Correspondence

To Protect Those Who Serve

N Engl J Med 2001; 344:1018-1019March 29, 2001

Article

To the Editor:

Drazen and Koski (Nov. 30 issue)1 argue persuasively that research institutions should adopt a uniform policy regarding financial conflicts of interest in order to protect the integrity of clinical research. In articulating their case for such a policy, however, they make unrealistic pronouncements about the ethical responsibility of investigators, including that “it is the investigator who must always act in the subject's best interests” and that “clinical investigators must be primarily interested in protecting the welfare of the brave and unselfish persons who agree to serve as the subjects of our research.”

Much clinical research does not test the efficacy of diagnostic or therapeutic interventions but aims to improve the understanding of the disease. Because these studies pose risks to subjects without any compensating medical benefits, participation is not in their best interests. Moreover, even clinical trials aimed at evaluating treatments, especially those involving placebo controls, do not promote the best interests of all patients who volunteer to participate. Consequently, if the investigator always acted in the subject's best interests, much, if not most, clinical research would be impossible to conduct.

Clinical research is subject to an inherent ethical tension and a potential conflict between advancing science and protecting the well-being of research subjects.2 Minimizing or even eliminating financial conflicts of interest leaves the inherent ethical tension intact. The forthright recognition of the potential of clinical research to compromise the welfare of research subjects contributes to the careful assessment of the scientific value and validity of research protocols, the determination of acceptable levels of research-related risks, scrupulous efforts to obtain informed consent, and the adequate monitoring of volunteers.3

(The opinions expressed in this letter are those of the author and do not necessarily reflect the policy of the National Institutes of Health, the Public Health Service, or the Department of Health and Human Services.)

Franklin G. Miller, Ph.D.
National Institutes of Health, Bethesda, MD 20892-1156

3 References

1. 1

   Drazen JM, Koski G. To protect those who serve. N Engl J Med 2000;343:1643-1645
   Full Text | Web of Science | Medline

2. 2

   Miller FG, Rosenstein DL, DeRenzo EG. Professional integrity in clinical research. JAMA 1998;280:1449-1454
   CrossRef | Web of Science | Medline

3. 3

   Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA 2000;283:2701-2711
   CrossRef | Web of Science | Medline

Author/Editor Response

Drs. Drazen and Koski reply:

Dr. Miller points out an important issue related to the conduct of clinical research: it is critical that the benefit derived from clinical research be worth the risk to the patient who becomes a subject. We believe that clinical researchers recognize the presence of an ethical tension when neither the patient nor the treating physician knows the exact nature of the treatment being tested; this tension must be tolerated if a treatment is to pass a rigorous test of its potential benefits before it is adopted for use by practicing physicians. Our point was that to add to this ethical tension a financial tension, due to ownership by the investigator of equity in the sponsoring entity, is unacceptable.

Jeffrey M. Drazen, M.D.
Editor-in-Chief,

Greg Koski, Ph.D., M.D.
Office for Human Research Protections,, Department of Health and Human Services, Rockville, MD 20852