MedBiquitous Annual Conference
April 9, 2013
Genesis of the ER/LA Opioid Analgesic REMS
Linda Kitlinski, Senior Director
Clinical Development & Medical Science Department, Endo
Co- Chair, CE Sub-team of the REMS Program Companies (RPC)
A REMS is…
•A risk management plan that the FDA has
determined is necessary to ensure that
the benefits of a drug outweigh the risks
of the drug.
http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/FDCAct
ChapterVDrugsandDevices/default.htm. Accessed March 15, 2013.
REMS Program Company (RPC) Members*

Apotex, Inc.

Purdue Pharma, L.P.

Endo Pharmaceuticals, Inc.

Ranbaxy Pharmaceuticals, Inc.

Impax

Rhodes Pharmaceuticals, L.P.

Janssen Pharmaceuticals, Inc.

Roxane Laboratories, Inc.

Mallinckrodt, Inc. (Covidien)

Sandoz, Inc.

Mylan Technologies, Inc.

The PharmaNetwork, LLC

Noven Pharmaceuticals, Inc.

VistaPharm, Inc.

Par Pharmaceuticals

Watson Laboratories

Pfizer, Inc.
* Updated March, 2013

Intersection of two major public health crises
 Opioid misuse & abuse, resulting in injury & death, has emerged as
major public health problem1
 Morbidity, mortality, disability & costs of pain for >116 million
Americans2

Broad impact of ER/LA Opioid Analgesic REMS
 1.4 million prescribers/potential prescribers in DEA registration
database
  320,000 active prescribers (wrote  1 ER/LA opioid Rx in 12 mo.)
 >4 million unique patients


First use of accredited CE for delivering REMS education
Collaboration among all stakeholders critical for success
1
2
http://www.fda.gov/downloads/drugs/drugsafety/informationbydrugclass/
ucm277916.pdf.
IOM (Institute of Medicine). 2011. Relieving Pain in America: A Blueprint for Transforming
Prevention, Care, Education & Research. Washington, DC:The National Academies Press.
FDA Opioid REMS
meeting with
Industry
(May 2011)
Public meeting with
IWG
(Dec 2009)
Letters to Sponsors
that REMS is
required (Feb 2009)
Stakeholder
meetings
(Apr 2009)
RPC Grants
Approved
(Jan 2012)
CE Blueprint in
Fed Reg
(Nov 2011)
Advisory Committee
meeting
(Oct 2010)
RPC CE RFAs
(Aug-Nov 2013)
' 09
Q1
2009
Q2-Q3
2009
Q4
2009
Q1
2010
Q2
2010
Q1
2011
Q2-3
2011
Q4
2011
Advisory Committee
meeting
(Jul 2010)
Q1-3
2012
Q4 2012Q1 2013
' 13
ER/LA Opioid
REMS approval
(w/final
Blueprint) (July
2012)
REMS letter to
Sponsors
(Apr 2011)
Sponsor meeting
(May 2009)
Public meeting of
"Interested Parties"
Q3-4
2010
Sponsors submit
proposed REMS
(Aug 2011)
MedBiq Working
Group Formed
(July 2012)
First REMS
CE (2/28/2013)
MEMS Specs &
Implementation
Guide (Feb 2013)


First time accredited CE utilized for REMS “training”
Central component of the ER/LA Opioid REMS is voluntary education for
DEA-registered prescribers delivered through accredited CE
 RPC provides educational grants to accredited providers who develop/provide the CE
 ACCME & other Accreditors’ standards already provide effective framework for assuring
independence of REMS CE
 The education must be provided at no cost, or nominal cost, to participants


Unprecedented opportunity for CE to positively impact patient safety and
public health
Unparalleled engagement among REMS stakeholders
 CE Community, FDA, RPC, HCPs, Professional Organizations, Patient & Consumer
Advocacy Groups, Pain & Addiction Treatment Communities, Government Agencies, etc.

Leadership & insights of Accreditors/Conjoint Committee on CME have
provided invaluable guidance to FDA & RPC on operationalizing the REMS

Utilizing CE for REMS “training” is a new paradigm
 Must adhere to FDA statutory/regulatory requirements, as well as the standards
for commercially-supported accredited CE
 Potential for confusion/misinterpretation because of differences in Regulatory vs
CE nomenclature

REMS Education Conundrum:
ACCME
= =
CE Providers
FDA
RPC
=
Continuing Education

REMS Success
Reflected in
Outcomes
(Misuse, abuse)
Uniform data set & collection system needed to aggregate data from
numerous Providers/Accreditors for FDA reporting
Opportunity
It is a Critical Time…
US healthcare is at a crossroads
Accredited CE is being asked to
provide solutions.
Opportunity for CE to address the
professional practice gaps of
learners.
CE is Effective…
Continuing education
is effective in assisting
professionals to modify
and improve their
practice
stakeholders…
Flashback….
Conjoint Committee on CME
November 2007 Summit
A new stakeholder…
ER/LA Opioid Analgesics Risk Evaluation and
Mitigation Strategy (REMS) – Food and Drug
Administration (08/2012)
“ The goal of this REMS is
to reduce serious
adverse outcomes
resulting from
inappropriate
prescribing, misuse, and
abuse of extendedrelease or long-acting
opioid analgesics while
maintaining patient
access to pain
medications.”
Role of the CE System
…Education for prescribers of these medications,
which will be provided through accredited
continuing education (CE) activities supported by
independent educational grants from er/la opioid
analgesic companies…
• FDA developed core messages to be communicated to
prescribers in the Blueprint for Prescriber Education
• FDA Blueprint will focus on the safe prescribing of ER/LA
opioid analgesics
• Accrediting bodies and CE providers will ensure that the
CE activities developed under this REMS will be in
compliance with the standards for CE of the Accreditation
Council for Continuing Medical Education (ACCME) or
another CE accrediting body as appropriate to the
profession.
FDA REMS Blueprint for
Prescriber Continuing Education – August 2012
Facilitating Conditions…
Validity of Requirements
FDA Blueprint for Prescriber
Education for ER/LA Opioid
Analgesics (08/2012)
“The expected results of the
prescriber education in this
REMS are that the
prescribers will:
a. Understand how to assess
patients…
b. Be familiar with how to
initiate therapy, modify
dose, and discontinue
use…
c. Be knowledgeable about
how to manage ongoing
therapy…
d. Know how to counsel
patients and caregivers…
e. Be familiar with general
and product-specific drug
information…”
Criteria 2. Incorporates into CME activities the
educational needs (knowledge,
competence, or performance) that
underlie the professional practice gaps of
their own learners.
Criteria 3. Generates activities/educational
interventions that are designed to change
competence, performance, or patient
outcomes as described in its mission
statement.
Criteria 5. The provider chooses educational formats
for activities/interventions that are
appropriate for the setting, objectives
and desired results of the activity.
Criteria 11. The provider analyzes changes in
learners (competence, performance, or
patient outcomes) achieved as a result of
the overall program’s
activities/educational interventions.
Independence
C7: The provider develops
activities/educational interventions
independent of commercial
interests (SCS 1, 2 and 6).
C8: The provider appropriately manages
commercial support (SCS3)
C9: The provider maintains a
separation of promotion from
education (SCS 4).
C10:The provider actively promotes
improvements in health care and
NOT proprietary interests of a
commercial interest (SCS 5).
Independence
“…REMS CE is a process not a product. Accredited CE will
develop as a range of activity formats intended for a diverse
target audience. We expect some (CE) will be present on the web,
or in print, and some will occur where prescribers live, work and
learn. As I wrote in June 2011, Accredited CE is a diverse array of
activities done by a range of providers in a multitude of formats on
many topics, to address many needs, and with a range of intended
outcomes. The decisions on each of these variables are made by
the CE providers. This diversity ensures that the right CE is
available to all the professionals. We expect that we will see this
same diversity in REMS CE and that the locus of control for these
decisions will remain with the providers.”
Letter from Murray Kopelow, MD, CEO of ACCME to
Industry Working Group – October 2011
FDA-mandated Requirements of the ER/LA Opioid
Analgesic REMS
Goal:
Reduce serious adverse outcomes resulting from inappropriate prescribing,
misuse, abuse, etc. while maintaining patient access to medications
REMS Requirements:
 Medication Guide to be dispensed with each Rx

RPC REMS website: www.ER-LA-opioidREMS.com
 No promotional content: REMS-related info only


Educational activities will be made available to all HCPs who prescribe
ER/LA opioid analgesics
“REMS-compliant CE” must:
 Include all elements of FDA Blueprint in the educational activity/materials
 Include post-activity assessment covering all sections of FDA Blueprint
 Be subject to independent audit (CE Accreditors = auditors)
 At least 10% of activities will be audited for compliance with Blueprint, compliance
with assessment requirements & compliance with Accreditors’ standards for
commercially-supported CE
ER/LA Opioid Analgesic REMS Website

First REMS CE must be available by March 1, 2013
 Boston University launched first CE activity February 28, 2013
 Searchable listing of RPC-supported REMS-compliant CE are posted at
www.ER-LA-opioidREMS.com

FDA-mandated “goals” for # of HCPs completing CE on full Blueprint
 80,000 by March 2015 (25% of 320,000 active prescribers)
 160,000 by March 2016 (50% of 320,000 active prescribers)
 192,000 by March 2017 (60% of 320,000 active prescribers)

REMS & REMS CE notification letters with copy of Patient Counseling
Document sent to:
 All DEA-registered prescribers for Schedule II & III drugs
 Professional Organizations & Licensing Boards

Assessments to FDA at 6 mo. post-REMS approval & annually thereafter
http//www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformation
for PatientsandProviders/UCM311290.pdf Accessed March 12, 2013
Central component of the ER/LA Opioid Analgesics REMS is education for:
 Patients
 Medication Guide to be dispensed to each patient along with Rx
 Patient Counseling Document on risks/safe use to be utilized by Providers
 Prescribers: Physicians, NPs, PAs, other “Prescribers” of ER/LA opioids

Prescriber education (see FDA Blueprint) must include information on:
 Assessing patients for treatment
 Initiating therapy, modifying dosing & discontinuing therapy
 Managing therapy & monitoring patients
 How to recognize evidence of/potential for opioid misuse, abuse & addiction
 Counseling patients & caregivers on safe use
 General drug information (class-wide characteristics)
 Specific drug information (table listing key safety info for each ER/LA opioid)

Training/education will be developed & conducted by accredited CE
providers under educational grants awarded by RPC
Easiest path to site:
Google “FDA ER LA
Opioid REMS”
distribution mechanism
Hours of
Activities Instruction
132,768
952,736
ACCME
Accredited
N = 687
NonPhysician
Physician
Participants Participants
13,741,621
9,558,789
2011 Reporting Year
State
Medical
Society
Accredited
N = 1,392
Where they live, work, learn
Activities
Courses
Regularly scheduled series
Internet (live)
Test-item writing
Committee learning
Performance improvement
Internet searching and learning
Internet (enduring materials)
Enduring materials (other)
Learning from teaching
Journal CME
Manuscript review
66,509
22,766
2,078
132
598
502
587
27,624
7,097
665
4,136
74
~133,000
Hours of Instruction
384,881
451,040
6,144
997
1,731
7,137
3,879
47,829
39,549
2,442
6,870
238
~953,000
Role of MEMS
2009 MEMS: Data standard for
organizations to bring together data
from multiple systems about CE
activities.
2013 MEMS 2.0: Revised to include
standards for compiling data about
REMS CE activities.
Role of MEMS
CE Providers
 record data about CE activities according to
MEMS 2.0 standard
 transmit to accreditors in XML format
ACCME and other Accreditors
 Accept data about CE activities into their
databases which have been designed to conform
to the MEMS 2.0 standard
 Transmit data about REMS-compliant CME
activities to third-party aggregator
PARS currently…
•
•
Data descriptive of
CME activities
provided by ACCME
and some SMSaccredited providers
Used by providers
each year to enable
ACCME to:
– select activities for
demonstration of
Practice in
Performance
– create ACCME’s
Annual Report.
PARS currently…
Required Data that must be
provided for each CME activity:
•
•
•
•
•
•
•
Activity Type , Title, Date, and, if
applicable, Location
Sponsorship (Direct or Joint)
Hours of Instruction
Designed to change (Competence,
Performance or Patient Outcomes)?
Changes in (Competence, Performance
or Patient Outcomes) evaluated?
Number of physicians and nonphysicians who participated in the
activity
Commercial Support Received? (Y/N)
- If Yes, # of Commercial Supporters,
and nature of support (Monetary and/or
in-kind)
Optional Data that may be
provided for each CME
activity:
•
•
•
•
•
•
•
Provider activity identifier
Description of the activity content,
Subcategories for courses,
AMA PRA Category 1 Credits
Designated,
Names of joint sponsors and
commercial supporters,
Nature of in-kind support, and
Some activity-specific income and
expense information
MEMS 1.0 Compliant
PARS for REMS-compliant
Required Data that will be collected for each
REMS-Compliant CME activity:
•
•
•
•
•
•
•
•
Activity Type, Title, Date, and, if applicable, Location
Provider activity identifier
Sponsorship (Direct or Joint)
Hours of Instruction
Designed to change (Competence, Performance or Patient
Outcomes)?
Changes in (Competence, Performance or Patient Outcomes)
evaluated?
Number of physicians and non-physicians who participated
in the activity
Commercial Support Received? (Y/N)
- RPC Funded vs. Non-RPC Funded
•
•
•
# of Prescribers that Successfully Completed the Activity
# of Prescribers by Profession (i.e. physician, nurse
practitioner or pharmacist)
# of Prescribers by Practice Type (i.e. primary care, pain
specialist, non-pain specialist)
MEMS 2.0
Compliant
Accredited Provider Perspective
Emma Trucks, MPH(c)
Administrative Manager
Boston University School of Medicine
www.scopeofpain.com
When the rubber meets the road!
• Implementing specifications while MEMS 2.0
was still in development
• Considering the Learners’ Perspective:
– How will a learner interpret a question?
– Do questions make sense for our target audience?
– Are there too many questions that will become a
barrier to completion?
• Considering the Provider’s Perspective
– Will we collect the information that we need?
www.scopeofpain.com
Registration:
Not as simple as it
seems!
Defining Prescribers
• Vital for RPC and FDA reporting requirements
www.scopeofpain.com
Are you currently licensed to prescribe schedule II
and schedule III opioid analgesics?
2%
11%
YES
NO
Not Sure
87%
n (completers) = 246
www.scopeofpain.com
Within the last 12 months, have you prescribed
opioids for any patients for equal to/greater than 3
months?
47%
53%
YES
NO
n (completers) = 246
www.scopeofpain.com
Within the last 12 months, have you prescribed
extended release long-acting (ER-LA) opioids?
46%
54%
YES
NO
n (completers) = 246
www.scopeofpain.com
Within the last 12 months, have you
prescribed opioids for any patients
for equal to/greater than 3 months?
Of those saying yes, how many are
prescribing ER/LA opioids?
47%
53%
YES
NO
n (completers) = 246
www.scopeofpain.com
Profession
• Certificates vs.
Reporting
• FDA Requirements
vs. CME
perspective
Profession
n (completers) = 246
www.scopeofpain.com
Practice Type
• What is the background of our participants?
12%
41%
• Clearly Defined Categories
34%
13%
PCP
Pain Specialist
Non-Pain Specialist
N/A
www.scopeofpain.com
Specialty
• Helpful outcomes
tool
• Not required by
FDA
n (completers) = 246
www.scopeofpain.com
REMS Assessment Reports to FDA:
Bringing Our Collective Efforts Together

Compliance in implementing REMS requirements
 Dear HCP Letter to ±1,400,000 registered prescribers plus
Professional Orgs & Licensing Boards
 Call center established & reports of call activity
 Website active & reports of website activity
 Training through accredited CE Providers made available to all
prescribers

Attainment of “training” performance goals
 Number of prescribers completing CE as per timelines set by FDA
 First goal: 80,000 by Feb 28, 2015
 Annual reports for 2013 & 2014 will detail progress toward goals


Results of independent audits
Long-term evaluation of CE outcomes
 Prescriber knowledge, practice changes 6‐12 mo. post-CE

Prescriber Survey

Patient Survey

Changes in adverse outcomes
 Levels of knowledge
 Changes in practice
 Awareness of REMS
 Knowledge and awareness
 Receipt of Med Guide & Patient Counseling Document
 Misuse, abuse, overdose, addiction, death
 Surveillance monitoring


Interventions to Address Surveillance Findings
Evaluation of drug utilization patterns
 Levels of knowledge
 Changes in practice
 Awareness of REMS



ER/LA Opioid REMS = unparalleled opportunity for real
collaboration to address a public health imperative
Despite complexities, the “can do” attitude of all
stakeholders has resulted in meeting all goals to date
Open, transparent communication is imperative
 Interpretations, nuances & terminology differences can lead to
misunderstandings – don’t hesitate to ask clarifying questions


RPC is 100% committed to effective implementation of this
important patient safety/public health initiative
Your role is critical to the ultimate success of the REMS &
we very much appreciate your assistance!