine whether these advantages truly exist.

15 Due to their infrequent nature, many severe adverse events are not detected in small, short-term studies, as evidenced recently by reports of several cases of hemorrhagic or necrotizing pancreatitis in patients taking exenatide.

16 A step in the right direction was taken last month when a panel of FDA advisors recommended that, besides lowering blood sugar, all drugs designed to control type 2 diabetes should also be tested through long-term cardiovascular trials.

17 However, we also advocate the use of real-world, retrospective evaluations of these medications as these studies can potentially include more patients than clinical trials, thus improving the chances of detecting infrequent adverse events. In addition, such studies can compare the use of a variety of drugs in a way that represents actual clinical practice, unlike controlled clinical trials which typically compare 1 study drug to placebo.

The evidence presented by VanDeKoppel et al. is consistent with that presented earlier this year by the ADA and the

European Association for the Study of Diabetes (EASD) as the

ADA-EASD 2008 Consensus Algorithm.

18 The ADA-EASD algorithm shows expected A1c reductions in the range of 0.5%-1.0% with both exenatide and pramlintide and lists “weight loss” as an “advantage” with both agents, compared with expected A1c reduction in the range of 0.5-0.8% with sitagliptin and “weight neutral” as an “advantage.”

We should incorporate the best evidence available on newly approved medications while continuing to study and monitor these drugs to be able to adequately and accurately place them within the spectrum of diabetes treatment. Diabetes medications that aid in glycemic control while demonstrating beneficial, or at least non-harmful, effects on body weight and biomarkers such


The Benefits and Risks of New Therapies for Type 2 Diabetes as serum lipids will potentially be important tools in treating this disease. We do agree, however, that more research is needed to determine the proper therapeutic place for these new medications. With the ADA-EASD 2008 Consensus Algorithm using the word “expensive” to describe each of these new medications, economic analyses are especially important. Information from clinical trials in which the drugs were compared against placebo is valuable in the FDA approval process. But comparative effectiveness and cost-effectiveness studies using real-world data are also important, particularly in diabetes treatment where there are already 9 different classes of medications and plenty of opportunities to compare multiple treatment options.

Authors

CARL V. ASCHE, PhD, is Research Associate Professor and Director of Graduate Studies, and RICHARD E. NELSON, PhD, is Health

Economics and Outcomes Research Fellow, Pharmacotherapy

Outcomes Research Center, University of Utah College of Pharmacy,

Salt Lake City, UT.

AUTHOR CORRESPONDENCE: Carl V. Asche, PhD, University of

Utah College of Pharmacy, 421 Wakara Way, #208, Salt Lake City,

UT 84108. Tel.: 801.587.9715; E-mail: carl.asche@pharm.utah.edu

DISCLOSURES

The outcomes research center at The Pharmacotherapy Outcomes Research

Center receives grants from manufacturers of diabetes drugs. Asche has performed diabetes work for Novartis on a University of Utah grant that was not drug specific and has served on a Novo Nordisk diabetes advisory board.

Nelson reports no relationships with manufacturers of diabetes drugs.

8. Hartley H, Coleman CL. News media coverage of direct-to-consumer pharmaceutical advertising: implications for countervailing powers theory.

Health (London).

2008;12(1):107-32.

9. Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years.

Curr Med Res Opin.

2008;24(1):275-86.

10. Singh-Franco D, Robles G, Gazze D. Pramlintide acetate injection for the treatment of type 1 and type 2 diabetes mellitus. Clin Ther. 2007;29(4):535-62.

11. Wysham C, Lush C, Zhang B, Maier H, Wilhelm K. Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes. Curr Med Res Opin. 2008;24(1):79-85.

12. Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial.

Diabetes Obes Metab.

2007;9(2):194-205.

13. Feldstein AC, Nichols GA, Smith DH, Rosales AG, Perrin N. Weight change and glycemic control after diagnosis of type 2 diabetes. J Gen Intern

Med.

2008; 23(9):1339-45.

14. Nathan DM. Finding new treatments for diabetes--how many, how fast... how good?

N Engl J Med. 2007;356(5):437-40.

15. Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch CL. Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database

Syst Rev. 2008(2):CD006739.

16. U.S. Food and Drug Administration. Information for healthcare professionals: exenatide (marketed as Byetta). Updated August 18, 2008. Available at: www.fda.gov/CDER/drug/InfoSheets/HCP/exenatide2008HCP.htm


17. U.S. Food and Drug Administration. Guidance for industry - diabetes mellitus: developing drugs and therapeutic biologics for treatment and prevention. February 2008. Available at: www.fda.gov/cder/guidance/7630dft.

htm Accessed August 22, 2008.

18. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin

R Zinman B. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes

Care. 2008;31(1):173-75. Available at: www.care.diabetesjournals.org/cgi/ reprint/31/1/173 Accessed August 20, 2008.

REfEREnCES

1. National Diabetes Information Clearinghouse: National Diabetes

Statistics, 2007. Available at: www.diabetes.niddk.nih.gov/dm/pubs/statistics/ Accessed August 22, 2008

2. American Diabetes Association. Economic costs of diabetes in the U.S. in

2007. Diabetes Care. 2008;31(3):596-615. Available at: www.care.diabetesjournals.org/misc/econcosts.pdf Accessed August 20, 2008.

3. Standards of medical care in diabetes—2008. (suppl) Diabetes Care .

2008;31 Suppl 1:S12-54. Available at: www.care.diabetesjournals.org/cgi/ reprint/31/Supplement_1/S12 Accessed August 20, 2008.

4. Hoerger TJ, Segal JE, Gregg EW, Saaddine JB. Is glycemic control improving in U.S. adults? Diabetes Care. 2008;31(1):81-86.

5. Riedel AA, Heien H, Wogen J, Plauschinat CA. Loss of glycemic control in patients with type 2 diabetes mellitus who were receiving initial metformin, sulfonylurea, or thiazolidinedione monotherapy.

Pharmacotherapy.

2007;27(8):1102-10.

6. Boccuzzi SJ, Wogen J, Fox J, Sung JC, Shah AB, Kim J. Utilization of oral hypoglycemic agents in a drug-insured U.S. population. Diabetes Care.

2001;24(8):1411-15.

7. VanDeKoppel S, Choe HM, Sweet BV. Managed care perspective on three new agents for type 2 diabetes.


2008;14(4):363-80.

Available at: www.amcp.org/data/jmcp/JMCPMaga_363-380.pdf www.amcp.org Vol. 14, No. 57 September 2008 JMCP Journal of Managed Care Pharmacy 657

E D I T O R I A L

Diabetes Drug Therapy – First Do No Harm

Frederic R. Curtiss, PhD, RPh, CEBS, and Kathleen A. Fairman, MA

I n the November/December 2006 issue of JMCP, Watkins et al. reported the estimated value of exenatide in treating obese patients with type 2 diabetes over a 30-year time horizon, as calculated using the Center for Outcomes Research

Diabetic Model, a validated Markov model that predicts clinical and economic end points over time horizons up to 100 years in duration.

1 Adopting the premise that “sophisticated disease-based economic models can be substituted” when

“long-term outcomes data are lacking,” the authors sought to provide guidance to managed care organizations making formulary decisions about new products. In fact, development of the model, a collaborative effort between exenatide’s manufacturer and a 1.6 million member health plan with an active formulary review process, began several months before approval of the product by the U.S. Food and Drug

Administration (FDA). The model’s findings for exenatide, including incremental cost-effectiveness ratios of $13,000 per quality-adjusted life-year compared with insulin and $32,000 compared with generic glyburide, were used as a basis for the health plan’s decision to cover exenatide after a step-therapy trial of metformin.

Two key assumptions used in this pharmacoeconomic analysis are noteworthy. First was an assumed 8.5% (about 15-20 pound) weight loss associated with exenatide treatment in a hypothetical patient population with mean body mass index (ratio of weight in kilograms to height in meters squared [kg/m 2 ]) of 35 kg per m 2 , assumed to result in mean reductions of 10 mm Hg in systolic blood pressure, 20 mg per dL in low-density lipoprotein cholesterol, 59 mg per dL in triglycerides, and corresponding reductions in medical costs to treat cardiovascular events. These assumptions were extrapolated liberally from the approximate

3% weight loss observed in the 30-week clinical trials that were cited in the product label and the approximate 5% weight loss observed in the open-label follow-up for 314 (57.0%) of 551 subjects randomized to exenatide who completed 82 weeks of therapy. Second and more important, the study by Watkins et al. failed to include the cost to treat adverse drug events in the pharmacoeconomic model, in effect assuming that these were $0 or equal across treatment arms, but did acknowledge that more patients discontinued therapy with exenatide compared with placebo.

As often happens with pharmacoeconomic modeling performed early in a product’s history, the actual data from realworld use ultimately do not support and potentially could even contradict the model assumptions.

2 Absent evidence to support the assumption of sustained weight loss with exenatide or what this weight loss might mean in actual cardiovascular event risk reduction, validation of this key assumption is currently an empirical question. Notably, the model’s assumption regarding the unimportance of adverse events was quickly found to be fundamentally flawed. Less than a year after the study by

Watkins et al. was published, the FDA announced that it had reviewed 30 cases of acute pancreatitis associated with the use of exenatide 3 and announced that the manufacturer had agreed to

“update Byetta’s label to discuss pancreatitis.” 4 Ten months later on August 18, 2008, the FDA updated its warning regarding acute pancreatitis with a notice to health care professionals that 6 cases involved hemorrhagic or necrotizing pancreatitis, all 6 cases required hospitalization, and 2 patients died.

5 The upgraded warning includes a contraindication for the use of exenatide in patients with a history of pancreatitis. This example highlights one of the shortcomings of pharmacoeconomic modeling for new drugs — that efficacy outcomes are more likely to be known than are adverse effects for drugs that are new to market.

In this issue of JMCP, Asche and Nelson comment on a previous review by VanDeKoppel et al. of the place in therapy of 3 new agents for diabetes: exenatide, pramlintide, and sitagliptin.

6

Asche and Nelson call for research with administrative claims and other post-marketing surveillance to help better define the safety and effectiveness of these new diabetes drugs.

7 However, there is already quite a bit known about the adverse effects associated with these drugs, particularly sitagliptin and exenatide.

Valdez in her commentary in this issue of JMCP expresses hope for the superiority of newer diabetes agents in providing some advantage over existing agents, 8 certainly a need given the explosion in the number of cases of type 2 diabetes in the United

States and worldwide.

9 However, there is only limited evidence, primarily from animal models, of some potential value of the dipeptidyl peptidase-4 (DPP-4) inhibitors in possibly preserving beta-cell function, the foundation for the hope expressed by

Valdez in her commentary.

Both Valdez, and Ashe and Nelson, acknowledge the recent

(April 2008) Cochrane Systematic Review of DPP-4 inhibitors in their commentaries but stop short of informing us of the substance of this systematic review of 25 studies. This Cochrane

Systematic Review (CD006739) included only randomized controlled trials (RCTs) of at least 12 weeks duration for adult patients with type 2 diabetes.

10 From 1,083 publications regarding DPP-4


Diabetes Drug Therapy – First Do No Harm inhibitors, 52 were evaluated in detail and 25 of these were rejected as reviews or overviews. Of the 25 studies (reported in

27 publications) that met the inclusion criteria, 11 RCTs involved a total of 6,743 patients randomized to sitagliptin and 14 RCTs involved 6,121 patients randomized to vildagliptin, a drug not yet approved by the FDA. This 134-page systematic review showed that sitagliptin and vildagliptin in meta-analysis of the combined clinical trial results had modest effects on A1c (–0.7% for sitagliptin and –0.6% for vildagliptin). Adverse event outcomes showed a significantly higher incidence of all-cause infections with sitagliptin and a possibly higher incidence with vildagliptin, but comparison with placebo was not statistically significant for vildagliptin. Since the DPP-4 inhibitors may affect immune function, the 2008 Cochrane Review called for additional data on the long-term safety of these drugs.

Letters posted on the FDA website last year mentioned “hypersensitivity post-marketing adverse reaction data,” and the label for

Januvia (sitagliptin) was revised in October 2007 to include in the “Warnings and Precautions” section the following additional wording, “There have been postmarketing reports of serious allergic and hypersensitivity reactions in patients treated with Januvia such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome.” 11 Dermatologic reactions may be characteristic of the class of DPP-4 drugs since the use of vildagliptin (Galvus) in monkeys has been associated with dermatologic reactions that have reportedly kept vildagliptin off the U.S. market, and in November 2007, dose-related elevations in liver enzymes were discovered with vildagliptin 100 mg once daily, making entry to the U.S. market more unlikely.

12

The Cochrane Review published in April 2008 was preceded by a systematic review and meta-analysis (Amori et al.) in July

2007 of the safety and efficacy of incretin therapy, 13 which encompasses glucagonlike peptide 1 (GLP-1) drugs such as exenatide that mimic incretin, and the DPP-4 inhibitors such as sitagliptin that enhance the effect of incretin. This earlier review included many of the RCTs of the DPP-4 inhibitors that were evaluated in the Cochrane Review that followed in 2008. However, Amori et al. noted an unexplained increased risk of headache with DPP-4 inhibitors and put some context around the concern about the possible adverse effect on immune function — patients with diabetes are more likely to develop urinary tract infections (UTIs) and are at a higher risk of complications, including death from urosepsis. Amori et al. used the example of a seemingly small relative risk of 1.52 for UTIs, which in their estimate potentially increases the number of UTIs by 1 million new cases per year in a population of 20 million persons with type 2 diabetes.

For the GLP-1 drugs, Amori et al. reported that nausea was the most common side effect, and 4% of clinical trial patients who received exenatide withdrew because of nausea and vomiting.

Zinman et al. (2007) found in a 16-week trial of add-on therapy

(added to thiazolinedione [TZD] with or without metformin) that 16% of the patients who received exenatide versus 2% who received placebo did not complete the clinical trial because of adverse events; 40% of exenatide patients versus 15% of placebo patients experienced nausea, and 13% of exenatide patients versus 1% of placebo patients experienced vomiting.

14 Also, despite only 16 weeks duration, 29% of the exenatide patients and 14% of placebo patients did not complete the study.

Nathan et al. in the 2008 Consensus Algorithm from the

American Diabetes Association and the European Association for the Study of Diabetes find no place in therapy for pramlintide, exenatide or sitagliptin in patients with type 2 diabetes.

15

Separately, Nathan criticized the FDA for approving sitagliptin despite the “paucity of published data from long-term clinical trials.” 16 The evidence of the risk of adverse events with new

GLP-1 and DPP-4 antidiabetic drug therapies combined with 5 risk-warning events in 2007 for the 2 TZDs (rosiglitazone and pioglitazone) 17 and the absence of conclusive evidence of reduction in macrovascular risk with any of the FDA- approved drugs for type 2 diabetes, 18 provide more context for the recommendation by the FDA outside expert panel in July this year to require more evidence than A1c reduction for FDA approval of new drug applications for antidiabetic therapies.

19,20 More evidence of the safety of new drugs for type 2 diabetes is sorely needed.

Authors

FREDERIC R. CURTISS, PhD, RPh, CEBS, is Editor-in-Chief of the

Journal of Managed Care Pharmacy. KATHLEEN A. FAIRMAN, MA, is Associate Editor and Senior Methodology Reviewer of the Journal of

Managed Care Pharmacy.

AUTHOR CORRESPONDENCE: Frederic R. Curtiss, PhD, RPh,

CEBS, Academy of Managed Care Pharmacy, 100 North Pitt St., Suite

400, Alexandria, VA 22314. Tel.: 830.935.4319; E-mail: fcurtiss@ amcp.org

DISCLOSURES

The authors report no conflicts of interest related to the subjects or products discussed in this article.

REfEREnCES

1. Watkins JB, Minshall ME, Sullivan SD. Application of economic analyses in U.S. managed care formulary decisions: a private payer’s experience. J

Manag Care Pharm. 2006;12(9):726-35. Available at: www.amcp.org/data/ jmcp/726-735.pdf.

2. Fairman KA, Curtiss FR. It’s only a pharmacoeconomic model—believe it or not. J Manag Care Pharm.

2007;14(1):83-85. Available at: www.amcp.

org/data/jmcp/JMCPMaga_JanFeb%2008_083-085.pdf.

3. U.S. Food and Drug Administration. Information for healthcare professionals – exenatide (marketed as Byetta). October 16, 2007. Available at: www.fda.gov/CDER/drug/InfoSheets/HCP/exenatideHCP.htm. Accessed

August 20, 2008.

4. Anonymous. FDA says diabetes drug may cause pancreatitis. Wall Street

J. Oct 17, 2007:B15.


Diabetes Drug Therapy – First Do No Harm

5. U.S. Food and Drug Administration. Information for healthcare professionals - exenatide (marketed as Byetta). Updated August 18, 2008. Available at: www.fda.gov/CDER/drug/InfoSheets/HCP/exenatide2008HCP.htm.


6. VanDeKoppel S, Choe HM, Sweet BV. Managed care perspective on three new agents for type 2 diabetes. J Manag Care Pharm.

2008;14(4):363-80.

Available at: www.amcp.org/data/jmcp/JMCPMaga_363-380.pdf.

7. Asche C, Nelson R. The benefits and risks of new therapies for type 2 diabetes. J Manag Care Pharm.

2008;14(7):655-657.

8. Valdez CA. New agents in the management of type 2 diabetes: do they provide an opportunity for a shift in the treatment paradigm? J Manag Care

Pharm.

2008;14(7):650-654.

9. International Diabetes Federation. Diabetes prevalence. Available at: www.idf.org/home/index.cfm?node=264. Accessed August 24, 2008.

10. Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch CL. Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database

Syst Rev. 2008(2):CD006739.

11. U.S. Food and Drug Administration—safety labeling changes approved by the FDA Center for Drug Evaluation and Research (CDER) — October

2007. Available at: www.fda.gov/Medwatch/safety/2007/oct07.htm. Accessed

August 24, 2008.

12. Reuters News Service. Novartis diabetes drug delayed – liver-safety worry slows drug’s path to Europe market.

Wall Street J. Nov 7, 2007:D8.

13. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes. JAMA.

2007;298(2):194-206. Available at: www.jama.amaassn.org/cgi/content/full/298/2/194. Accessed August 24, 2008.

14. Zinman B, Hoogwerf BJ, Garcia SD, et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes.

Ann Intern Med. 2007;146(7):477-85. Available at: www.annals.org/cgi/ reprint/146/7/477.pdf. Accessed August 24, 2008.

15. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care.

2008; 31(1):173-75. Available at: www.care.diabetesjournals.org/cgi/reprint/31/1/173. Accessed August 24, 2008.

16. Nathan DM. Finding new treatments for diabetes—how many, how fast…how good?

N Engl J Med. 2008;356(3):437-40.

17. Starner CI, Schafer JA, Heaton AH, Gleason PP. Rosiglitazone and pioglitazone utilization from January 2007 through May 2008 associated with five risk-warning events. J Manag Care Pharm.

2008;14(6):523-31. Available at: www.amcp.org/data/jmcp/JMCPMaga_523-531.pdf.

18. Joffe HV. Cardiovascular assessment in the pre-approval and postapproval settings for drugs and biologics developed for the treatment of type

2 diabetes mellitus. Presentation to the FDA Endocrinologic and Metabolic

Drugs Advisory Committee, July 1-2, 2008. Available at: www.fda.gov/ ohrms/dockets/ac/08/slides/2008-4368s1-08-FDA-Joffe.ppt. Accessed

August 24, 2008.

19. U.S. Food and Drug Administration. Center for Drug Evaluation and

Research. Background introductory memorandum. The role of cardiovascular assessment in the pre-approval and post-approval settings for drugs and biologics developed for the treatment of type 2 diabetes mellitus. Guidance for industry: diabetes mellitus: developing drugs and therapeutic biologics for treatment and prevention. February 13, 2008. Available at: www.fda.gov/ cder/guidance/7630dft.htm. Accessed August 24, 2008.

20. Anonymous. FDA panel calls for more testing of diabetes drugs. Medline

Plus. July 3, 2008. Available at: www.nlm.nih.gov/medlineplus/news/fullstory_66518.html. Accessed August 25, 2008.


E D I T O R I A L

Rethinking the “Whodunnit” Approach to Assessing the Quality of Health Care Research – A Call to Focus on the Evidence in

Evidence-Based Practice

Kathleen A. Fairman, MA, and Frederic R. Curtiss, PhD, RPh, CEBS

W hen we wrote our March, 2008 editorial in JMCP regarding the lack of evidence of value in valuebased insurance design (VBID), 1 we correctly anticipated that those working in the “trenches” of managed care pharmacy would appreciate an objective evaluation of the evidence about prescription drug cost-sharing. What we did not anticipate was a query we received from a consultant about our real reasons for writing the editorial. He asked about our business interest in the topic and why we had not disclosed the financial relationships that must have prompted our work.

It was apparently inconceivable that 2 journal editors would closely examine the research evidence underlying a health care management tool for no reason other than an interest in determining the quality of the evidence. Apparently equally unthinkable was the fact that we had no conflicts of interest to disclose.

We wonder if the cynical perspective evident in the question posed to us is unavoidable. We work in an industry in which most research is funded by parties with a commercial interest in the study outcomes. It is easy to conclude that a relationship between economic interest and research findings is inevitable.

Adriane Fugh-Berman, author of numerous books and articles about complementary medicine, tells a similar tale: “When a university or medical society invites me to speak, I am often asked which company sponsors my talks. Not whether a company sponsors me, but which company.” 2

Why So Cynical? Widely Publicized

“Scientists Behaving Badly” 3

Speculation about the relationship between business interest and the conduct of research is understandable given the media attention paid to financially-motivated unethical behavior – real or alleged – in the medical research enterprise in the past few years. Richard Smith, who edited the British Medical Journal from

1979 to 2004, described medical journals as “an extension of the marketing arm of pharmaceutical companies in publishing trials that [favor] their products.” 4 In April, 2008, reports of excessive pharmaceutical manufacturer influence over publications in several major research journals prompted the editor of the Journal of the American Medical Association (JAMA) to describe the “manipulation” of the research literature as “disgusting.” 5-7

Eyebrows were raised when Jeffrey Lisse, the first author of the Assessment of Differences between Vioxx and Naproxen to Ascertain Gastrointestinal Tolerability and Effectiveness

(ADVANTAGE) trial, (Annals of Internal Medicine, 2003), told a

New York Times reporter in 2005 that he had not actually had any role in the trial but had merely lent his name to a manuscript written by the manufacturer.

8 In response, an editorial published in Annals in 2005 declared that the frank admission of ghostwriting had “sent more than a few shivers up the spines of the editors.” 8 Sismondo described such practices as “ghost management”

(i.e., marketing masquerading as science) of research articles in the medical literature.

9 However, the raised eyebrows were later singed when new allegations emerged from the rofecoxib product liability litigation. Paid consultants for the plaintiffs contended that the manufacturer of rofecoxib not only ghost-managed the research and the ensuing publication but did so in a business practice known as “seeding,” in which a drug manufacturer funds a clinical trial not only for research purposes but also to “jumpstart” sales by raising awareness of a drug among likely prescribers.

10 The manufacturer has denied the allegation.

11

Clashes between journal editors and authors over relationships between research findings and commercial interests are not uncommon. In one particularly high-profile example in 2005, a conflict developed between the editors of the New England

Journal of Medicine (NEJM) and the authors of the Vioxx (rofecoxib) Gastrointestinal Outcomes Research (VIGOR) trial report

(2000) 12 over what the editors described as “inaccuracies in data” about cardiovascular risk.

13 The debate had been prompted by the court-ordered discovery of the manufacturer’s internal documents, which suggested that 3 additional myocardial infarctions in the rofecoxib treatment group were known to the manufacturer more than 4 months prior to publication but not reflected in the report’s data analysis.

13 The VIGOR trial authors not employed by the manufacturer countered that because the infarctions had occurred after an a priori data collection and unblinding cutoff date, it would have been inappropriate to include them in the analysis.

14 A subsequent (2008) analysis of the same manufacturer’s internal documents indicated that elevated mortality risk associated with rofecoxib treatment (pooled hazard ratio [HR] of 2.99; 95% confidence interval [CI] = 1.55-5.77) was known in 2001 but was not reported to the U.S. Food and Drug

Administration (FDA) in timely fashion or clearly disclosed in study reports published in 2004 and 2005.

6 The manufacturer has denounced the allegation that it failed to disclose known risks as “false and misleading.” 7

The journal peer review process, widely considered to be a hallmark of scientific integrity and quality, has also recently www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 661

Rethinking the “Whodunnit” Approach to Assessing the Quality of Health Care Research –

A Call to Focus on the Evidence in Evidence-Based Practice found itself the unwitting victim of bad behavior. In January,

2008, testimony before the U.S. Senate Finance Committee suggested that a prominent diabetes researcher, who had been reviewing a manuscript for NEJM, allegedly violated peer review confidentiality rules by leaking the manuscript to a pharmaceutical manufacturer that was likely to be negatively affected by its publication.

15 A less-publicized but fascinating incident occurred at the Journal of General Internal Medicine in 2004 when editors sent a manuscript to peer review. Coincidentally, one of the assigned peer reviewers had been asked in the previous year to lend her name to it even though she had not done any of the work; the actual author was a medical education company employee.

2

When the reviewer realized that the medical education company had successfully recruited another named author for the ghostwritten work, she reported the deception to the journal’s editors, who rejected the paper, implemented new authorship disclosure policies, and publicly expressed concerns about the publication of literature that “injects bias and untruth into the scientific dialogue in order to enhance corporate profits.

16

Ghost Writing, Truth-Burying, and Other

Bad Behavior: The Trees, Not the Forest

Although allegations of ethical lapses – such as inaccuracies in authorship lists, deliberate failure to disclose drug safety issues, or information leaks – are important and make for salacious reading, sole focus of our attention on these issues will draw our attention away from a broader and more important question: In assessing the credibility of research information, are decision-makers limited to the simplistic foregone conclusion that financial interest will dictate research outcomes irrespective of actual evidence? Are decision-makers’ evaluations of what they can believe limited to a superficial assessment of whom they can believe? Or can they turn to more objective standards in assessing the quality of research information?

To address this broader question, we begin by examining current evidence of a relationship between financial interest and research outcomes that has caused justifiable concern among many observers. We explain why the approach taken in many proposed solutions to the problem is likely to be ineffective. We propose as an alternative a more direct examination of quality of evidence, using available standards for conducting and reporting research. After reviewing key research standards and discussing evidence of widespread nonadherence to these basic standards, we propose a way forward.

Financial Interest and Research Results: Empirical Evidence

The view that financial interest ispo facto equates to results is supported by evidence closely linking study sponsorship to reported research outcomes. In a meta-analysis of 324 RCTs of cardiovascular devices and drugs published between January, 2000 and

July, 2005 in 3 prominent journals (JAMA, Lancet, and NEJM) ,

Ridker and Torres identified a strong relationship between funding and positive outcomes for newer treatments. Of 205 drug trials, the proportions finding clinical superiority for the newer treatment were 39.5% for those with not-for-profit funding, 54.4% for those that were jointly funded, and 65.5% for those funded by for-profit companies ( P = 0.002).

17 In an analysis of 504 studies of inhaled corticosteroids, Nieto et al. found a strong inverse relationship between pharmaceutical manufacturer funding and the likelihood of identifying adverse effects for a study drug; 34.5% of 275 studies funded by pharmaceutical manufacturers versus

65.1% of 229 studies with other funding reported that the study drug of interest had significantly higher rates of adverse effects than its comparators.

18

Survey data provide direct evidence that scientists perceive, and sometimes respond to, pressure from their funding sources.

In a 2002 survey of 3,427 scientists who had received financial support from the National Institutes of Health, 15.5% admitted to “changing the design, methodology, or results of a study in response to pressure from a funding source” in the previous

3 years. Although only 0.3% admitted to “falsifying or ‘cooking’ research data,” 13.5% said that they had used “inadequate or inappropriate research designs,” and 10.8% acknowledged

“withholding details of methodology or results in papers or proposals.” 3 The problem was, according to the scientists surveyed, not limited to their own work; 12.5% of the survey respondents admitted to “overlooking others’ use of flawed data or questionable interpretation of data.” 3

Proposed Solutions to the Problem of Money Driving the Evidence

Given this background, it is not surprising that many recent proposals to reform the manuscript publication system have focused primarily on methods to either detect or respond to violations of ethical improprieties, particularly authorship and sponsorship disclosure requirements. One observer has suggested that journal editors should share a “publicly available, regularly updated database of conflicts of interest and ethical transgressions” to enable medical editors to “punish transgressors.” 2 (As editors, we choose not to think too carefully about how such punishment might be carried out.) A 2005 editorial in the Annals of Internal

Medicine urged academicians to “insist” that articles “reflect their own interpretation of the evidence,” to demand full disclosure of all authors and contributors, and to ensure that all authors take responsibility for the manuscripts that bear their names. The

Annals editorial further committed to reporting ethical breaches to academic institutions and encouraged those institutions to

“mandate adherence” to ethical policies.

8 A 2006 editorial in

Health Services Research (HSR) emphasized disclosure not only of financial arrangements but also of evidence of bias, for example, public stands taken on policy issues. Somewhat in contrast to the positions taken by other journal editors, the HSR editors emphasized that both transparent disclosure and “peer reviewed evaluation of the appropriateness and quality of methods” were



A Call to Focus on the Evidence in Evidence-Based Practice

TABLE 1 Guidelines for Conducting and Reporting Research

GUIDELINE NAME

Systems to Rate the Strength of Scientific Evidence

Uniform Requirements for

Manuscripts Submitted to

Biomedical Journals

Guidelines on Good Publication

Practice (GPP) 28

ISPOR Code of Ethics 29

Checklist for Medication

Compliance and Persistence

Studies 30

Retrospective Database

Checklist 31

27

25,26

SOURCE OR ORGANIZATION DESCRIPTION

GENERAL STANDARDS FOR ALL TYPES OF RESEARCH

AHRQ

ICMJE

Compilation and synthesis of 121 sources (scales, checklists or guidance documents) that

“can be used in the production of systematic evidence reviews and technology assessments.” Systems were characterized with respect to “important domains and elements” that safeguard against bias or are “long-accepted” research practices.

Covers (a) the role of editors, authors and peer reviewers and good ethical practices for each; and (b) standards for content of study reports. Does not discuss methodology or analytic technique in detail, but refers readers to CONSORT and its offshoots (e.g., STROBE,

STARD, QUORUM, and MOOSE) for detailed guidelines.

Pharmaceutical company employees; working group

ISPOR

ETHICAL STANDARDS

Devoted primarily to ethical issues of authorship and sponsorship. Refers readers to ICMJE and CONSORT for more complete standards.

Brief statement of ethical standards for design and conduct of research, sponsorship, publication, and relationships with students and employees.

OBSERVATIONAL RESEARCH AND CLAIMS DATABASE ANALYSES

ISPOR Medication Compliance and Persistence Special Interest

Group

ISPOR working group

EQUATOR network

EQUATOR network

EQUATOR network

Checklist of items to be “included, or at least considered,” in retrospective database analyses of medication compliance or persistence. Includes definitions of commonly used terms.

Refers to the ISPOR Retrospective Database Checklist for detailed standards to be used in assessing work derived from administrative claims databases.

Checklist to assist decision makers in assessing quality of analyses of administrative databases; covers numerous areas including relevance, reliability and validity, methodological considerations unique to claims databases, statistical analysis and interpretation.

Standards for reporting of meta-analyses of observational epidemiological studies, including background, search criteria, methods of selection and analysis, and presentation of findings and implications.

Best practices for reporting of observational research at every stage including study rationale, design, measurement, analysis, results, limitations, and discussion; includes citations to 237 references that can be accessed for additional information and examples.

Consistent with CONSORT; explicitly addresses issues common in nonrandomized studies that examine the effects of interventions.

Meta-Analysis of Observational

Studies in Epidemiology

(MOOSE) 32

Strengthening the Reporting of Observational Studies in

Epidemiology (STROBE) 33

Transparent Reporting of

Evaluations with

Nonrandomized Designs

(TREND) 34

Consolidated Standards of Reporting Trials

(CONSORT) 35

EQUATOR network

RANDOMIZED CONTROLLED TRIALS

Standards for the reporting of randomized controlled trials including study rationale, design, measurement, analysis, results, limitations, and discussion; includes citations to

204 references that can be accessed for additional information and examples. Main focus is validity (internal and external).

Standards for conducting and reporting analyses of economic end points incorporated into clinical trials.

Good Research Practices:

Randomized Clinical Trials

-- Cost-Effectiveness

Analysis (RCT-CEA) 36

ISPOR working group

Chicago Guides 37,38

Cost-Effectiveness in Health and Medicine 39

Principles of Good Practice for

Decision Analytic Modeling

Quality of Health Economic

Studies (QHES) 41

40

STATISTICAL ANALYSES AND MODELS

Chicago University Press Comprehensive textbook standards for data analysis and reporting.

U.S. Public Health Service Panel on Cost Effectiveness in Health and Medicine – expert panel convened in 1993

ISPOR Task Force

Guidelines for the conduct and reporting of cost-effectiveness analyses.

Comprehensive, detailed quality assessment document for decision analytic modeling.

Emphasizes transparency, sensitivity analyses, empirically-based assumptions, and incorporation of new evidence as it becomes available.

Panel of 8 health economics experts; validated in a survey of

30 clinicians and 30 health economists

Quality scoring system for cost-minimization, cost-effectiveness and cost-utility analyses, based on 19 previous guidelines and checklists and validated against expert assessment of quality. Primarily focused on technical details specific to cost-effectiveness (e.g., time horizon, perspective, economic model structure).

OTHER RESEARCH TYPES

Patient Reported Outcomes

(PRO) Harmonization Group report 42

Quality of Reporting of Metaanalyses (QUORUM) 43

Standards for Reporting of

Diagnostic Accuracy (STARD) 44

Representatives from ISOQOL,

ISPOR, PhRMA-HOC, and

ERIQA

EQUATOR network

EQUATOR network

Evolving standards for instruments and reporting of patient-reported data.

Similar to CONSORT in concept, but addresses issues specific to meta-analyses of RCTs.

Checklist of standards for reporting studies of diagnostic test accuracy.

AHRQ = Agency for Healthcare Research and Quality; EQUATOR = Enhancing the QUAlity and Transparency Of health Research; ERIQA = European Regulatory Issues on

Quality of Life Assessment; ICJME = International Committee of Medical Journal Editors; ISOQOL = International Society for Quality of Life Research, ISPOR = International

Society for Pharmacoeconomics and Outcomes Research; PhRMA-HOC=Pharmaceutical Manufacturer’s Association Health Outcomes Committee; RCT = randomized controlled trial.



A Call to Focus on the Evidence in Evidence-Based Practice crucial to evaluation of the quality of research evidence.

19 For our part, the JMCP disclosure forms for authors have been revised many times in response to instances of apparent ghost writing or ghost management. These JMCP disclosure forms require the corresponding author to certify the percentage contribution of every person that contributed in any way to the manuscript, including study concept and design, data collection, data interpretation, writing and revising the manuscript.

20

In 2001, the editors of JAMA supplemented the journal’s enhanced disclosure policies with an additional response to the problems of “data misrepresentation … and selective reporting.” 21

Submissions of manuscripts reporting industry-sponsored studies must be accompanied by certification that the data analysis was conducted by “an academic statistician who is not employed by the sponsor and who is at an academic center, such as a medical school, or is an employee of a government research institute.”

This approach was intended to provide “an additional layer of oversight for the integrity of the data analysis and reporting” and to rely on academic centers’ usual “mechanism for investigation” of possible improprieties. JAMA’ s editors expressed considerable confidence in their policy change: “If all journals would have similar policies,” they opined, “the likelihood of manipulation of data, inappropriate data analysis and selective reporting of results could be substantially decreased.” 21

To their point, Mello et al. (2005) surveyed 107 medical school research administrators who had authority over contracts with industry research sponsors for the conduct of clinical trials. Respondents were presented with a list of potential contract provisions and asked which would be acceptable or unacceptable to them. Allowing sponsors to “alter the study design after the agreement is executed” was viewed as acceptable by 62% of respondents and unacceptable by 27%. Allowing sponsors the right to insert their own statistical analyses in manuscripts was seen as acceptable by 24% of respondents; 47% said that this provision would be unacceptable and 29% were not sure. A remarkably high 50% of the respondents said that they would permit the sponsor to “write up the results for publication and the investigators may review the manuscript and suggest revisions,” although 40% viewed such a provision as unacceptable.

23

Thus, an information consumer whose only approach for assessing quality of evidence is identifying who is “good” (e.g., who has pure motives, good training, etc. ) is hopelessly relegated to making judgments with inadequate information, thereby inevitably rejecting some high-quality work and accepting some poor-quality work. We embrace a different and more effective approach. Instead of looking at the motives or quality of people – an exercise that is fraught with inherent uncertainty – we propose a more intense focus on the quality of work output using currently available standards for the conduct and reporting of research.

Information consumers who rely on basic research quality standards will be in a strong position to distinguish poor-quality from high-quality work, no matter who performed or paid for it.

Replacing the “Whodunnit” Approach:

A Sharper Focus on Quality of Evidence

These proposed solutions focus primarily on “whodunnit” questions – who paid for the study, who conducted it, who interpreted the data, who wrote the report, and who enforced ethical standards. Although full disclosure of financial interests and authorship arrangements is clearly important, addressing the health care research literature’s current problems through the “whodunnit” approach alone is unlikely to be effective.

The requirement that analyses be conducted by an academician instead of a for-profit company employee misses 3 key points: first, that high-quality work can be, and often is, produced by for-profit companies; second, that academicians, like all of us, are fallible human beings who can make errors or be influenced by bias; and third, that academicians are potentially just as vulnerable as other scientists to funding source pressures.

As Ridker and Torres point out in their meta-analytic assessment of research with for-profit and nonprofit sponsorship, design problems in trials conducted in academic settings have been observed in the literature, 17 such as in a 2006 investigation of high-dose statin therapy that was led by a medical school academician and published in a prominent journal despite having no control group.

17,22 Additionally, Ridker and Torres observe that even academicians may “nevertheless be under pressure to present results in the best possible light, in particular emphasizing favorable subgroup analyses when an overall neutral effect was observed for the primary end point.” 17

Research Standards: Are They Usable?

The report of a roundtable discussion of the use of real-world data in managed care decision-making, published in the April,

2008 issue of JMCP , observed that standards for the conduct and reporting of research are seldom used, perhaps because they are either not clearly available, not clearly understood, or both.

24

Confusion over the availability and utility of research standards is understandable, since a “Google” search on the term “research standards” yields dozens of entries ranging from vague admonitions to conduct scientifically valid and ethical work to detailed

“how-to” publications.

Our analysis of the available tools to assess evidence quality examined documents that specifically address a question that is critically important to decision-makers: how to distinguish credible from less credible health care research results. Of those documents (Table 1), 25-44 many address technical issues relevant to only a single type of work (e.g., decision analytic modeling, studies of diagnostic test sensitivity and specificity) or to specific problems (e.g., ghost authorship, sponsorship ethics) rather than principles broadly applicable to all types of health care research.

The documents included in our analysis (shown in bold print in the table) met the following criteria:

(a) Address the question of how to conduct and/or report research.




Research reporting is especially critical because publications are typically a decision-maker’s only potentially valid and reliable source of information about the conclusions reached by study authors. No information consumer should rely solely on popular press accounts.

(b) Provide specific guidance rather than vague admonitions. For example, the advice that study groups should be appropriate is accurate but not especially helpful to a decision-maker unfamiliar with research methods. In contrast, the guidance that study groups should be comparable with respect to demographic and clinical characteristics, including age, gender, payer type, industry type, benefit design, and comorbidities, is sufficiently specific to be usable.

(c) Address quality measures that are applicable to many types of health care research rather than being limited to specific technical issues. For example, the Quality of Health Economic

Studies instrument, a quality-assessment checklist for costeffectiveness analyses, is not included in our detailed review because it addresses primarily technical issues (e.g., perspective of analysis, time horizon, discounting method) but not broader issues (e.g., how a literature review should be performed and reported or how to present implications of study findings for policy or future research.) for manuscript submissions).

evidence.

27

41

(d) Use is complementary with other guidelines (e.g., the AMCP dossier format for formulary submissions or the International Committee of Medical Journal Editors (ICMJE) standards

For example, a managed care decision-maker assessing material for dossier inclusion or an author assessing studies for inclusion in a literature review may need to refer to detailed standards for quality of research

TABLE 2 Key Principles in Conducting and Reporting Research

Transparency

• Study selection criteria are specified in detail

• Quantitative effect of each sampling criterion on sample size is disclosed explicitly; a sample derivation flow chart or table is preferred.

• Details of intervention and comparison conditions are described explicitly

• Methods are described in sufficient detail to enable replication

• Specific contribution of each author and other contributors is disclosed.

a

Hierarchy of evidence quality

• To maximize internal validity (accurate causal inference) design mini mizes the effects of confounding

• Randomized designs are ideal; quasi-experimental is acceptable

• Results of studies with simple pre-post or cross-sectional designs are given lesser weight

Quantitative exploration of possible bias

• Report includes a demonstration (not just assertion) that study groups are comparable

• Studies of claims databases address potential confounding factors specific to that data source

• Possibility of bias is explored using sensitivity analyses on alternative methodological decisions or decision model inputs

Basic logic

• Study report reflects a basic logical and evidence-based connection, or

“plausible mechanism” between input and outcome

• Interpretation does not confuse association with causation (e.g., white hair does not increase the risk of mortality) b

Recognition of the meaning and limitations of statistical methodologies

• Statistical significance is distinguished from practical or clinical signifi cance

• Descriptive analyses of study outcomes are presented

• Multivariate analyses are presented only if necessary (e.g., if simpler bivar iate analyses do not sufficiently address the research question because of confounding factors)

• If multivariate (adjusted) analyses are used, descriptive (unadjusted) statis tics are also presented

• Degree of precision and amount of uncertainty around statistical estimates are presented a Implementation of a contributorship policy is recommended by the International

Committee of Medical Journal Editors.

27 b From an example by Jane Miller in The Chicago Guide to Writing About

Multivariate Analysis 38

Although our review was not intended to be comprehensive of every research guideline available, it covers respected organizations and information sources frequently used by researchers in the managed health care field. These include:

(a) University of Chicago Press reference guides to writing about numbers 37 and about multivariate analyses 38 (these 2 books provide virtually identical guidance);

(b) International Society for Pharmacoeconomics and Outcomes

Research (ISPOR) code of ethics and standards for conducting and reporting studies of medication compliance and persistence, cost-effectiveness analyses, decision analytic models, patient-reported outcomes, and retrospective analyses of administrative claims; 29-31,36,40,42

(c) Key standards cited by the Enhancing the QUAlity and

Transparency Of health Research (EQUATOR) network funded by the National Library for Health and the National

Institute for Health Research; these include reporting guidelines for RCTs (Consolidated Standards of Reporting Trials

[CONSORT]), 35 observational research (Strengthening the Reporting of Observational Studies in Epidemiology

[STROBE]), 33 and intervention studies conducted in nonrandomized groups (Transparent Reporting of Evaluations with

Nonrandomized Designs [TREND]); 34 and,

(d) Guidelines promulgated by the U.S. Department of Health and

Human Services and its agency arms, the U.S. Public Health

Service (USPHS) and the Agency for Healthcare Research and

Quality (AHRQ); these include a review of systems to rate the strength of scientific evidence 25,26 and the report of the

Panel on Cost-Effectiveness in Health and Medicine, which was charged in 1993 with making recommendations for the conduct of cost-effectiveness analyses “to improve their quality and encourage their comparability.” 39 www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 665



TABLE 3 Summary of Key Guideline Documents: Standards for Conducting and Reporting Research

CHICAGO

GUIDE a

INTRODUCTION AND BACKGROUND

Rationale for study is apparent and reasonable

Rationale for methodology (e.g., design, intervention, definitions used) is explained in the context of published evidence and theory; decision analytic model specifies an evidence-based “event pathway” 30,31,33,34,37-40

How previously published or standard methods informed the present study is explained 26,30,31,33-35,37,38,40

METHODS

Research is designed to minimize bias or confounding; method of minimizing bias is explained

Design reflects understanding of “hierarchy of evidence:” (a) randomization is ideal for internal validity,

(b) well-done pseudo-randomized designs are acceptable, (c) a comparison group is nearly always essential, and (d) cross-sectional and pre-post designs are weak and may produce invalid results 26,31,35,37-39

If design is nonrandomized, comparison group is as similar as possible to intervention group (in all respects except for exposure to intervention) 26,31,33,34,37-39

Methods used to adjust, mitigate, or compensate for potential biases are described 26,29-31,33-39

Study design was a priori, not post hoc

A priori plan, and departures from that plan, are disclosed and explained 29,31,33-36,42

Method for determining sample size is specified; a priori power calculations are preferred 26,30,31,33,35,36

Explicit description of study inclusion and exclusion criteria

Study selection criteria are explicit (e.g., list used for selection, specific ages and diagnoses, location, type of clinic, etc.); description should be specific enough to enable reader to determine applicability to his/her population 26,30,31,33,35,37-39

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Sample derivation flow chart is provided 33-35

Effect of subject refusal or withdrawal (e.g. survey response rate, refusal rate) on sample size is reported 26,33-35,37-39,42

Reasons for dropouts are reported; at a minimum, dropouts for reasons relevant to outcomes (e.g., death) are reported separately from those irrelevant to outcomes (e.g., lost address) 33,35,37,38

Intervention details are disclosed fully and specifically – treatment, settings, administration method 26,31,33-35,37-40

• In intervention trials, including drug trials, report includes explicit description of intervention (e.g., dose, administration schedule, blinding procedures, method for disguising placebo, qualifications of personnel administering intervention)

• In drug benefit studies, formulary, step therapy, PA requirements, caps, deductibles, copayment struc tures, and other key details such as the proportion of mail order claims are described specifically

• Carveouts, capitated arrangements, changes in reimbursement arrangements, or other policies that would affect findings, are disclosed if applicable

• In decision analytic models, events and transitions associated with both interventions and alternatives are described explicitly

Outcome measures are valid and explicit

Methods section clearly and specifically defines outcome measures, including specific intermediate or end point outcomes, time horizon, measurement method, in sufficient detail to make replication possible 26,30,31,33,35,37-40

• Decision analytic model specifies input values, data sources, and calculation methods explicitly

• Claims data study report provides detailed definitions of all variables used (e.g., ICD-9-CM, GPI, CPT-4 codes)

• Inclusion of sufficient detail may require technical appendix if journal space is scarce

Validated instruments, measures, and methods are used, or validity of new measures is assessed 26,30,36,39,40,42

Q uantitative procedures are clear.

Calculation procedures and statistical methods are described in sufficient detail and specificity that a knowledgeable reader with access to the data could replicate the analysis 33,37-40

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“Multiple comparison” problem is addressed using post hoc testing or P value adjustment (e.g., Bonferroni,

Tukey’s Honestly Significant Difference Test) 26,30,31,33,35,36,42

√ Subgroup effect assessments are made using interaction terms or other direct comparisons of groups, not by comparing P values across different groups 33,35-38

Sensitivity analyses test effects of various methodological options

If more than 1 methodological decision rule was possible or appropriate, researcher examines effects of different decision rules (e.g., time periods, diagnoses, number of claims required for inclusion) for selecting study subjects 30,31,33,36-39

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If more than 1 method for measuring utilization would have been appropriate, researcher tests different methods for measuring utilization or cost (e.g., disease-related or treatment-related) 31,36,39

Quantitative effects of potential bias are explored. Observational studies estimate potential effects of confounding bias, selection, bias, information bias. Decision analytic models assess degree of sensitivity to model assumptions 26,31,33,37-40

Length of follow-up is disclosed explicitly; in studies with variable length of follow-up, descriptive statistics about follow-up time (e.g., mean, median, range) are reported for each group to assess possibility of differential loss to follow-up 26,30,33,35,36,39

Representativeness of the sample is explored: subjects included are compared with those not included in final analysis (e.g. refused, did not meet sampling criteria, lost to follow-up) or with population to which results will be generalized 26,31,33,34,37-39

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RESULTS: ANALYSIS AND INTERPRETATION OF DATA

Key attributes of study population and setting are described transparently; readers are given enough information to assess appropriateness of study group(s)

Descriptive statistics on demographics, clinical profile, setting, potential confounders are presented

In studies with multiple groups, descriptive information is presented for each group 26,33-35,37-39

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Report includes unadjusted descriptive statistics for study outcome measures (not a sole reliance on multivariate model results) 33,35,37,38

For continuous data, report mean and SD or SE (SD more commonly cited) 33,35,36-38

For skewed continuous data, present median and IQR 33,35,37,38

For continuous data, report range (minimum and maximum) 37,38

For grouped or categorical data, report category limits 33,37,38

Show counts of subjects or patients included in each analysis 33,35,37,38

Sources of uncertainty, confounding, and bias are addressed

Measures of statistical precision (e.g., confidence intervals) are presented 26,30,33,35-40

Potential for unmeasured confounding factors is recognized and assessed when using a multivariate model

(e.g., measures of predictive accuracy or model fit) 30,31,33,37-39

Quantitative details are presented (e.g., coefficients for statistical models, parameters for decision analytic models) 26,37-40

Modeling process is described specifically (e.g., variable selection process, distribution assumed for statistical models; causal pathway for decision analytic models) 26,30,31,33,37-40

Handling of technical issues is explained

Techniques are appropriate for distribution (e.g. linearity, curvilinearity, skewness) 26,30,31,33,36-38

Amount and handling of missing data, including dropouts, are reported 26,31,33-38,42

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Association is distinguished from causation

The process that produces an association between variables is explored (e.g., a “plausible mechanism,”

“causal pathway,” or “biologic credibility.”) Report recognizes that findings of association(s) between variables could be spurious 31,33-38

Alternative explanations for study findings, including bias, confounding, or reverse causation, are explored and reported specifically 26,31,33-35,37,38

Clinical or practical significance (not just statistical significance) is presented

Results are presented as outcome effect sizes (e.g., amount of reduction in cost, number of additional months of persistence, NNT, absolute risk reduction), not just P values 26,30,33-39,42

Researcher recognizes phenomenon of statistical power; large sample sizes can produce findings that are statistically significant but without clinical or practical significance, and small sample sizes can produce clinically significant but statistically insignificant findings; both statistical and practical significance are taken into account in interpretation 26,30,31,33,35,37-39,42

Results are discussed in light of previous research

Report makes specific quantitative comparisons to findings of previously published studies 30,33,35,37-40

Report explains reasons for similarities and differences compared with previously published work 30,33,37-40

Limitations of methods and design are discussed (e.g., potential biases, confounding) 26,30,31,33,36-39

ETHICS

Rights of research subjects are recognized and protected (e.g., evidence of IRB, explanation of IRB exemption, informed consent by subjects affected by research) 29,30,36-38

Full disclosure of sponsorship or business relationships related to research 26,29,30,33,35,39

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CHICAGO

GUIDE a


STROBE/

TREND c

Authorship list is accurate 29 √

SPECIAL CONSIDERATIONS WHEN USING DATABASES INITIALLY DESIGNED FOR BILLING AND PAYMENT PURPOSES

HHS d

Quality (accuracy and completeness) of data has been considered; in a claims database analysis, assurance checks and remedies for quality problems are performed, even when data have been pre-processed by a third party prior to delivery to researcher 30,31,37-39

In an analysis of insured populations, eligibility for health care services is accounted for, either by requiring continuous eligibility for study inclusion or by using appropriate measures (e.g. per member per month, rate per person-year of follow-up) 30,31

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CPT-4 = Current Procedural Terminology, Fourth Edition; GPI = Generic Product Identifier; ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical

Modification; IQR = interquartile range; IRB = institutional review board; NNT = number needed to treat; PA = prior authorization a The Chicago Guide to Writing About Numbers 37 and The Chicago Guide to Writing About Multivariate Analysis 38 b International Society for Pharmacoeconomics and Outcomes Research. Includes:

• Code of Ethics 29

• Checklist for Medication Compliance and Persistence Studies 30

• Retrospective Database Checklist 31

• Good Research Practices: Randomized Clinical Trials – Cost-Effectiveness Analysis 36

• Principles of Good Practice for Decision Analytic Modeling 40

• Patient Reported Outcomes Harmonization Group (in conjunction with European Regulatory Issues on Quality of Life Assessment, International Society for Quality of

Life Research, and Pharmaceutical Manufacturer’s Association Health Outcomes Committee) 42 c From the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network. Includes:

• Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 33

• Consolidated Standards of Reporting Trials (CONSORT) 35 d

• Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) 34

U.S. Department of Health and Human Services. Includes:

• Agency for Healthcare Research and Quality Systems to Rate the Strength of Scientific Evidence 25,26

• U.S. Public Health Service: Cost-Effectiveness in Health and Medicine 39

Table 2 shows key principles reflected in the guideline documents. Table 3 contains a detailed quality checklist summarizing the guidance provided by each information source, sorted approximately in the order of sections in a typical research paper.

Key principles include:

Key Principle: Transparency

All sources emphasize transparency in reporting every phase of a research project. First, study selection criteria should be specified in sufficient detail that readers can clearly determine the applicability of the study sample to their populations. For example, the results of a benefit design intervention study conducted in a hospitality industry sample consisting primarily of young adults paid at minimum wage probably do not inform the expected results of the same intervention implemented in an information technology company consisting of highly paid middle-aged white collar executives and computer programmers. Similarly, results obtained in primary care clinics serving low-income patients are unlikely to predict outcomes in a clinic that accepts only private insurance. For this reason, guidelines that discuss sampling procedures state that inclusion and exclusion criteria – such as age range, diagnoses, period of time for qualification into study, location, setting, or any factor that potentially could influence outcomes – should be specified explicitly.

26,30,31,33,35,37-39

Similarly, to enable the reader to assess how sampling procedures could have affected study validity, most guidelines emphasize that the quantitative effect of each sampling criterion on sample size should be disclosed explicitly.

30,31,33-35,37,38

CONSORT and STROBE guidelines recommend a sample selection flowchart, 33-35 a JMCP requirement (e.g., Figure 1 in Stockl et al.) 45 Some but not all guidelines recommend comparisons (e.g., on demographic and clinical characteristics) of cases included in the sample with either cases excluded from the sample or benchmark data (e.g., data for a sample of patients with diabetes could be compared with similar nationwide data from the

American Diabetes Association).

26,31,33,34,37-39 Guidelines for studies of patient-reported outcomes include reporting of the participation rate, such as a survey response rate.

42

Guideline documents also recommend complete disclosure of the details of interventions and outcomes, including time horizon, measurement method, and codes used (e.g., International

Classification of Diseases, Ninth Revision, Clinical Modification

[ICD-9-CM], Current Procedural Terminology, and Health Care

Common Procedural Coding System codes). Although the specific content of recommendations varies by type of study, the principle of complete disclosure is remarkably consistent. For example, in

RCTs of drug treatments, standards call for disclosure of dose, administration schedule, procedures used to blind participants



A Call to Focus on the Evidence in Evidence-Based Practice and investigators to placebo and active treatment, and qualifications of personnel administering the intervention.

26,35 In drug benefit studies, guidelines call for disclosure of benefit design details, such as formularies, step therapy and prior authorization requirements, carveouts, mail order incentives, or any other arrangements that could potentially affect study findings.

31

TREND guidelines for intervention evaluation studies employing nonrandomized designs describe as “critical” the reporting of “sufficient detail so that a reader has an understanding of the content and delivery of both the experimental intervention and the services in the comparison condition.” 34

Guideline sources, particularly those that address calculation methodologies in detail, are consistent with the ICMJE standard that statistical methods should be described “with enough detail to enable a knowledgeable reader with access to the original data to verify the reported results.” 27 Both the USPHS recommendations for cost-effectiveness analyses and the ISPOR guidelines for decision analytic models include specification of all input values, data sources, and calculation methods.

39,40

CONSORT authors effectively summed up the guidance on transparency: “Readers should not have to speculate; the methods used should be transparent, so that readers can readily differentiate trials with unbiased results from those with questionable results. Sound science encompasses adequate reporting, and the conduct of ethical trials rests on the footing of sound science.” 35

Key Principle: Hierarchy of Evidence Quality

Guideline documents that address research design uniformly recognize that a key element in evidence quality is, as an AHRQ working group described it, “the extent to which all aspects of a study’s design and conduct can be shown to protect against systematic bias, nonsystematic bias, and inferential error.” 25 Key to this assessment is the minimization of confounding, defined as the degree to which subjects in intervention and control (or comparison) groups differ on a factor, other than the intervention, that might affect the study outcome(s). Randomization of study groups is widely recognized as the “gold standard” method to ensure the absence of confounding.

35 Quasi-experimental designs, such as those that compare pre-intervention versus postintervention outcomes across 2 groups (i.e., a group that receives the intervention vs. a similar group that does not) are recognized as a reasonable alternative to randomization. Cross-sectional designs, which compare outcomes for nonrandomized groups during a single time period, and designs that compare pre-intervention versus post-intervention outcomes without a comparison group are recognized as more prone to producing invalid results because they are subject to confounding effects (e.g., unmeasured group differences or changes that would have occurred over time even without the intervention). This recognition is clear both in guideline documents and in methods textbooks.

26,31,35,37-39,46

For nonrandomized designs, a demonstration that study groups are comparable with respect to demographic and clinical characteristics and other potentially confounding factors is recognized in guidelines as important.

26,31,33-34,37-38 Potential confounders vary by study topic, but would include, for example: (a) baseline compliance in a study of whether a disease management program affects medication persistency; (b) comparability of drug formularies in a study of whether particular benefit design features affect patient outcomes; or (c) baseline drug expenditure in a study of the effects of an intervention on payer or out-ofpocket cost. In the AHRQ’s assessment of systems to rate the strength of scientific evidence, all 12 instruments that were used to grade quality of observational research included comparability of subjects as a standard.

25 Thus, guidelines specify the need for a descriptive table comparing study groups on relevant factors.

26,31,33-34,37-38 For the author to merely state, rather than show, that study groups are comparable is recognized as inadequate.

Additionally, guidelines for analyses of claims databases identify possible confounding factors that are specific to that data source.

30,31 First and most important is that eligibility for health insurance benefits must be addressed, either by limiting analyses to members continuously eligible for insurance benefits during the study period or by using outcomes measures that adjust for eligibility (e.g., cost per month of enrollment). Second is an assessment of whether features specific to particular health plans could affect data quality or capture. For example, in a study of cost and utilization of mental health services, the researchers must address whether a “carveout” arrangement with an external vendor for the provision of some or all mental health services could have affected the capture of claims in the dataset. When dealing with samples in which under-reporting of data is common, such as patients with mental illness or enrollees who are aged 65 or older and therefore Medicare-eligible, researchers should describe explicitly how potential concerns about data capture and completeness have been addressed.

Although all guidelines recognize the importance of validity, the authors of the CONSORT guidelines are particularly dismissive of the idea that departures from internal validity (i.e., accuracy in making causal inferences) are acceptable if they enhance external validity (i.e., the degree to which the data represent “realworld” conditions): “Internal validity is a prerequisite for external validity: the results of a flawed trial are invalid and the question of its external validity becomes irrelevant.” 35

Key Principle: Quantitative Exploration of Possible Bias

Closely related to the understanding of hierarchy of evidence is the admonition in guideline documents that researchers should explore in quantitative fashion the possibility of alternative explanations for study findings.

26,31,33-35,37,38 For example, in an observational study that has found higher medication persistence rates for Drug X than for Drug Y, the researcher should explore the possibility that the patients treated with Drug X were more compliant at baseline (e.g., by examining history of compliance with other therapeutic classes in the pre-treatment year). In a www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 669


A Call to Focus on the Evidence in Evidence-Based Practice study in which ICD-9-CM codes of 296.2 (major depression, single episode) and 296.3 (major depression, recurrent episode) were used to select patients with depression, sensitivity analyses should explore the use of other diagnostic codes, such as 311

(depressive disorder not elsewhere classified), because of the possibility that diagnoses of major depression were deliberately or inadvertently miscoded in the bill submitted by the provider for payment. Readers should be especially alert for, and suspicious of, research in which multiple definitions or approaches could reasonably have been used, but the study authors have chosen just 1 of these and performed no sensitivity analyses to assess the effects of their choices.

The need for sensitivity analyses is featured prominently in guideline documents for decision analytic and cost-effectiveness modeling.

39,40 ISPOR’s recommendations for best practice in modeling studies indicate that “model results should never be presented as point estimates or as unconditional claims of effectiveness or cost,” but instead should be “represented as conditional upon the input data and assumptions, and they should include extensive sensitivity analysis to explore the effects of alternative data and assumptions on the results.” 40

Key Principle: Basic Logic

A common theme that emerges from review of the guideline documents is that of a logical and evidence-based connection or “plausible mechanism” between input and outcome; findings should have “biologic credibility.” 31,33-38 Guidelines for decision analytic models emphasize the need for an evidence-based “event pathway,” explicitly showing the reader the relationships among study variables to make the rationale for the calculations clear.

39-40

Weinstein et al., in writing about the ISPOR recommendations for modeling studies, note that a model’s value “lies not only in the results it generates, but also in its ability to reveal the logical connection between inputs (i.e., data and assumptions) and outputs in the form of valued consequences and costs.” Thus, readers should be able to understand the “logic behind [the model’s] results … at an intuitive level.” 40

Guidelines for observational research emphasize that a plausible event pathway is especially critical to avoid confusion between association and causation. In a marvelous tongue-incheek example of how not to interpret observational data, statistician Jane Miller points out that a naïve researcher, noting that the mortality rate among people with white hair is higher than the rate for those whose hair has remained its original color, might write something like this: “White hair increased the risk of dying by 400%.” 38 Extending Miller’s example to an error commonly committed in observational analyses in health care, one might see a naïve researcher report that, given the association between white hair and elevated risk of hospitalization and death, we could save millions of dollars and hundreds of thousands of lives each year if only everyone of a certain age would simply make a small investment in the cost of hair coloration products.

Presentation of an evidence-based logical pathway between input and outcome also helps the reader feel confident in another aspect of study design that is widely recognized as important – the use of a priori rather than post hoc methodologies.

29,31,33-36,42

For example, if the research literature uniformly defines Disease

X as a 3-month history of symptoms, a researcher who, without explanation, selects a study population based on a 6-month symptom history opens the analysis to criticism. Without a clear evidence-based explanation for the sample selection criterion, it appears to readers that methods were hand-picked to produce a desired answer rather than specified in advance.

Key Principle: Meaning and Limitations of Statistical Methodologies

Guideline documents, especially those that specifically address the topic of statistical methods, emphasize in several ways the dangers of over-interpreting or misinterpreting statistical analytic results. A first key example, cited by every guideline source, is the need to distinguish between statistical significance and clinical or practical significance.

26,30,31,33,35,37-39,42 In analyses with very large sample sizes, which are common in retrospective analyses of claims databases, virtually any result will be statistically significant; however, practical significance must be assessed carefully using absolute, rather than relative, measures of effects on outcomes. For example, in a study comparing medication possession ratios for Drug X versus Drug Y with sample sizes of 30,000 in each group, very small differences of less than 0.5 percentage points, or about 1.5 days of pharmacotherapy per year, will be statistically significant but have no practical meaning whatsoever. Conversely, some studies may be underpowered by insufficient sample size; for example, a 1-year persistency rate of 67% for Drug X versus 50% for Drug Y, with sample sizes of

30 in each group, suggests a possibly clinically important difference that has not been tested adequately. Using a 2-tailed test and alpha (Type I error) of 0.05, the number necessary for 80% power to detect a difference of 67% versus 50% is 130 in each group.

Thus, a finding of no significant difference between the groups is not interpretable.

Additional admonitions common to guidelines for statistical analyses address a common phenomenon in health care research, the use of multivariate analyses to adjust for baseline differences in studies with observational designs. Guidelines specify that: (a) descriptive analyses of study outcomes should always be presented, (b) multivariate analyses should be presented only if necessary, and (c) multivariate analyses should never be presented without accompanying descriptive statistics.

33,35,37,38

While recommendations for the content of descriptive analyses vary slightly by source, Chicago Guide recommendations include mean and standard deviation, or median and interquartile range for skewed data, minimum and maximum (range), and counts of subjects or patients included in each analysis.

37,38

Finally, guidelines emphasize that researchers should report



A Call to Focus on the Evidence in Evidence-Based Practice degree of precision around statistical estimates, such as 95% confidence intervals in analyses of randomized trials or observational data, or “bootstrapping” estimates of uncertainty for decision analytic models.

31,38

26,30,33,35-40 All sources also note the importance of recognizing the possibility of unmeasured confounding factors.

26,31,33,36-39 Thus, reports of multivariate models should include estimates of model adequacy, such as goodness of fit measures or a measure of predictive accuracy (e.g., R square for linear regression).

Consistent But Not Consistently Used:

Problems in the Published Literature

The remarkable consistency in the content of published guidelines is matched by an equally remarkable inconsistency in adherence to them. In 2002, a review of the quality of evidence in the medical literature described the problems of “poor methodology and reporting” as “widespread.” 47 The review documented that the prevalence rates of serious methodological errors in published randomized trials in multiple medical disciplines were high. For example, 25% of 364 reports in surgery journals failed to specify eligibility criteria for study inclusion. The percentages of articles failing to report the intervention allocation method were 89% of 196 reports in rheumatoid arthritis journals, 48% of 206 reports in obstetrics/gynecology journals, and 44% of 80 reports in general medical journals. Of 196 reports in rheumatoid arthritis journals, 63% analyzed multiple observations using inappropriate statistical techniques, and of 50 reports in general medical journals, 58% used incorrect techniques in comparing subgroups.

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Similar problems have been identified in the observational research literature. The STROBE group reported that in an analysis of observational studies of stroke, 17 of 49 reports did not specify eligibility criteria for study inclusion.

33 In a review of studies that used multivariate statistical methodologies, only 93 of 169 articles (55%) stated clearly how the variables were entered into the model. A survey of published epidemiologic studies found that “some information regarding” participation rates was provided in only 59% of case-control and cross-sectional studies, and only 32% of cohort studies.

33 A study of 132 articles published in cancer journals found that only about one-half provided information about length of follow-up.

33 A recent study of abstracts of 222 articles published in leading medical journals found that when relative risks were reported, absolute risks were reported in

62% of RCT abstracts but only 21% of cohort study abstracts.

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In Pocock et al.’s (2004) study of epidemiological publications in prominent journals, most exposures (e.g., dietary habits, lifestyle factors, or genetic markers) were grouped into categories without any stated rationale for the groupings, and most articles failed to explain the variables used to adjust for confounding; the authors described as “serious” the “risk that some epidemiological publications reach misleading conclusions.” 48

In some instances, the poor quality of the extant literature has become an impetus for the development of guideline documents. In a particularly troubling example, the TREND group was formed in 2003 after a group of researchers tried unsuccessfully to synthesize multiple studies of behavioral interventions in patients with human immunodeficiency virus. So many study reports had “failed to include critical information (e.g., intervention timing and dosage, effect size data)” that the researchers were unable to complete their work.

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Flaws of this type may have clinical consequences. A discussion of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for ranking types of evidence notes that the recommendation of hormone replacement therapy to reduce cardiovascular risk in post-menopausal women, which had been “dutifully applied” by primary care physicians for about a decade, was based on observational research that ultimately was shown to have produced erroneous findings. “Had a rigorous system of rating the quality of evidence been applied at the time,” noted the GRADE observers in 2008, “it would have shown that because the data came from observational studies with inconsistent results, the evidence for a reduction in cardiovascular risk was of very low quality.” 49

In a similar sequence of events described by Jefferson and Di

Pietrantonj in 2007, studies conducted in the decades prior to

2006, employing mostly observational designs, documented a widely accepted association between use of influenza vaccines in persons aged 65 and older and reduced all-cause death rate.

When Jefferson and Di Pietrantonj pointed out that vaccine use was associated with only the all-cause death rate, not the death rate from pneumonia or influenza, making the association biologically implausible and probably due to confounding, they became the target of “much support and some scorn …

Eminent immunologists told readers that our interpretations were evidently false.” 50 Yet, in 2007, a review of the evidence concluded that the observational study results were attributable to selection bias, and sided with Jefferson and Di Pietrantonj.

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These examples are unfortunately not unique; a 1999 examination of the methodological quality of clinical practice guidelines found that only 13% of the guideline development documents had graded their recommendations according to strength of the supporting evidence.

51

Problems in Quality of Evidence: Preventable with Insistence on Better Reporting

Perhaps the best evidence that quality problems are preventable comes from research studies in which the authors directly reported data that either called the authors’ conclusions into question or entirely refuted them, yet the data were not reflected in the interpretation appearing in the study report.

For example, in a comparison of entecavir with lamivudine in the treatment of hepatitis B, Chang et al. reported that the study’s primary end point outcome, the rate of “histologic improvement,” was higher for entecavir than for than lamivudine (72% vs. 62%; www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 671



P = 0.009).

52 However, the study’s primary data table showed that the percentages of patients with “no improvement” did not significantly differ by drug, and the counts of the “histologic improvement” and “no improvement” subgroups did not sum to the total number of study patients. A footnote to the data table explained the discrepancy; the denominators used in the calculations included patients who had no follow-up biopsy specimens, while the numerators excluded them. Excluding patients with missing follow-up specimens from both the denominator and the numerator, the percentages of cases with histologic improvement were 77% for entecavir and 72% for lamivudine, yielding a non-significant P value of 0.204 for the comparison (Fisher’s exact test). Nonetheless, the study abstract reported superiority for entecavir.

53

Yank et al. reported a similar problem in their systematic review of meta-analyses of antihypertensive medications that had been published from 1983-2004. When they compared studies funded by a single drug manufacturer with those funded by other sources (i.e., multiple funding sources, non-profit, and undisclosed), a financial tie to a drug manufacturer was not significantly associated with favorable results (i.e., objective findings, odds ratio [OR] = 0.65, P = 0.25). However, manufacturer funding was significantly associated with favorable conclusions

(i.e., interpretation, OR = 4.09, P = 0.016). Yank et al. opined that their results reveal “a failure of peer review. Both editors and peer reviewers must have read manuscript versions of those metaanalyses containing discordant results and conclusions, yet they did not prevent publication of biased conclusions.” 54

Notably, as an example of the need for data analyses by academic statisticians, the JAMA editorial on pharmaceutical industry influence cited a secondary analysis of a 2005 trial of the use of rofecoxib in patients with mild cognitive impairment.

6,21,55 As the secondary analysis noted, the 2005 report did not reflect the higher all-cause mortality rate for rofecoxib compared with placebo, even though this difference had been disclosed in internal manufacturer documents about 4 years previously.

6 Yet, examination of the original study report suggests problems in reporting and calculation. The sample selection flow chart shows the numbers of patients in each group who experienced an “adverse event,” but does not show how many of those events were fatalities. Additionally, the report’s text discloses that in the “off-drug follow-up” period, for which data were available for “less than half of the patients,” the death rates were 4.8% (17/356) for rofecoxib and 1.6% (5/307) for placebo; the statistical significance of this difference (Fisher’s Exact Test P = 0.029) was not reported.

55

Attention to Quality: The Best Solution to Quality Problems

It is tempting to think that if research is simply turned over to smart people who have no overt commercial interest in its outcome, concern over the quality of research evidence will become a thing of the past. Such a solution requires little real effort on the part of information consumers; simply ensure that the right people are doing the work and settle back to enjoy the fruits of their labors. However, in an environment in which basic standards for quality of evidence are widely available and yet commonly ignored, this approach suggests abrogation of responsibility by information consumers, as well as peer reviewers and editors. We believe that the solution to the current problems with the quality of peer-reviewed health care literature does not lie solely, or even primarily, in a focus on “whodunnnit” but rather in renewed attention to basic standards for quality of evidence.

These standards represent nothing more complicated or difficult to understand than lessons repeated in undergraduate-level methodology classes that have been taught for decades, coupled with a little common sense. Using these standards does not take a degree in research methodology or statistics; it takes only the commitment to adhere to them.

As the editors of Journal of General Internal Medicine sagely observed 3 years ago in discussing the effect of pharmaceutical manufacturer funding on the research literature, “perfection is an asymptote, a goal that can be approximated, but never reached.” 16 Yet, to strive for the goal of disseminating only highquality evidence, it is necessary to assess distance from the goal.

Comparisons of research standards with the characteristics of much of the published health care literature suggest that we have a long way to go.

A cynical perspective on health care research, although understandable, is neither inevitable nor wise. What is needed is critical analysis of the quality of the evidence, regardless of who did the research. It is more important to determine what evidence to trust than whom to trust. In managed care, the central focus should be on the customers – the patients, pharmacists, physicians and other care givers – who deserve accurate and transparent information about the expected clinical and economic effects of treatment options. All stakeholders, but especially patients, have a lot to lose when studies of treatment options are not validated against accepted standards for conducting and reporting research.

Authors

KATHLEEN A. FAIRMAN, MA, is Associate Editor and Senior

Methodology Reviewer of the Journal of Managed Care Pharmacy.

FREDERIC R. CURTISS, PhD, RPh, CEBS, is Editor-in-Chief of the

Journal of Managed Care Pharmacy.

AUTHOR CORRESPONDENCE: Kathleen A. Fairman, MA,

Kathleen Fairman LTD, PO Box 31278, Phoenix, AZ 85046. Tel.:

602.867.1343; E-mail kathleenfairman@qwest.net.

DISCLOSURES

The authors report no conflicts of interest related to the subjects or products discussed in this article.




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A B S T R A C T S

Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference

T he following poster presentations have been prepared for the Academy of Managed Care Pharmacy’s 2008 Edu ca tional Conference, October 1518, 2008, in Kansas City,

Missouri. Poster presentations are selected by the Program

Planning and Development Committee from proposals that are submitted to AMCP. Authors of posters are responsible for the accuracy and completeness of the data presented in the posters and in the abstracts published here.

For more information about the studies described below, please contact the corresponding authors, indicated by an aster isk (*), whose addresses are listed in full. The names of individ uals who are scheduled to present at the meeting are in bold.

RESULTS: Mean MPR for case patients with anxiety/depression ranged between 0.47 (shortacting beta agonists) and 0.72 (long acting anticholinergics). Mean MPR for case patients was 3%7% lower than for controls in each drug class ( P < 0.05). The case group also had a lower proportion of highly adherent patients, defined as MPR > 80%, in each drug class ( P < 0.05). Drug classes with the highest fraction of highly adherent patients were long acting anticholinergics (50% and 57% for case and control, respectively), longacting beta agonists (43% and 49%, respec tively), and bronchodilator/corticosteroid combinations (34% and

40%, respectively). Case patients had lower 1year persistence rates than control patients for each COPD drug class (7%17% for case patients vs. 11%24% for controls; average difference was

6 percentage points).

CONCLUSIONS: COPD patients with comorbid anxiety and/or depression exhibit lower levels of adherence and persistence to all classes of inhaled COPD drugs than those without these condi tions. Further research is needed to better understand the impact of anxiety and depression in patients with COPD.

■■ ADHERENCE AND PERSISTENCE OF INHALED

THERAPIES IN COPD PATIENTS WITH ANXIETY

AND/OR DEPRESSION

Toy EL, Rosenblum D, Gosselin A, Plauschinat CA,* Duh MS.

*Novartis Pharmaceuticals Corporation, 59 Rte. 10, East Hanover,

NJ 07936; craig.plauschinat@novartis.com, 862.778.2431

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Significant comorbid conditions are likely in COPD patients, including a higher preva lence of anxiety and/or depression. Comorbid anxiety/depression may diminish adherence to COPD therapies.

OBJECTIVE: To compare adherence and persistence of COPD patients with and without anxiety/depression among 7 classes of inhaled COPD drugs: short and longacting beta agonists, short and long acting anticholinergics, inhaled corticosteroids, bronchodilator combinations, and bronchodilator/corticosteroid combinations.

METHODS: Administrative claims data from January 2003 through

December 2006 were extracted from the Medstat Marketscan database, which includes medical and pharmacy claims from

69 million patients. The case group (N = 109,861) consisted of patients with at least 1 diagnosis of COPD (ICD9CM codes

491, 492, 493.2, 496) plus anxiety and/or depression (ICD9CM codes 296.2, 296.3, 311, 300.0). The control group (N = 329,583) was selected by matching 3 COPD patients with no anxiety/ depression diagnoses to each case patient based on age and gender. Adherence to each drug class was measured by the medi cation possession ratio (MPR), defined as the ratio of drug days supply to the days between the first and last refills of a drug class.

A patient was considered persistent until a gap of > 30 days in drug supply was observed.

■■ ANALYSIS OF THE DOSE RELATIONSHIP BETWEEN

EPOETIN ALFA AND DARBEPOETIN ALFA IN PATIENTS

WITH CHRONIC KIDNEY DISEASE NOT ON DIALYSIS

Horowitz J, Cangialose C,* Agarwal A, Phelan M, Audhya P.

*Amgen Inc., One Amgen Center Dr., MS 28-3-A, Thousand Oaks,

CA 91320; ccangial@amgen.com, 805.447.8616

BACKGROUND: Previous studies have used various methods to evaluate dose conversion between epoetin alfa and darbepoetin alfa. However, these nonclinical trialbased methods are more likely to be confounded by differences in patient demographics, comorbidities, hemoglobin (Hb) target, and erythropoiesisstim ulating agent (ESA) dose frequency.

OBJECTIVE: This post hoc analysis was conducted to assess the dose conversion relationship between epoetin and darbepoetin when patients with chronic kidney disease were converted from stable weekly (QW) or everyotherweek (Q2W) epoetin to Q2W darbepoetin titrated to the same Hb range.

METHODS: Subjects were ≥ 18 years of age, had an estimated glom erular filtration rate (eGFR) ≥ 15 and ≤ 60 mL per min per 1.73m

2 , were not receiving dialysis, and had Hb ≥ 11 and ≤ 13 g per dL, which was the acceptable Hb range at the time this study was designed. Subjects were converted from QW or Q2W epoetin to

Q2W darbepoetin utilizing a conversion schedule similar to the

U.S. package insert (PI) for darbepoetin. The darbepoetin dose was adjusted to maintain a Hb level ≥ 11 and ≤ 13 g per dL. The www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 675

Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference dose conversion ratio (DCR) between maintenance epoetin at study baseline and maintenance darbepoetin over weeks 2533 was calculated consistent with the U.S. darbepoetin using a simple linear regression equation on logtransformed values.

RESULTS: A total of 117 subjects were included in this analysis;

60% were male, 71% were white, and the mean (SD) age was

70.9 (11.7) years. Thirtyfive percent were receiving QW epoetin at baseline. Mean (SD) baseline eGFR was 27.7 (9.1) mL per min per 1.73m

2 . Mean (SD) baseline and Hb levels at weeks 2533 were 11.7 (0.6) and 11.8 (0.8) g per dL, respectively. The study population DCR between maintenance epoetin and maintenance darbepoetin at weeks 2533 was 330.6:1.

CONCLUSIONS: In this analysis, the dose relationship between epoetin and darbepoetin was analyzed in a controlled clinical study setting where subjects were converted from epoetin to dar bepoetin titrated to the same Hb range. The results indicate that subjects who converted from stable QW or Q2W epoetin to stable

Q2W darbepoetin had a maintenance DCR of approximately

331 units epoetin to 1 mcg darbepoetin.

dosing, and 16.1% increased their dose after initiating standard dosing. Among the 28% with elevated dosing, costs were 31.3% higher. Applying these results to the full adalimumab cohort generated drug costs that were 8.9% higher than if all patients had consistently received standard dosing.

CONCLUSIONS: The percentages of RA patients with dose elevation on subcutaneous TNF antagonists do not determine ultimate budgetary impact. This likely occurs because dose increases vary in timing of first occurrence, magnitude, and duration, impact ing costs in a dynamic pattern that cannot be captured in static percentages. Payers may wish to establish baseline costs which assume that all patients consistently receive standard dosing and compare these to actual costs from their own utilization data.

Actual costs register the collective impact of all forms of elevated dosing. This method places any observed dose increases into the proper context and may increase budgetary predictability.

■■ ASSESSING THE COSTS OF DOSE ELEVATION

AMONG RHEUMATOID ARTHRITIS PATIENTS RECEIVING

SUBCUTANEOUS TNF ANTAGONISTS

Huang X,* Shechter D, Lyons A, Thomas J. *Amgen Inc.,

One Amgen Center Dr., MS 28-3-A, Thousand Oaks, CA 91320; xingh@amgen.com, 805.313.6468

■■ ASSESSMENT OF HOSPITALIZATION RISK AMONG

PATIENTS WITH SCHIZOPHRENIC DISORDERS TREATED

WITH ANTIPSYCHOTIC THERAPY IN A LARGE STATE

MEDICAID PROGRAM

Lang K, Jackel J, Lee SP, Sikirica M, Crivera C,*

*Ortho-McNeil Janssen Scientific Affairs, LLC,

Dirani R, Menzin J.

1125 Trenton-Harbourton Rd., Titusville, NJ 08560; ccrivera@omjus.jnj.com, 609.730.4506

BACKGROUND: The advent of novel, expensive drug therapies creates challenges to managing costs. For tumor necrosis factor

(TNF) antagonists, published claims analyses suggest that these agents are not always dosed as recommended by prescribing information (PI). Additionally, studies may measure elevated dos ing in ways that obscure the true cost impact.

OBJECTIVE: To clarify the limitations of current dose escalation measurements and quantify the impact of elevated dosing on costs.

METHODS: Using a large managed care claims database, rheuma toid arthritis (RA) patients first receiving a subcutaneous TNF antagonist were followed for 12 months. For each drug, we cal culated the percentage of patients who (1) started and maintained standard PI dosing or (2) exceeded standard dosing at any time point, by any amount, or for any duration. Drug costs were calcu lated for these groups both individually and in combination.

RESULTS: Among etanercept patients, 89% received standard dosing, 2.8% started treatment at elevated dosing, and 8.2% increased their dosage after initiating standard dosing. Among the 11% with elevated dosing, costs were 7.7% higher. Applying these results to the full etanercept cohort generated drug costs that were 0.8% higher than if all patients had consistently received standard dosing. Among adalimumab patients, 72% received standard dosing, 11.9% started treatment at elevated

BACKGROUND: Hospitalization is a concern for patients with schizophrenic disorders, particularly among those who are non adherent to prescribed antipsychotic therapy.

OBJECTIVE: To evaluate rates and assess key predictors of hospital ization among patients with schizophrenic disorders.

METHODS: A retrospective cohort analysis was conducted of Florida

Medicaid recipients who had 1 inpatient or 2 outpatient medical claims indicating a schizophrenic disorder (ICD9CM code 295.

xx) and filled at least 1 prescription for an antipsychotic medica tion between July 1, 2004, and June 30, 2005. Patients were fol lowed for 1 year after the first antipsychotic prescription (index).

Patients were required to be continuously eligible for Medicaid

(with no dual Medicare eligibility) 1 year before (baseline) and

1 year after index. Additionally, patients had to receive at least

1 additional antipsychotic in the followup period to ensure a true

“treated” population. Adherence was measured using the medica tion possession ratio (MPR) defined as the number of outpatient treated days divided by the number of outpatient days in the

1year followup. Multivariate logistic regressions controlling for age, concomitant diagnoses and medications, and nonadherence

(defined as MPR < 0.8) were used to identify predictors of all cause and mental disorderrelated (ICD9CM codes 290.xx319.

xx) hospitalization.

RESULTS: 12,032 patients met eligibility criteria. Mean (SD) patient age was 43.2 (13.0) years, 52% were female, and most


Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference patients were white (38%) or black (25%). Approximately 18% and 39% had preexisting diagnoses of substance abuse and other psychiatric conditions, respectively. In the followup period,

37% of patients were hospitalized for any reason, and 32% were hospitalized with a psychiatric diagnosis. Patients had an aver age (SD) of 0.9 (3.5) psychiatric hospitalizations and 1.1 (3.6) allcause hospitalizations in the followup period. Concomitant substance abuse or other psychosis diagnoses, baseline use of antidepressants, and nonadherence to antipsychotic therapy were associated with a greater risk of allcause hospitalization. Younger age, concomitant substance abuse or other psychosis diagnoses, and nonadherence to antipsychotic therapy were associated with a greater risk of psychiatric hospitalization.

CONCLUSIONS: These data demonstrate several characteristics potentially predictive of hospitalization among patients with schizophrenic disorders receiving antipsychotics.

outpatient costs ($2,238 vs. $938). The differences were statisti cally significant. Differences in pharmacy ($19,591 vs. $16,785) and surgical costs ($265 vs. $352) were not statistically sig nificant. Also, patients who switched had higher resource utiliza tions in all categories. In the regression analysis after controlling for age, gender, and comorbidity level, patients who switched had significantly higher total health care costs (odds ratio = 2.67,

95% confidence interval = 1.634.35).

CONCLUSIONS: Switching antiTNF therapy in AS patients was associated with higher health care costs. Further studies to exam ine the reasons for switching as well as the clinical consequences are recommended.

■■ ASSOCIATION OF SWITCHING AMONG ANTI-TUMOR

NECROSIS FACTOR AGENTS AND HEALTH CARE COSTS

IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Tang B,* Changolkar AK, McKenzie S, Piech C. *Centocor Ortho

Biotech Services, LLC, 850 Ridgeview Dr., H-2-3, Horsham, PA

19044; btang@cntus.jnj.com, 215.325.2164

BACKGROUND: Few longitudinal data exist regarding switching patterns among antitumor necrosis factor (antiTNF) therapies in patients with ankylosing spondylitis (AS).

OBJECTIVE: To evaluate the relationship among switching between antiTNF agents and total health care costs in patients with AS.

METHODS: A retrospective study using managed care claims from the PharMetrics database was conducted. The first antiTNF encounter (index biologic date) in AS patients between January 1,

2000, and December 31, 2006, was identified. Patients were required to have a minimum of 18 months of continuous plan eligibility, defined as 6 months prior to and 12 months following their index biologic date because patients were followed up for

12 months after the index biologic date. Switching among anti

TNF medications (infliximab, etanercept, or adalimumab) was recoded. Inflationadjusted health care costs between patients who switched versus patients who did not switch were com pared.

RESULTS: A total of 537 patients were analyzed; more than onethird (37.6%) of patients were female, and the mean age was

45.7 years. Age and gender were similar between the 2 cohorts, while patients who switched had a higher Charlson comor bidity index (1.91 vs. 1.15, P = 0.02). During the study period,

43 patients (8.01%) switched. Compared with patients who did not switch, patients who switched had higher mean total health care costs ($53,081 vs. $24,926), primarily attributable to inpatient ($15,280 vs. $3,216), emergency room ($540 vs. $183), lab ($409 vs. $141), physician services ($3,709 vs. $2,050), and

■■ BEHAVIORAL IMPACT OF AN EVIDENCE-BASED

PLAN DESIGN: AN INNOVATIVE HEALTH AND RESOURCE

CONSUMPTION MANAGEMENT STRATEGY

Nguyen J, Thuppal S.*, Engmann S. *CVS/Caremark,

2211 Sanders Rd., Northbrook, IL 60062; joy.medrano@caremark.com, 847.559.5793

BACKGROUND: Burden of illness significantly affects employers’ productivity and capital investment. With the continued pro jected increase in health care cost, employers and managed care organizations continue to develop innovative ways to control cost and utilization. Evidencebased plan design (EBPD) is a condition management strategy that includes incentives for the use of medi cations that are proven to be of clinical value. EBPD is an emerg ing benefit design concept among employer groups that may help increase productivity and workforce health and, ultimately, help control health care resource consumption.

OBJECTIVE: To examine the behavioral impact of prescription utilization by decreasing plan participant outofpocket cost for

4 common chronic conditions.

METHODS: A retrospective observational study of a 34,000 member employer group examined a therapeutic class EBPD with a focus on behavioral impact. Plan participant outofpocket costs were lowered by 50%, and compliance, resource consump tion, and gaps in care were examined. Compliance was measured as medication possession ratio (MPR), resource consumption as the number of users, and gaps in care as plan participants following therapy guidelines.

RESULTS: After copayment reduction for medications used to treat diabetes, asthma, hypertension, and high cholesterol, there was a 14%, 8%, 9%, and 13% significant increase ( P < 0.010) in the number of users from 2005 and 2006 for those conditions, respectively. During the same time period, there was a statistically significant increase in the average days of therapy per month for all 4 conditions. From 2005 to 2006, there was a 6% increase in the number of plan participants who continuously utilized maintenance asthma medications and a 1% decrease in the num ber of plan participants who utilized acute asthma medications, www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 677

Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference indicative of better symptom control among those plan partici pants. Among the diabetic population, there was an increase of 9% and 7% in the number of plan participants who were taking lipid therapy and angiotensinconverting enzymes and angiotensin II receptor blockers, respectively, suggesting better adherence to evidencebased treatment guidelines. Compliance increased in all 4 therapeutic categories during the observation period.

CONCLUSIONS: impact on plan participant behavior. Upon implementation of the benefit, a positive correlation was found between compliance, resource consumption, and reduction in copayment.

■■

There is an indication that EBPD has a positive

COMPARISON OF HEALTH CARE COST IN METASTATIC

COLORECTAL CANCER PATIENTS TREATED WITH

CAPECITABINE- OR 5-FLUOROURACIL-BASED REGIMENS

IN A LARGE MANAGED CARE PLAN

Wenhui W,* Halpern R, Zelt S. *Roche, 340 Kingsland St., Bldg. 1,

5th Fl., Nutley, NJ 07110; wenhui.wei@roche.com, 973.562.2464

BACKGROUND: Intravenous (IV) 5fluorouracil (5FU) is a widely used cytotoxic agent in colorectal cancer (CRC). However, IV treatments require catheter insertion and/or infusion pumps, which are costly and often associated with increased morbidity.

Capecitabine is an oral fluoropyrimidine that has shown similar clinical efficacy to 5FU.

OBJECTIVE: We analyzed retrospective claims data from a large

U.S. managed care plan to compare health care costs in metastatic

CRC (mCRC) patients treated with capecitabine or 5FUbased regimens.

METHODS: Patients were included if they were diagnosed with mCRC and received chemotherapy between January 1, 2005, and December 31, 2006. Patients could have a claim with a

CRC diagnosis (or indication of metastasis) from July 1, 2001, to December 31, 2006. Cost measures included allcause and chemotherapyrelated adverse event (AE), ambulatory, emergency room, inpatient stay, total medical, total pharmacy, and total health care (medical + pharmacy) costs. General linear model regressions were used to examine allcause and AErelated monthly care costs during chemotherapy treatment episodes, controlling for baseline characteristics.

RESULTS: Of 1,459 patients, 67% had 1 treatment episode. Total health care costs were significantly higher for 5FU treatment episodes compared with capecitabine counterparts (see Table).

Capecitabinebased therapy was associated with significantly lower allcause and AE, ambulatory, total medical, and total health care costs.

CONCLUSIONS: mCRC patients treated with capecitabine regimens had significantly lower total health care costs compared with those treated with 5FU regimens. This suggests that capecit abine offers a feasible alternative to IV 5FU in mCRC patients.

TABLE Distribution of Episode-Level Unadjusted

Health Care Costs for Chemotherapy

Treatment Episodes

Parameter

Health care costs

Total ($U.S.)

Ambulatory

Emergency room

Inpatient stay

Total medical

Total pharmacy

Adverse event-related health care costs

Total ($U.S.)

Ambulatory

Emergency room

Inpatient stay

Total medical

Capecita bine 5-FU

17,335 a

11,474 a

12

1,170 a

12,904 a

4,431 a

2,940 a

1,680 a

6

1,052 b

2,774 a

166 b

26,507

20,467

22

3,853

25,509

998

8,222

4,251

4

3,430

7,826

Total pharmacy 396 a P < 0.001 versus corresponding 5-FU regimen.

b P < 0.005 versus corresponding 5-FU regimen.

Capecitabine

+ Oxaliplatin

5-FU +

Oxaliplatin

42,040 a

33,340 a

20

2,820

36,603 a

5,437 a

12,204 a

9,764 a

19

2,010

11,854 a

350 a

60,311

52,798

52

4,146

58,704

1,607

25,799

21,126

15

3,610

24,868

930

■■ COMPARISON OF HEALTH CARE RESOURCE

UTILIZATION, ASSOCIATED COSTS, AND LOST

PRODUCTIVITY AMONG CHRONIC MIGRAINE

AND EPISODIC MIGRAINE POPULATIONS:

RESULTS FROM THE AMERICAN MIGRAINE

PREVALENCE AND PREVENTION STUDY (AMPP)

Manack A, Serrano D, Buse DC, Chiao E,* Lipton RB. *Xcenda,

4114 Woodlands Pkwy., Ste. 500, Palm Harbor, FL 34685; evelyn.chiao@xcenda.com, 484.927.4055

BACKGROUND: Differences in symptom profiles suggest that chronic migraine (CM) and episodic migraine (EM) popula tions will differ with respect to health care resource utilization, headacherelated quality of life, and productivity.

OBJECTIVE: To compare physician office and emergency room visit costs and lost productivity between CM and EM populations from the American Migraine Prevalence and Prevention (AMPP) study.

METHODS: The AMPP study is a longitudinal, prospective, popula tionbased, mailed survey initiated in 2004. Screening of 120,000

U.S. households resulted in an initial pool of 32,000 individuals who reported severe headache, from which a random sample of

24,000 have been prospectively sampled annually from 2005 to

2008. Two populations of respondents who met defined criteria for migraine were identified: CM (≥ 15 headache days/month) and EM (08 headache days/month). Costs of headacherelated


Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference services were assessed based on wholesale acquisition costs and

Current Procedural Terminology codes. Lost productive time

(LPT) was calculated as the summed hours of absenteeism and impairmentweighted hours of time at work due to headache.

Costs of acute and preventive medications for migraine have not been included.

RESULTS: Of the respondents who completed the 2005 AMPP survey, 655 had CM and 10,609 had EM. Over 1 year when compared with EM, CM respondents made significantly more headacherelated visits to physicians (primary care, neurolo gist) and/or emergency departments ( P < 0.050) for an annual perpatient cost of $594.66 for CM and $182.85 for EM. CM respondents who were employed full time or part time had lost more than twice the productive time of EM respondents (7.98 vs.

3.4 mean hours per week, P < 0.001).

CONCLUSIONS: Patients with CM are a relatively small subset of all individuals with migraine. However, in the sample, this subset consumed 3 times the costs associated with utilization of head acherelated resources and demonstrated a greater amount of LPT than EM patients. The appropriate and effective use of preventive therapy in this subset of individuals with CM may reduce health care resource utilization and associated costs.

Sponsorship: Research was funded through an unrestricted grant to the

National Headache Foundation by OrthoMcNeil Neurologics, Inc., Titusville,

NJ, and Allergan Inc., Irvine, CA.

■■ CONSEQUENCES OF STOPPING CLOPIDOGREL

THERAPY FOLLOWING ACUTE MYOCARDIAL INFARCTION

HOSPITALIZATION OR CORONARY STENT INSERTION:

THE MANAGED CARE PERSPECTIVE

Wiederkehr D,* Ogbonnaya A, Casciano R, Makenbaeva DJ,

Mozaffari E, Corbelli JC. *Analytica International, 450 Park Ave. S.,

12th Fl., New York, NY 10016; DWiederkehr@analyticaintl.com,

212.686.4100

from 20022007. The occurrence of AMI and/or ACSrelated procedures (coronary artery bypass graft, percutaneous coronary intervention with/without stent insertion) was tracked up to 1 year after initial hospitalization. Using a timedependent covariate for clopidogrel therapy, multivariate Cox regression was used to assess the association between stopping clopidogrel and the risk of AMI rehospitalization or ACSrelated procedure while adjust ing for demographics, comorbidities, cardiovascular procedures at initial hospitalization, and followup time.

RESULTS: A total of 31,835 patients had an AMI hospitalization or coronary stent procedure followed by at least 30 days of clopidogrel therapy. Average followup was 284 days. More than twothirds (68.5%) of the patients stopped refilling clopidogrel before the end of 1 year. The average duration of therapy was

130 days for those who stopped therapy earlier than 1 year.

Approximately 10% (n = 3,212) of all patients experienced an

AMI rehospitalization or ACSrelated procedure during the year.

Patients who stopped therapy prior to 1 full year were 33% more likely to have a subsequent AMI rehospitalization or ACSrelated procedure (heart rate 1.34, 95% confidence interval 1.251.44).

CONCLUSIONS: Stopping clopidogrel prior to 1 full year of therapy following an AMI hospitalization or coronary stent insertion is associated with a significant higher risk of AMI hospitalization or ACSrelated procedures. The findings from this nationally representative managed care population are consistent with prior realworld studies in a veteran population, demonstrating increased risk of negative clinical outcomes following clopidogrel discontinuation.

■■ COST OF CARE AMONG PATIENTS WITH

COLORECTAL CANCER: WHAT NEEDS TO BE INCLUDED?

Chu E,* Cartwright T, Wei W, Schulman KL. *Yale University School of Medicine, 333 Cedar St., WWW-221, New Haven, CT 06520; chueyale@yahoo.com, 203.785.6879

BACKGROUND: Clopidogrel has been shown to reduce the risk of recurrent acute coronary syndrome (ACS) events in both random ized controlled trials and realworld observational studies and has been recommended by the American College of Cardiology/

American Heart Association guidelines since 2002.

OBJECTIVE: To evaluate the clinical impact of stopping clopidogrel therapy earlier than the longest ideal recommendation of 1 year in ACS patients with or without coronary stenting in a nationally generalizable managed care setting.

METHODS: This retrospective cohort study included patients having an acute myocardial infarction (AMI; STelevation myocar dial infarction [STEMI] or nonSTEMI) and/or coronary stent insertion, followed by at least 30 days of clopidogrel therapy.

Patients’ medical encounters and medication fills were extracted from a database of large nationally representative managed care plans (PharMetrics, Inc., Watertown, MA, United States)

BACKGROUND: The increasing costs of cancer treatment faced by managed care organizations (MCOs) are largely due to higher drug acquisition costs. However, agents with lower unit costs also include charges associated with their administration and possibly higher secondary costs due to increased toxicity.

OBJECTIVE: To determine the contribution of chemotherapy related costs (drug acquisition cost, drug administration cost, chemotherapyrelated complication cost) to the total direct medi cal expenditure among patients with colorectal cancer (CRC) receiving oral capecitabine or intravenous 5fluorouracil (5FU) based regimens.

METHODS: Patients with CRC receiving capecitabine or 5FU between 2003 and 2006 were identified from the Thomson

Healthcare MarketScan research databases. Propensity score matching was used to obtain balanced casecontrol groups in each treatment setting. Data for direct health care utilization and www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 679

Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference expenditures were collected from patient medical and pharmacy claims generated during chemotherapy.

RESULTS: A total of 4,729 patients were studied. In the adjuvant setting, 1,396 received monotherapy; in the metastatic setting,

2,544 received monotherapy; and 789 received combination therapy (capecitabine or 5FU with oxaliplatin). In the adju vant setting, 34% of the total direct medical expenditures was chemotherapyrelated among patients receiving 5FU mono therapy (1% drug acquisition cost, 14% administration cost,

19% complicationrelated cost) versus only 22% among patients receiving capecitabine monotherapy (12% drug acquisition cost,

1% administration cost, 9% complicationrelated cost). In the metastatic setting, the proportion of chemotherapyrelated cost in the total direct medical expenditures was similar in both monotherapy regimens (29% in capecitabine group vs. 27% in

5FU group) and combination regimens (71% in capecitabine

+ oxaliplatin group vs. 70% in 5FU + oxaliplatin group). Overall, for capecitabine regimens, the proportion of drug acquisition cost in the total direct medical expenditures was higher than for 5FU regimens, but was offset by the lower proportions of administra tion and complicationrelated costs.

CONCLUSIONS: As MCOs are paying the total cost of care for patients, assessment of chemotherapyrelated cost should include the cost of administering medications as well as the costs associ ated with toxicity. The impact on total direct medical expendi tures of all chemotherapyrelated complications may be a more accurate measure of the cost of cancer treatment than drug acquisition cost alone.

METHODS: The computer dosage calculation program for liquid

250 mg per 5 mL amoxicillin (based on 77 mg per kg per day) was introduced in the EMR during March 2006. All orders for this form and dosage of amoxicillin among patients aged 2 months to 12 years who weighed 30 kg or less (along with actual patient weight at time of order) were identified within automated medi cal record data for a 2year period. Differences in amoxicillin orders—which were determined to be too low (< 60 mg per kg per day), appropriate (60100 mg per kg per day), or too high (> 100 mg per kg per day) for patient weight—were examined 1 year prior to implementation (March 1, 2005February 1, 2006) and

1 year postimplementation (April 1, 2006March 31, 2007).

RESULTS: For patients weighing 30 kg or less, 50% of orders were too low for patient weight prior to implementation of the dosage calculation program compared with 39% postimplementation

( P < 0.001).

CONCLUSIONS: While decision support for dosing in the EMR improved amoxicillin ordering, a substantial number of orders

(39%) were still too low for patient weight based on current recommendations. Providers appear to be adjusting the dose calculated by the EMR. Especially when recommendations change, implementation of computerassisted ordering may not be successful without accompanying provider education.

■■ ECONOMIC BURDEN OF MOOD DISORDERS

AMONG COMMERCIALLY INSURED PATIENTS

WITH DIABETIC NEUROPATHIC PAIN

Patel C, Boulanger L,* Zhao Y, Lamothe K, Russell M.

*Abt Bio-Pharma Solutions, Inc., 181 Spring St., Lexington, MA

02421; luke.boulanger@abtbiopharma.com, 781.372.6628

■■ DECISION SUPPORT FOR AMOXICILLIN DOSING

IN THE ELECTRONIC MEDICAL RECORD: IF YOU BUILD IT,

WILL THEY USE IT?

Nordin JD, Jackson JM,* Molitor BA, Bruzek R, Palattao K,

Rolnick CJ. *HealthPartners, Research Foundation, P.O. Box 1524,

MS 21111R, Minneapolis, MN 55440; jody.m.jackson@healthpartners.com, 952.967.7032

BACKGROUND: A sizeable literature exists suggesting that the elec tronic medical record (EMR) can dramatically reduce prescribing errors, particularly when decision support tools are incorporated.

A weightbased dosage calculation program for amoxicillin order ing was introduced within the EMR of a large integrated health system. The rationale for the dosage calculation was based on

2004 American Academy of Physicians and American Academy of

Family Practice recommendations. Due to the emergence of resis tant pneumococci, this recommendation doubled the previously advised dosage of 2045 mg per kg per day to 8090 mg per kg per day for otitis media and similar infections in children.

OBJECTIVE: To examine the experience of the health system in reducing dosage errors after implementing computerassisted ordering for amoxicillin within a pediatric population.

BACKGROUND: Diabetic neuropathic pain (DNP) is a common complication of diabetes that can lead to development of mood disorders in many diabetic patients. Scant research has been con ducted to assess resource use and costs associated with treating

DNP patients with or without mood disorders.

OBJECTIVE: To assess economic factors among commercially insured DNP patients with and without mood disorders.

METHODS: This retrospective cohort study employed claims data to assess resource use and costs over a 1year followup period among DNP patients. Patients aged 1864 years who had at least

1 diagnosis of diabetic neuropathy in 2005 (first observed DNP claim denoted as the index date) and at least 1 pain medication dispensed in the previous 12 months were identified. Two cohorts of patients were constructed for individuals with depression or anxiety (DA; DNPDA) or without (DNPonly). Use of pain and other medications, medical services, and costs were compared between cohorts. Multivariate linear regression was performed to assess whether DNPDA patients have higher health care costs than DNPonly patients while controlling for demographic and clinical characteristics.


Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference

RESULTS: We identified 11,675 DNPonly patients and 2,728 DNP

DA patients. DNPonly patients were older (55.2 vs. 53.8 years,

P < 0.01) and more likely to be male (50% vs. 40%, P < 0.01) com pared with DNPDA patients. DNPDA patients had a higher prev alence of most diabetesrelated comorbidities and were dispensed

1.4 (4.0 vs. 2.6, P < 0.01) additional unique pain medications in the previous 12 months. Over the 12month followup period, 66% of DNPDA patients versus 51% of DNPonly patients had at least

1 DNPrelated agent filled; on average, DNPDA patients received a mean of 0.5 and 1.6 additional unique DNPrelated agents and pain medications, respectively (both P < 0.01). DNPDA patients also had a mean 7.5 additional office visits ( P < 0.01) and were more likely to have an emergency room visit (38% vs. 25%,

P < 0.01) and hospital admission (44% vs. 29%, P < 0.01) resulting in an average of 3 additional hospital days ( P < 0.01). After control ling for differences in demographic and clinical characteristics,

DNPDA patients had accrued $10,358 ( P < 0.01) additional total health care costs than patients with DNPonly.

CONCLUSIONS: These findings indicate that there is a significant economic burden associated with mood disorders among patients with DNP.

following discharge. Severe bleeding events were associated with significantly higher hospital charges and increased length of stay (LOS) compared with hospitalizations without bleeding events (initial ACS hospitalization: charges = $128,213 vs. $35,394,

P < 0.01; LOS = 18 days vs. 5 days, P < 0.01; subsequent hospital ization: charges = $75,740 vs. $24,288, P < 0.01; LOS = 12 days vs. 5 days, P < 0.01). After adjusting for patient characteristics, inhospital ACSrelated procedures, and LOS, a severe bleed increased the initial ACS hospitalization charges by $48,114

( P < 0.01) and subsequent hospitalization charges by $23,262

( P < 0.01).

CONCLUSIONS: Severe bleeding events significantly increase hospitalization charges and resource use among ACS patients in a realworld setting. Reducing the risk of bleeding may lead to decreased resource utilization and costs for payers. Future research should explore how the different definitions of bleeding used in trial settings impact the assessment of economic conse quences in the real world.

■■ ECONOMIC CONSEQUENCES OF SEVERE BLEEDING

IN ACUTE CORONARY SYNDROME PATIENTS

Berenson K,* Krukas M, Casciano R, Makenbaeva DJ, Mozaffari E,

Corbelli JC. *Analytica International, 450 Park Ave. S., New York,

NY 10016; kberenson@comcast.net, 212.686.4100

■■ ECONOMIC IMPACT OF THE BP DOWNSHIFT PROGRAM

ON BLOOD PRESSURE CONTROL AMONG COMMERCIAL

DRIVER LICENSE EMPLOYEES

Greene BL, Brown M*, Miller JD, Harshman RS, Richerson G,

Doyle JJ.

*Abt Bio-Pharma Solutions Inc., 181 Spring St., Lexington,

MA 02421; michelle_Brown@abtassoc.com, 781.372.6518

BACKGROUND: Bleeding is associated with poor outcomes in patients with acute coronary syndromes (ACS). Previous studies have demonstrated increased costs associated with bleeding in clinical trials, but no study to date has examined the economic impact of bleeding in the naturalistic setting.

OBJECTIVE: To examine the economic consequences of severe bleeding events among ACS patients in a realworld setting.

METHODS: We retrospectively studied ACS patients who were enrolled in an integrated commercial health plan from 19952007, evaluating resource utilization for patients with and without severe bleeding. Each patient’s medical encounters and resource utilization were extracted from health care claims submitted to the plan. Severe bleeding events were defined as having an inhos pital claim code for either bleeding plus blood transfusion, intra cranial hemorrhage, or bleeding followed by death. These events were identified during the initial ACS admission and subse quently for the 2 years following discharge. The economic impact of bleeding was assessed by quantifying the hospital charges assigned to the resource utilization. Multivariate analyses were used to assess the impact of a severe bleed on hospital charges.

RESULTS: A total of 11,266 ACS patients were identified;

928 patients had a severe bleed during the initial ACS hospital ization, and 860 patients had a severe bleed during the 2 years

BACKGROUND: Rising health care costs to large, selfinsured employers have prompted interest in programs to manage and prevent chronic conditions, such as cardiovascular disease. The

BP DownShift Program, an employerbased hypertension educa tional and awareness program, was designed to improve blood pressure (BP) outcomes among commercial driver license (CDL) employees based on the Department of Transportation’s (DOT)

Hypertension (HTN) Guidelines for CDL certification.

OBJECTIVE: To assess the economic consequences of the BP

DownShift Program on direct and indirect employer costs among

CDL employees at a large southeastern U.S. utility company.

METHODS: An economic model was constructed to evaluate the

2year impact of the BP DownShift Program on direct and indi rect employer costs associated with changes in HTN for a random sample of 499 CDL employees. Clinical data were extracted from employee DOT Medical Exam Reports (gender, age, body mass index, DOT HTN classification category), patientreported medi cal histories, and Framingham Heart Study risk equations. Cost parameters (2007 U.S. dollars) were obtained from employer records and published literature and included costs for treat ment of chronic disease (coronary heart disease, stroke, HTN, diabetes), CDL certification exams, and employer lost time and productivity.

RESULTS: A 16.3% reduction in total employer costs for the 499

CDL employees was observed over 2 years (preBP DownShift: www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 681


$3,312,220; postBP DownShift: $2,771,094), primarily due to a 31.0% decrease in the number of employees classified with uncontrolled BP (preBP DownShift, n = 129; postBP DownShift, n = 89). Cost savings were attributable to improvements in lost time and productivity ($552,103) and fewer CDL certification reexaminations ($8,410). Cost increases were incurred for treat ment of HTN and chronic disease ($19,387). Average overall reduction in total costs was estimated to be $1,084 per CDL employee.

CONCLUSIONS: The BP DownShift Program was associated with significant reduction in CDL employer costs attributable to fewer

CDL employees with uncontrolled BP. Further investigation is warranted to assess the longterm economic impact of the BP

DownShift Program given the continuing and increasing costs for the treatment and control of HTN and its sequelae.

RESULTS: ePrescribing had a statistically significant positive impact on GDR and PFCR. The impact on MDR was positive but not statistically significant at P < 0.05. Specifically, the use of ePrescribing resulted in 850 basispoint increases in GDR,

60 basispoint increases in MDR, and 430 basispoint increases in PFCR. ePrescribing also had a significant positive impact on the providerlevel GDR for SSRIs, HMGs, and ACEs and on PFCR for SSRIs. Overall, ePrescribing use was associated with a cost savings of $7.82 per prescription.

CONCLUSIONS: ePrescribing use significantly increased providers’

GDR, MDR, and PFCR and resulted in significant cost savings per prescription.

■■ ELECTRONIC PRESCRIBING LEADS TO INCREASED

GENERIC DISPENSING AND FORMULARY COMPLIANCE

Roman B,* Myhre C. *CVS/Caremark, 620 Epsilon Dr., Pittsburgh,

PA 15238; brian.roman@caremark.com, 412.967.8235

■■ EVALUATION OF CHOLESTEROL-LOWERING

THERAPY ADHERENCE: A RETROSPECTIVE ANALYSIS

Hopper AM,* Standish J, Ansani NT. *Rite Aid Health Solutions,

333 Rouser Rd., Bldg. 4, Ste. 503, Moon Township, PA 15108; ahopper@riteaid.com, 717.691.6255

BACKGROUND: Electronic prescribing (ePrescribing) programs are designed to expedite the prescription process, increase patient safety, and reduce health care costs by allowing health care providers to securely generate prescriptions using a handheld personal digital assistant or desktop computer. A large Blue

CrossBlue Shield health plan enrolled 275 of their providers into an ePrescribing program between January 1, 2006, and June 30,

2007.

OBJECTIVE: To evaluate the impact of the ePrescribing program on mail dispensing rate (MDR), generic dispensing ratio (GDR), preferred/formulary compliance ratio (PFCR), and associated cost savings.

METHODS: This retrospective, controlled, pre/post intervention study used an integrated database of administrative pharmacy claims and provider data. The intervention group comprised

275 providers who actively used ePrescribing software for at least

1 month. The matched control group comprised 267 providers who never used ePrescribing. Matching criteria included the time period of analysis, provider degree, provider specialty, geographic location, and baseline prescribing practices. Patient populations of the intervention and control providers were also matched on age, gender, plan design, and urban/rural residence. The pre intervention period comprised the 6 months prior to initiation of ePrescribing. Data analysis involved the generation of descriptive statistics and use of ordinary least squares regression modeling to estimate the impact of ePrescribing on study outcomes overall and by selected therapeutic classes (i.e., selective serotonin reuptake inhibitors [SSRIs], protonpump inhibitors, coenzyme

A reductase inhibitors [HMGs], and angiotensinconverting enzyme inhibitors [ACEs]).

BACKGROUND: Cholesterol medications (statins) are among the most commonly prescribed therapies, with evidence supporting their cardiovascular morbidity and mortality benefits. However, data also demonstrate that nonadherence to statin therapy is common. Education programs may be beneficial to improve statin adherence.

OBJECTIVE: To evaluate baseline statin adherence rates in a pharmacy benefit management (PBM) program and correlate demographics to adherence rates to develop a targeted adherence education program.

METHODS: A retrospective pharmacy claims analysis was con ducted using START software to calculate adherence measures.

All patients receiving a statin at this PBM between June 1, 2006, and April 1, 2008, were included. Patients < 18 or > 90 years of age were excluded. Thirty and 90day front and backend wash out periods, respectively, were implemented. Primary outcomes included medication possession ratio (MPR) at 6 and 12 months, persistence, and median gap. Demographic data were evaluated to determine correlations with adherence, and data were handled using intenttotreat analysis. Descriptive statistics and chisquare test were used.

RESULTS: A total of 15,744 patients on statin therapy met the inclusion criteria. After applying washout periods, adherence data were analyzed for 8,013 patients. Results show an MPR of

0.82 and 0.61 at 6 and 12 months, respectively. Fortynine per cent of patients remained on statin therapy at 1 year. The median gap was 9.4 days. Patients who were male, > 65 years of age, and whose copayment was < $20 were more likely to remain on therapy at 1 year ( P < 0.05 for each).

CONCLUSIONS: Baseline analyses demonstrate that 1year adher ence to statin therapy is not optimal. Patients who are > 65 years of age, male, or whose copayment is < $20 are more likely to


Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference remain on statin therapy at 1 year. The opportunity exists to develop a targeted adherence education program to optimize statin therapy management for PBM patients.

CONCLUSIONS: MPR distribution from this database suggests good adherence rates for both HIV and SOT patients. The sample size is large and provides many opportunities for further exploratory analyses that could identify individual patients and perhaps groups of patients who could benefit from custom care management.

■■ EXPLORATORY ANALYSIS OF THE MEDICATION

POSSESSION RATIO OF 4,085 SOLID-ORGAN TRANSPLANT

AND 2,715 HIV PATIENTS RECEIVING PRESCRIPTION

MANAGEMENT FROM A SPECIALTY PHARMACY

McAndrews P.* *PrecisionRx Specialty Solutions,

2825 W. Perimeter Rd., Indianapolis, IN 46241;

Patrick.McAndrews@wellpoint.com, 317.484.4465

■■ IMPACT OF A GENERIC COPAYMENT WAIVER

PROGRAM ON GENERIC CONVERSION

Shenouda L,* Coulen C. *CVS/Caremark, 2211 Sanders Rd.,

Northbrook, IL 60062; lydia.shenouda@caremark.com, 847.559.5633

BACKGROUND: Adherence to a medication regimen is particularly important for patients with a solidorgan transplant (SOT) or human immunodeficiency virus (HIV) infection. Nonadherence with immunosuppressant therapy in a transplant setting is highly correlated with graft loss or death. In the treatment of HIV, adherence rates of 95% are felt to be needed to suppress viral replication and prevent resistance. Analysis of pharmacy refill data has proven useful in estimating medication adherence for groups of patients. Much research has been published detailing the complex nature of medication consumption patterns, propos ing strategies for improving adherence, and measuring the impact of those strategies.

OBJECTIVE: An exploratory analysis of the prescription refill data maintained by a specialty pharmacy enterprise was conducted to better understand the adherence patterns of HIV and SOT patients and to inform decisions about clinical management program design aimed at improving patient outcomes and reduce overall cost of care.

METHODS: Prescription refill data from October 1, 2006, to

March 31, 2008, were searched. Patients being treated for HIV or SOT were identified using ICD9CM codes and maintenance medication National Drug Codes (NDCs); diagnosis was con firmed for patients identified using NDCs. Prescription refill data were then extracted and included patient ID, medication name, days supply, and date of refill. The medication possession ratio

(MPR) was calculated for each prescription by dividing total days of medication by total days of therapy. For patients with multiple medications, the sum of days supply for all medications was divided by the sum of days of therapy for all medication.

Overall MPR was calculated by pooling all patients with HIV or

SOT transplant.

RESULTS: 6,800 patients were identified (2,715 HIV; 4,085 SOT);

625 patients (217 HIV; 408 SOT) had not exhausted the sup ply from their first fill and were excluded from further analysis.

67,706 refill records (30,669 HIV; 37,037 SOT); 32,998 prescrip tions (15,300 HIV; 17,698 SOT). The MPR for HIV patients was distributed: < 0.8: 43; 0.80.94: 363; ≥ 0.95: 2,092. The MPR for SOT patients was as follows: < 0.8: 145; 0.80.89: 333; ≥ 0.9:

3,199.

BACKGROUND: It has been suggested that reducing a patient’s outofpocket cost could increase the use of therapeutic drugs, thereby leading to improved health outcomes. Moving from a brand to a generic drug would offset the cost of increased medica tion use to the plan.

OBJECTIVE: To determine whether a generic copayment waiver provides sufficient incentive for exclusive brand users to change to generic equivalents as well as maintain use of generic equiva lents.

METHODS: As an incentive to generic conversion, a large health plan waived the copayment for 1 generic fill (up to 90day supply) of initial use of the generic substitute for several brand medications. The waiver was offered to plan participants with exclusive brand utilization of the targeted medications between

March and September 2006. Eligible plan participants were notified by mail of the savings opportunity in early October 2006 and were evaluated for conversion potential and sustained generic conversion between October 15, 2006, and April 30, 2007. The rate of conversion to generics and sustained conversion for selected medications within the targeted group were compared with the conversion rates of a comparison population using a chisquare test to determine whether the copayment waiver was an attractive incentive to change as well as maintenance of the change. Furthermore, logistic regression was used to adjust for the influence of age, gender, and retail brandgeneric copayment differential on generic conversion and sustained conversion.

RESULTS: Users of the following medications were statistically significantly more likely to convert to generic equivalents com pared with the control group (Table), even when adjusting for age, gender, and retail brandgeneric copayment differential:

Amaryl, Effexor, Flonase, Glucophage, Glucotrol, Miacalcin,

Mobic, Prava chol, Proscar, Prozac, Toprol, Zoloft, ZocorCrestor

Lescol, and AciphexPrilosecProtonix. Users of the following medications were statistically significantly more likely to convert to generic equivalents and not change back to the brand medi cation compared with the control group, even when adjusting for age, gender, and retail brandgeneric copayment differen tial: Accupril, Amaryl, Effexor, Flonase, Glucophage, Mobic, www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 683


TABLE Generic Conversion and Sustained

Generic Conversion Rates for

Target Group and Comparison Group

Targeted Brand

Accupril a

Allegra

Amaryl a,b

Conversion Rate

Target Comparison Target Comparison

31.5%

33.0%

36.6%

23.8%

28.6%

27.6%

Sustained

Conversion Rate

30.5%

30.6%

32.6%

21.8%

26.5%

24.1%

Cardizem

Celexa

Effexor a,b

Flexeril b

Flonase a,b

Glucophage a,b

Glucotrol b

Glucovance

Miacalcin

Mobic

Prozac

Toprol

Zantac

Zestril a,b

Pravachol

Proscar a,b

Vasotec a a,b b a,b

Zoloft a,b

ZocorCrestorLescol a,b

11.1%

25.1%

40.6%

31.6%

47.7%

22.5%

23.7%

25.4%

22.3%

75.2%

50.5%

63.5%

20.0%

15.8%

15.8%

5.3%

16.3%

78.7%

25.2%

AciphexPrilosecProtonix a,b 10.0%

21.0%

26.4%

5.1%

13.0%

42.3%

14.2%

20.3%

21.9%

9.6%

67.9%

30.3%

51.9%

14.7%

15.0%

13.0%

21.7%

14.4%

75.3%

21.6%

1.9%

7.9%

23.4%

35.3%

27.6%

45.7%

20.0%

20.1%

19.0%

16.3%

73.0%

47.7%

60.8%

16.2%

14.3%

14.4%

5.3%

16.3%

74.8%

24.2%

8.8%

14.4%

22.8%

3.6%

13.0%

41.2%

12.1%

18.6%

19.7%

7.1%

66.2%

28.7%

50.0%

10.5%

13.4%

12.3%

21.7%

12.5%

71.2%

20.9%

1.6% a Sustained conversion rate for target group statistically significantly different than in comparison group (P < 0.050) controlling for age, gender, and retail brand/generic copay differential.

b Conversion rate for target group statistically significantly different than in comparison group (P < 0.050) controlling for age, gender, and retail brand/generic copay differential.

Pravachol, Proscar, Prozac, Toprol, Zoloft, ZocorCrestorLescol, and AciphexPrilosecProtonix.

CONCLUSIONS: A temporary generic copayment waiver has proven to be an effective incentive for generic conversion and also for sustained conversion for selected medications.

BACKGROUND: The drug class of protonpump inhibitors (PPIs) is one of the most expensive, if not the most expensive, therapeu tic drug classes for most health plans. Within the class of PPIs, efficacy and safety of the available products are similar. Recently, the acquisition price of omeprazole has dropped to a price point at which many payers are implementing programs and initiatives to providers and members to increase the use of omeprazole.

OBJECTIVE: To determine the impact of targeted physician clinic collaboration on the ratio of omeprazole to brandname PPI pre scriptions. The secondary objective is evaluation of the process and its expandability.

METHODS: In 2007, the health plan created several strategies in an effort to increase the use of omeprazole within the PPI class. As a pilot project, a proposal was created in collaboration with the clinic manager and discussed with the medical director and lead physician at the clinic site to switch members from a branded

PPI to omeprazole. The health system’s electronic medical record system was used to identify members who filled brandname PPIs written by physicians in a clinic. Members were identified who filled a brandname PPI between April 4, 2007, and September 30,

2007. Member information was given to the physician clinic. The clinic created a letter to send to members that included member specific and physicianspecific information. Each member also received a prescription for omeprazole with 6 refills. Member profiles were updated within the electronic medical record at the physician office. Prescription claims were analyzed several months after the letters were sent to determine how many mem bers filled the omeprazole prescriptions.

RESULTS: Letters containing a prescription for omeprazole were sent to 245 patients from their respective physicians in October

2007. Within that month, 33 (13%) members filled the omepra zole prescription. Within the next 3 months, another 42 (17%) members filled the omeprazole prescription. The clinic pre scribing rate is compared with the entire book of business from

1 quarter prior to the initiative and 2 quarters after the initiative

(Table).

CONCLUSIONS: Working in collaboration with a physician clinic increased the rate of omeprazole use, resulting in cost savings for the health plan and members. This program will be rolled out to additional clinics within the health system.

■■ IMPACT OF PHYSICIAN CLINIC COLLABORATION

ON GENERIC PRESCRIBING RATIO IN THE CLASS OF

PROTON-PUMP INHIBITORS (PPIs)

Mitchell M,* Cannon E, Buckley B, Dunn J. *SelectHealth,

4646 W. Lake Park Blvd., Ste. N3, Salt Lake City, UT 84107; matt.mitchell@selecthealth.org, 801.442.7817

TABLE

Year

2007, Q3

2007, Q4

2008, Q1

Q =quarter.

Market Share of Omeprazole

With the PPI Class

Clinic With Collaboration

23.7%

40.4%

49.1%

Book of Business

28.0%

34.0%

39.7%



■■ IMPACT OF SAVINGS MESSAGING PROGRAMS

ON PARTICIPANT CHOICE OF LOWER-COST

PRESCRIPTION DRUGS

Thuppal S,* Ricci J, Shenouda L. *CVS/Caremark,

2211 Sanders Rd., Northbrook, IL 60062; shalini.thuppal@caremark.com, 847.559.4631

BACKGROUND: A large employer organization implemented a savings messaging program for 15,881 plan participants. Plan participants received personalized messages about lowercost drugs over the telephone, by mail, or by both channels. Eligible plan participants with saving opportunities based on prescrip tion history were offered messages regarding savings in ≥ 1 of the following categories: shifting from retail to mail service, shifting from multisource brand drugs to genericequivalent drugs, or shifting from nonpreferred drugs to preferred drugs.

The telephone consultation program was implemented from July to December 2006, and personalized mailings were sent to plan participants in September 2006.

OBJECTIVE: To analyze the impact of a personalized telephone consultation program and a mailing program that provided costsaving messages to qualified plan participants based on prescription history.

METHODS: This retrospective control intervention study of pharmacy claims compared the intervened plan participants with a randomly selected matched control group who did not receive the interventions. In the period following the intervention, each plan participant’s choice with respect to what was messaged was analyzed. Differences in savings between the intervention and the control groups were tested for statistical significance.

RESULTS: The results demonstrated that both the mailing and telephone programs had a significant impact in changing plan participants’ behavior toward choosing mail delivery channel www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 685

Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference and generic drugs (Figure). The mailings alone increased plan participants’ choice of mail by 8%, generic drugs by 11%, and mail and generics simultaneously by 12%. The telephone inter vention alone increased plan participants’ choice of mail by 14% and mail and generics simultaneously by 32%. When both pro grams were implemented in tandem, the program increased plan participants’ choice of mail by 23%.

CONCLUSIONS: Telephone consultations and mailings targeting plan participants with costsavings opportunities provide a cost effective method for changing plan participants’ utilization of pharmacy benefits. The savings generated from such programs will enhance the plan design’s effect on reducing prescription drug costs for plan participants as well as clients.

Furthermore, 75% of infliximabtreated respondents indicated being extremely or very satisfied with treatment compared with

55% using 5ASAs, 49% taking antibiotics, 41% taking IMMs, and

32% taking steroids.

CONCLUSIONS: Patientreported adherence to treatment regimens was higher among infliximab users and notably higher than adherence to other treatment interventions. Satisfaction with infliximab was also rated highly. Optimizing compliance rates across treatments may help improve patient outcomes. Further studies are needed to understand the interaction of compliance rates and patient satisfaction in this patient population

Reference: Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a selfreported measure of medication adherence. Med Care .

1986;24(1):6774.

■■ INFLAMMATORY BOWEL DISEASE PATIENTS:

ADHERENCE TO AND SATISFACTION WITH TREATMENT

Waters H,* Annunziata K, Naim A, Freedman D, Piech C.

*Centocor Ortho Biotech Services, LLC, 800 Ridgeview Dr., H-2-3,

Horsham, PA 19044; hwaters@cntus.jnj.com, 215.325.2328

■■ LEUPROLIDE THERAPY COMPLIANCE WITH AMERICAN

COLLEGE OF OBSTETRICS AND GYNECOLOGY GUIDELINES:

A NEED FOR SPECIALTY PHARMACY INTERVENTION

Foster LA.* *PrecisionRx Specialty Solutions,

2825 W. Perimeter Rd., Indianapolis, IN 46241; leigh.foster@wellpoint.com, 317.484.5607

BACKGROUND: Patient satisfaction with and adherence to treatment are important factors to consider in the effectiveness of inflamma tory bowel disease (IBD) treatments. Gaining an understanding of these factors is important to patient outcomes.

OBJECTIVE: To assess patient compliance and satisfaction with treatments for IBD, including Crohn’s disease (CD) and ulcerative colitis (UC).

METHODS: Data were collected via the National Health and

Wellness Survey (NHWS) during quarters 1 through 3 of 2007.

Invitations were sent to a sample of Internet panel participants aged ≥ 18 years and were stratified by gender, age, and race.

Respondents were given a 4question standardized scale (refer ence 1) to measure adherence to prescribed treatment regimens.

Satisfaction with treatment was rated on a 7point Likert scale where 1=extremely dissatisfied and 7 = extremely satisfied. Results were weighted on age, gender, and ethnicity to ensure that they were representative of the U.S. population.

RESULTS: The NHWS survey was completed by 63,012 people, of whom 776 selfidentified as being diagnosed with CD (n = 330;

45% female; average age = 46.8 years) or UC (n = 446; 59% female; average age = 51.5 years). Use of the following medications was reported: aminosalycilates (5ASAs, n = 298), steroids (n = 85), immunomodulators (IMMs, n = 61), antibiotics (n = 45), infliximab

(n = 28), and other antitumor necrosis factors (n = 7). Approximately

65% of patients reported good to complete compliance with their IBD medications. Forgetting to take the medication was the mostcited reason for noncompliance. A greater percentage of respondents indicated complete or good compliance with infliximab (75%) compared with other medications including steroids (69%), IMMs (72%), 5ASAs (63%), and anti biotics (47%).

BACKGROUND: Endometriosis is a painful chronic disease that affects 5.5 million females in the United States and Canada.

Medical costs per patient per month (PPPM) for women with endometriosis were 63% greater ($706 PPPM) than those of the average female PPPM ($433) in 2003. The 2004 American College of Obstetricians and Gynecologists Practice Bulletin recommends

Level A evidence that empiric treatment with gonadotropin releasing hormone (GnRH) agonists without laparoscopy is an acceptable approach to treatment. GnRH agonists are a cost effective method for treatment, but they are not without side effects. Hot flashes/night sweats and decreased libido make

GnRH therapy undesirable to many patients. Other effects that are not physically noticeable, such as bone density loss, are also a detractor to therapy that may lead patients to seek surgical treatment options. The addition of “addback” therapy (ABT; oral norethindrone 5 mg daily or other estrogen/progestin com bination) is effective in preserving bone density and decreasing the percentage of patients experiencing hot flashes. Side effect management leads to increased compliance and therapy comple tion, resulting in decreased need for surgery and savings for the payer.

OBJECTIVE: With the knowledge that ABT improves leuprolide adherence and thus decreases longterm costs, it is to our advan tage as a payerowned pharmacy to maximize ABT prescribing.

METHODS: Patients treated with leuprolide for endometriosis were identified from the specialty pharmacy prescription database.

A query was then performed within the prescription and phar macy benefit management claims databases to identify the number of patients within this population who were receiving


Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference concomitant therapy with ABT. The duration of therapy in both groups was then compared.

RESULTS: Thirtytwo of 233 patients were found to have been prescribed leuprolide plus ABT concomitantly within a 36month period. Data exhibited a median 4month duration of Lupron plus ABT (minimum 1 month/maximum 13 months) therapy compared with a median of 3.5 months (minimum 1 month/ maximum 7 months) of therapy for patients who did not receive

ABT.

CONCLUSIONS:

Bates J,*

Only 13.7% of endometriosis patients with pre scriptions for leuprolide received concomitant ABT. This repre sents an opportunity to intervene and improve ABT use, which should lead to deceased costs and improved patient outcomes for endometriosis patients.

■■ MEDIATORS OF MEDICATION NONADHERENCE IN

BIPOLAR DISORDER: A CROSS-SECTIONAL SURVEY

Whitehead R, Kim E. *Bristol-Myers Squibb, 29 Chestnut

Hill Ln., Stamford, CT 06903; jay.bates@bms.com, 203.461.9622

BACKGROUND: Bipolar disorder is a chronic disorder that is optimally managed by longterm medication treatment. Causes of medication nonadherence may include efficacy, tolerability, and sociodemographic variables.

OBJECTIVE: To identify factors associated with medication nonad herence in patients with bipolar disorder.

METHODS: A crosssectional Webbased study surveyed a conven ience sample from an existing cohort (Lightspeed Panel,

Consumer Health Sciences). The primary outcome was the

Morisky Compliance Scale, and it was used to define patients as adherent (total score 01) or nonadherent (total score 24).

Bivariate analysis compared differences between adherent and nonadherent subjects with respect to collected demographic, socioeconomic, and diseaserelated variables. Additional vari ables studied included the Liverpool University Neuroleptic Side

Effect Scale (LUNSERS) and the Satisfaction with Antipsychotic

Medication (SWAM) scale.

RESULTS: Of 1,164 eligible subjects, 575 (49.4%) were adherent and 589 (50.6%) were nonadherent. Nonadherent subjects were older, had more children < 18 years of age living in their house hold ( P = 0.009), and had a higher number of depressive and manic episodes ( P = 0.005 and 0.009, respectively). Nonadherent patients had higher total LUNSERS scores and scores on all indi vidual items ( P < 0.001) as well as lower total scores on the SWAM scale ( P < 0.001).

CONCLUSIONS: Medication nonadherence is commonplace in bipolar disorder. Reasons for nonadherence are related to demo graphics, disease severity, and medication side effects.

■■ MEDICATION PERSISTENCE AND HEALTH CARE

EXPENDITURES AMONG ASTHMATICS IN A

MANAGED MEDICAID POPULATION

Rogers T,* Kaye T, Simmons J. *Passport Health Plan,

305 W. Broadway, Ste. 300, Louisville, KY 40202; thea.rogers@amerihealthmercy.org, 502.585.8445

BACKGROUND: In the United States, asthma affects approximately

22 million persons with an estimated cost of 18 billion dollars annually. Nonpersistence to therapy accounts for approximately

60% of asthmarelated hospitalizations.

OBJECTIVE: To evaluate the influence of medication persistence on utilization of health care resources in asthmatics enrolled in a

Medicaid Managed Care plan.

METHODS: A retrospective review of administrative data was con ducted from October 1, 2007, to February 29, 2008, to identify members aged 256 years with pharmacy claims for an asthma controller medication. Members were continuously enrolled and were required to have received > 3 consecutive months of control ler medications and an asthma ICD9CM diagnosis. Health care service utilization was measured by the percentage of patients who had at least 1 claim for an inpatient, emergency room (ER), home health, office, or other outpatient visit. Health care costs included pharmacy, medical, and total cost (pharmacy + medical) and were reported as asthmarelated and allcause.

RESULTS: A total of 748 asthmatics met the study criteria. Of the

748, 671 (90%) persisted with therapy without gaps during the 5month study. The remaining 76 (10%) were nonpersistent with controller therapy. Nonpersistent asthmatics had higher utilization rates for asthmarelated ER and home health visits than did persistent asthmatics, whereas persistent asthmatics had more office and outpatient visits. No difference was found in inpatient days. Allcause health care utilization was higher among nonpersistent asthmatics for ER, inpatient, and home health visits. Asthmarelated health care costs were 25% of the total medical cost. Mean asthmarelated medical costs were greater in the nonpersistent cohort at $577.62 versus $323.03. Asthma related pharmacy and total health care costs were lower in the nonpersistent cohort at $494.80 versus $901.70 and $1,072.42 versus $1,224.73, respectively. Similar findings were observed for allcause health care costs, with greater medical costs among nonpersistent asthmatics compared with persistent asthmatics.

CONCLUSIONS: Nonpersistent use of controllers impacts the utiliza tion of health services and medical costs associated with asthma.

This study further supports the need for targeted interventions to address nonpersistence to asthma controller medications. We are continuing to investigate the influence of specific controller medications on health care utilization and cost to further identify opportunities to optimize appropriate drug therapy.



■■ PATTERNS AND PREDICTORS OF PATIENT ADHERENCE:

ANALYSIS OF A LARGE PHARMACY CLAIMS DATABASE

Egan B, Jain N, Vedarajan G, Marta A, Kaminski D.*

*AstraZeneca LP, 1800 Concord Pike, Wilmington, DE 19850;

David.Kaminski@astrazeneca.com, 302.885.8966

■■ PATTERNS OF RITUXIMAB USE AMONG PATIENTS

IN A MANAGED CARE SETTING: RESULTS FROM A

U.S. CLAIMS DATA ANALYSIS

Pelletier EM,* Yu E. *IMS Consulting, 311 Arsenal St., Watertown,

MA 02472; epelletier@us.imshealth.com, 617.393.8319

BACKGROUND: Patient nonadherence to drug therapy limits the benefits of medication therapy. Assessing nonadherence factors may identify new methods to manage patient care.

OBJECTIVE: To describe patterns of patient adherence to medica tions for 4 drug classes, examine the impact of selected factors on adherence, and determine the proportion of physicians with highly versus poorly adherent patients.

METHODS: In a retrospective study of a proprietary pharmacy claims database, prescription data were evaluated for proton pump inhibitors (PPIs), atypical antipsychotics, statins, and aromatase inhibitors. Data included gender, age, prescription fill dates, number of comorbidities, days of supply (DOS), out ofpocket costs (such as copayments), type of payer (commer cial, Medicaid, cash), and prescriber identification numbers.

Physicians’ data were collected to examine their role in the medication adherence of their patients. Adherence measures included 4 or 12month medication possession ratio (MPR),

DOS dispensed within 4 or 12 months after the first prescrip tion fill, patient compliance (DOS divided by days on therapy), and patient persistency (continuous therapy with no breaks

> 120 days [PPIs, statins], > 90 days [atypical antipsychotics],

> 60 days [aromatase inhibitors] over a 12month period).

RESULTS: Data were collected on 415.8 million prescriptions.

Fourmonth patient MPRs ranged from 55% for PPIs to 67% for statins; the 12month MPR for aromatase inhibitors was 68%.

Patient compliance ranged from 77% for PPIs to 88% for aro matase inhibitors. Persistency was low, ranging from 17% for

PPIs to 46% for aromatase inhibitors. Predictors of adherence with a positive impact included DOS and low outofpocket cost. Negative predictors of adherence included younger age and lower socioeconomic background. Interestingly, the number of treated comorbidities favored adherence to PPIs and statins, but decreased adherence for aromatase inhibitors. Physician data showed a range of adherence among the therapeutic classes, with the lowest adherence rates for PPIs and the highest range for aro matase inhibitors.

CONCLUSIONS: Patient adherence to drug therapy was low in all medication classes studied. Patient adherence rates within a medication class varied by physician. These results imply that adherence rates can be positively affected by convenience factors as well as physician guidance.

BACKGROUND: Rituximab is indicated for the treatment of rheuma toid arthritis (RA); however, limited data exist regarding the use of rituximab in a realworld setting.

OBJECTIVE: To determine patterns of rituximab use among RA patients in managed care plans across the United States.

METHODS: Patients ≥ 18 years of age with a rituximab claim from

July to December 2006 were identified from a large, nationally representative database of adjudicated medical and pharmaceuti cal claims from > 90 U.S. health plans. Patients were required to be continuously enrolled in their health plan for a minimum of 6 months prior to and 6 months following the first (index) rituximab claim in the study window; patients also had to have a diagnosis of RA (ICD9CM 714.xx) during the preindex period.

Patients were excluded from the study if they had evidence of nonHodgkin’s lymphoma or chronic lymphocytic leukemia during the preindex period or ankylosing spondylitis, psoriasis, psoriatic arthritis, Crohn’s disease, or ulcerative colitis at any time during the study. Patients were followed for a minimum of

6 months to determine total rituximab courses (complete course defined as a minimum of 2 rituximab infusions within 60 days) and the time to rituximab retreatment.

RESULTS: Seventyone patients with rituximab claims met all inclusion and exclusion criteria; mean age was 51 years, 14% were male, and 97% were insured under a commercial plan.

Approximately 17% and 9% of patients had a concurrent history of lupus and vasculitis, respectively; 17% had evidence of prior rituximab use, and 31% had used a biologic diseasemodifying antirheumatic drug in the preindex period. Of the 71 patients,

39 (55%) patients had ≥ 2 courses of rituximab in the followup period. During the first rituximab course, 64 patients had

> 1 infusion; 39 (61%) of these patients had 14 days between the first and second infusion, while 12.5% had 712 days between infusions. Among patients who had a subsequent course, the average time between the first and second rituximab courses was

199 days (median = 201 days).

CONCLUSIONS: This study represents one of the first analyses to examine patterns of rituximab use in a realworld setting.

Approximately onehalf of all RA patients who completed a first course of rituximab therapy also completed a second course, and the mean number of days between courses was 199. The majority of patients received the second infusion within 14 days of the first infusion, indicating that physicians are following the treatment guidelines on the label.



■■ PHARMACY BENEFIT ENROLLMENT TURNOVER

OVER 5 YEARS

Carruth SE, Hale BC.* *Allergan, Inc., 2525 Dupont Dr., Irvine, CA

92612; Hale_Brent@allergan.com, 714.246.4781

BACKGROUND: The unknown longevity of member enrollment in health plans has been a concern for pharmacy benefit decision makers in determining policy or appropriate interventions.

OBJECTIVE: To determine how many patients remain with the same pharmacy benefit national payer after 1, 2, 3, 4, and 5 years.

The analysis examined how the turnover rate varied between commercial and Medicare plans or with the age of the patient.

METHODS: A large database of prescription claims identified

> 34 million patients with a prescription claim in the first quar ter of 2002. Patients identified in 2002 were followed in each subsequent year until a prescription claim was identified for that year. Patients with Medicare Part D coverage were identified for a second cohort in the first quarter of 2006 and then followed for a prescription claim in 2007. Patients were followed until

November 2007.

RESULTS: Patient enrollment in the same pharmacy benefit dropped by 27% after 1 year and by 73% after 5 years. Older patients in commercial and Medicare plans dropped out at a slower rate than their younger counterparts. Medicaid enrollees tended to remain with their plans longer than their counterparts in commercial plans regardless of age. Medicare patients also had less benefit turnover than their commercial counterparts.

CONCLUSIONS: Fiftyeight percent of patients stayed with the same pharmacy benefit plan for at least 2 years. After 3 years, about onehalf of the patients had switched to another pharmacy benefit. Older patients and patients with Medicaid or Medicare benefits were less likely to switch benefits than their younger or commercial counterparts.

METHODS: Transcripts from 185 physicianpatient interactions from previously conducted studies were analyzed. Analyses of categoryspecific medication adherence discussions were con ducted on 171 (92%) of these interactions. A total of 1,337 utter ances about medications for each respective therapeutic area of study were coded for 2 linguistic features: message/content and metamessage/emotion.

RESULTS: Although physicianpatient dialogues contained some features promoting medication adherence, gaps in communica tion were observed. Sixty percent of conversations were emotion ally neutral, and references to therapy often lacked substance (e.g., mentioning drug names vs. discussing drugs risks and benefits).

Side effect and benefit discussions contained emotional “charge” that impacted patients’ views against or in favor of adherence, respectively. Discussions of new medications contained nearly twice as many adherencerelated statements as those in which no new drug was prescribed, and their tone was more “adher ence promoting.” Physicians overestimated patients’ motivation, understanding, and adherence to treatment.

CONCLUSIONS: Overall, the interactions studied contain dialogues that are insufficient to promote longterm patient adherence to medication, with gaps in communication observed across special ties and therapeutic areas. Further research is needed to validate specific communication techniques; however, capitalizing on existing positive dynamics and implementing adherencepromot ing behaviors into the physicianpatient dialogue can result in a number of measurable improvements in adherence.

■■ PREDICTORS OF TREATMENT INITIATION

OF DULOXETINE VERSUS VENLAFAXINE XR

FOR PATIENTS WITH MAJOR DEPRESSION DISORDER

IN MANAGED CARE SETTINGS

Clark T, Ye W,* Zhao Y, Robinson R, Swindle R. *Eli Lilly and

Company, Lilly Corporate Center, Indianapolis, IN 46285; ye_wenyu@lilly.com, 317.651.8408

■■ PHYSICIAN-PATIENT DIALOGUE

AND MEDICATION ADHERENCE

Nelson M, Eagan C, Heilman J, Osterberg L.* *Stanford University

School of Medicine, 3801 Miranda Ave., Palo Alto, CA 94304; larso@stanford.edu, 650.493.5000 ext. 63683

BACKGROUND:

OBJECTIVE:

Nonadherence to treatment is one of the most pressing problems in contemporary medicine. Health care pro fessionals need to ensure that they effectively communicate with their patients.

An analysis combining 4 previously conducted, in office linguistic studies in 4 therapeutic areas (adjuvant hormonal therapy, type 2 diabetes, dyslipidemia, hypertension care) was conducted to evaluate physicianpatient communication regard ing adherence.

BACKGROUND: Major depressive disorder (MDD) is a severe recurring illness affecting approximately 121 million people worldwide. Duloxetine and venlafaxine extended release (XR) are the 2 serotoninnorepinephrinereuptake inhibitors (SNRIs) used in treating patients with MDD. Understanding variations in patient and treatment history characteristics associated with

SNRIs may provide insight into predicting medication use patterns for health plans.

OBJECTIVE: To assess the impact of prior medication use and comorbidities on treatment initiation with duloxetine versus venlafaxine XR for patients with MDD using retrospective claims data.



METHODS: Using the PharMetrics database, we studied commer cially insured individuals aged 1864 years who initiated treat ment with duloxetine or venlafaxine XR between July 2005 and July 2006, had ≥ 1 prior diagnosis of MDD, and had con tinuous enrollment during 12 months prior to the initiation date.

Initiation was defined as the first use of a medication preceded by 3 months without a prescription of the same medication. Chi square testing was used for categorical variables and 2 sample t tests for continuous variables. Logistic regression analysis of patients’ demographics, pastyear medication use, and comor bidities assessed predictors of initiations with duloxetine versus venlafaxine XR.

RESULTS: A total of 12,662 patients (73.8% female) initiated treatment with duloxetine and 14,801 (72.1% female) with venlafaxine XR. Compared with venlafaxine XR patients, sig nificantly more duloxetine patients had previously received

≥ 3 unique antidepressants (39.5% vs. 25.2%), ≥ 3 unique pain medications (25.8% vs. 15.1%), selective serotoninreuptake inhibitors (SSRIs; 55.5% vs. 41.2%), tricyclic antidepressants

(TCAs; 12.5% vs. 7.5%), analgesics (63.6% vs. 51.6%), anticon vulsants (31.3% vs. 19.2%), or hypnotics (31.5% vs. 22.0%) and had ≥ 8 unique comorbid medical conditions (38.8% vs.

29.5%) and diagnoses with pain (76.4% vs. 67.1%) (all P values

< 0.001). Regression results revealed that the significant factors for duloxetine initiation versus venlafaxine XR were prior use of ≥ 3 unique antidepressants (odds ratio [OR]=1.34); ≥ 3 unique pain medications (OR = 1.24), SSRIs (OR = 1.51), TCAs (OR = 1.19), analgesics (OR = 1.12), anticonvulsants (OR = 1.45), and hypnot ics (OR = 1.25); as well as prior medical comorbidities of pain

(OR = 1.11) (all

CONCLUSIONS:

P values < 0.001).

The results suggest that duloxetine patients with

MDD are likely to have more medical conditions and complex prior medication treatments than venlafaxine XR patients.

Patients aged 264 years with 3 years of continuous health plan eligibility and > 1 medical claim with an ICD9CM diagnosis code for AR (477.xx) between January 2004 and December 2006 were included. Clinical characteristics, diseaserelated medica tion use, and resource utilization were assessed for 12 months prior to the first AR medication claim (index) in 2006. Patients with a concomitant asthma diagnosis were excluded from this analysis.

RESULTS: A total of 322,009 AR patients were identified. Adult patients (mean age = 43.3 ± 11.8 years) were primarily female

(57.6%); 20.3% had sinusitis, and 32.4% had more than 2 or more

AR physician visits in the prior year. Pediatric patients (mean age = 9.95 ± 4.4 years) were primarily male (52.3%); 24.2% had acute upper respiratory infection and 19.2% had sinusitis in the prior year, while 32.0% had 2 or more physician visits for AR.

Nearly onehalf of the patients (49.9%) had no AR prescription medication claims throughout 2006. Among patients with AR pharmacy claims (N = 161,352), those receiving a single index medication (N = 124,975) were prescribed cough/cold/allergy combination medications (28.7%), intranasal steroids (26.2%), antihistamines (26.0%), oral corticosteroids (12.6%), or leuko triene modifiers (4.5%). Among patients with 2 or more prescrip tions for AR medications filled within 30 days of each other

(N = 34,731), the most frequently occurring concurrent medica tions were intranasal steroids and antihistamines (21.3%), intra nasal steroids and cough/cold/allergy combination medications

(15.8%), antihistamines and cough/cold/allergy combination medications (8.1%), oral corticosteroids and cough/cold/allergy combination medications (6.3%), and leukotriene modifiers and antihistamines (5.9%). These patterns were consistent for analy ses examining adult and pediatric patients separately.

CONCLUSIONS: The majority of patients with AR pharmacy claims were prescribed a single AR medication. The absence of AR pharmacy claims for almost onehalf of patients may reflect the availability of OTC AR medications and patients’ ability to self treat this condition.

■■ PRESCRIPTION MEDICATION USE AMONG PATIENTS

WITH ALLERGIC RHINITIS IN A COMMERCIALLY INSURED

POPULATION

Bollinger M, Diette G, Allen-Ramey F,* Chang C, Stephenson J,

Fan T, Sajjan S. *Merck & Co., Inc., Sumneytown Pike, WP39-170,

West Point, PA 19486; felicia_ramey@merck.com, 215.652.7546

■■ PROFILING THE TREATMENT OF PSORIASIS

Waters H,* Freedman D, Naim A, Annunziata K, Piech C.



BACKGROUND: Allergic rhinitis (AR) is often viewed as a nuisance disease that can be treated with overthecounter (OTC) medica tions. These OTC medications may not be sufficient for control ling AR symptoms.

OBJECTIVE: To estimate the occurrence of AR in a commercially insured population and describe the types and patterns of AR prescription medications used by patients.

METHODS: A retrospective analysis of a U.S. commercially insured managed care population using medical and pharmacy claims from the HealthCore Integrated Research Database was conducted.

BACKGROUND: With many new treatments on the market for pso riasis, it is important to understand current treatment patterns and identify opportunities for improved treatment regimens.

OBJECTIVE: To evaluate patientreported use of various medica tions used to treat psoriasis.

METHODS: Data were collected via the National Health and

Wellness Survey (NHWS) during quarters 1 through 3 of 2007.

Invitations were sent to a sample of Internet panel participants aged ≥ 18 years who were stratified by gender, age, and race.



RESULTS: The NHWS survey was completed by 63,012 people, of whom 1,651 were self identified as being diagnosed with pso riasis (50% female, average age = 50.4 years). When asked about their disease severity, 66% reported mild disease, 26% moderate, and 7% severe. Thirtyeight percent of all patients reported using overthecounter (OTC) or herbal treatments and 44% reported treatment with prescription medication, while 26% reported using OTC treatments only, 9% reported using phototherapy, and 30% reported no current treatment. Of those patients on pre scription medication, 42% used topical steroids, 34% used topical nonsteroids, 12% used biologic therapies, and 13% use systemic therapies other than biologics. Patients who classified their disease as being moderate or severe were more likely to report use of biologics and systemic treatments, while those with mild disease were more likely to use topical treatments. However, 21% of moderate and severe patients reported using only OTC prod ucts. Furthermore, 21% of moderate and 15% of severe patients reported that they did not currently receive medication.

CONCLUSIONS: A wide variety of medications are used to treat psoriasis, and the majority of patients report using an OTC.

A large number of patients with severe disease are using only OTC products or no treatment at all. Further research on the appropri ate treatment of moderate to severe patients is warranted.

National Drug Code numbers distinguished psychotropic (anti depressants, antimanics, antipsychotics, anxiolytics, sedatives, hypnotics, mood stabilizers, amphetamines) versus nonpsycho tropic medications. We compared mean 2year total health care, inpatient, outpatient, and pharmacy costs following each patient’s index claim. Skewed data were log transformed.

RESULTS: Among 2,924,412 Medicaid enrollees, 85 POCD patients were matched to 963 PD patients. Although total health care costs were not significantly different between groups, POCD patients incurred significantly greater 2year mean pharmacy costs than

PD patients ($3,294 [SD = $4.50] vs. $1,988 [SD = $3.00], respec tively; P = 0.009). Further analysis showed no significant differ ences between groups with respect to costs for nonpsychotropic medications, but costs for psychotropics were significantly greater for POCD than for PD patients ($1,808 [SD = $5.50] vs. $665

[SD = $3.30], respectively; P < 0.001). Similarly, although there were no significant differences between groups with respect to number of fills for nonpsychotropic medications, the average number of fills for psychotropics was significantly greater for

POCD patients (35.1 [SD = 28.6] vs. 17.8 [SD = 14.3], respectively;

P < 0.001).

CONCLUSIONS: The greater number of psychotropic fills and costs for patients with POCD versus PD may reflect the greater com plexity of OCD or a tendency for patients with OCD to receive inappropriate treatment.

■■ “PURE OBSESSIVE-COMPULSIVE DISORDER” VERSUS

“PURE DEPRESSION”: 9-YEAR CLAIMS ANALYSIS OF

FLORIDA MEDICAID ENROLLEES

Hankin C,* Dunn J, Knispel J, Levin A, Wang Z, Bronstone A.

*BioMedEcon, LLC, P.O. Box 129, Moss Beach, CA 94038; chankin@ biomedecon.com, 650.563.9475

■■ REAL-WORLD DOSING OF ANTI-TUMOR NECROSIS

FACTOR THERAPIES IN THE TREATMENT OF ADULTS

WITH CROHN’S DISEASE

Waters H,* Meekins T, Bewtra A, McKenzie S, Tang B, Piech C.



BACKGROUND: Whereas the health care burden of depression is well documented, this is not the case for obsessivecompulsive disorder (OCD), an anxiety disorder with an estimated U.S. prevalence of 2%.

OBJECTIVE: Using 9 years of claims data (Florida Medicaid,

19972006), we compared health care costs of newly diagnosed patients with “pure OCD” (POCD) with a matched sample of newly diagnosed patients with “pure depression” (PD).

METHODS: Adults (aged > 18 years) with ≥ 1 OCD diagnosis and

2 years of data preceding and following their first (index) OCD claim were selected. POCD patients were identified as having no diagnoses of depression, psychoses, bipolar disorder, organic mental disorders, pervasive developmental disorders, nonpsy chotic brain damage, developmental delays, or mental retardation in this 4year period. PD patients were selected similarly except that the index claim was depression and exclusion diagnoses included OCD rather than depression. Each POCD patient was matched to ≥ 1 PD patient on sex, race/ethnicity, medical illness severity, and age and year at index diagnosis. Primary diagno ses (ICD9CM) distinguished medical versus psychiatric care.

BACKGROUND:

OBJECTIVE:

METHODS:

Two antitumor necrosis factor (TNF) therapies, adalimumab and infliximab, are approved for treating adults with Crohn’s disease.

To compare realworld versus labeled antiTNF dosing in adults with Crohn’s disease.

A retrospective claims analysis was conducted for patients with Crohn’s diease aged ≥ 18 years using Wolters Kluwer

Health’s Source Lx Longitudinal patient database. Newly initi ated adalimumab or infliximab patients, determined by a 90day absence of claims for the respective agent, who had continuous enrollment and therapeutic persistence for the study duration were analyzed. The labeled dosage was calculated monthly as the cumulative sum of adalimumab 40 mg syringes or infliximab

100 mg vials required from the first day of the index month through December 31, 2007, inclusive of induction and main tenance dosing. The infliximablabeled dosage assumed 4 vials per infusion, which represents the lowest labeled dosage (5 mg per kg) for an average patient weighing 71 kg. Mean cumulative www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 691


TABLE

2007

Index

Month

March

April

May

June

July

August

September

October

November

December

Cumulative Utilization (From Index Month Through December 31, 2007)

Months on

Therapy

10

9

6

5

8

7

2

1

4

3

New Starts

N = 1,299

99

124

123

137

141

149

110

140

141

135

Adalimumab

Labeled Dose

# of Syringes

24

22

20

18

16

14

12

10

8

6

Mean Prescribed

# of Syringes

28.59

24.04

26.82

21.76

23.63

20.74

16.89

18.71

13.28

10.62

New Starts

N = 2,118

266

224

210

181

224

218

186

234

247

128

Infliximab

Lowest Labeled

Dose # of Vials

28

24

20

20

20

16

16

12

12

8

Mean Prescribed

# of Vials

22.24

19.22

20.57

18.65

20.55

13.81

12.44

10.76

7.92

8.85

utilization was analyzed monthly for each drug and compared with the labeled dosage.

RESULTS: There were 1,299 patients with adalimumab (average age = 41.6; 61% female) and 2,118 patients with infliximab (aver age age = 42.9; 57% female; Table). For adalimumab, 48.6% of patients were at or below the labeled dosage, while 51.4% were above the labeled dosage. For infliximab, 65.2% patients were at or below the lowest labeled dosage, while 34.9% were above the labeled dosage. The average difference between mean prescribed dosage and labeled or lowest labeled dosage, respectively, was

+5.51 syringes for adalimumab and –2.10 vials for infliximab.

CONCLUSIONS: In Crohn’s disease, results revealed that most adalimumab patients were above its labeled dosage, while most infliximab patients were at or below its lowest labeled dos age. Mean prescribed units were above the labeled dosage for adalimumab but below the lowest labeled dosage for infliximab.

Payers should analyze their own data to determine whether these same trends are seen and, if so, how these dosing patterns impact effectiveness.

■■ RELATIONSHIP BETWEEN GLYCEMIC CONTROL AND

HEALTH CARE RESOURCE UTILIZATION AMONG PATIENTS

WITH TYPE 2 DIABETES MELLITUS: AN ANALYSIS OF

MANAGED CARE DATA

Menzin J,* Zhang B, Cohen JH, Lobo FS, Korn JR, Friedman M,

Neumann PJ. *Boston Health Economics, Inc., 20 Fox Rd., Waltham,

MA 02451; jmenzin@bhei.com, 781.290.0808

BACKGROUND: New evidence is needed on the relationship between glycemic control and health care utilization in managed care set tings given current practice patterns, new diabetes treatments, and tighter targets for glycemic control.

OBJECTIVE: To assess the relationship between levels of glycemic control and hospitalization rates for patients with type 2 diabetes.

METHODS: This retrospective cohort study used automated databases from a managed care organization and clinic in

Massachusetts. Eligible patients had 2 or more diagnoses of diabetes and 2 or more HbA1c test results within a 1year period between January 2002 and December 2006. Patients were assigned to 3 cohorts based on their average HbA1c values during their followup periods: good glycemic control (HbA1c

< 7%), unsatisfactory glycemic control (HbA1c 7 to < 9%), and poor glycemic control (HbA1c ≥ 9%). Hospitalizations with listed diagnoses for diabetesrelated complications (e.g., hypoglycemia, microvascular and macrovascular complications) and associated charges were evaluated across study cohorts. Multivariate analy ses were used to control for differences in age, gender, number of

HbA1c tests, followup time, and diagnosis of cancer.

RESULTS: There were 9,887 patients (5,649 patients with HbA1c

< 7%, 3,749 with HbA1c 7 to < 9%, 489 with HbA1c ≥ 9%) who met cohort selection criteria. Mean age was 66.6 (SD = 12.4) years, and 48.1% were female. Of the study patients, 28.7% had at least

1 hospitalization for diabetesrelated complications, with a total of 5,873 stays. Multivariate analyses showed that the number of inpatient stays, proportion of patients hospitalized, and charges for inpatient stays increased with HbA1c levels. On an annualized basis, the adjusted rate of hospitalization varied from 13.3 per

100 patients with good glycemic control to 17.1 per 100 patients with unsatisfactory glycemic control to 25.1 per 100 patients with poor glycemic control ( P < 0.05). The adjusted average hospitaliza tion charge per patient (across all admissions for diabetes compli cations) also increased with worsening glycemic control ($10,449,

$11,535, and $20,121 for good, unsatisfactory, and poor glycemic control, respectively).

CONCLUSIONS: In this managed care population, poor glycemic control was associated with an increase in hospitalizations


Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference for diabetesrelated complications and associated charges over

≥ 3 years of followup.

CONCLUSIONS: Psoriasis patients have higher psychiatric comor bidities compared with patients without psoriasis. Psychiatric disorders were associated with high health care costs in psoriasis patients.

■■ RISK OF PSYCHIATRIC DISORDERS AND HIGHER

HEALTH CARE COSTS AMONG PATIENTS WITH

MODERATE TO SEVERE PSORIASIS

Han C,* Zhao N, Tang B, Waters H, Schenkel B. *Johnson & Johnson

Pharmaceuticals Services, LLC, Worldwide Health Economics &

Pricing, 200 Great Valley Pkwy., Malvern, PA 19355; chan3@cntus.jnj.com, 610.651.6657

■■ SELECTION BIAS AND PROPENSITY SCORE MATCHING

IN A CLAIMS DATABASE ANALYSIS OF THE FREQUENCY

AND COST OF CHEMOTHERAPY-RELATED COMPLICATIONS

Chu E,* Wei W, Schulman KL. *Yale University School of Medicine,

333 Cedar St., WWW-221, New Haven, CT 06520; chueyale@yahoo.com, 203.785.6879

BACKGROUND: The risk of psychiatric disorders and the impact on health care costs in patients with moderate to severe psoriasis is unclear.

OBJECTIVE: To evaluate psychiatric burden in patients with mod erate to severe psoriasis using data from health care claims.

METHODS: Psoriasis patients and controls without psoriasis were identified from the PharMetrics health care claims database using the ICD9CM code 696.x. Patients with moderate to severe pso riasis (N = 7,971) were defined as those who had been diagnosed with psoriasis in both 2003 and 2004 and who had been treated with systemic therapies including cyclosporine, methotrexate, acitretin, biologics, and phototherapies. Controls (N = 31,884) were matched with psoriasis cases with a 4:1 ratio by gender, age, region, and previous time in plan. Psychiatric disorders (anxiety, bipolar disorder, delirium, dementia, depression, schizophrenia, other psychosis) and antipsychiatric therapies (antidepressants, antipsychotics, anxiolytics, antimanic) in 2004 were identified using ICD9CM codes or therapeutic class indictors and were compared between psoriasis and control groups. Odds ratios

(ORs) and 95% confidence intervals (CIs) were estimated using

MantelHaezel methods.

RESULTS: Psoriasis was almost equally distributed between males (50.6%) and females, and the mean age was 47.2 years.

Approximately onehalf of the patients received antiinflamma tory drugs, 33.3% received biologic therapy, and 36.7% had pho totherapy. Compared with controls, patients with moderate to severe psoriasis had a statistically significantly higher prevalence of anxiety (6.94% vs. 4.37%, OR = 1.63), depression (9.17% vs.

5.32%, OR = 1.80), bipolar disorder (1.10% vs. 0.51%, OR = 2.16), and delirium (0.25% vs. 0.14%, OR = 1.74) ( P < 0.01). No differ ence was found between psoriasis patients and controls in the prevalence of dementia or schizophrenia ( P > 0.05). Compared with controls, a greater proportion of psoriasis patients had been treated with antidepressants (6.12% vs. 0.90%, OR = 7.18), anxi olytics (5.03% vs. 0.75%, OR = 7.04), antipsychotics (5.90% vs.

0.89%, OR = 6.97), or antimanics (4.89% vs. 0.74%, OR = 6.93).

Among psoriasis patients, those who had any psychiatric disor ders had higher total health care costs ($18,046.70) than those without psychiatric disorders ($10,503.50, P < 0.001).

BACKGROUND: Retrospective studies using claims databases are gaining increasing popularity as a tool to examine the clinical and economic outcomes of cancerspecific therapies. However, researchers using claims databases must minimize the impact of the selection bias inherent in the decision to treat.

OBJECTIVE: To implement methodologies to remediate selection bias when comparing outcomes between chemotherapy regi mens.

METHODS: Patients with breast, colorectal, or gastroesopha geal cancers who received chemotherapy between 2003 and

2006 were identified from the Thomson Healthcare Marketscan research databases. Chemotherapy treatment episodes were classed by treatment setting and type of chemotherapy. Prior to comparing clinical and economic outcomes between capecitabine and alternative treatment regimens, 7 propensity score models were used to obtain balanced cohorts by first modeling the prob ability that an individual used the capecitabinebased regimen, adjusting for observed characteristics, and then matching them to patients in the relevant treatment group who had a similar predicted probability. Matching was performed using the nearest neighbor method, without replacement, at a match ratio of 1:1 or

2:1 depending on the sample size of the case and control group, with caliper thresholds applied to improve the quality of match ing (see Table).

RESULTS: Prior to propensity matching, there were significant group differences in demographic and clinical characteristics.

Patients treated with capecitabinebased regimens were more likely to be older; have metastatic disease; reside in the western part of the United States; and have had prior surgical resection, radiation, or chemotherapy. All significant group differences were removed after matching. Cox proportional hazard and general linear models were subsequently used to predict the risk and cost of complications.

CONCLUSIONS: In observational studies examining the outcomes of cancerspecific therapies, propensity score models are effective in addressing selection bias issues.



TABLE Propensity Model Summary

Cancer Type/

Treatment Setting

Adjuvant

Metastatic

Metastatic

Metastatic

Case Control Match

Ratio

Colorectal

Capecitabine 5FU

Caliper

1:1 1/6

Capecitabine 5FU

Capecitabine

+ oxaliplatin

5FU

+ oxaliplatin

1:1

1:2

1/4

None

Capecitabine

+ irinotecan

5FU

+ irinotecan

Gastroesophageal

Capecitabine 5FU

1:2 None

1:1 1/4

Breast

Capecitabine Gemcitabine 1:1 1/4

Capecitabine Vinorelbine 1:1 1/4

5-FU = 5-fluorouracil.

starting dose was 20 mg per kg per day at 97% of clinics. Reduced blood phenylalanine (Phe) level was used by all respondents to determine their response to sapropterin; however, additional determinants used by centers to assess clinical benefit included dietary Phe tolerance (66%), patient behavior (38%), blood tyrosine (Tyr) concentration (24%), time to response (24%), blood Phe:Tyr ratio (10%), decrease in other medications (3%), and “other parameters” (3%). Seventytwo percent of centers reported testing patients for response for 4 weeks; 14% tested for

12 weeks, and 14% tested for other lengths of time (shorter and longer than 4 weeks).

CONCLUSIONS: A clinical response was based on a reduction in blood Phe concentration in all responding patients, but centers also utilized other factors in addition to Phe reduction to assess clinical benefit, such as improved behavior or reduction in blood

Phe:Tyr ratio. Most centers tested for 1 month to determine response to sapropterin; a few reported shorter (12 weeks) or longer intervals (6 weeks) to determine response. Academic centers used several criteria for assessing the clinical benefit of sapropterin dihydrochloride for PKU patients. During the initial responsetesting phase, most centers started patients at a dose of

20 mg per kg per day and assessed patients on sapropterin for at least 4 weeks.

■■ SELECTION OF PHENYLKETONURIA PATIENTS

BY ACADEMIC MEDICAL CENTERS FOR THE SAPROPTERIN

EXPANDED ACCESS PROGRAM AND DETERMINATION OF

RESPONSE TO SAPROPTERIN DIHYDROCHLORIDE THERAPY

Jurecki E,* Lai K, Nicely H. *BioMarin Pharmaceutical, Inc.,

9565 Broadmoor Dr., San Ramon, CA 94583; ejurecki@bmrn.com,

925.828.5077

BACKGROUND: The Sapropterin Expanded Access Program (SEAP) is a Food and Drug Administrationapproved program providing sapropterin dihydrochloride prior to launch of drug therapy to patients with hyperphenylalaninemia due to phenylketonuria

(PKU) who are aged ≥ 9 years and who did not participate in the sapropterin dihydrochloride clinical trials.

OBJECTIVE: We surveyed selection criteria used by health care providers at U.S. academic institutions for PKU patients enrolled in the SEAP for sapropterin and evaluated the criteria used for determination of patients’ responses to therapy.

METHODS: bioStrategies, an independent market research organi zation, invited all SEAP clinics (n = 41) to complete a Webbased survey using forcedchoice and openended questions regarding protocols they implemented for this study and then analyzed results.

RESULTS: 29 clinics (71%) responded to the survey. Each clinic actively followed a median of 50 (range, 3200) PKU patients.

Thirtyone percent of these clinics offered enrollment into the

SEAP for all PKU patients, whereas 69% of clinics offered enroll ment to selected PKU patients. For clinics that limited enroll ment, selection for challenge with sapropterin was prioritized for moderate or severe disease over mild disease as well as older patients struggling with diet over younger patients. The reported

■■ SYNCHRONIZATION OF TREATMENT

WITH ERYTHROPOIESIS-STIMULATING AGENTS

AND CHEMOTHERAPY

Nordstrom BL,* Fraeman KH, Collins JM, Luo W, O’Malley CD,

Whyte JL, Nordyke R. *United BioSource Corporation, 101 Station

Landing, Medford, MA 02155; beth.nordstrom@unitedbiosource.com,

781.960.0250

BACKGROUND: Erythropoiesisstimulating agents (ESAs) are effective treatments for anemia in patients with nonmyeloid malignancies in which anemia is due to the effect of concomi tantly administered chemotherapy. The extent to which ESA administrations increase the burden of treatment visits that are needed beyond those for chemotherapy alone has not been assessed.

OBJECTIVE: To examine the extent to which dosing of the ESAs darbepoetin alfa and epoetin alfa is synchronized (i.e., occurs during the same visit) with chemotherapy in patients on con comitant chemotherapy and ESAs.

METHODS: Data were obtained from the Varian Medical Oncology database of outpatient oncology electronic medical records.

Patients with breast, lung, or colorectal cancer or lymphoma who received a chemotherapy regimen containing at least 1 conven tional myelosuppressive agent and at least 2 ESA administrations between 2002 and 2007 were included. Schedules of adminis tration of chemotherapy and ESAs were calculated and cross tabulated. Each ESA administration was coded as either occurring


Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference or not occurring on the same day as a chemotherapy adminis tration. The proportion of ESAs administered on the same day as chemotherapy was examined separately for darbepoetin and epoetin.

RESULTS: A total of 8,044 patients met all inclusion criteria, with

4,484 on darbepoetin and 3,560 on epoetin. The mean age was

60 years, and 71% were female. The cancer type was breast in

40%, lung in 31%, colorectal in 17%, and lymphoma in 12%.

Most patients received darbepoetin every 2 weeks, although an increasing proportion received it every 3 weeks starting in 2006.

Epoetin was most often administered weekly. ESA administra tions occurred on the same day as chemotherapy in 70.8% of cases for darbepoetin and 63.2% of cases for epoetin ( P < 0.001).

The proportion of ESA administrations synchronized with che motherapy decreased with increasing intervals between chemo therapy administrations ( P < 0.001 for chemotherapy schedules every 2, 3, and 4 weeks vs. weekly).

CONCLUSIONS: More than 30% of ESA treatments were admin istered in separate visits from chemotherapy administrations.

Epoetin was associated with more nonchemotherapy clinic visits than darbepoetin. The impact of synchronized versus asyn chronized treatment on patients and medical practices warrants investigation.

TABLE Future Outlook for Nebraska Counties

Parameter

Counties with no pharmacy

Counties with 1 pharmacy

Number of rural pharmacies

Current

19

17

126

Future

26

31

78

Percent

Change

+ 36.8

+ 82.4

–38.1 pharmacies to a Nebraska Medicaid Cost of Dispensing (COD) survey. Counties were classified into risk levels based on pro jected available prescription volume and the number of pharma cies in each county. Projected available prescription volume was estimated based on average prescription volume per Nebraskan by age group, reduced by number of longterm care beds in the county, and adjusted for recent population trends.

RESULTS: Regression analysis of the respondent pharmacies from the Nebraska COD survey indicated that the breakeven prescription volume ranged from 44,790 to 49,246 prescriptions annually. The number of counties in Nebraska with no pharma cies was projected to increase from 19 to 26, and the number of counties with 1 pharmacy was projected to increase from 17 to 31 (Table). The number of rural Nebraska pharmacies was projected to decrease from 126 to 78.

CONCLUSIONS: Novel approaches to delivery of rural pharmacy services must be investigated to ensure that quality health care is available to individuals in areas with low population density.

■■ USE OF BREAK-EVEN ANALYSIS OF NEBRASKA

COMMUNITY PHARMACY INDUSTRY’S OPERATIONAL

COSTS IN PREDICTING FUTURE ECONOMIC OUTLOOKS

Keast S,* Jacobs E. *University of Oklahoma, College of Pharmacy,

ORI-W4403, P.O. Box 26901, Oklahoma City, OK 73126-0901; shellie-gorman@ouhsc.edu, 405.271.9039 ext. 47347

BACKGROUND: The demographics of rural America have changed in the last 2 decades. Rural residents are more likely to be lowincome workers relying on Medicare, Medicaid, or State

Children’s Health Insurance programs than their urban counter parts. These changes add to concerns surrounding health care access for rural areas. This access is not limited to physicians and hospitals, but also includes pharmacies. A method for calculating the point at which the business future for a community pharmacy is not attractive enough to recruit a new generation of pharmacy ownership, perhaps resulting in pharmacy closure, is an impor tant issue that must also be studied.

OBJECTIVE: To determine the average breakeven points (based on prescription volume) for rural Nebraska pharmacies and the ability of each pharmacy’s geographic market (based on county population) to meet or exceed the pharmacy’s breakeven point to achieve a return on investment so that the pharmacy has the potential to serve future health care needs of the county’s popula tion beyond current ownership.

METHODS: This research relied on data collection and regression analysis of the operational cost data provided by responding

■■ USTEKINUMAB REDUCES WORK LIMITATIONS,

INCREASES WORK PRODUCTIVITY, AND DECREASES

WORKDAYS MISSED DUE TO PSORIASIS IN PATIENTS WITH

MODERATE TO SEVERE PSORIASIS

Reich K, Schenkel B,* Han C, Szapary P, Li S, Lebwohl M,

Langley R. *Johnson & Johnson Pharmaceuticals Services, LLC,

850 Ridgeview Dr., MS-H-1-2, Horsham, PA 19044; bschenk9@cntus.jnj.com, 215.325.3614

BACKGROUND: Ustekinumab is a novel human monoclonal antibody against interleukin 12/23p40 that has demonstrated significant efficacy in moderate to severe plaque psoriasis patients and may be a treatment option for patients who are not candi dates for conventional systemic therapy.

OBJECTIVE: To examine the effect of ustekinumab on work limita tions, productivity, and number of workdays missed due to pso riasis.

METHODS: In PHOENIX 2, a Phase 3 trial in patients with moderate to severe psoriasis, 1,230 patients were randomized

1:1:1 to ustekinumab 45 mg, ustekinumab 90 mg, or placebo.

In the ustekinumab groups, patients received treatment at www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 695

Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference weeks 0, 4, and every 12 weeks thereafter. Patients random ized to placebo at baseline crossed over to receive ustekinumab

45 or 90 mg at week 12. Work limitations were assessed using the Work Limitations Questionnaire (WLQ). The WLQ assesses work limitations due to health in 4 areas: physical, time manage ment, mentalinterpersonal, and output demands. Each demand is scored from 0 (limited none of the time) to 100 (limited all of the time). Productivity was assessed using a visual analog scale

(VAS, 010). The number of workdays missed due to psoriasis in the last 4 weeks was evaluated and compared at baseline and at week 12.

RESULTS: At baseline, 75% of patients were employed. At week 12, mean changes in scores of physical, time management, mental interpersonal, and output demands were –6.33, –7.85, –7.67, and

–6.09, respectively, in ustekinumabtreated patients compared with mean changes of –0.20, 0.74, 1.11, and 1.08, respectively, in the placebo group ( P < 0.01 for each comparison of ustekinumab vs. placebo). The mean change in productivity score from base line to week 12 was –2.55 for the combined ustekinumab group versus 0.0 for the placebo group ( P < 0.001). The mean reduction from baseline to week 12 in the number of workdays missed due to psoriasis in the last 4 weeks in the combined ustekinumab group was 0.2 days compared with a reduction of 0.04 days in the placebo group. On an annual basis, this represents a reduc tion of 2.1 workdays missed in the ustekinumab group versus the placebo group. At week 24, patients in the placebo group who crossed over to ustekinumab at week 12 achieved similar improvements in work limitations, productivity, and workdays missed due to psoriasis compared with patients initially random ized to ustekinumab.

CONCLUSIONS: Ustekinumab significantly improved work limi tations, increased productivity, and reduced workday loss in moderate to severe psoriasis patients.


R E S I D E N C I E S , F E L L O W S H I P S , A N D O T H E R P R O G R A M S

Managed Care Pharmacy Residencies,

Fellowships, and Other Programs

■■ AMERICAN HEALTH CARE

Post Graduate Year One (PGY1) Managed Care Pharmacy

Accredited: AMCP/American Society of Health-

Systems Pharmacists (ASHP)

Length of Program: 12 months

Number of Positions: 1

Affiliation: None

Application Deadline: Open

Starting Date: July 1

Estimated Stipend: $43,000 and up

Onsite Interview: Yes

Educational/Special Requirements: PharmD with California pharmacist license or eligible for license

Fringe Benefits: Medical/dental/vision insurance, holidays, vacation, attendance at national conference(s)

Special Features: Activities the resident will be involved in include (but are not limited to): Pharmacy and Therapeutics

(P&T) Committee participation and presentations; formulary management and review; one-on-one physician correspondence on evidence-based medicine with current clinical studies reviewed and presented, focusing on actual patients that may benefit from this information; new drug review and its placement with available therapies; clinical participation and set-up; client summary report write-up and delivery; and participation in various education conference and clinical studies.

Contact Information:

Nazly Westernoff

American Health Care

2217 Plaza Dr., Ste. 100

Rocklin, CA 95765

916.773.7227

916.773.7210 (fax) n.westernoff@americanhealthcare.com

■■ BLUE CROSS AND BLUE SHIELD OF ALABAMA

Managed Care Pharmacy

Accredited: AMCP/ASHP



Affiliation: None

Application Deadline: January 15

Starting Date: July 1 (flexible)

Estimated Stipend: $34,000


Educational/Special Requirements: National Matching Services

(NMS) Code Number: 201514, PharmD or equivalent experience

Fringe Benefits: Paid vacation, personal holiday leave, health/ dental insurance, no on-call responsibilities, no weekends or holidays

Special Features: The program provides the resident with the opportunity to experience a true integrated medical system, including medical and pharmacy claims. The areas of focus will include pharmaceutical care, drug information, formulary management, clinical program management, disease state management and outcome studies, specialty pharmacy, and Medicare

Part D. The resident also will complete a research project suitable for publication. This program will incorporate personal, communication, and time management skills.


Jerry Wong, PharmD, MBA, Residency Director

Blue Cross and Blue Shield of Alabama

450 Riverchase Pkwy. East

Birmingham, AL 35244

205.220.6526

205.220.2939 (fax) jwong@bcbsal.org

■■ BLUE CROSS AND BLUE SHIELD OF NEBRASKA


Accredited: Seeking



Affiliation: University of Nebraska Medical Center


Starting Date: June 29


Onsite Interview: Required

Educational/Special Requirements: PharmD degree from an

Accreditation Council for Pharmacy Education (ACPE)-accredited college of pharmacy, licensed pharmacist in the United States or eligibility for licensure (successful candidate must be fully licensed at the start of residency), application, writing sample,

3 professional letters of recommendation, on-site interview with short formal presentation

Fringe Benefits: 10 days paid vacation, holidays, health insurance, paid travel and registration to AMCP Educational Conference and

Annual Meeting

Special Features: The Blue Cross and Blue Shield of Nebraska residency will offer exposure to various aspects of managed care pharmacy through health plan and pharmacy benefit management (PBM) exposure as well as direct patient care through clinical rotations. The residency will offer participation and exposure www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 697

Managed Care Pharmacy Residencies, Fellowships, and Other Programs to the following areas: pharmacy benefit design, utilization management, formulary management, pharmacy trend management, drug information, health economic/outcomes research, pharmacy benefit management, and disease state management quality assurance initiatives. This unique program also allows the resident the option to participate in teaching or didactic coursework through the University of Nebraska Medical Center.


Clint Williams, Director of Pharmacy

Blue Cross and Blue Shield of Nebraska

7261 Mercy Rd.

Omaha, NE 68180

402.390.1853

402.548.4683 (fax) clint.williams@bcbsne.com

■■ BLUE SHIELD OF CALIFORNIA

Managed Care Pharmacy Systems




Affiliation: University of California—San Francisco

(UCSF)





Educational/Special Requirements: PharmD degree from an accredited school of pharmacy, completion of a managed care pharmacy practice or pharmacy practice residency, 3 letters of recommendation, letter of intent, on-site interview

Fringe Benefits: Health/dental/vision benefit, 20 days paid time off including professional leave (with travel allowances), 9 holidays, no on-call responsibilities

Special Features: The purpose of Blue Shield of California’s

Managed Care Pharmacy Practice Residency Program is to prepare pharmacists to work competently in a managed care setting.

The program is customized to residents based on their experience in managed care and their personal and professional goals.

Residents participate in the following rotations: drug information/ formulary management, quality improvement/population-based disease management, contracting, operations, administration/ strategy, and drug utilization review. Residents assist in maintaining formularies, gain an understanding of pharmacy benefit designs, develop quality-improvement programs, and learn to respond to the challenges affecting health care. Project management, process orientation, and analytical thinking skills will be developed. These proficiencies will prepare the pharmacist for a career in a managed care system.


Tara Abrams, Director, Residency Program; Sr. Clinical Pharmacist,

Quality Improvement

Blue Shield of California

50 Beale St.

21-C0354

San Francisco, CA 94105

415.229.6424

415.229.6011 (fax)

Tara.Abrams@blueshieldca.com

http://www.blueshieldca.com/residencyprogram/

■■ BLUE SHIELD OF CALIFORNIA

PGY1 Managed Care Pharmacy

Accredited: Application submitted



Affiliation: UCSF





Educational/Special Requirements: PharmD degree from an accredited school of pharmacy, completion of a managed care pharmacy practice or pharmacy practice residency, 3 letters of recommendation, letter of intent, on-site interview

Fringe Benefits: Health/dental/vision benefit, 20 days paid time off including professional leave (with travel allowances), 9 holidays, no on-call responsibilities

Special Features: The purpose of Blue Shield of California’s

Managed Care Pharmacy Practice Residency Program is to prepare pharmacists to work competently in a managed care setting.

The program is customized to residents based on their experience in managed care and their personal and professional goals.

Residents participate in the following rotations: drug information/ formulary management, quality improvement/population-based disease management, contracting, operations, administration/ strategy, and drug utilization review. Residents assist in maintaining formularies, gain an understanding of pharmacy benefit designs, develop quality-improvement programs, and learn to respond to the challenges affecting health care. Project management, process orientation, and analytical thinking skills will be developed. These proficiencies will prepare the pharmacist for a career in a managed care system.


Tara Abrams, Director, Residency Program; Sr. Clinical Pharmacist,

Quality Improvement

Blue Shield of California

50 Beale St.

21-C0354

San Francisco, CA 94105

415.229.6424

415.229.6011 (fax)

Tara.Abrams@blueshieldca.com

http://www.blueshieldca.com/residencyprogram/


Managed Care Pharmacy Residencies, Fellowships, and Other Programs

■■ CLINICAL PHARMACOLOGY SERVICES, INC.

Ambulatory Care/Clinical Research

Accredited: No



Affiliation: None

Application Deadline: February 1




Educational/Special Requirements: None

Fringe Benefits: Sponsorship to Professional Meeting and

Southwestern Residency Conference

Special Features: None


Daniel Buffington, PharmD, MBA, Director

Clinical Pharmacology Services

6285 E. Fowler Ave.

Tampa, FL 33617

813.983.1500

813.983.1501 (fax) danbuffington@cpshealth.com

http://www.cpshealth.com

■■ COVENTRY HEALTH CARE OF KANSAS, INC.

Health Plan/Managed Care Pharmacy

Accredited: Seeking



Affiliation: University of Missouri - Kansas City

(UMKC)






ACPE-accredited college of pharmacy, licensed pharmacist in the United States or eligibility for licensure (successful candidate must be fully licensed at the start of residency), application, letter of intent, curriculum vitae, writing sample, official transcripts,

3 professional letters of recommendation, on-site interview with short formal presentation in Kansas City

Fringe Benefits: 2 weeks paid vacation; holidays; medical/dental insurance; paid travel and registration to AMCP Educational

Conference, AMCP Annual Meeting, ASHP Midyear Meeting, and

FMCP program

Special Features: Residency opportunities are available in all managed care core competencies: pharmacy benefit management, utilization management, formulary management, clinical consultation service, drug information, new technologies assessment, provider network relations, Medicare plan interventions, disease state management, health and wellness initiatives, quality assurance/improvement activities, marketing and sales, contracting, health economics/outcomes, rotations with pharmaceutical industry, teaching experience through UMKC, and PharmD experiential rotation oversight.


Diana Toe, Regional Clinical Pharmacist

Coventry Health Care of Kansas, Inc.

8320 Ward Pkwy.

Kansas City, MO 64114

866.795.3995

866.795.3992 (fax) dctoe@cvty.com

http://www.cvty.com

■■ CVS CAREMARK




Number of Positions: 2 (in Texas)

Affiliation: None



Estimated Stipend: Competitive


Educational/Special Requirements: PharmD with experiential- or internship-based experience in the managed care/PBM industry

Fringe Benefits: Comprehensive medical/dental/life insurance plan, 2 weeks paid vacation, holidays, employee stock purchase program, flexible spending program, travel budget

Special Features: Caremark’s General Managed Care Residency

Program is rotationally based and includes both on-site and offsite learning experiences. This residency will allow the resident to be involved in the day-to-day operations of a pharmacy benefit management company. The resident will be offered the opportunity to experience a variety of different areas including: formulary management process, medical affairs, client management, health plan operations, research, disease state management, clinical program development, and specialty pharmacy.


Melissa Jay, Client Benefits Clinical Manager

CVS Caremark

750 W. John Carpenter Fwy.

Irving, TX 75039

469.524.5832

469.524.5858 (fax) melissa.jay@caremark.com



CVS CAREMARK

Managed Care Specialty/Analytics and Outcomes

Accredited: No



Affiliation: University of Illinois at Chicago;

Midwestern University—Chicago

College of Pharmacy





Educational/Special Requirements: PharmD with experiential- or internship-based experience in the managed care/PBM industry

Fringe Benefits: Comprehensive medical/dental/life insurance plan, 2 weeks paid vacation, holidays, employee stock purchase program, flexible spending program, travel budget

Special Features: CVS Caremark is the largest provider of prescriptions and related health care services in the nation. The

Company fills or manages more than 1 billion prescriptions annually. Through its unmatched breadth of service offerings,

CVS Caremark is transforming the delivery of health care services in the United States. The Company is uniquely positioned to effectively manage costs and improve health care outcomes through its approximately 6,300 CVS/pharmacy stores; its pharmacy benefit management, mail order, and specialty pharmacy division, Caremark Pharmacy Services; its retail-based health clinic subsidiary, MinuteClinic; and its online pharmacy, CVS.

com. The Analytics and Outcomes Residency will provide the resident a unique opportunity to work on initiatives that foster proactive management of pharmaceutical and overall health care costs. It offers the ability to work with large data sets and perform various pharmaceutical cost analyses such as plan design modeling, formulary analysis, and clinical outcomes. The resident will have the opportunity to interact directly with clients, consultants, and various other benefit providers as well as internal areas to develop analytic tools and methods to support all customers.

While the focus is on analytics, the resident will be exposed to various areas in pharmacy benefit management such as clinical program development and implementation, clinical management, disease management, specialty, P&T, and so forth.


Lydia Shenouda, Manager, Analytic Consulting Services

Residency Coordinator

CVS Caremark

2211 Sanders Rd.

Northbrook, IL 60062

847.559.5633

847.559.5475 (fax) lydia.shenouda@caremark.com





Number of Positions: 1 (Pittsburgh, PA)

Affiliation: University of Pittsburgh School of

Pharmacy





Educational/Special Requirements: PharmD from an ACPEaccredited school or college of pharmacy with experiential- or internship-based experience in the managed care/PBM industry, currently licensed or eligible for pharmacy licensure in the state of Pennsylvania

Fringe Benefits: Comprehensive medical/dental/life insurance plan, 2 weeks paid vacation, paid holidays, employee stock purchase program, flexible spending program, travel budget

Special Features: CVS Caremark, the nation’s premier integrated pharmacy services provider, offers an opportunity to practice in a dynamic PBM environment and gain a clinical and administrative perspective in the management of pharmacy benefit plans for a wide variety of clients. Multifaceted experience will include both on-site and off-site learning experiences including: handson involvement with the formulary management process, client management, health plan operations, mail service, research, health management, clinical program development, and specialty pharmacy. Additionally, through an affiliation with the

University of Pittsburgh School of Pharmacy, the resident will participate in undergraduate and graduate student instruction as well as development of educational programs for the CVS

Caremark professional staff.


Julie Legal, Supervisor of Clinical Services

CVS Caremark

620 Epsilon Dr.

Pittsburgh, PA 15238

1.800.814.6600 ext. 75492

412.968.2704 (fax) julie.legal@caremark.com


Managed Care

Accredited: No



Affiliation: University of Arizona College of

Pharmacy







Educational/Special Requirements: PharmD from an ACPEaccredited school or college of pharmacy with experiential- or internship-based experience in managed care/PBM industry, currently licensed or eligible for pharmacy licensure in the state of Arizona

Fringe Benefits: Comprehensive medical/dental/life insurance plan, paid holidays, employee stock purchase program, flexible spending program, travel budget

Special Features: CVS Caremark, the nation’s premier integrated pharmacy services provider, offers an opportunity to practice in a dynamic PBM environment and gain a clinical and administrative perspective in the management of pharmacy benefit plans.

Multifaceted experience will include both on-site and off-site learning experiences including: hands-on involvement with the formulary management process, client management, health plan operations, mail service, research, health management, clinical programs development, and specialty pharmacy. Additionally, through an affiliation with the University of Arizona College of

Pharmacy, the resident will participate in undergraduate and graduate student instruction as well as development of educational programs for the CVS Caremark professional staff.


Elizabeth Wilmeth, Clinical Manager/Residency Coordinator

CVS Caremark

9501 E. Shea Blvd.

MC-139

Scottsdale, AZ 85260

602.431.4005

480.314.6376 (fax) elizabeth.wilmeth@caremark.com

■■ GROUP HEALTH COOPERATIVE





Affiliation: None





Educational/Special Requirements: PharmD or equivalent experience

Fringe Benefits: Full medical ($35/month paid by employee) and dental coverage (cost varies depending on plan chosen by employee), 7 days vacation, paid registration and some fees to attend professional meetings

Special Features: Residents are trained in the role of the pharmacist in the development and implementation of clinical practice guidelines, formulary development, and management as well as drug use policy development. In addition, residents are trained to function as leaders in implementing pharmaceutical care plans for specific patients in an integrated health plan and delivery system setting.


Jim Carlson, Director, Clinical Pharmacy and Health Plan Services

Group Health Cooperative

12400 E. Marginal Way South

Seattle, WA 98168

206.901.4425

206.901.4410 (fax) carlson.j@ghc.org

http://www.ghc.org/about_gh/employ/rxresidency.jhtml

■■

PGY1 Pharmacy Residency

Accredited: ASHP



Affiliation: Massachusetts College of Pharmacy and

Health Sciences





Educational/Special Requirements: PharmD or BS in Pharmacy with at least 3 years experience

Fringe Benefits: Comprehensive medical plan, 2 weeks paid vacation

Special Features: Academic appointment: Adjunct Instructor in

Pharmacy Practice


Kathy Zaiken, PharmD

Massachusetts College of Pharmacy & Health Sciences

179 Longwood Ave.

Boston, MA 02115

617.732.2740

617.732.2244 (fax) kathy.zaiken@mcphs.edu

http://www.mcphs.edu

■■

HARVARD VANGUARD MEDICAL ASSOCIATES

HEALTH NET PHARMACEUTICAL SERVICES


Accredited: Pursuing joint accreditation by AMCP/

ASHP



Affiliation: University of the Pacific, California

Northstate



Estimated Stipend: $50,000 www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 701



Educational/Special Requirements: Graduate of an ACPEaccredited college of pharmacy, licensed pharmacist or eligible for licensure in the state of California, completed application form, letter of intent (not to exceed 500 words) summarizing applicant’s motivation for pursuing a residency in managed care as well as short-term and long-term career goals, current resume or curriculum vitae, 3 letters of recommendation, 1 official transcript sent directly from applicant’s school of pharmacy, completion of an on-site interview

Fringe Benefits: Competitive residency stipend; full benefits as a Health Net Associate including: paid holidays, medical/dental/ pharmacy/vision coverage, paid time off, 401K program, and health club reimbursement program; support to attend various professional meetings

Special Features: Health Net Pharmaceutical Services manages the pharmacy benefits, drug spend, and clinical programs for the health plans of Health Net, Inc. The Managed Care Pharmacy

Practice resident will gain experience in formulary management, prior authorization, strategic benefit design, and pharmacy operations and will participate in Health Net’s National P&T

Committee and Clinical Pharmacy Advisory Committee.


Cathrine Misquitta, Director, Clinical Pharmacy Services

Health Net Pharmaceutical Services

10540 White Rock Rd., Ste. 280

Rancho Cordova, CA 95670

916.463.9602

916.463.9750 (fax) cathrine.v.misquitta@healthnet.com

■■ HEALTH PLAN OF SAN JOAQUIN





Affiliation: University of the Pacific, San Joaquin

General Hospital





Educational/Special Requirements: PharmD from an ACPEaccredited college of pharmacy or equivalent experience, eligible for California licensure, good academic standing, excellent written and verbal communication skills

Fringe Benefits: Health/dental/vision/life/disability insurance available, vacation time allotted, professional travel and stipend available, no weekends or holidays, no staffing requirements in a pharmacy

Special Features: The program is unique in providing a balanced exposure to institutional clinical practice, longitudinal ambulatory care practice, and operation of a Medicaid managed care health maintenance organization (HMO). Primary emphasis is placed on the application of clinical skill on the development and implementation of medication use management initiatives and policies, clinical programs, formulary and disease management, pharmacoeconomic and outcome assessment, drug information, and effective communication. The resident will be involved in classroom teaching and precepting clerkship students from

University of the Pacific. All pharmacy preceptors are Board

Certified Pharmacotherapy Specialists (BCPSs).


Allen Shek, Residency Program Director, Associate Professor

Health Plan of San Joaquin, University of the Pacific

7751 S. Manthey Rd.

French Camp, CA 95231

209.461.2209

209.461.2409 (fax) ashek@hpsj.com

http://www.hpsj.com/english/careers/pharmacy-intern.aspx

■■ HEALTHESYSTEMS, LLC

Managed Care

Accredited: Applying



Affiliation: Under discussion with University of

Florida College of Pharmacy




Onsite Interview: Preferred

Educational/Special Requirements: PharmD preferred, Florida registered pharmacist or eligible for licensure

Fringe Benefits: Health insurance for employee and family, employees responsible for a portion of the monthly pre-tax premium, eligible for this benefit on the first business day of the month following 90 days of employment; 401K company-sponsored plan, employees are eligible for this plan on the first business day following 90 days of employment; 10 days paid time off

(PTO) during residency plus 2 floating holidays, vacation begins accruing on the start date, eligible to begin taking vacation after

90 days of employment, 6 paid holidays in addition to PTO

Special Features:


Ralph Kendall, Vice President of Clinical Service

HealtheSystems, LLC

5109 W. Lemon St., Ste. A

Tampa, FL 33609

813.769.1897

813.769.1811 (fax)

RKendall@Healthesystems.com



■■ HEALTHPARTNERS





Affiliation: None





Educational/Special Requirements: PharmD

Fringe Benefits: Health insurance, vacation, holidays

Special Features: Travel/registration for 1 national meeting


Vyvy Vo, Clinical Pharmacy Program Manager

HealthPartners

8170 33rd Ave. South

Mailstop 21111B

Bloomington, MN 55425

952.967.5133

952.883.5875 (fax) vyvy.k.vo@healthpartners.com

http://www.healthpartners.com

■■ HEALTHSPRING, INC.

Managed Care

Accredited: No, but intend on seeking



Affiliation: None





Educational/Special Requirements: Graduate of accredited school of pharmacy, PharmD preferred, eligible for Tennessee licensure, application, curriculum vitae, 3 professional letters of recommendation

Fringe Benefits: Health/dental/vision/life/disability benefits available, PTO, holidays, relocation allowance, conference travel

Special Features: The residency focuses on the development of the knowledge and skills that pharmacists need to assume leadership roles within a managed care organization. The resident will gain a clinical and administrative perspective of the roles and responsibilities of a health care professional within a health plan.

Residency activities include: development and administration of a research project, formulary development, participation in medication therapy management, involvement in legislative and regulatory aspects of managed care pharmacy, development of drug policies and drug monographs, experience analyzing pharmacy reports, and exposure to quality guidelines and initiatives to improve health outcomes and pharmacy benefit management.

Additionally, the resident will have the opportunity to develop expertise in the following areas: prior authorizations, medication counseling, claims adjudication, drug utilization reviews, and overall pharmacy operations.


Annie Rakoczy, Clinical Pharmacy Manager

Texas HealthSpring

2900 N. Loop West, Ste. 1300

Houston, TX 77092

615.565.8110 ext. 8796

615.291.7025 (fax) annie.rakoczy@healthspring.com

http://www.healthspring.com

■■ HENRY FORD HEALTH SYSTEM


Accredited: No



Affiliation: None





Educational/Special Requirements: PharmD, pharmacy practice residency desirable

Fringe Benefits: Health care, 2 weeks paid vacation, travel to

1 meeting

Special Features: The resident will design system enhancements and participate in ongoing utilization management, disease manage ment, and compliance intervention programs. He/she will participate in formulary management and design clinical indications of effectiveness for guidelines. The resident will formulate and answer a research question using scientific principles, with a strong emphasis on outcomes, pharmacoeconomics, and quality-of-life research. Experiences will include: exposure to our HMO (Health Alliance Plan) and involvement with the

Center for Clinical Effectiveness, health system studies, Quality

Improvement Center, and clinical pharmacy services. Direct patient care responsibilities in one of our ambulatory clinics will be ongoing throughout the year.


Vanita Pindolia, Director, Pharmacy Care Management

Health Alliance Plan

2850 W. Grand Blvd., Tower 14, Ste. 200

Attention: Pharmacy

Detroit, MI 48202

248.443.8849

248.443.8614 (fax) vpindoli@hap.org



■■ HILL PHYSICIANS MEDICAL GROUP





Affiliation: None






ACPE-accredited college of pharmacy, 3 letters of recommendation, letter of intent, on-site interview, licensed or eligible for licensure in California, organizational and human relations skills, self-motivation, ability to take charge and implement change, excellent communication and presentation skills, ability to travel within Northern California

Fringe Benefits: off including professional leave (with travel allowances), 9 holidays, no on-call responsibilities

Special Features: leadership and health data analysis team in development and implementation of clinical measures and population-based disease management, in addition to providing support/analysis for contracting, claims, and health resource management. This program teaches residents to conceptualize, integrate, and transform accumulated experiences and knowledge into improved quality of care for patients.


Katherine Ramos, Clinical Pharmacy Coordinator

Hill Physicians Medical Group

2401 Crow Canyon Rd.

San Ramon, CA 94583

925.362.6227

Health/dental/vision benefit, 20 days paid time

Residents will work with the physician katherine.ramos@hpmg.com

■■ HORIZON NJ HEALTH


Accredited: No



Affiliation: Horizon Blue Cross Blue Shield





Educational/Special Requirements: PharmD or equivalent experience, eligible for New Jersey state licensure

Fringe Benefits: Paid vacation, full medical/dental/retirement benefits, attendance to at least 1 national conference

Special Features: ment courses

Horizon NJ Health

210 Silvia St.

609.718.9001

609.538.1698 (fax)

Medicaid managed care HMO, unique focus on government programs, pharmacy case management, formulary and disease state management, development of clinical policies, outcomes research, assistance with PharmD student oversight, ambulatory care experience, and professional develop-


Jennifer Gauweiler, Pharmacy Clinical Manager

West Trenton, NJ 08628

Jennifer_Gauweiler@horizonnjhealth.com

■■ HUMANA INC.





Affiliation: None





Educational/Special Requirements: Graduate of an accredited school of pharmacy, PharmD preferred, minimum GPA of 3.2 (on a 4.0 scale), eligible for pharmacy licensure

Fringe Benefits: Health/dental insurance, 401K plan, 3 weeks vacation, 2 floating holidays, relocation allowance, travel expenses paid for 2 professional meetings

Special Features: Humana Inc., headquartered in Louisville,

Kentucky, is one of the nation’s largest publicly traded health benefits companies with more than 11 million covered lives.

Humana offers integrated health benefits for both medical and pharmacy to employer groups, government-sponsored plans, and individuals. Humana’s residency program offers a broad range of programming within the pharmacy management department.

The residency will offer exposure to various aspects of managed care pharmacy within operations and management of the organization, formulary management, clinical strategy, network relations, trend management, industry relations/contracting, outcomes research, and medication therapy management.


Jane Stacy, Manager, Professional Development

Humana Inc.

500 W. Main St.

Louisville, KY 40202

502.580.1591

502.508.1591 (fax) jstacy1@humana.com



■■ KAISER FOUNDATION HEALTH PLAN

OF THE MID-ATLANTIC STATES, INC.

PGY1 Pharmacy

Accredited: ASHP



Affiliation: None





Educational/Special Requirements: PharmD required, pharmacy licensure eligibility in Washington D.C., Maryland, or Virginia

Fringe Benefits: Medical benefits; selected holidays; sick, vacation, and education leave for ASHP Midyear Clinical Meeting and

Eastern States Residency Conference

Special Features: In addition to direct patient care core rotations, the resident will assist in the development of new and innovative pharmacy services, conduct patient education classes, provide continuing education programs for pharmacy staff members and physicians, assist with teaching pharmacy students, participate in regional P&T Committee meetings, and complete several population-based projects.


Kristen Fink, PharmD, CDE, Residency Program Director, Clinical

Pharmacy Specialist II

Kaiser Permanente Health Plan of the Mid-Atlantic States

4920 Campbell Blvd.

White Marsh, MD 21236

410.933.7621

410.933.7667 (fax)

Kristen.M.Fink@kp.org

■■ KAISER PERMANENTE—CALIFORNIA

Medical Care/Drug Information

Accredited: ASHP


Number of Positions: 3 (Postgraduate Year Two [PGY2]

Affiliation:

Residency in Drug information)

None





Educational/Special Requirements: PharmD, PGY1 residency, excellent communication skills, eligible for California licensure,

3 letters of recommendation; per the rules for the Resident

Matching Program, this residency site agrees that no person at this site will solicit, accept, or use any ranking-related information from any residency applicant

Fringe Benefits: Medical/dental/vision insurance, 10 days time off, attendance at 1 pharmacy conference

Special Features: This PGY2 specialty residency in Drug

Information Practice offers extensive training within a large, progressive drug information center. The resident will gain knowledge, skills, and experience from responding to inquiries from health care professionals, using and maintaining our national pharmacy intranet site, and writing numerous drug information publications. Teaching activities include: precepting pharmacy students and PGY1 residents in our Inquiry Service and presenting formal lectures at local schools of pharmacy (University of Southern California, Western University). The resident will participate in formulary management and attend regional and local P&T Committee meetings. Longitudinal experiences and discussions in pharmacy outcomes research and data analysis, management activities, and quality assurance take place throughout the year.


Mirta Millares, PharmD, FCSHP, FASHP

Kaiser Permanente

12254 Bellflower Blvd., Ste. 106

Downey, CA 90242

562.658.3640

562.658.3758 (fax) mirta.millares@kp.org

http://www.kaiserpharmacyresidency.org

■■ KAISER PERMANENTE—COLORADO

Managed Care/Primary Care

Accredited: ASHP


Number of Positions: 6 (PGY2 Ambulatory Care Pharmacy

Residency)

Affiliation:





Educational/Special Requirements: PharmD, PGY1 residency, eligibility for licensure in Colorado required

Fringe Benefits: Health insurance, paid sick and vacation leave, paid holidays, travel support to ASHP Midyear Meeting and

Western States Residency Conference, online library and computer privileges

Special Features: This unique PGY2 residency provides the opportunity to acquire advanced knowledge and skill in ambulatory care pharmacotherapy in a managed care environment.

Core experiences include: primary care, Clinical Pharmacy

Anticoagulation Service (6,500 patients), and longitudinal rotation in the Clinical Pharmacy Cardiac Risk Service

(10,000 patients). Four elective rotations are available for indepth exposure into disease state management (asthma/allergy, cardiology/heart failure, continuing care, endocrinology, oncology, infectious diseases, psychiatry, neurology, nephrology, www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 705

Managed Care Pharmacy Residencies, Fellowships, and Other Programs palliative care). A research project of publishable quality is required. Evaluation of quality and financial outcomes is emphasized.


Rachana Patel, Clinical Pharmacy Specialist

Kaiser Permanente

1375 E. 20th Ave.

Denver, CO 80205

303.764.4479

303.861.3668 (fax) rachana.j.patel@kp.org

■■

CALIFORNIA

Pharmacy Practice and Drug Information Practice

Accredited: ASHP



Affiliation: None





Educational/Special Requirements: Graduate of an accredited college of pharmacy, licensed or eligible for licensure in California, good communication skills required, resident will develop a project with targeted care outcomes and present at Annual Western

States Conference

Fringe Benefits: Medical/dental/optical insurance, holidays, vacation/sick leave

Special Features: Hospital and ambulatory care experiences in the nation’s largest health maintenance organization, preventive and disease state management in an integrated managed care setting


Elaine Watanabe, Pharmacy Services Manager—Recruitment

Kaiser Permanente Pharmacy Operations Services—

California Division

9521 Dalen St.

Downey, CA 90242

714.796.4809

714.796.4826 (fax)

Elaine.G.Watanabe@kp.org

http://kaiserpharmacyresidency.org

■■

KAISER PERMANENTE MEDICAL CARE PROGRAM—

KAISER PERMANENTE MEDICAL CARE PROGRAM—

CENTRAL VALLEY AREA





Affiliation: Kaiser Permanente



Estimated Stipend: $22.70 per hour


Educational/Special Requirements: Must be a graduate from an accredited school or college of pharmacy by June 30, 2008,

PharmD preferred. Must meet all qualifications of licensure in

California, must meet Kaiser Permanente’s employee requirements

Fringe Benefits: 7 paid holidays, medical/vision/dental insurance, vacation/sick leave, paid educational travel opportunities

Special Features: This program offers training in a variety of practice settings and provides opportunities to gain valuable clinical and administrative experience in a managed care organization. Core experiences include direct patient care, business administration and management, population-based pharmaceutical care, and drug information. Residents participate on the P&T

Committee, serve as preceptors for pharmacy students, and are an integral part of the pharmacy management team. Professional and career development is encouraged throughout the residency.


Laura Morodomi, Clinical Operations Manager

Kaiser Permanente Medical Care Program—Central Valley Area

7373 West Ln.

Attention: Susan Coburn, 3rd Fl. Pharmacy

Stockton, CA 95210

209.476.3474

209.476.3062 (fax) laura.morodomi@kp.org

http://kaiserpharmacyresidency.org/programs/mcCentralValley/

■■ KAISER PERMANENTE MEDICAL CARE PROGRAM—

INLAND EMPIRE SERVICE AREA

General Pharmacy Practice

Accredited: ASHP



Affiliation: None





Educational/Special Requirements: Graduate of accredited college of pharmacy, licensed or eligible for California licensure, pharmacy school transcript, 3 letters of recommendation, letter of intent, curriculum vitae

Fringe Benefits: 2 weeks paid vacation, health benefits including dental/optical, paid holidays, office space, reimbursement for off-site experiences

Special Features: Kaiser Permanente is the nation’s largest nonprofit health plan serving more than 8.4 million members in

9 states. The Inland Empire Service Area consists of 2 medical


Managed Care Pharmacy Residencies, Fellowships, and Other Programs centers and 18 satellite medical offices for 710,000 members in the

San Bernardino and Riverside counties of southern California.


Patricia Gray, Clinical Operations Manager

Kaiser Permanente Inland Empire Service Area

9310 Sierra Ave.

Fontana, CA 92335

909.427.3838

909.427.3830 (fax) patricia.l.gray@kp.org


LOS ANGELES MEDICAL CENTER

PGY1 Pharmacy

Accredited: ASHP



Affiliation: None





Educational/Special Requirements: Applicants must be a graduate of an accredited college of pharmacy, licensed or eligible for licensure in California, good communication skills required, resident will develop a project with targeted care outcomes and present at Annual Western States Conference


Special Features: The Kaiser Permanente Los Angeles Medical

Center is the tertiary care center for Kaiser Permanente in

Southern California and provides comprehensive inpatient, outpatient, and ambulatory care services to Kaiser Permanente members. This residency program provides development and training for recently graduated pharmacists, with an emphasis on pharmaceutical care and leadership to a diverse community. This program will allow residents to become familiar with pharmacy practice in an integrated health care program.


Steve Litsey, Area Pharmacy Director

Kaiser Permanente Pharmacy Operations Services

1515 N. Vermont Ave., Ste. 237

Los Angeles, CA 90027

323.783.8306

323.783.7609 (fax) toni.a.rodriguez@kp.org

http://www.kaiserpharmacyresidency.org/


TRI-CENTRAL SERVICE AREA

Managed Care Organization

Accredited: ASHP

Length of Program: 1 year


Affiliation: None





Educational/Special Requirements: Applicant must be a graduate of an accredited school or college of pharmacy, eligible for licensure in the state of California, submit: application, current curriculum vitae, 3 letters of recommendation, official school or college of pharmacy transcript, copy of pharmacy intern license, letter of intent, sample of recent school work (presentation or journal article)

Fringe Benefits: 2 weeks paid vacation, 6 paid holidays, sick leave, health benefits including dental/optical (also dependents), uniforms, office space, reimbursement for off-site experiences

Special Features: The Tri-Central Kaiser Permanente PGY1

Pharmacy Residency Program offers unique opportunities for residents to develop their skills in health care within a large managed care setting. Residents will learn from a team of dedicated preceptors across 3 medical centers in Southern California (Baldwin

Park, Bellflower, South Bay). Residents will gain extensive training in various pharmacy practice areas: acute care, ambulatory care, outpatient pharmacy, and administrative management.

Within these areas of pharmacy practice, the residency program offers a higher level of specialization in pharmaceutical care such as neonatal intensive care unit, integrated cardiovascular disease care management, heart failure management, integrated pain management, and adult and pediatric oncology. As part of an integrated health organization, residents will also gain valuable experience through participation in the P&T Committee, drug formulary management, drug information services, physician drug education, and pharmacy operations. Completion of the

Tri-Central Residency Program results in marketable skill sets for any pharmacy profession and a strong foundation for future pharmacy practice.


John Sie, Pharmacy Residency Program Coordinator,

Pharmacy Clinical Operation Manager

Kaiser Permanente Medical Care Program

Tri-Central Pharmacy Residency Program—Pharmacy Administration

1011 Baldwin Park Blvd.

Baldwin Park, CA 90706

626.851.5602

626.851.5813 (fax) john.l.sie@kp.org

http://www.kaiserpharmacyresidency.org




WEST LOS ANGELES

PGY1 Pharmacy

Accredited: ASHP



Affiliation: None





Educational/Special Requirements: Graduate of an accredited college of pharmacy, licensed or eligible for licensure in California, good communication skills required, resident will develop a project with targeted care outcomes and present at Annual Western

States Conference


Special Features: Hospital and ambulatory care experiences in the nation’s largest integrated care organization, preventive and disease state management in an integrated managed care setting, flexible program molded to resident’s interests


Michael Cinnamond, PharmD, Inpatient Pharmacy Director,

Residency Program Director

Kaiser Permanente Medical Care Program—West Los Angeles

6041 Cadillac Ave.


323.857.2044

323.857.2870 (fax) michael.d.cinnamond@kp.org



WEST LOS ANGELES





Affiliation: None





Educational/Special Requirements: Graduate of an accredited college of pharmacy, licensed or eligible for licensure in

California, good communication skills required, resident will develop a project with targeted care outcomes and present at

Annual Western States Conference

Fringe Benefits: Paid medical/dental/vision insurance, holidays, vacation/sick days

Special Features: The Kaiser Permanente West Los Angeles

Medical Center provides comprehensive inpatient, outpatient, and ambulatory care services to Kaiser Permanente members.

This residency program provides development and training for recently graduated pharmacists, with an emphasis on pharmaceutical care and leadership to a diverse community. This program will allow residents to become familiar with managed care pharmacy practice in an integrated health care program.


Giselle Willick, PharmD, Residency Program Coordinator

Kaiser Permanente Medical Care Program—West Los Angeles

Pharmacy Operations

6041 Cadillac Ave.


323.857.3381

323.857.2155 (fax) giselle.h.willick@kp.org

http://www.kaiserpharmacyresidency.org/


NORTH SACRAMENTO VALLEY AREA





Affiliation: Kaiser Permanente





Educational/Special Requirements: Graduate from an accredited school or college of pharmacy, PharmD preferred; must meet all qualifications of licensure in the state of California, must meet

Kaiser Permanente’s employee requirements; per the rules for the

Resident Matching Program, “This residency site agrees that no person at this site will solicit, accept or use any ranking-related information from any residency applicant.”

Fringe Benefits: 7 paid holidays, medical/vision/dental insurance, vacation/sick leave

Special Features: This program provides a unique learning opportunity for managed care pharmacy practice resident training. Our integrated health delivery system provides and coordinates the entire scope of inpatient and outpatient care for our members. Core experiences include direct patient care, business administration and management, population-based pharmaceutical care, and drug information. Residents participate on the P&T

Committee and are an integral part of the management team.

Professional and career development is encouraged throughout the residency.


Bonnie Matsuoka, Ambulatory Care Supervisor



Kaiser Permanente Medical Center

3240 Arden Way

Sacramento, CA 95825

916.486.5124

916.486.5106 (fax) bonnie.matsuoka@kp.org


■■ KAISER PERMANENTE NORTHWEST—

PORTLAND, OREGON

Pharmacy Practice With Emphasis in Managed Care

Accredited: No



Affiliation: None




Onsite Interview:

Educational/Special Requirements: PharmD preferred, eligible for Oregon and Washington licensure

Fringe Benefits: Health benefits, travel support to ASHP Midyear

Clinical Meeting and Western States Residency Conference

Special Features: Multidisciplinary collaborative drug therapy management including cardiovascular risk factor management, hypertension, diabetes, anticoagulation, depression, pain, and asthma; drug information; drug use management; formulary application; academic detailing; P&T Committee support; and research and teaching opportunities. Other opportunities include inpatient pharmacy, home infusion pharmacy, long-term care pharmacy, and outpatient pharmacies located in our medical offices.


Nancy Lee, Director of Clinical Pharmacy Services

Kaiser Permanente Northwest

5717 N.E. 138th Ave.

Portland, OR 97230

503.261.7570

503.261.7537 (fax)

Nancy.Louie.Lee@kp.org

■■ KAISER PERMANENTE OF GEORGIA





Affiliation: None





Educational/Special Requirements: PharmD preferred, eligible for Georgia licensure

Fringe Benefits: Medical/dental/vision benefits, holidays, vacation/sick leave

Special Features: Ambulatory care, acute care, drug information, and administration


Diane Erdman, PharmD, BCPS, CDE, Residency Program Director

Kaiser Permanente

750 Townpark Ln.

Kennesaw, GA 30144

770.514.5451

770.514.5493 (fax)

Diane.Erdman@kp.org

■■ KANSAS CITY VETERANS AFFAIRS MEDICAL CENTER





Affiliation: None





Educational/Special Requirements: PharmD, U.S. citizenship, college transcript, curriculum vitae, 3 letters of recommendation

Fringe Benefits: 13 days each of annual and sick leave, 10 paid federal holidays, professional leave, health insurance, paid staffing

Special Features: Special features include practical application of pharmacoeconomic principles to formulary management and outcomes evaluation; didactic pharmacoeconomic, leadership, and clinical lectures; quality assurance; and clinical duties.

Projects involve local, network, and national levels of the Veterans

Administration (VA) integrated health care system. As adjunct faculty of the UMKC School of Pharmacy, the resident will gain experience in didactic teaching and precepting of on-site students. Development of future leaders in managed care is a goal of the residency.


Lauri Witt, PharmD

Kansas City Veterans Affairs Medical Center

Pharmacy Department (119)

4801 E. Linwood Blvd.

Kansas City, MO 64128

816.861.4700 ext. 57423

816.922.3314 (fax) lauri.witt@med.va.gov



■■ KELSEY-SEYBOLD CLINIC/UNIVERSITY OF HOUSTON

PGY1 Pharmacy Practice Residency

Accredited: ASHP



Affiliation: University of Houston






Fringe Benefits: State of Texas benefits, 10 days vacation, support to attend AMCP, ASHP, and Texas Society of Health-

System Pharmacists’ conferences and either Alcalde or Mid-West

Residency Conference

Special Features: Ambulatory care focused, administrative and clinical responsibilities, collaborations with other University of

Houston residents


Natasha Jackson, Pharmacy Administrator of Clinical Services

Kelsey–Seybold Clinic

Pharmacy Administration

8900 Lakes at 610 Dr.

Houston, TX 77054

713.442.6248

713.442.5253 (fax)

Natasha.Jackson@kelsey-seybold.com

http://pharmacy.uh.edu/residency_program/

States. Marshfield Clinic serves more than 6,000 patients a day at

41 locations throughout northern, central, and western Wisconsin.

The Clinic has more than 700 physicians practicing in more than

80 specialties and subspecialties and employs some 5,500 support personnel. The Marshfield Clinic pharmacy system consists of a Clinical Pharmacy Services unit, Managed Care Pharmacy

Practice-Security Health Plan of Wisconsin, outpatient dispensing pharmacies, a 340(b) pharmacy, sterile product pharmacies, and an investigational drug program. A research project is a requirement of the residency program, and unique research opportunities exist at Marshfield Clinic in collaboration with nationally recognized thought leaders in pharmacogenomics and clinical informatics. Available rotations that may also offer research opportunities include community pharmacy, dermatology, drug information, internal medicine, managed care, outpatient cardiology, outpatient oncology/hematology, pediatric oncology/hematology, pharmacy management, quality improvement/care management, supply chain management, and the community health care/indigent drug program.


Sara Griesbach, Pharmacy Residency Program Director

Marshfield Clinic

1000 N. Oak Ave.

Marshfield, WI 54449

1.800.541.2895

715.387.5163 (fax) griesbach.sara@marshfieldclinic.org

http://www2.marshfieldclinic.org/education/residency/ residency_fellow/pharmacy/overview.asp

■■ MARSHFIELD CLINIC

Nonprofit Multispecialty Clinic

Accredited: Pre-candidate status



Affiliation:



Estimated Stipend: $40,000-$45,000

Onsite Interview:

Educational/Special Requirements: Graduate of an accredited school of pharmacy, curriculum vitae, application form, official college transcripts, 3 letters of recommendation, eligibility for

Wisconsin licensure

Fringe Benefits: See Salary/Benefits section of Marshfield Clinic

PGY-1 Web site

Special Features: Marshfield Clinic is a private, not-for-profit, multispecialty group practice dedicated to serving patients through accessible, high-quality health care, research, and education. Founded in 1916, Marshfield Clinic has become one of the largest fully integrated health care systems in the United

■■ MAXOR CORRECTIONAL PHARMACY


Accredited: Yes



Affiliation: Various universities





Educational/Special Requirements: Graduate of an accredited school of pharmacy, must obtain license before residency begins

Fringe Benefits: Matching 401K (up to 2.5%), full medical/ dental/vision benefits, training material and guidance for Board

Certification in pharmacotherapy specialty

Special Features: During your residency, you will be assigned to a client whom you will assist in providing the most cost-effective care.


Alexander Tunnell, Residency Director

Maxor Correctional Pharmacy

416 Mary Lindsay Polk Dr., Ste. 515



Franklin, TN 37067

440.808.8719

615.771.4580 (fax) alexander.tunnell@maxorcps.com

■■ MEDCO HEALTH SOLUTIONS, INC.





Affiliation: None





Educational/Special Requirements: BS or PharmD degree, eligibility for New Jersey licensure, managed care rotation or experience preferred, 3 letters of recommendation, curriculum vitae, letter of intent, transcript, on-site interview

Fringe Benefits: Paid vacation, holidays, sick day, 5 personal days, medical/dental/life insurance, paid travel/registration to professional meetings, leadership development training/education, paid NJ pharmacist licensure

Special Features: Medco’s residency is an organized PGY1 managed care pharmacy practice training program that focuses on development of the knowledge and skills that pharmacists need in order to assume leadership roles within a managed care practice setting. Residents will also have direct patient contact throughout the residency, with responsibility in the Medicare

Part D Medication Therapy Management Program. In addition to defined clinical, coverage management, and elective rotations, residents attend and present at a national P&T meeting and are exposed to legislative and regulatory aspects of pharmacy as well as innovative pharmacy models, automation, and information technology. Results of the resident’s research will be presented at a professional pharmacy conference. The resident will prepare a final manuscript suitable for submission for publication.


Doris Fishman, Executive Director, Clinical Therapeutics & Coverage

Appeals Management

Medco Health Solutions, Inc.

100 Parsons Pond Dr.

Mail Stop F2-3

Franklin Lakes, NJ 07417

201.269.6270

201.269.1035 (fax)

MedcoRProg@medco.com

■■ NOVARTIS PHARMACEUTICALS CORPORATION

Health Economics and Outcomes Research Fellowship

Accredited: No

Length of Program: 2 years

Number of Positions: 1-2 (the Rutgers’ program recruits on even years only)

Affiliation: Scott & White Health Plan/University of Texas at Austin, Rutgers University

Application Deadline: December 31




Educational/Special Requirements: Advanced degree in health services research, public health, health policy, pharmacy, economics, medicine, or other related areas, with some experience in outcomes research

Fringe Benefits: Medical insurance, vacation

Special Features: The fellows will gain familiarity with outcomes research principles/application and experience in designing research studies that examine economic, clinical, and humanistic outcomes. The first year is spent at the managed care institution, and the second year is spent with Novartis’s Evidence-Based

Medicine Department (Rutgers: both years at Novartis).


Helen Lau, MS, Assistant Director,

Health Economics & Outcomes Research, Evidence-Based Medicine

Novartis Pharmaceuticals Corporation

One Health Plaza

East Hanover, NJ 07936-1080

862.778.8883

973.781.2664 (fax) helen.j.lau@novartis.com

■■ OPTIMA HEALTH PLAN/SENTARA HEALTHCARE

Managed Care

Accredited: No



Affiliation: None





Educational/Special Requirements: PharmD from an accredited school of pharmacy or equivalent experience, on-site interview, eligible for Virginia licensure

Fringe Benefits: 2 weeks paid vacation, uninterrupted stipend during minor illness, health insurance plan, travel assistance for continuing education events and other professional activities

Special Features: The resident will have exposure to an integrated health care system and system-wide pharmacy services, including a Drug Information Center. The resident will have the opportunity to precept students from the Virginia

Commonwealth University and Hampton University Schools of

Pharmacy and work with medical residents from Eastern Virginia

Medical School.




Elizabeth Brusig, PharmD, Clinical Pharmacist

Optima Health Plan

4417 Corporation Ln.

Virginia Beach, VA 23464

757.552.7519

757.687.6231 (fax) elbrusig@sentara.com

http://www.sentara.com/Sentara/Employment/Pharmacy/Residency/

■■ ORTHO-MCNEIL JANSSEN SCIENTIFIC AFFAIRS, LLC

Drug Information

Accredited: No



Affiliation: Rutgers University (RU)



Estimated Stipend: Competitive, through RU


Educational/Special Requirements: None

Fringe Benefits: Yes, through RU

Special Features: Medical Information Fellowship Program


Seema Patel, Manager, Medical Communications

Ortho-McNeil Janssen Scientific Affairs, LLC

1000 Rte. 202 South

Raritan, NJ 08869

908.927.4545

908.927.3166 (fax) spatel60@omjus.jnj.com

http://pharmafellows.rutgers.edu/

■■ ORTHO-MCNEIL JANSSEN SCIENTIFIC AFFAIRS, LLC

Pharmaceutical Industry, Department of Outcomes Research

Accredited: No



Affiliation: Thomas Jefferson University


Starting Date: June 2009 (flexible)



Educational/Special Requirements:

Fringe Benefits:

Special Features: Fellows spend the first year of the program working on outcomes research projects in an academic setting and the second year in the pharmaceutical industry. Fellows have the opportunity to take coursework in biostatistics, epidemiology, economics, and other outcomes-related subjects.


Michael Durkin, Director, Outcomes Research

Ortho-McNeil Janssen Scientific Affairs, LLC

1125 Trenton-Harbourton Rd.

Titusville, NJ 08560

609.730.2867

mdurkin@omjus.jnj.com

■■ OUTCOMES PHARMACEUTICAL HEALTH CARE


Accredited: Candidate



Affiliation: University of Iowa





Educational/Special Requirements: Doctor of Pharmacy degree

(ACPE-accredited school), eligible for licensure in Iowa, curriculum vitae, 3 letters of recommendation, official copy of transcripts

Fringe Benefits: 80 hours PTO, health savings account (HSA), paid holidays, reimbursement for company-approved professional organizations/development and travel

Special Features: The Outcomes’ Clinical Services Residency

Program offers a unique learning experience on how pharmacists can impact the rising cost of health care by providing patient-oriented, care-based, medication therapy management

(MTM) services. Goals of this residency include account management, marketing and communication, pharmacoeconomic data collection and analysis, claims assessment, development and implementation of MTM program, development and implementation of research projects, training of pharmacists and support staff, and serving as a preceptor to PharmD clerkship students.


Jessica Frank, PharmD

Outcomes Pharmaceutical Health Care

601 E. Locust St., Ste. 200

Des Moines, IA 50309

515.237.0001

515.237.0002 (fax) jfrank@getoutcomes.com

■■ PERFORMRx





Affiliation: None








ACPE-accredited college of pharmacy, Pennsylvania pharmacist license or eligibility for licensure, completed application, letter of intent, curriculum vitae, 3 letters of recommendation, official college transcripts, on-site interview (by invitation)

Fringe Benefits: Benefits package including medical/dental/ vision, 10 days paid vacation, 5 personal days, paid holidays, funding available for attendance to professional meetings, tuition reimbursement available

Special Features: PerformRx is a pharmacy benefit management company dedicated to providing quality, cost-effective care to members of Medicaid and Medicare programs. Through managing this type of patient population, the resident is provided an ideal environment to develop expertise in the following areas: prior authorization, drug utilization review, health outcomes and disease management, formulary management, injectable drug management, pharmacy network management, new business implementation, and pharmacy call center services.


Andrew Maiorini

PerformRx

200 Stevens Dr.

Philadelphia, PA 19113

215.937.8565

215.937.5313 (fax) andrew.maiorini@performrx.com

PHARMACORR

Managed Care

Accredited: New program



Affiliation: St. Louis College of Pharmacy





Educational/Special Requirements: PharmD from an accredited school of pharmacy, Missouri license or eligibility for licensure, excellent communication skills, willingness to precept students, discipline to pioneer a path for future residents; resident will be expected to publish and complete a major project with presentation at the Midwest Pharmacy Resident’s Conference; program may be tailored for PGY1 or PGY2

Fringe Benefits: Comprehensive benefits including health/ dental/vision, meeting expenses, office space with laptop and

Blackberry, administrative support, no weekends/holidays or staffing

Special Features: This residency program will submerge the resident in the unique environment of correctional medicine and pharmacy. The resident will be integrated into the managed care

(Correctional Medical Services) and pharmacy (PharmaCorr) components of the organization. The resident will be precepted by an administrative team with several years of clinical and administrative pharmacy experience. Furthermore, with the support of executive leadership, the resident will be expected to improve and expand the role of clinical pharmacy services within correctional medicine.


Chris Shain, Director, Clinical Pharmacy Services

PharmaCorr

12647 Olive Blvd.

St. Louis, MO 63141

314.919.9711

314.919.8909 (fax) cshain@cmsstl.com

■■ PRESCRIPTION SOLUTIONS





Affiliation: None





Educational/Special Requirements: PharmD, licensed to practice in California

Fringe Benefits: 2 weeks paid vacation, paid holidays, professional leave to attend conferences, reimbursement for expenses from professional meetings

Special Features: Program involves clinical program development, formulary management, health outcomes research, client management, legal and regulatory affairs, industry relations, and specialty pharmacy. Residents will gain valuable experience in managed care by rotating through clinical program development, clinical formulary management, clinical/Part D analytics, clinical quality/compliance, client management, legal and regulatory affairs, industry relations, and specialty pharmacy. Residents will attend the ASHP Midyear Clinical Meeting,

California Society of Health-System Pharmacists Seminar, AMCP

Educational Conference, AMCP Annual Meeting, and Western

States Conference.


Heidi Lew, Director, Clinical Programs

Prescription Solutions

2300 Main St.

Mail Stop CA134-0404

Irvine, CA 92614

949.252.4305

949.474.4237 (fax) heidi.lew@rxsol.com

http://www.rxsolutions.com/b/residency/ www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 713


■■ REGENCERx





Affiliation: Regence BlueCross BlueShield





Educational/Special Requirements: Bachelor of Science degree in pharmacy or Doctor of Pharmacy degree from an ACPEaccredited college of pharmacy, licensed or eligible for licensure in Oregon, strong motivation to pursue a dynamic career in managed care pharmacy, interview required

Fringe Benefits: Health/dental/vision/life/disability insurance; vacation time; professional travel and stipend; no weekends or holidays; no staffing requirements in a pharmacy; commute expense reimbursement available for safe, convenient public transportation; membership available to 24-hour on-site fitness center

Special Features: RegenceRx is an internal pharmacy benefit program for Regence, a not-for-profit Blues plan that serves more than 4 million members. Regence is the largest affiliation of health care plans in the Pacific Northwest/Mountain region:

Asuris Northwest Health Regence (Washington based), Regence

BlueShield of Idaho, Regence BlueCross BlueShield of Oregon,

Regence BlueCross BlueShield of Utah, Regence BlueShield

(Washington), and Regence Life and Health (Oregon based). This residency will be primarily based in Portland, Oregon, headquarters for Regence. The resident will participate in the full array of pharmacy benefit management services offered by RegenceRx: author a medication monograph and class reviews, present to the Regence P&T Committee, develop medication coverage policies, provide academic detailing to community physicians, gain exposure to pharmacy contracting and data analysis, recommend coverage determinations while supporting the prior authorization and customer service units, and participate in medication therapy management program development and implementation.

Residents are prepared for careers in managed care, pharmacy benefit management, industry, or drug information. Regence is a nationally recognized pioneer of evidence-based medicine in managed care. Regence uses scientific evidence to guide medication coverage policies and safely promote medications that provide the most value. The RegenceRx clinical review/formulary process was adopted by the Academy of Managed Care Pharmacy and is now known as the AMCP Formulary Submission Process.


Sean Karbowicz, PharmD

RegenceRx

P.O. Box 1071

M/S 2P

Portland, OR 97207-1071

503.225.5367

888.437.1510 (fax) shkarbo@regence.com

■■ ROCHE

Drug Information

Accredited: No



Affiliation: None




Onsite Interview: Upon invitation

Educational/Special Requirements:


Special Features: The purpose of the Roche Drug Information specialty residency is to prepare those interested in the pharmaceutical industry with grounding in industry-based drug information practice. Residents receive intensive, experiential training in drug information practice including: working in a contact center, developing medical response databases, using sophisticated informatics technology, implementing service quality metrics, leading change, and so forth. Longitudinal experience includes working with drug safety, marketing, pharmacoeconomics/outcomes research, regulatory affairs, and others. In addition, a 5-week rotation in an academic Drug Information Center provides the resident with the requisite skills to conduct drug use evaluations, prepare formulary packages for P&T Committees, and so forth.


Mona Gandhi, Residency Program Director

Roche

340 Kingsland St.

Nutley, NJ 07110

973.562.5549

973.562.2866 (fax)

Mona.gandhi@roche.com

■■ RUTGERS UNIVERSITY/HORIZON BLUE CROSS

BLUE SHIELD OF NEW JERSEY

Managed Care Organization

Accredited: No



Affiliation: Ernest Mario School of Pharmacy/

Horizon Blue Cross Blue Shield





Educational/Special Requirements: PharmD, eligible for New

Jersey state licensure



Fringe Benefits: Full medical coverage, dental and retirement benefits, paid holidays, vacation, sick leave, travel expenses to

AMCP national meeting

Special Features: No weekend or staffing requirements, mandatory teaching and precepting, graduate courses offered at Rutgers

University, industry and PBM perspectives of managed care.

Residents will be trained to be an integral part of the formulary management, P&T process, evaluation of drug literature and utilization review, medical and pharmacy policies development, support disease state management programs, medication therapy management for Medicare Part D members, benefit design, new technologies, and research projects. Residents will play an active role in the pharmacy department at Horizon Blue Cross Blue

Shield of New Jersey. Residents will also get a good industry and

PBM perspective of managed care through routine business meetings and collaborative projects. Other required activities include teaching and precepting at Rutgers Pharmacy School and presentation of research at the Spring AMCP national meeting.


Saira A. Jan, Associate Professor, Rutgers University; Director,

Pharmacy Management at Horizon BCBSNJ

Rutgers University/Horizon Blue Cross Blue Shield of NJ

Three Penn Plaza East

PP-13Q

Newark, NJ 07105

973.466.4575

973.466.6266 (fax) saira_jan@horizon-bcbsnj.com

http://www.horizonblue.com

■■ SCOTT & WHITE HEALTH PLAN

Managed Care (nonprofit)

Accredited: No



Affiliation: College of Pharmacy, The University of

Texas at Austin

Application Deadline: February 1 (early January preferred)


Estimated Stipend: $36,346-$43,057, depending on prior practice experience or previous residency


Educational/Special Requirements: PharmD, eligible for Texas state licensure

Fringe Benefits: Fully paid medical/dental coverage, expenses covered for attendance at 2 national and 1 regional meeting(s),

2 weeks paid vacation

Special Features: Teaching, preceptoring, research, retrospective pharmacy claims database analysis, industry and PBM managed care perspectives, marketing and sales exposure, participation in formulary and drug policy decision processes at a 200,000-member nonprofit staff-model HMO


Paul Godley, PharmD, or Barry Browne, PharmD,

Pharmacy Managed Care Residency Program Directors

Scott & White Health Plan

Pharmacy Administration Offices

4236 Lowes Dr.

Temple, TX 76502

254.298.6143 (Dr. Godley) or 254.724.5287 (Dr. Browne)

254.724.1731 (fax) pgodley@swmail.sw.org or babrowne@swmail.sw.org

■■ RUTGERS—ERNEST MARIO SCHOOL OF PHARMACY

(EMSOP)

Pharmaceutical Industry Fellowship

Accredited: N/A

Length of Program: 12-24 months


Affiliation: Ernest Mario School of Pharmacy


Starting Date:

Estimated Stipend:

July 1


Educational/Special Requirements: PharmD


Special Features:


James Alexander, Director

Rutgers, EMSOP

160 Frelinghuysen Rd., Rm. 405

Piscataway, NJ 08854

732.445.5215

ifellows@rci.rutgers.edu

■■ SELECTHEALTH (A SERVICE OF

INTERMOUNTAIN HEALTHCARE)





Affiliation: None



Estimated Stipend: Approximately $47,000


Educational/Special Requirements: Graduate from an ACPEaccredited pharmacy program with a doctor of pharmacy degree with a minimum GPA of 3.0 on a 4.0 scale, must obtain Utah pharmacist licensure within the first 60 days of the program

Fringe Benefits: Health/dental/life insurance, staff discounts,

10 days vacation leave, 10 holidays www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 715


Special Features: Travel benefits to either the ASHP Midyear

Clinical Meeting or the AMCP Educational Meeting and the

Western States Conference


Jeffrey Dunn, Formulary and Contract Manager

SelectHealth (formerly known as IHC Health Plans)

4646 W. Lake Park Blvd., Ste. N3

Salt Lake City, UT 84120

801.442.7984

801.442.3006 (fax) jeffrey.dunn@selecthealth.org

http://www.selecthealth.org


Christie Barreuther, RPh

Southern Arizona Veterans Administration Health Care System

3601 S. Sixth Ave.

Pharmacy Service 5-119

Tucson, AZ 85723

520.792.1450 ext. 5388

520.629.4700 (fax) christine.barreuther@va.gov

http://www.tucson.va.gov/careers/Pharmacy_Residency_Program.asp

■■ SOUTHERN ARIZONA VETERANS ADMINISTRATION

(VA) HEALTH CARE SYSTEM

PGY1 Pharmacy Practice

Accredited: ASHP-accredited since 1984



Affiliation: University of Arizona, Midwestern

University—Glendale, University of

Southern Nevada, Creighton University,

Western University



Estimated Stipend: $38,257 plus benefits

Onsite Interview: Interview required, on-site preferred

Educational/Special Requirements: Curriculum vitae, 3 letters of recommendation, college transcripts, 1 writing sample, U.S. citizenship

Fringe Benefits: Residents accumulate 13 days of paid vacation time during the residency year. Sick leave is accrued at the rate of

4 hours every 2 weeks. Educational leave is provided to attend the

Arizona Pharmacy Alliance Annual Meeting, the ASHP Midyear

Clinical Meeting, and the Western States Conference for pharmacy residents, fellows, and preceptors. Travel funds are available to offset some of the expenses for these educational meetings.

Residents have access to the same medical plans that are offered to full-time employees of the VA, including a wide range of HMO and preferred provider organization (PPO) health plans. Tucson also has a wide range of outdoor activities and excellent weather year round.

Special Features: This comprehensive residency includes a balance of inpatient and outpatient clinical pharmacy experiences.

Residents work in the areas of internal medicine, cardiology, neurology clinics, primary care, geriatrics, hospice, surgery/ nutritional support, mental health, practice management, drug use evaluation, P&T Committee activities, drug literature evaluation, drug policy development, teaching, research, and enhancing communication abilities. Two months of elective experience are available.

■■ TENNESSEE PHARMACISTS ASSOCIATION

Health Policy and Outcomes Research

Accredited: No



Affiliation: Tennessee Pharmacists Research &

Education Foundation

Application Deadline: March 15




Educational/Special Requirements: PharmD, licensed in

Tennessee

Fringe Benefits: 100% health care benefits provided, 401K, travel/ meeting support, professional liability, 2 weeks vacation, parking

Special Features: In addition to health policy and experience in outcomes research, the resident will also gain experience in association management, MTM delivery and support, and payer systems.


Denise Barker, Director of Professional Practice

Tennessee Pharmacists Association

500 Church St., Ste. 650

Nashville, TN 37219

615.256.3023

615.255.3528 (fax) tpa@tnpharm.org

http://www.tnpharm.org

■■ TEXAS HEALTHSPRING

Managed Care

Accredited: No, but intend on seeking



Affiliation: University of Houston







Educational/Special Requirements: Graduate of accredited school of pharmacy, PharmD preferred, eligible for Texas licensure, application, curriculum vitae, 3 professional letters of recommendation

Fringe Benefits: Health/dental/vision/life/disability benefits,

PTO, holidays, conference travel

Special Features: The residency focuses on the development of the knowledge and skills that pharmacists need in order to assume leadership roles within a managed care organization.

Residents will gain a clinical and administrative perspective of the roles and responsibilities of a health care professional within a health plan. Residency activities include: development and administration of a research project, formulary development, participation in medication therapy management, involvement in the legislative and regulatory aspects of managed care pharmacy, development of drug policies and drug monographs, exposure to quality guidelines and initiatives to improve health outcomes, and pharmacy benefit management. Additionally, residents will have the opportunity to develop expertise in the following areas: prior authorizations, medication counseling, claims adjudication, drug utilization reviews, and overall pharmacy operations.


Annie Rakoczy, Clinical Pharmacy Manager

Texas HealthSpring

2900 N. Loop West, Ste. 1300

Houston, TX 77092

615.565.8110 ext. 8796

615.291.7025 (fax) annie.rakoczy@healthspring.com

http://www.healthspring.com

■■ UMASS CLINICAL PHARMACY SERVICES





Affiliation: University of Massachusetts Medical

School





Educational/Special Requirements: PharmD degree, eligibility for licensure in Massachusetts, valid drivers license, letter of intent including goals, college transcripts, curriculum vitae, 3 letters of recommendation, personal on-site interview

Fringe Benefits: Health/dental/vision/disability/life insurance, earned time accrual for vacation, state/federal holidays, office space with computer, travel/conference allowance (ASHP Midyear

Clinical Meeting, AMCP Conference)

Special Features: After orientation to the department, the resident will begin a series of longitudinal rotations and other activities designed to meet the goals and objectives of the

Commonwealth Medicine Managed Care Pharmacy Residency

Program. The resident will work with multiple program directors and clinical pharmacists to gain a thorough understanding of clinical medication management and cost-containment strategies.

Activities will include preparing and presenting monographs for medication/class reviews, participating in the planning and rollout of clinical pharmacy initiatives, and precepting pharmacy students on clinical rotations.


Karen Lee, Associate Director for Professional Development

Commonwealth Medicine

UMass Clinical Pharmacy Services

333 South St.

Shrewsbury, MA 01545

508.856.4545

877.208.7428 (fax)

Karen.Lee@umassmed.edu

http://www.umassmed.edu/cps

■■ UMASS CLINICAL PHARMACY SERVICES

Fellowship in Health Outcomes and Pharmacoeconomics

Research

Accredited: No



Affiliation: University of Massachusetts

Medical School

Application Deadline: January 15 (every other year)

Starting Date: July 1 (every other year)



Educational/Special Requirements: PharmD degree, eligibility for licensure in Massachusetts, valid drivers license, letter of intent including goals, college transcripts, curriculum vitae, 3 letters of recommendation, personal on-site interview

Fringe Benefits: Health/dental/vision/disability/life insurance, earned time accrual for vacation, state/federal holidays, office space with computer, travel/conference allowance (ASHP Midyear

Clinical Meeting, AMCP Conference)

Special Features: The Fellowship in Health Outcomes and

Pharmacoeconomics Research provides a 2-year opportunity for the fellow to engage in highly individualized training in the scientific processes governing quality research conducted in both managed care and ambulatory care settings.




Karen Lee, Associate Director for Professional Development

Commonwealth Medicine

UMass Clinical Pharmacy Services

333 South St.

Shrewsbury, MA 01545

508.856.4545

877.208.7428 (fax)

Karen.Lee@umassmed.edu

http://www.umassmed.edu/cps

■■ UNITEDHEALTH PHARMACEUTICAL SOLUTIONS

Managed Care Pharmacy With Emphasis on Data Analytics and Strategic Development

Accredited: No



Affiliation: N/A

Application Deadline: January 10 or until filled


Estimated Stipend: $48,000*

Onsite Interview: Strongly preferred

Educational/Special Requirements: PharmD and eligibility for pharmacy licensure in Minnesota required, experience in a community pharmacy setting an asset; a second-year specialty residency will be considered for individuals who have completed a general practice residency (with stipend adjustment)

Fringe Benefits: 15 days paid time off (including sick/vacation leave), paid holidays, reimbursement to attend the AMCP

Educational Conference or Annual Meeting, on-site fitness center,

*stipend adjusted because resident is responsible for procurement of own health insurance

Special Features: Gaining experience with the second-largest commercial insurer in the nation, this residency is an ideal opportunity for future MBA study. The residency will focus on pharmacy analytics and strategic planning as related to prescription product tiering. The resident will work with a leading analytic team to develop and present analyses that measure patterns of medication use and outcomes using claims data, assist with evaluation of pharmacoeconomic and clinical data, mentor pharmacy students, support integration of acquisitions/mergers, and drive fact-based and data-driven decisions.


Lida Etemad, PharmD, MS, Senior Director, PDL Development

UnitedHealth Pharmaceutical Solutions

5901 Lincoln Dr.

MN012-S234

Edina, MN 55436

952.992.5882

952.992.7266 (fax) lida_etemad@uhc.com

■■ UNIVERSITY AT BUFFALO

Ambulatory Care

Accredited: Pending



Affiliation: University

Application Deadline: October 1

Starting Date: January 1



Educational/Special Requirements: PharmD or equivalent experience required

Fringe Benefits: Health/dental/vision insurance, paid vacation, conference travel funds

Special Features: Unique experience designed to further refine skills in pharmaceutical care in addition to developing skills in program development as well as personnel and resource management. The resident is involved in coordination of clinical activities in a high-volume lobby-based pharmacy and a health clinic– based ambulatory care pharmacy. The resident will participate in medication histories, adherence counseling, and education programs. Development and implementation of disease management initiatives, patient education, and medical informatics as well as supervision of PharmD students are also significant aspects. This residency will allow ample latitude for the resident to explore interests and further develop skills as a practitioner. The resident will also be appointed as a Clinical Instructor at the University of

Buffalo, School of Pharmacy and Pharmaceutical Sciences.


Ed Bednarczyk, PharmD

University at Buffalo

School of Pharmacy and Pharmaceutical Sciences

311 Hochstetter Hall

Buffalo, NY 14260

716.645.2828

716.645.2886 (fax) eb@buffalo.edu

■■ UNIVERSITY OF ILLINOIS AT CHICAGO &

WALGREENS HEALTH INITIATIVES

Fellowship—Outcomes Research

Accredited: No



Affiliation: University of Illinois & Walgreens

Health Initiatives





Educational/Special Requirements: PharmD or MD (or equivalent), completed pharmacy practice or managed care residency



Fringe Benefits: Yes

Special Features: This is a 2-year fellowship jointly offered by Walgreens Health Initiatives and the Center for Pharmacoeconomic Research at the University of Illinois at Chicago. The aim of the program is to train clinical pharmacists to conduct research in drug therapy outcomes and pharmacoeconomics in the managed care setting. Knowledge and experience will be gained in the use of research tools to evaluate economic, humanistic, and clinical outcomes of drug therapy. Presentation and publication of research findings in peer-reviewed venues is expected. The fellowship is designed to facilitate career opportunities in managed care, health provider organizations, consulting, academia, or the pharmaceutical industry.


Glen Schumock, PharmD, MBA

University of Illinois at Chicago

Center for Pharmacoeconomic Research

833 S. Wood St.

MC 886

Chicago, IL 60612

312.996.7961

312.996.2754 (fax) schumock@uic.edu

http://www.uic.edu/pharmacy/research/cpr/

■■ UNIVERSITY OF MARYLAND SCHOOL OF PHARMACY/

CAREFIRST BLUECROSS BLUESHIELD


Accredited: No



Affiliation: CareFirst BlueCross BlueShield of Maryland


Starting Date: July 1 (flexible)



Educational/Special Requirements: Graduate degree in pharmacy

Fringe Benefits: Health insurance, parking, support for national meeting attendance and poster presentation

Special Features: Appointment as a Clinical Instructor at the

University of Maryland School of Pharmacy, Ambulatory Care

Clinics at HMO; office with computer/references at managed care organization. University of Maryland is an AA/EEO/ADA employer. Minorities and women are encouraged to apply.


Catherine Cooke, Clinical Associate Professor

University of Maryland School of Pharmacy

5106 Bonnie Branch Rd.

Ellicott City, MD 21043

410.480.5012

410.480.5012 (fax)

Rxservices@hotmail.com

http://www.pharmacy.umaryland.edu/pps/residents

■■ UNIVERSITY OF TEXAS MEDICAL BRANCH (UTMB)

CORRECTIONAL MANAGED CARE

PGY1 Pharmacy Residency Program With Emphasis in

Managed Care

Accredited: ASHP



Affiliation: UTMB





Educational/Special Requirements: Pharmacy degree from an accredited college of pharmacy, Texas or eligible for Texas licensure

Fringe Benefits: UTMB is an AA/EO employer; closed major holidays and weekends; generous vacation, holiday, and sick leave; competitive benefits

Special Features: Program strengths include automated technology, telemedicine technology, ambulatory care, and managed care


Stephanie Zepeda, Director of Pharmacy

UTMB Correctional Managed Care

2400 Avenue I

Huntsville, TX 77340

936.437.5363

936.437.5311 (fax) sdzepeda@utmb.edu

http://www.utmb.edu/cmc

■■ UNIVERSITY OF PITTSBURGH MEDICAL CENTER

(UPMC) HEALTH PLAN





Affiliation: UPMC Health System, University of

Pittsburgh School of Pharmacy




Onsite Interview: Preferred

Educational/Special Requirements: Completed Doctor of

Pharmacy degree, eligible for Pennsylvania licensure, pharmacy practice residency recommended but not required, letter of intent, curriculum vitae, college transcript, list of references (3) with contact information, 3 letters of recommendation submitted separately www.amcp.org Vol. 14, No. 7 September 2008 JMCP Journal of Managed Care Pharmacy 719


Fringe Benefits: Health/dental/eye care/life/disability insurance available, vacation time allotted, professional travel and stipend available, no weekends or holidays, no staffing requirements in a pharmacy

Special Features: UPMC Health Plan is owned by the UPMC, which is one of the nation’s top-ranked health systems. The

Health Plan covers commercial, Medical Assistance, and Medicare populations. UPMC Health Plan has integrated resources from

Community Care Behavioral Health, University of Pittsburgh

School of Pharmacy, as well as UPMC Health System. UPMC

Health Plan provides access to the complete health management of plan members (i.e., inpatient admissions, outpatient laboratory values, diagnosis, and so forth). Residency experience will include: drug utilization review criteria development and review, clinical intervention activities, P&T monograph development and presentation, formulary management, policy development, medication therapy management protocol development and review, research project for publication, and development of educational programs for the Health Plan staff. Residents will have the opportunity to do an off-site PBM rotation. Additionally, the resident will participate in student instruction through the University of

Pittsburgh School of Pharmacy.


Jessica Daw, Clinical Pharmacy Specialist

UPMC Health Plan

Two Chatham Center, 17th Fl.

112 Washington Pl.

Pittsburgh, PA 15219

412.454.7822

412.454.5295 (fax) dawjr@upmc.edu

■■ VA CINCINNATI MEDICAL CENTER

PGY1 Pharmacy

Accredited: ASHP



Affiliation: None






Fringe Benefits: Vacation, paid holidays, sick days, administrative time off for selected meetings

Special Features: This pharmacy residency provides experience in both acute care and outpatient primary care while allowing for a variety of elective experiences as well. The pharmacy resident will work under a collaborative practice agreement with a medical team to facilitate achievement of therapeutic goals through evidence-based disease state management. The resident will have learning experiences in critical care, internal medicine, practice management, drug policy development, education, and teaching.

Upon completion of this residency program, the pharmacy resident will have achieved advanced practice skills that will enable the graduate to feel confident to function effectively in multiple health care environments and roles. The resident will also receive a teaching certificate from the University of Cincinnati College of

Pharmacy.


Jo-Ann Caudill, Residency Program Director

Department of Veterans Affairs Medical Center

3200 Vine St.

Pharmacy 119

Cincinnati, OH 45220

513.475.6322

513.475.6981 (fax)

Jo-Ann.Caudill@va.gov

■■ VA PHOENIX HEALTH CARE SYSTEM


Accredited: Pre-candidate application



Affiliation: University of Arizona, Drake University,

University of Washington




Onsite Interview: Interview required, on-site preferred

Educational/Special Requirements: PharmD degree from an accredited school of pharmacy, U.S. citizenship, valid pharmacy license, personal statement, curriculum vitae, academic transcripts, 3 letters of recommendation

Fringe Benefits: The resident accumulates 13 days of paid vacation and 10 days of paid federal holidays during the residency year. Sick leave is accrued at the rate of 4 hours every 2 weeks.

Tuition and travel funds are available to offset the expenses of educational meetings. The resident has access to the same health care plans offered to full-time employees of the VA, including a wide range of HMO and PPO health plans. Free parking is provided.

Special Features: Exposure to local, regional, and national pharmacy benefit management activities, opportunity to develop skills necessary for applying pharmacoeconomic principles to health policy decisions, experience using a data warehouse and performing outcomes research


Michelle Wilhardt, Clinical Specialist, Pharmacoeconomics

Phoenix VA Health Care System

650 E. Indian School Rd. (119)

Phoenix, AZ 85012

602.277.5551 ext. 6753



602.212.2053 (fax) michelle.wilhardt@va.gov

http://www.phoenix.va.gov

■■ VA SAN DIEGO HEALTHCARE SYSTEM





Affiliation: University of the Pacific School of Pharmacy





Educational/Special Requirements: PharmD plus first-year residency or equivalent experience, U.S. citizenship, personal statement, curriculum vitae, transcripts, 3 letters of recommendation

Fringe Benefits: 2 weeks vacation, health care benefits, free parking, $6,000 in paid tuition and travel to required events, office with up-to-date computer systems, paid administrative leave for conferences and educational events

Special Features: This second-year residency will provide the skills necessary for the practical application of pharmacoeconomic principles to formulary management and outcomes research in integrated health care systems. Education will include formal pharmacoeconomics training classes and hands-on application of principles. Work activities will encompass the Veterans

Affairs San Diego Healthcare System, Veterans Integrated Service

Network 22 (VISN 22) Pharmacy Benefits Management (i.e.,

Southern California Regional VA), and VA National Formulary tasks. Out-of-state and in-state travel is required. This is a university-affiliated, teaching, integrated health care system with

100% computerized medical records, cutting-edge patient safety, pharmacy-managed clinics, pharmacist specialty practices, and a dedicated Pharmacy Health Outcomes Division with 4 full-time pharmacoeconomists. The pharmacy service has outstanding leadership with a long positive track record for innovation and excellence at the local, state, and national level and a well-trained, well-published staff, most with residencies. This is an exciting opportunity to learn and start your career.


Melissa Christopher, PharmD, Director,

Pharmacoeconomics & Formulary Management

VA San Diego Healthcare System

Pharmacy Service (119)

3350 La Jolla Village Dr.

San Diego, CA 92161

858.552.8585 ext. 2783

858.552.4369 (fax)

Melissa.Christopher@va.gov

http://www.san-diego.med.va.gov

■■ VA SIERRA PACIFIC NETWORK (VISN 21)





Affiliation: University of Nevada, Idaho State

University






ACPE-accredited college or school, completion of a PGY1 residency or equivalent experience, current pharmacy licensure in any state, U.S. citizenship, academic transcript, letter of intent,

3 letters of recommendation, curriculum vitae

Fringe Benefits: Health/dental benefits, 13 days vacation,

13 days sick leave, 10 holidays, paid tuition and travel to approved events, office with up-to-date computer systems, paid administrative leave for conferences and educational events

Special Features: This progressive program is designed to teach the knowledge, skills, and abilities necessary to provide population-based care using an extensive data warehouse, formulary management techniques, metrics and performance measures, pharmacoeconomics, and health outcomes in 6 integrated VA health care systems with over 200,000 patients. Collaboration with pharmacoeconomic pharmacists, database managers, and clinical program coordinators from these sites provides formulary management and evidence-based care to our veteran population.

The VA Sierra Pacific Network (VISN 21) includes 6 VA Medical

Centers in Northern California, Northern Nevada, and Hawaii.

Each facility offers primary, secondary, and tertiary care from multiple community-based outpatient clinics as well as complex and large inpatient hospitals. All facilities are affiliated with academic programs and universities in their geographic areas.

The PBM is located in Reno, Nevada, with opportunities to work throughout VISN 21 and with the data warehouse managers, pharmacy clinicians, physician staff, and facility administrators.

This is a multisite program coordinating and managing quality and economic pharmacy programs for 6 large medical centers providing care to over 200,000 veterans in a large geographic area. Components of the program are coordinated through virtual learning, communication, and computer techniques. The resident will also be encouraged to have a longitudinal clinical practice site.




Jannet Carmichael, PharmD, BCPS, FCCP,

VISN 21 Pharmacy Executive

VA Sierra Pacific Network (VISN 21)

Pharmacy Benefits Management Group

1000 Locust St., 10N21R

Reno, NV 58502

775.328.1279

775.328.1400 (fax) jan.carmichael@va.gov

■■ WALGREENS HEALTH INITIATIVES





Affiliation:





Educational/Special Requirements: PharmD from an ACPEaccredited school of pharmacy

Fringe Benefits: Medical plan, 2 weeks vacation, holidays, professional meeting travel and membership

Special Features: This managed care pharmacy residency program is designed to allow residents to work within the various clinical departments of a pharmacy benefits management firm including, but not limited to, care management, drug use policy,

PBM operations, clinical sales, and specialty pharmacy. Residents will gain practical experience and develop skills related to disease management, health outcomes, medication management strategies, formulary management, drug utilization review, drug information, and other clinical services. Additionally, residents will have the opportunity to be involved in professional organizations and precept to pharmacy students.


Judith Sommers-Hanson, Manager Clinical Education and

Shared Faculty

Walgreens Health Initiatives

1415 Lake Cook Rd.

MS# L444

Deerfield, IL 60015

847.964.8331

847.374.2669 (fax) judith.sommers-hanson@walgreens.com

■■ WELLPOINT NEXTRx





Affiliation: Blue Cross of California, PrecisionRx,

University of Southern California





Educational/Special Requirements: PharmD from an ACPEaccredited college of pharmacy or equivalent experience, eligible for California licensure, good academic standing, excellent written and verbal communication skills

Fringe Benefits: Health insurance; 2 weeks paid vacation; paid holiday and sick days; attendance at the Western States

Conference, a national pharmacy organization meeting, and a

WellPoint NextRx National P&T meeting

Special Features: The program is designed to provide the resident with an overall managed care experience. The resident rotates through several areas within the PBM including: drug information, therapy management, senior- and state-sponsored business, prior authorization centers, mail order pharmacy, clinical analytic strategies, and pharmaceutical contracting and industry relations. The program also includes rotations at Blue Cross of California health plan and University of Southern California direct patient care sites.


Niraj Sharma, Clinical Pharmacy Resident

WellPoint NextRx

8407 Fallbrook Ave.

MS CAAF01-0007

West Hills, CA 91304

818.313.5084

818.313.5110 (fax) niraj.sharma@wellpoint.com



■■ XCENDA

Health Outcomes Research Fellowship

Accredited: No



Affiliation: University of South Florida, College of

Public Health





Educational/Special Requirements: PharmD or equivalent

(residency preferred)

Fringe Benefits: Competitive salary, health insurance, vacation,

401K, tuition for required classes, travel expenses to 1 national meeting per year

Special Features: This 2-year, degree-granting fellowship provides a unique research and education experience in an outcomes consulting environment. Research activities include, but are not limited to: quality improvement programs, database analysis, economic modeling, and development of research-based manuscripts. In addition, the fellow will obtain a MSPH or MPH degree from the University of South Florida, College of Public Health.


James H. Jackson IV, PharmD, MPH, Senior Director

Xcenda

4114 Woodlands Pkwy., Ste. 500

Palm Harbor, FL 34685

727.771.4100

727.771.4145 (fax) jay.jackson@xcenda.com

http://www.xcenda.com


Issue

volume fourteen • number seven

September 2008

The Scout Sculpture Overlooking Kansas City

Richard Cummins

Editorial Policy

Author Guidelines

Sources and Types of Discrepancies Between Electronic Medical

Records and Actual Outpatient Medication Use

Prevalence and Humanistic Impact of Potential Misdiagnosis of

Bipolar Disorder Among Patients With Major Depressive Disorder in a Commercially Insured Population

2008: A Tipping Point for Disease Management?

New Agents in the Management of Type 2 Diabetes: Do They Provide an Opportunity for a Shift in the Treatment Paradigm?

The Benefits and Risks of New Therapies for Type 2 Diabetes

Diabetes Drug Therapy – First Do No Harm

Rethinking the “Whodunnit” Approach to Assessing the Quality of Health Care Research – A Call to Focus on the Evidence in

Evidence-Based Practice

Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference

Managed Care Pharmacy Residencies,

Fellowships, and Other Programs

Related documents

Products

Support

Issue

volume fourteen • number seven

September 2008

The Scout Sculpture Overlooking Kansas City

Richard Cummins

Editorial Policy

Author Guidelines

Sources and Types of Discrepancies Between Electronic Medical

Records and Actual Outpatient Medication Use

Prevalence and Humanistic Impact of Potential Misdiagnosis of

Bipolar Disorder Among Patients With Major Depressive Disorder in a Commercially Insured Population

2008: A Tipping Point for Disease Management?

New Agents in the Management of Type 2 Diabetes: Do They Provide an Opportunity for a Shift in the Treatment Paradigm?

The Benefits and Risks of New Therapies for Type 2 Diabetes

Diabetes Drug Therapy – First Do No Harm

Rethinking the “Whodunnit” Approach to Assessing the Quality of Health Care Research – A Call to Focus on the Evidence in

Evidence-Based Practice

Abstracts From Professional Poster Presentations at AMCP’s 2008 Educational Conference

Managed Care Pharmacy Residencies,

Fellowships, and Other Programs

Related documents

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