Zelen's Proposal for Randomizing Clinical Trials Draws CommentsAuthor(s): Carol LevineSource: IRB: Ethics and Human Research, Vol. 1, No. 7 (Nov., 1979), p. 10Published by: The Hastings CenterStable URL: http://www.jstor.org/stable/3563662 .

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mercial protection. Furthermore, pre- mature disclosure interrupts the process of validation, and may result in misleading data. Potentially disastrous consequences may result, says NIH, from the premature release of in- complete or invalidated data in clin- ical trials. The entire trial, costing millions of dollars and involving thou- sands of subjects, may be jeopardized. Observational epidemiological studies are also particularly vulnerable to dis- ruption from premature disclosure.

The EAB heard public testimony on these proposals at its September meet- ing. At the meeting expert witnesses testified that the EAB needs more spe- cific evidence in order to approve the CDC and NIH proposals. The EAB will continue to discuss the issue.

Meanwhile, as already reported ("Update," August/September 1979, p. 8), the Supreme Court will rule in the fall on another issue related to the Freedom of Information Act. The case of Forsham v. Califano concerns the re- lease of records of data gathered under NIH grants by the University Group Diabetes Program.

In yet another case related to the Freedom of Information Act, John Cary Sims and Dr. Sidney M. Wolfe, associ- ates of Ralph Nader, have won a lim- ited victory in their suit against the CIA (New York Times, Aug. 10, 1979). U.S. District Court Judge Louis Ober- dorfer ordered the CIA to disclose the names of universities involved in drug and human behavior experimentation in project MK-ULTRA. Oberdorfer, however, gave the agency until Octo- ber 1 to disclose the names and advised the agency how to classify the names of the schools under other laws. He said that the release of records could con- stitute a "clearly unwarranted invas- ion of privacy" of the individual researchers. The CIA, Oberdorfer said, should contact each researcher and ask whether he or she objected to the re- lease of identity.

Zelen's Proposal for Randomizing Clinical Trials Draws Comments

Marvin Zelen's new plan for ran- domizing clinical trials, proposed in the New England Journal of Medicine (May 31, 1979, pp. 242-45) and reported in IRB in "Annotations" (October 1979, p. 12), has drawn several vigorous re- sponses. The "Letters" section of the October 4 issue of the NEJM presents views ranging from "strong support" to "legerdemain."

Paul Armstrong, M.D., of Queen's

University in Kingston, Ontario, writes that he has been following precisely the scheme outlined by Zelen-form- ing two groups at random and then asking consent only from the subjects assigned to the investigational treat- ment. In his study of the effects of phar- macologic therapy with myocardial infarction, Dr. Armstrong has found that "the acceptance to date by pa- tients, physicians and nurses has been excellent."

However, Edwin B. Cox, M.D., of the Duke University Medical Center, says that "many patients treated conven- tionally without being party to the de- cision to exclude them from the experimental treatment will be exceed- ingly angry when they find out that the alternatives were not explained to them."P

Robert K. Stuart, M.D., of the Johns Hopkins Oncology Center warns that the new trials "may generate new trib- ulations for the clinical investigator." He feels that the investigator may be inclined to see that a large proportion of the patients assigned to the experi- mental treatment group give consent, and may become "unconsciously biased toward the experimental treat- ment." Like Dr. Cox, he is uneasy about a situation in which patients are ran- domized, without their knowledge or consent, to standard therapy or to the opportunity to receive investigational treatment. Both writers predict that the selection will not long remain a se- cret.

Putting aside ethical questions, David D. Rutstein, M.D., Countway Li- brary of Boston, points out that Dr. Zelen's proposal is impractical. Con- trol subjects must be informed because they must be followed if the study re- sults are to be meaningful, he asserts.

Another question is raised by Doro- thy Vawter of Georgetown University. She writes that Dr. Zelen has misun- derstood the term "subject at risk" in the Code of Federal Regulations and "has failed adequately to calculate the risks to which patients receiving stand- ard treatment are subject in research." Furthermore, she claims that Zelen's proposal does not respect personal au- tonomy.

Finally, Alexander Morgan Capron, J.D., of the Unversity of Pennsylvania, calls Dr. Zelens' proposal "legerde- main." According to Capron, Zelen does not give empirical proof of the need for the type of procedure he pro- poses, and only asserts that clinical in- vestigators refuse to participate in randomized studies because of their al- leged compromising effect on the "pa- tient-physician relationship."

Capron asks "Would it not be more informative, and just as likely to be at- tractive to patients who are really will- ing to participate in clinical trials, to say that researchers are constantly try- ing to improve on existing therapies and that they believe that the new one being tested is as good as any existing alternative and may (but may not) prove to be better?"

Dr. Zelen, responding to these let- ters, suggests that Drs. Cox, Capron and Stuart raise some questions such as investigator bias that apply to all clinical trials. In reply to Dr. Capron, he says, "I think that it is better for a patient to give informed consent for an experimental treatment that he or she may actually receive (as in my pro- posal) than to consent to participate in a study without knowing which treat- ment will be given until after provid- ing consent."

Carol Levine

TLTTERS

Placebos, Deception, and Research Design

The case study' in the June/July is- sue should have been entitled "The Use of Placebo and Deception: A Question of Research Design," for a close read- ing reveals how a question of ethics may be inextricably linked to the quality of the research design.

Since the study under review in the article was designed to evaluate cer- tain dietary regimens in lowering serum levels of cholesterol, the admin- istration of a pill, in this instance a placebo, to only one group seemed to be not only unnecessary, but inap- propriate in terms of the objectives and structure of this protocol. Therefore, the IRB's decision to eliminate the placebo was judicious from both a sci- entific and ethical standpoint.

There has been some debate on whether IRBs should be responsible for assessing the scientific as well as the ethical quality of a research project. This case illustrates why IRBs ought to be able and free to consider all aspects of the research.

Karin Meyers, M.A. Consultant in Bloethics

White Plains, N.Y.

'Saber, F A. and Reece, R.D.: The use of placebo and deception. IRB: A Review of Human Sub- jects Research 1:4 (June/July 1979), 4-6.

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