Considerations on Testing Secondary Endpoints in Group Sequential Design

Abstract

ABSTRACTIn the fixed sample size design, when the null hypothesis for the primary endpoint is rejected at trial completion, secondary endpoints sometimes are tested at the full alpha level in a prespecified hierarchical order, and this strategy strongly controls the overall Type I error rate. However, in a group sequential setting, this hierarchical testing strategy may not control the overall Type I error rate for the secondary endpoints in the strong sense. Thus, when there is one interim analysis, there are proposals for an alpha spending function for testing secondary endpoints. Motivated by a Phase 3 oncology trial, we explored whether there is a less stringent approach to control the Type I error rate for testing one or more secondary endpoints in a prespecified order for the settings where there are more than one interim analysis.