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Catherine
D. DeAngelis, MD, MPH; Editor, JAMA
University-based educators and researchers, as well as private
practitioners, are in frequent contact with representatives from
for-profit companies that provide "gifts" and financial
support for teaching and research. The enticement begins
very early in a physician's career: for my classmates and me, it
started with black bags.
Dr Kassirer's colleague (1) is not alone in remembering which pharmaceutical
company provided them. The timing of presenting the black bags early
in our first year was wonderfully strategic, as was the inscription
of our names on each. I must admit I was very happy to finally have
a real symbol of the medical profession after so many hours of what
seemed like year 5 of college. It took me a few days to come back
to reality and store the bag in my closet. I'm not sure what happened
to it, but I never carried it after that first day. On the other
hand, at that time I did not have the courage to publicly state
my unease with the unearned "gift."
Subsequently, offers came for "free" lunches, dinners,
and tickets to various events followed by offers to serve as an
"expert" with the usual lineup of speaking engagements
and serving on advisory panels and boards, for an "honorarium"
of course. There should be little question
about the expected effects of accepting free food, tickets, and
even black bags. It has been shown that clinicians'
decisions are affected by their interactions with pharmaceutical
companies. (2) This is no revelation; why else would anyone
provide these "free" gifts except ultimately to assist
in the selling of a product? The public is well aware of this problem,
and it has become a favorite subject of recent newspaper articles.(3,4)
The issue of receiving reimbursement for providing time and expertise,
as a speaker (teacher), advisor, or researcher, is more complex.
Persons asked to provide expertise as teachers or researchers generally
are selected from a pool of those best prepared and experienced
in the field. Who is better equipped to teach or perform the studies,
and why shouldn't they be rewarded for their work? The problem lies
in the conflict of interest that results from these relationships.
It is vitally important to understand that a conflict of interest
does not necessarily result in an outcome different than the result
would have been without such conflict. The potential for differing
results is the problem at hand.
Balance must be maintained between the need for research projects
to be reasonably funded and performed by the best possible investigators
and the relative paucity of public funds for clinical research.
In 1999, the National Institutes of Health (NIH) provided $17.8
billion for research, and the major proportion was expended for
basic research; the top 10 pharmaceutical companies spent $22.7
billion, primarily on clinical research (Hamilton Moses III, MD,
The Boston Consulting Group, personal communication, 2000). The
likelihood that a clinical investigator would be funded by private
vs public funds is substantial. Furthermore, a recent study
by USA Today revealed that more than half
of the advisors to the Food and Drug Administration (FDA)
have financial relationships with pharmaceutical companies that
have an interest in FDA decisions. (5)
When an investigator has a financial interest
in or funding by a company with activities related to his or her
research, the research is:
- lower in quality (6,7)
- more likely to favor the sponsor's
product (8-11)
- less likely to be published (12,13)
- more likely to have delayed publication
(14)
Institutional safeguards can substantially mitigate the negative
effects of funding from companies with a vested interest in the
results.
Boyd and Bero (15) provide a case study of the University of California,
San Francisco faculty's financial relationships with industry. By
1999, 225 researchers (almost 8% of total faculty investigators)
had been involved in 488 disclosures. One can only postulate the
results from other institutions that accept private funding for
research, and it is an unusual institution that does not do so.
Therefore, all research universities should emulate Boyd and Bero's
study to determine the extent of their faculty members' involvement
with industry and to institute proper oversight.
Cho et al (16) report on the content of conflict of interest policies
at 89 biomedical research institutions receiving the most NIH funding
in 1998. Their results show that while there appears to be a lack
of specificity about the exact nature of the relationships of their
faculties with industry, the vast majority (89%) at least had mechanisms
for disclosure to the institution. However, only 19% had specific
prohibitions or limitations of activities related to research or
teaching, and 38% had institutional committees to review conflicts
of interest. As the amount and proportion of funding from private
corporations for research increase, it is vital that all institutions
that accept these funds develop methods for disclosure and oversight.
In a Commentary, Korn (17) addresses the complexities of ensuring
that academic medical centers preserve the confidence and support
of the public and government agencies while maintaining the funding
necessary to remain on the cutting edge of research. He discusses
how the inevitable conflict of interest issues must be managed by
academic centers.
Finally, Kahn and colleagues (18) illustrate what can happen when
disagreement occurs between the funding sponsor and the investigators
when the sponsor has a proprietary interest in the findings.
The investigators report that some data were not made available
to them by the sponsor. The integrity of the research
process rests on a sound study design and the disclosure of all
pertinent results, whether positive or negative, based on analysis
of all necessary data.
In this case the data set is incomplete, but the investigators,
peer reviewers, and editors believe it to be of sufficient merit
to warrant the conclusions. Our decision to publish this study is
based on the belief that the integrity of the research process must
be protected and preserved. The authors have provided the best research
possible under the circumstances. If further data are or become
available that refute or alter the conclusion of this study, I welcome
submission of such material. Science is a dynamic and ongoing process,
and we must allow it to continue.
Unlike the majority of, if not all, for-profit businesses in our
capitalistic society, managed health care corporations have not
provided funding for research and development (education). This
is true despite the advantages they derive from the research and
education provided primarily by academic medical centers. Furthermore,
there is little chance that sufficient funding for important clinical
research, especially expensive clinical trials, will be forthcoming
from sources other than sponsors with a vested interest in the results.
Those best prepared and experienced to carry out such complex studies
generally are faculty in academic institutions. Therefore, it
is vitally important that these institutions develop conflict of
interest policies, have oversight mechanisms in place, and continuously
monitor the relationships of faculty with sponsoring companies and
agencies.
Without these policies and procedures, the academic institutions
where most clinical research is based and their faculty members
who perform the research are in grave danger of losing the support
and respect of the public. Without this support and respect, trust
in new medical discoveries and their applications will not be forthcoming.
Without trust, medical research is doomed.
References
1.
Kassirer JP. Financial indigestion. JAMA. 2000;284:2156-2157.
2. Chren MM, Landefeld CS. Physicians' behavior and their interactions
with drug companies. JAMA. 1994;271:684-689.
3. Peterson M. What's black and white and sells medicine? New
York Times. August 27, 2000;sect 3:1.
4.
Cohen R. Conference call. New York Times. September 24, 2000:
Magazine section:30-32.
5.
Cauchon D. FDA advisers tied to industry. USA Today.
September 25, 2000:01A.
6.
Rochon P. Evaluating the quality of articles published in journal
supplements compared with the quality of those published in the
parent journal. JAMA. 1994;272:108-113.
7. Bero LA, Rennie D. Influences on the quality of published drug
studies. Int J Technol Assess Health Care. 1996;12:209-237.
8. Bero LA, Galbraith A, Rennie D. The publication of sponsored
symposiums in medical journals. N Engl J Med, 1992;327:1135-1140.
9. Rochon P, Gurwitz JH, Simms RW, et al. A study of manufacturer-supported
trials of nonsteroidal anti-inflammatory drugs in the treatment
of arthritis. Arch Intern Med, 1994;154:157-163.
10. Cho MK, Bero LA. The quality of drug studies published in
symposium proceedings. Ann Intern Med 1996;124:485-489.
11. Stelfox HT, Chua G, O'Rourke K, Detsky AS. Conflict of interest
in the debate over calcium-channel antagonists. N Engl J Med 1998;338:101-106.
12. Blumenthal D, Campbell EG, Anderson MS, et al. Withholding
research results in academic life science. JAMA 1997;277:1224-1228.
13. Rennie D. Thyroid storm. JAMA. 1997;277:1238-1243.
14. Friedberg M, Saffran B, Stinson TJ, et al. Evaluation of conflict
of interest in economic analyses of new drugs used in oncology.
JAMA. 1999;282:1453-1457.
15. Boyd EA, Bero LA. Assessing faculty financial relationships
with industry: a case study. JAMA 2000;284:2209-2214.
16. Cho MK, Shohara R, Schissel A, Rennie D. Policies on faculty
conflicts of interest at US universities. JAMA 2000;284:2203-2208.
17. Korn D. Conflicts of interest in biomedical research. JAMA
2000; 284:2234-2237.
18. Kahn JO, Cherng DW, Mayer K, Murray H, Lagakos S. Evaluation
of HIV-1 Immunogen, an immunologic modifier, administered to patients
infected with HIV having 300 to 549 106/L CD4 cell counts: a randomized
controlled trial. JAMA 2000; 284:2193-2202.
Journal of the American Medical
Association November 1, 2000
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