Efficient group-sequential designs for monitoring two time-to-event outcomes in clinical trials

[[abstract]]We discuss logrank test-based methods for early efficacy or futility evaluation in group-sequential clinical trials designed to compare two interventions using two time-to-event outcomes. We consider three typical situations (1) both events are non-composite and nonfatal, (2) both events are non-composite but one event is fatal, and (3) one event is composite but other is fatal and non-composite. We outline strategies for rejecting the null hypothesis associated with two inferential goals, evaluating if a test intervention is superior to a control intervention on: (1) both outcomes (multiple co-primary endpoints: MCPE), and (2) at least one outcome (multiple primary endpoints: MPE). We provide an example to illustrate the methods and discuss practical considerations when designing these trials