Show Me the Evidence!
Identifying the Truth about Rx Drugs
Enter event/location
May 19, 2008
1
Faculty Disclosure
Your Name Here, MD
Dr. Your Name Here reports that he has No
Conflict of Interest with this presentation.
In accordance with the requirements of the Standards for Commercial Support of the Accreditation
Council for continuing Medical Education adopted by the AMA and the Oregon Medical Association,
each instructor is asked to disclose any affiliations with, or financial interests in, companies whose
products are discussed in his/her presentation.
Event/Location of Lecture CME Presentation
May 19, 2008
2
Learning Objectives



Recognize cost and health impact of
inappropriate or excessive utilization of
prescription drugs
Increase awareness of biased information
and pharmaceutical industry marketing
practices.
Describe strategies that can reduce the
influence of biased information.
Learning Objectives, con’t.



Describe how evidence-based approaches can
be used to guide prescribing decisions.
Provide reliable sources of unbiased prescribing
information and practice guidance.
Provide educational resources for more in-depth
information regarding pharmaceutical industry
marketing and use of evidence-based methods
to make prescribing decisions.
US Health Spending in 2006



$2.1 trillion or $7,026 per person
Health care inflation generally outpaces
increase in GDP.
When health care costs rise faster than the
overall economy, affordability and
range/quality of benefits decrease.
Health Affairs 2008;27(1):14-29
Healthy Life Expectancy & Per Person
HEALTHY LIFE EXPECTANCY AND PER PERSON
MEDICAL EXPENDITURES FOR 22 OECD COUNTRIES
Medical Expenses: 22 Developed Countries
76.0
Health
LifeLife
Expectancy
Healthy
Expectancy 2002
Japan
75.0
74.0
Sweden
Switzerland
73.0
72.0
71.0
70.0
United States
69.0
68.0
$0
$1,000
$2,000
$3,000
$4,000
Person
Annual
Expenses
Per Per
Person
Health
CareMedical
Expenditures
2001
$5,000
$6,000
Trends in health care
Millions
Rx Costs Are a Large Part of Overall
Health Care Spending
$200
$181
$180
$154
$160
$140
$120
$111
$100
$80
$60
$90
$72
$52
$40
$20
$0
OHP
Oregon State
Alcohol and Drug Community Mental
antipsychotics
/
Hospital
Treatment
Health Programs
Source:
antidepressants
Programs
2007 DMAP class 07/11 expenditures (total fund, excludes rebates)
http://www.oregon.gov/DHS/aboutdhs/budget/07-09budget/index.shtml (accessed 6/10/08)
http://www.oregon.gov/DAS/BAM/GRB0709.shtml (accessed 6/10/08)
Public Health
Division
Parks and
Recreation
Department
Prescription Drug
Expenditures




Increased at a faster rate than any other area
of health care over the last 15 years
Major contributor to rising health care costs
Responsible for a large portion of insurance
cost increases
Costs increased because of


Increased utilization (prescribing rate)
Increased price per prescription
Factors Driving Utilization
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Increase in prescription drug coverage
Marketing
Aging population

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More chronic conditions
Impact of Medicare Coverage
Increased Price Per RX

Price increases for existing drugs exceed
inflation

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Largest driver of increased Rx spending
Newer drugs replace older less expensive
agents

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Shorter approval time
Marketing of newer agents drives market share
Premiums, Earnings & Inflation
20.0
Rate of Increase (%)
18.0
16.0
14.0
12.0
10.0
8.0
6.0
4.0
2.0
0.0
'88
'89
'90
'93
Health Insurance Premiums
'96
'99
'00
'01
Workers Earnings
Source: Kaiser/HRET Survey of Employer-Sponsored Health Benefits
'02
'03
'04
Overall Inflation
Implications of Current Trends

Health care affordability continues to
deteriorate

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Health costs, including Rxs, expected to rise
faster than economy
Increased consumer out-of-pocket costs 
increased premium share, deductibles, coinsurance, and co-payments
State & Federal budget deficits
Increased rate of uninsured/underinsured
Conclusions About Costs

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Currently, the US spends more per capita on
health care than any other developed country,
yet is ranked near the bottom in terms of quality.
Continuing on the current path has huge societal
implications. How much more can we spend?
The alternative is to spend more wisely.
Payers are looking at all options to contain
health care and pharmaceutical costs, and to get
better value.
This creates a great opportunity for prescribing
physicians.
Quality of care issues with
prescription drugs

Over-medicalization (disease mongering)
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Poly-pharmacy
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Treatment of non-disease or trivial entities
Premature intervention in less severe conditions
Increasing med side effects leading to more
medications
Unpredictable interactions and greater potential
for errors
Off-label use
Disease Mongering
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US has 5% of the worlds population but 50% of
drug consumption
Strategies to expand markets
Promotional campaigns change the way people
think about common ailments


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Menopause becomes hormone deficiency
Shyness becomes social anxiety disorder
Acid indigestion becomes gastroesophageal reflux
disease
Lowering thresholds for treating common conditions
Selling Sickness by Moynihan and Cassels
What the FDA does

Approves new drugs and devices based on:

The medicine or device is “effective”

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Endpoint may be a surrogate such as lowering
cholesterol as opposed to longer life
Usually 2 RCTs required to prove clinical efficacy for
drugs
The medicine or device is “safe”
Charged with oversight of DTC materials


Small number of DTC materials are actually reviewed
Regulatory letters are often delayed and marginally
effective.
What the FDA doesn’t do!


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Does not assess cost vs benefit for a drug or
device.
Does not determine whether one drug is
better than another.
Does not approve every use to which a
product may be put.
Does not require large trials that will identify
all potentially rare complications.
Important Contributions by the
Pharmaceutical Industry


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Development of new treatments that improve health and
well-being
Substantial contributions to educational, health care and
professional organizations
Provide samples and free meds to many patients
…but, their main goal is to make profits for their
shareholders and they spend enormous amounts to
influence all involved, including legislators, providers,
patients, and the general public, to help them maintain or
increase those profits.
2007 Fortune 500 Profits
J &J
21%
Pfizer
37%
Merck
20%
Abbott
8%
Wyeth
21%
BMS
9%
Eli Lilly
17%
Amgen
21%
Schering
11%
Pharmaceutical Industry Methods
for Increasing Market Share
Marketing expenditures
 Drug reps
 DTC advertising
 Journal ads
 Prescriber data
 What can be done?

Promotional Spending
and Advertising, 2005
Detailing to
doctors 22%
$6.78 billion
DTC ads 14%
$4.24 billion
Journal ads 2%
$429 million
Samples 62%
$18.44 billion
Total spending: $29 billion
(Source: IMS Health, in Donohue, NEJM 2007)
Socolar D, Sager A. Pharmaceutical marketing and research spending: the evidence does not support PhRMA’s Claims.
http://dcc2.bumc.bu.edu/hs/sager/pdfs/120601/DrugIndustryMarketingStaffSoarswhileReserchStaffingStagnates5Dec01.pdf; Accessed 3/6/08
Pharmaceutical
Representatives

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Remains the major marketing focus
~ 100,000 reps in 2005 vs 38,000 in 1995
1 rep/6 MDs in US and 1 rep/2.5 targeted
MDs
6 million detail visits annually
Cost estimate $12-$13K/MD for detailing
Industry spends $150K annually/primary care
rep and $330K/specialty rep*
*Med Ad News 2004;23(3):1
Docs’ Perception vs. Brutal Reality


Studies consistently show physicians do not
believe that promotion affects their
prescribing habits*, but…
Studies consistently show drug promotion
increases prescribing of targeted drugs**
*Sigworth SK et al. JAMA. 2001;286(9):1024-5.McKinney WP et al. JAMA
1990;264(13):1693-7
**Chren MM et al. JAMA 1994 Mar 2;271(9):684-9; Lurie N et al. J Gen Int
Med 1990;5:240-243; Wazana A. JAMA 2000 Jan 19;283(3):373-80.
.
Details of Detailing:
Impact on Prescribing & Costs
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Increased likelihood of formulary requests for
targeted drugs
Increased awareness, preference and rapid
prescribing of new drugs
Higher prescribing costs
Less use of lower cost, but equally effective,
generics
Less rational prescribing
(Wazana A, JAMA 2000)
Direct to Consumer (DTC) Ads
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Directly target consumers & general public
1997: FDA relaxed regulations

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Eliminated requirement to list all side-effects by
simply referring to additional sources of
information, e.g., 1-800 number or website
As of 2005, the US and New Zealand only
developed nations with DTC Rx advertising
DTC Expenditures Are Huge…
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$4.5 billion spent on DTC in 2005*
296.4% increase from 1997-2005*
14% of total industry marketing for DTC**
Hoechst spent $580K on 60-second Allegra ad***
Merck spent $161M advertising on 1 drug, Vioxx,
whereas total annual ad budgets: Dell ($160M),
Budweiser ($146M), Pepsi ($125M) or Nike
($78M)****
*Shuchman, NEJM, 2007
**Donohue et al. NEJM, 2007
***Eaton, Stanford University Press, 2004
****Gellad et al. Amer J Med, 2007
But, DTC Ads Pay Off
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1998-1999: 25 most advertised drugs account
for 43% growth in Rx sales compared to 13.3%
for all other drugs*
1998: Claritin, Allegra, and Zyrtec increase
sales by 32%, 50% and 56%*
2002: >53M patients discuss DTC-advertised
meds with their doctors**
*Eaton, Stanford University Press, 2004
**Rosenthal, NEJM, 2002
32
The Quantity and Quality of
Scientific Info in Journal Ads
1999 review of pharm ads from 10 US journals:

498 unique ads (3,185 total)

74 unique graphs

36% of graphs: “numeric distortion”

66% of graphs: “chart junk”
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54% list intermediate outcomes
JGIM 2003;18:294-297
Big Brother (Pharma) Knows
What You Are Doing
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Industry has access to AMA managed
databases that track prescribing patterns of
most practicing providers
Such data is used to more precisely target
specific providers with specific types of
products or messages
AMA has an “opt out” option
But You Can “Opt-out”

Physicians can enroll at:
www.ama-assn.org/go/prescribingdata
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Purchasers of the data must agree to restrict
prescriber profiling by reps for those who
have opted out.
Must be renewed every three years and
manufacturers have 90 days to comply after
opt-out is exercised.
Ann Intern Med 2007;146:742-48
What Clinicians Can Do To
Reduce Marketing Impact?

Reduce or eliminate contact with industry
representatives
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“Just say no”
Identify/use unbiased and independent
sources of prescribing information
Opt out of use of your data in the AMA
master profile
CME: Incentives and Gifts
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Free Meals
Payment for attendance at lectures and
conferences
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Stipend
Time
Travel
Registration fees
Industry Support of Continuing
Medical Education
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In 2006, half of the $2 billion dollars spent on
CME came from industry sponsorship
Medical Education and Communication
Companies (MECCs)

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Organize meetings, find speakers for grand
rounds and symposia, develop written materials
About 76% income from industry
Medical Schools
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Industry provides almost two thirds (62%) of
CME income to medical schools (ACCME)
Source: ACCME, Annual Report Data
2006
Does this Affect Prescribing?

Attending drug company–sponsored CME
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5-19% increase in rate of prescription of sponsor’s
drug vs. competitor’s drug (P<.05)
Funding for travel or lodging to attend
educational symposia

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Increased formulary requests for the sponsor's
drug
Increased rate of prescribing of sponsor’s drug
Impacted hospital prescribing practices 2 years
later
(Wazana A, JAMA 2000)
Does the Source of Funding
Affect the Content of CME?


Content analysis of two different CME
courses sponsored by two different drug
companies, each discussed 3 calcium
channel blockers
Drug company–sponsored CME
preferentially highlighted the sponsor's
drug(s) compared with other CME programs

2.5-3 times more likely to mention positive
effects of sponsor’s drug and negative or
equivocal effects of competitor’s (P<.05)
(Bowman MA, Mobius1986)
Deal With Conflicts of Interest

Eliminate the conflicts whenever possible
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Recognize tendency to rationalize

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Can be difficult and painful, especially with friendly reps
Even the perception of conflicts create credibility problems
“It’s an educational dinner”
“patients need samples”
Denial
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“It doesn’t affect my prescribing decisions”
“I take it with a grain of salt”
J Gen Int Med 2007;22:184-90
Sage Advice
“The best defense the physician can muster
against (misleading) advertising is a healthy
skepticism... cultivate a flair for spotting the
logical loophole, the invalid clinical trial . . .
and the unlikely claim. Above all, develop
greater resistance to the lure of the
fashionable and the new.”
P.R. Garai, 1964
Conclusions About Marketing
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Industry marketing is very influential and
definitely impacts decision making
Marketing can lead to ineffective prescribing
Current marketing practices are controversial
and opinions vary
Health professionals can make choices to
avoid undue influence
Need for evidence
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“First of all, do no harm” (Hippocratic Oath)
2008 version: Never offer treatment to a
patient without convincing evidence that it will
provide more help than harm.
Shouldn’t we also consider help/harm to the
patient’s family & overall community in this
equation?
Principles of Evidence-based
Medicine (EBM)

Decision making in clinical practice

What is EBM?

What EBM is not
Decision Making in Clinical
Practice

Unfortunately, many decisions are made based
on unreliable “evidence”

Expert opinion plays a heavy role in medical
decision making

Personal observation or anecdotal experience
can frequently overcome clear evidence to the
contrary
Clinical Decision Making
2.
Evidence
1. Patient data
Basic, clinical, and epidemiological research
3. Randomized trials
4. Systematic Reviews
Guidelines
1.
2.
Knowledge
Constraints
Formal policies, laws
Community standards
3. Time
4. Economics
Patient/Physician Factors
1. Cultural Beliefs
2. Personal values
3. Experiences
4. Education
Ethics
Mulrow: Ann Intern Med, Vol 126(5) 3/1/97, pp 389-91
What is EBM?
EBM is "the conscientious, explicit and
judicious use of best current evidence in
making decisions about the care of
individual patients.”
-David Sackett
What is EBM?

Evidence based medicine requires the
integration of the best research evidence with
our clinical expertise and our patient’s unique
values and circumstances.

Sharon E. Straus: Evidence Based Medicine 3rd
Edition
What is Evidence-Based Practice?

A process in which we:
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Ask – to precisely define a patient problem
Acquire – figure out what’s needed to answer the
question, conduct an efficient search of the
literature.
Appraise – Select the best of the relevant studies
and apply rules of evidence to determine their
validity
Apply – Extract the clinical message and apply it
to the patient problem
Assess – Determine if the action was helpful
Adjust – Use the outcomes of intervention to
modify the treatment
What EBM is not:





The same old thing we’ve always done
Something that can only be done from
ivory towers
A “cookbook” method of practice
A method for administrators to save costs
Restricted to randomized trials
Study Types – Evidence
Hierarchy
Systematic
Reviews
RCTs
Cohort Studies
Case Control Studies
Case Series
Case Reports
Editorials and Opinions
Lab studies and Animal Research
53
Advantages of an EBM Approach

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
Sorts through the marketing, opinions, and
theory to get an accurate assessment of the
proven and comparative benefits and risks of
various treatments.
Supports policies that reduce variations in
practice, especially expensive or inappropriate
prescribing.
Provides incentive to conduct research on more
meaningful questions, especially comparative
studies
Practical Application of
Evidence-Based Methods

Understand terms used in research and
comparative reviews, such as:

Generalizability/Applicability/Relevance

Number needed to treat

Target outcomes

Publication bias
Practical Application of
Evidence-Based Methods

Rely on systematic or comparative
reviews, rather than single studies
whenever possible

Recognize factors that truly impact findings,
e.g. strength of evidence and quality of
research methods
Find reliable and unbiased sources of
information for summary and comparative
reviews

PICOTS Framework for
Reviewing Evidence
Parameter
Example
Population
Adults with Major Depression
Interventions
SSRI
Comparators
Other antidepressants, meds plus
psychotherapy, non-pharm txs
Improved mood and other
symptoms, improved fx
Outcomes
Timing
6-12 months f/u
Settings
Primary care
Web Site Examples of CERs

http://effectivehealthcare.ahrq.gov

www.ohsu.edu/drugeffectiveness

www.OregonRx.gov
Unbiased Sources on Drugs
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Agency for Health Care Research and Quality’s
Effective Healthcare Program:
http://effectivehealthcare.ahrq.gov
National Institute for Clinical Excellence:
www.nice.org.uk
Cochrane Collaboration: www.cochrane.org
Canadian Common Drug Review:
www.cadth.ca/index.php/en/cdr
Unbiased Sources on Drugs
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Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/
Clinical Trials Database: http://clinicaltrials.gov/
Carlat Report (Psychiatric Drugs):
http://www.thecarlatreport.com/
Oregon Health Policy & Research
www.OregonRx.gov
Drug Effectiveness Review Program:
www.ohsu.edu/drugeffectiveness
Other Information Sources
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Consumer Union: www.prescriptionforchange.org
No Free Lunch: www.nofreelunch.org/
Pharmed Out: http://www.pharmedout.org/
DUR Newsletter:
www.pharmacy.oregonstate.edu/drug_policy/pages/dur_bo
ard/newsletter

DHS Pocket Drug Guide:
www.pharmacy.oregonstate.edu/drug_policy/prescriber_too
ls.html
Thank you
This work was made possible by a grant from
the state Attorney General Consumer and
Prescriber Education Program which is funded
by the multi-state settlement of consumer fraud
claims regarding the marketing of the
prescription drug Neurontin.