25 Sample Size Determination for Power Analysis with Hierarchical Endpoints in Group Sequential Designs

Oregon Convention Center 

The increasing demand for drug efficacy research underscores the importance of addressing the hypothesis testing problem in both primary and secondary endpoints during the designing phase of clinical trials. This necessitates for an adjustment of multiplicity, particularly in hierarchical endpoints, a concept known as multiple endpoint testing. However, in group sequential designs, the statistical procedure for adjustment of the overall type I error rate of multiple hypotheses becomes complex. While the existing literature on gatekeeping procedures and alpha splitting effectively controls the family-wise error rate (FWER) and ensures sufficient power for testing primary endpoints, it falls short of providing adequate power for testing the secondary endpoint. This article introduces a model-based method for comparing a treatment's primary and secondary endpoints with those of a control. Additionally, a flexible approach for selecting the critical boundary of the secondary endpoint is developed to enhance the power of the corresponding hypothesis. Simulation results demonstrate that the proposed model-based method provides better adequate power with smaller samples while strictly con

Hierarchical Endpoints

Group Sequential Design

FWER Control

Power Analysis