Group-sequential Methods in Clinical Trials when Considering Multiple Outcomes as Co-primary

Abstract

Recent clinical trials are often conducted with the objective of comparing a test intervention with that of a control intervention based on several outcomes as co-primary. “Co-primary” in this setting means that the trial is designed to evaluate if the test intervention is superior to the control on all endpoints, thus evaluating the intervention’s multidimensional effects. In this presentation, we consider group sequential methods in clinical trials with multiple co-primary endpoints when appropriate planning for the varying number of analyses and information space, is conducted, where the trial is designed to evaluate if the intervention is superior to the control on ALL endpoints. Then we investigate operating characteristics of several decision-making rules for rejecting the null hypotheses in terms of overall power, Type I error rate and sample sizes. We provide an example to illustrate the methods and discuss practical considerations.