Financial Conflict of Interest and
Medical Research
Stephen R. Marder, M.D.
Disclosure Information for
Stephen R. Marder, MD
•
Advisory board
– Abbott; Amgen; Roche; Shire; Otsuka America Pharmaceutical,
Inc.; Wyeth; Pfizer,
• Research Support
– Novartis; Glaxo Smith Kline; Sunovion; Psychogenics
Overview
• More than ever, there is an incentive for
academic researchers to work with industry
– NIH is not equipped to develop drugs and bring
them to market
– Industry researchers seldom translate the newest
biological findings into new pharmacological
approaches
• Ethical Concerns have led many to mistrust
research emerging from industry
Research Budget (billions): Top 5
Pharmaceutical Companies
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
billion
PFE
GLX
MRK
A/Zen BM/Sq NIMH
Drug Development’s Major Challenge: Improving Technical Success
Candidate Selection

100%
100%
1 year
Phase I
First
Human Dose
80%
1 ½ years
55%
50%
Phase II
First Efficacy
Dose
2 years
10%
2001 CMR Data
0
Development time - years
1
2 1/2
Phase III
First Registration
Dose
Submission
20%
Launch
3 years
11%
1 year 9%
4 1/2
8 1/2
Definition


A conflict of interest is a set of circumstances that
creates a risk that professional judgment or actions
regarding a primary interest will be unduly
influenced by a secondary interest.
Institute of Medicine Report, 2009
Cases example 1
• Nancy Fern Olivieri is a hematologist from
Toronto who participated in multi-site study of a
drug for thalassaemia.
• She became concerned about toxicity of the drug
and a lack of efficacy. She informed the ethics
board of the hospital and the company. The
board instructed her to notify study participants.
• The company informed her that her
confidentiality agreement prevented from
notifying subjects. She did anyway.
Case example 2
• A prominent psychiatrist-researcher wrote a
review in a very prominent journal that
focused on new experimental approaches to
treating depression.
• It turned out that the author had significant
COI’s for some of the approaches. These were
not disclosed in the article.
Is there evidence of bias in research?
• Research funded by industry is more likely to
report positive findings (Sismondo, 2008)
• Examination of comparisons of antipsychotics
found the funder’s drug superior 90% of the
time. (Heres, 2006)
• Sponsors can control when and where results
are published.
Neuman et al 2011
• Reviewed 14 practice guidelines
• Among members of panels writing clinical
practice guidelines, 52% had financial
conflicts.
• 138 were declared; 12 were not declared
A high proportion of Committee Chairs (81%) and
Committee members (55%) had conflicts.
Appelbaum and Gold
• Describe the Principal-Agent Problem where
the physician or investigator is engaged as an
agent of the drug company.
• Other principals may be the scientific
community, research subjects, the patients
who may benefit from study results
Approaches
• Disclosure of Financial conflicts
• Management of conflicts
• Eliminating conflicts
Approaches to Disclosure
• The 2010 Affordable Care and Patient
Protection Act contains sweeping sunshine
provisions including the development of a
searchable public Web site that will list
payments from drug, device, biological, and
medical products companies to physicians by
name.
Limitations of Disclosure
• Unclear if readers pay attention
• The details of the conflict are not reported
• Seldom included in abstracts
People can never be trusted to be unbiased.
The mind doesn’t work like that
“And thou shalt take no bribe; for a bribe
blinds the eye of the wise; and perverts
the words of the righteous”
Gold and Appelbaum
Raba stated: What is the reason for [the
prohibition against taking] a gift? Because as
soon as a man receives a gift from another he
becomes so well disposed towards him that
[the other person] becomes like his own
person, and no man sees himself in the wrong.
Managing Investigator COI
• AAMC recommends that researchers with
financial interests related to study results
should not participate or should give up the
interests.
IOM Recommendation
• Academic medical centers and other research
institutions should establish a policy that
individuals generally may not conduct
research with human participants if they
have a significant financial interest in an
existing or potential product or a company
that could be affected by the outcome of the
research.
IOM Recommendation (cont)
• Exceptions to the policy should be made
public and should be permitted only if the
conflict of interest committee (a) determines
that an individual’s participation is essential
for the conduct of the research and (b)
establishes an effective mechanism for
managing the conflict and protecting the
integrity of the research.
Summary
• Concerns about the public’s confidence in
medical research should be taken seriously
• Vital components of a study design, data analysis,
and interpretation should be reviewed by
individuals who are unconflicted.
• Academic scientists should have all agreements
with industry reviewed by their institutions to
assure that a company does not infringe on the
timely publication of all information.