On Jul. 22, 1993, revising a policy from 1977 that excluded women of childbearing potential from early drug studies, the U.S. Food and Drug Administration (FDA) issued guidelines calling for improved assessments of medication responses as a function of gender.

The FDA published a guideline related to the assessment of sex differences in clinical evaluation of drugs amidst growing concerns that the drug development process did not provide adequate information about the effects of drugs or biological products in women and a consensus that women should be allowed to determine for themselves the appropriateness of participating in early clinical trials [58 FR 39406].

Companies were encouraged to include patients of both sexes in their investigations of drugs and to analyze any gender-specific phenomena. The following critical changes from the guideline should be reflected in drug and biologic product protocols presented to IRBs:

First, the guideline lifts a restriction on participation by most women with childbearing potential from entering Phase 1 and early Phase 2 trials, and now encourages their participation. FDA believes that early drug and biologic trials can be safely conducted in women even before completion of all animal reproduction studies through protocol designs that include monitoring for pregnancy as well as measures to prevent pregnancy during exposure to investigational agents.

Second, sponsors should collect sex-related data during research and development and should analyze the data for sex effects in addition to other variables such as age and race. FDA requires sponsors to include a fair representation of both sexes as participants in clinical trials so that clinically significant sex-related differences in response can be detected.

In addition, three specific pharmacokinetics issues should be considered when feasible: (1) effect of the stages of the menstrual cycle; (2) effect of exogenous hormonal therapy including oral contraceptives; and (3) effect of the drug or biologic on the pharmacokinetics of oral contraceptives.

IRBs now have broader discretion to encourage the entry of a wide range of individuals into the early phases of clinical trials. FDA appreciates the cooperation of IRBs in assisting the Agency to foster changes in product development that will promote the overall health of all people. FDA urges IRBs not to needlessly exclude women or other groups.