A method for testing a prespecified subgroup in clinical trials

In clinical trials, investigators are often interested in the effect of a given study treatment on a subgroup of patients with certain clinical or biological attributes in addition to its effect on the overall study population. Such a subgroup analysis would become even more important to the study sponsor if an efficacy claim can be made for the subgroup when the test for the overall study population fails at a prespecified alpha level. In practice, such a claim is often dependent on prespecification of the subgroup and certain implicit or explicit requirements placed on the study results due to ethical or regulatory concerns. By carefully considering these requirements, we propose a general statistical methodology for testing both the overall and subgroup hypotheses, which has optimal power and strongly controls the familywise Type I error rate.