hypothesize that the responses of men and women differ substantially. Only by formulating scientifically meaningful questions and then testing them in rigorous studies can we expect to learn how women and men respond to therapy and how best to prevent and treat diseases.
Finally, avenues other than the clinical trial are available to help formulate hypotheses about the differential response of men and women to therapy. The case history has historically provided insight into subgroups. An unusual cluster of events may spark suspicion that a therapy is harmful to a subgroup of people. For example, the surprising occurrence of vaginal cancer in a group of young women led to the implication of DES in the etiology of vaginal abnormalities in daughters of women who had taken the drug during pregnancy.26
More formal approaches to observational studies include many epidemiologic methods, the “Phase IV” postmarketing study, and outcomes research.27 The pharmaceutical industry is currently studying some new approaches designed to expedite and improve the results of drug development activities. Such approaches include pharmacokinetic screens and the use of surrogate endpoints for pharmacodynamic measures. Another approach is meta-analysis, a set of techniques for combining data from various studies.28 Data from various demographic subgroups can be pooled across many studies to provide more information on treatment effect than is available from a single trial.
An armamentarium of methods to learn about subgroup responses to therapy is available and must be used. Research designs and analytic techniques must be appropriate to the specific questions being asked and data must be collected that will ultimately be useful for sorting out the relationships between sex and hormonal status and response to therapy. A global solution, such as the one proposed in Section 492B, cannot provide the answers to complex and varied questions about the effects of therapy on women.
In summary, neither adherence to quotas in the composition of a clinical trial’s study group nor the irrational exclusion of a subgroup of people can be supported scientifically. The determination of the number of women to be included in a trial should reflect reasonable hypotheses about the relationship of treatment efficacy to sex, not to global rules about the composition of study cohorts.