Guidelines Regarding Trials Involving Potentially Teratogenic Agents in Men and Women of Reproductive Potential

For trials involving potentially teratogenic agents, it may be appropriate to include a statement in the protocol document and in the informed consent that it is strongly recommended that women avoid pregnancy and men avoid fathering children while receiving treatment.

The Food and Drug Administration (FDA) has concluded that (1) exclusion of women from early trials is not medically necessary because the risk of fetal exposure can be minimized by patient behavior and laboratory testing, and (2) initial determinations about whether that risk is adequately addressed are properly left to patients, physicians, local IRBs and sponsors, with appropriate review and guidance by the FDA (58 FR 39406 [July 22, 1993]). The FDA stated that

appropriate precautions should be taken in clinical studies to guard against inadvertent exposure of fetuses to potentially toxic agents and to inform subjects and patients of potential risk and the need for precautions. In all cases the informed consent document and investigator’s brochure should include all available information regarding the potential risk of fetal toxicity. If animal reproductive toxicity studies are complete, the results should be presented, with some explanation of their significance in humans. If these studies have not been completed, other pertinent information should be provided, such as a general assessment of fetal toxicity in drugs with related structures or pharmacologic effects. If no relevant information is available, the informed consent should explicitly note the potential for fetal risk.