Correspondence
Protecting Research Subjects
N Engl J Med 2002; 346:2093-2095June 27, 2002
- Article
To the Editor:
The Health Policy Report by Steinbrook on the crisis at Johns Hopkins (Feb. 28 issue)1 skirts the key issues. There were 2600 protocols that required re-review as part of the corrective plan, as indicated in the article, but there is no indication of the total number of studies that were stopped when the Food and Drug Administration (FDA) intervened. Clearly, more research was affected. It was noted that the institutional review board (IRB) was criticized because it had to consider 800 new protocols — presumably its workload for a year — in addition to its annual reviews. The IRB met biweekly.
I have served on an IRB for more than five years. Judging from my experience, the workload at Johns Hopkins is huge. There is no way a cogent evaluation of studies can occur at this pace, especially when the members of the IRB must also perform their usual clinical, research, and administrative duties, as well as teach.
The FDA and the National Institutes of Health are demanding more and more each year from IRBs in terms of responsibility, education of their members, and professional accountability. It is patently impossible to meet these standards if IRBs are going to consist of members who serve for free, serve with virtually no administrative support, and receive no “academic” credit in the university system for their labors. A proper review of all the proposed studies at Johns Hopkins would require weekly meetings and four to six hours of preparation per week for each IRB member — about 10 percent of a faculty member's full-time effort. Such a requirement is not trivial.
You get what you pay for. If we continue to adhere to the present IRB system in the United States, we will have errors and tragedies. It is time to give IRBs and their members the resources and funding that will permit them to do their job: protecting research subjects.
1 ReferencesJeffrey L. Kaufman, M.D.
Vascular Services of Western New England, Springfield, MA 01107
kaufman@massmed.org 1
Steinbrook R . Protecting research subjects -- the crisis at Johns Hopkins. N Engl J Med 2002;346:716-720
Full Text | Web of Science | Medline
To the Editor:
In discussing the protection of human subjects, Steinbrook notes, “Many argue that [research involving healthy persons] requires a higher standard for minimizing risks than research involving people who are sick and who may die from their underlying disease.” I am not sure what is the ethical foundation for this claim. From the perspective of autonomy, adults can take risks, and it is irrelevant whether or not they are healthy, provided that they understand the risks and benefits of participation and their right not to participate. However, given the public's common confusion of the role of patient and the role of subject,1 one could argue that sick patients are — or at least may perceive themselves to be — less autonomous in terms of refusing to participate in such research. From the perspective of beneficence, physicians have an obligation to promote the best medical interests of their patients. When they take on the additional role of researcher, this duty does not disappear. Given this fact, physician-researchers ought to dissuade their patients from participating in nontherapeutic research if it exposes them to any clinical harm. Finally, from the perspective of justice, the Belmont report discussed the inappropriateness of placing further burdens on already “burdened” persons.2 A policy that allows sick persons to be exposed to greater risks in nontherapeutic research does just that and is therefore unjust.
No doubt Steinbrook would agree that all research should be designed to minimize the risks to research subjects. It is unclear why there ought to be a higher standard for the healthy volunteer. Ethics may suggest the opposite.
2 ReferencesLainie Friedman Ross, M.D., Ph.D.
University of Chicago, Chicago, IL 60637
lross@uchicago.edu 1
Katz J. Experimentation with human beings: the authority of the investigator, subject, professions, and state in the human experimentation process. New York: Russell Sage Foundation, 1972.
2
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont report: ethical principles and guidelines for the protection of human subjects of research. Washington, D.C.: Government Printing Office, 1978. (DHEW publication no. (OS) 78-0012.)
To the Editor:
As Steinbrook points out, the death of a research subject last year at Johns Hopkins was attributed to the drug hexamethonium and, in part, to the failure of investigators to conduct a complete review of the literature. McLellan1 has pointed out that many of the data on toxicity were published in the 1950s and thus were not — and currently are not — retrievable through PubMed's Medline, which goes back only to 1966. She notes that efforts are under way to rectify the situation with Oldmedline, which is being put into place by the National Library of Medicine. Once it becomes available, the older medical literature can really be a lifesaver.
1 ReferencesWilliam O. Robertson, M.D.
University of Washington, Seattle, WA 98199
robertso@wapc.org 1
McLellan F . 1966 And all that -- when is a literature search done? Lancet 2001;358:646-646
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Steinbrook replies:
To the Editor: In response to Kaufman: I have addressed many of the issues regarding the IRB system in the United States in a subsequent article (May 2 issue).1
In response to Ross: I would argue that clinical research should be designed to minimize the risk to the subjects. My point was to distinguish between research on healthy people who gain no direct benefit and therapeutic research on sick people who may benefit directly. Potential risks are an issue for a healthy volunteer, but potential therapeutic benefit is not. Researchers, IRBs, and sponsors must consider what level of potential risk is acceptable for healthy subjects. In research with no direct therapeutic potential, similar considerations should be applied regardless of whether the subjects are healthy or sick.
I agree with Robertson that the ability to obtain all relevant toxicity data on an experimental substance is an important issue. This need is one of the rationales for a centralized national reporting system for adverse events in studies of experimental substances.1
1 ReferencesRobert Steinbrook, M.D.
1
Steinbrook R . Improving protection for research subjects. N Engl J Med 2002;346:1425-1430
Full Text | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Patrina HY Caldwell, Sharon B Murphy, Phyllis N Butow, Jonathan C Craig. (2004) Clinical trials in children. The Lancet 364:9436, 803-811
CrossRef
