SCIENTIFIC WRITING

Co-Authored Papers

Caschetta MB, Chavkin W, McGovern.

FDA Policy on Women in Drug Trials [Letter} 329 (24): 1815
December 9, 1993

FDA Policy on Women in Drug Trials

To the Editor: We support the general direction in which the Food and Drug Administration (FDA) is moving regarding the inclusion of fertile women in clinical trials, as outlined by Merkatz et al. (July 22 issue).1 The previous policy prohibiting women with childbearing capacity from participating in the early phases of research lacked a coherent scientific foundation. Unfortunately, no consistent, logical approach has yet been developed that adequately addresses such important matters as fetal exposure and fully informed consent. We reviewed the informed-consent documents used in 36 clinical trials focusing on AIDS. Pregnant women were generally excluded but on inconsistent grounds. Exclusion based on potential teratogenicity was vaguely defined. Specific risks, when identified, were either barely described or described in prohibitively technical language, thus precluding genuinely informed consent. Table 1 summarizes our findings.

Table 1. Exclusion of Women from 36 AIDS Clinical Trials, as Specified in the Informed-Consent Documents.

	Categories of women excluded Pregnant Nursing Pregnant after enrollment Othe Reason for exclusion No reason given Teratogenic risk Specific teratogenic risk Other	Percent* 70 22 20 12 25 47 17 12
	*Values are percentages of trials; percentages do not add up to 100 because the categories overlap.

In the particular context of AIDS, clinical trials often provide the only access to life-saving therapies for women, and there remain unanswered questions about the progression of disease in pregnant women. We therefore think that the inclusion of pregnant women in clinical trials will advance the scientific agenda and reflect an acknowledgement of women's autonomy and ability to make informed decisions.

Mary Beth Caschetta
Sex Information and Education Council of the United States
New York, NY 10036

Wendy Chavkin, M.D., M.P.H.
Beth Israel Medical Center
New York, NY 10003

Theresa McGovern
HIV Law Project
New York, NY 10011

References
1. Merkatz RB, Temple R, Sobel S, Feiden K, Kessler DA, Working Group on Women in Clinical Trials. Women in clinical trials of new drugs -- a change in Food and Drug Administration policy. N Engl J Med 1993;329:292-296

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The authors reply:

To the Editor: Caschetta et al. raise two important issues in their letter: first, information about the safety and efficacy of drugs in pregnant and lactating women is needed, and second, informed-consent documents require careful attention to ensure the adequacy and clarity of the information they present.

As we stated in our article and in the FDA guideline for the inclusion of women in clinical trials,1 data from clinical trials involving pregnant women are needed both to develop rational therapeutic recommendations for pregnant women and to enable these women to make intelligent, informed choices about their participation in clinical trials. The FDA is moving ahead to address these issues.

With regard to enrolling pregnant women in clinical studies, there has been an understandable reluctance on the part of investigators and manufacturers to do so, for both ethical and medicolegal reasons. Our plan is to develop recommendations on this important topic that will facilitate the conduct of trials in pregnant women and result in more such trials. However, the potential risks of fetal injury, the definition of circumstances under which such risks are justified, and the design of trials that will properly address the risks raise many challenging medical, scientific, legal, and ethical questions. The FDA believes that it is critical to obtain a broad range of views on these matters from the public as well as from experts in the fields of medicine, health care, ethics, and the law, and we are committed to facilitating that exchange.

The issue of informed consent is also critical. According to FDA regulations and current clinical practice, the institutional review board plays a central part in assessing the adequacy and appropriateness of informed-consent documents. As part of our effort to ensure proper implementation of our new guideline,1 we are preparing a letter that will inform institutional review boards about the policy changes articulated in our guideline and will emphasize the need for the boards to pay close attention to reproductive toxicity as they review protocols and informed-consent forms. The letter will also invite members of institutional review boards to contact the FDA if they have questions or comments about difficulties that they encounter in this process, or if they have suggestions for handling informed consent.

David A. Kessler, M.D.
Ruth B. Merkatz, Ph.D., R.N.
Robert Temple, M.D.
Food and Drug Administration
Rockville, MD 20857

References
1. Center for Drug Evaluation and Research. Guideline for the study of and evaluation of gender differences in the clinical evaluation of drugs. Washington, D.C.: Food and Drug Administration, 1993.