On selecting the critical boundary functions in group-sequential trials with two time-to-event outcomes

We investigate selection of critical boundary functions for testing the hypotheses of two time-to-event outcomes as both primary endpoints or a primary and a secondary endpoint in group-sequential clinical trials, where (1) the effect sizes of endpoints are unequal, or (2) one endpoint is for short-term evaluation and the other for longterm evaluation. Bonferroni-Holm and fixed-sequence procedures are considered. We assess the effects of the magnitudes of the hazard ratios and the correlation between the endpoints on statistical powers and provide guidance for consideration.

Automated summary

The study investigated the selection of critical boundary functions for testing hypotheses of two time-to-event outcomes in group-sequential clinical trials. It considered unequal effect sizes of endpoints and different evaluation periods for the endpoints. The effects of hazard ratios magnitudes and correlation between endpoints on statistical powers were assessed to provide guidance for consideration.