UC Irvine

We consider the repeated group sequential testing of a survival endpoint with a time-varying treatment effect using a weighted logrank statistic. The emphasis of this paper is on the monitoring of this statistic where information growth is non-linear. We propose using a constrained boundaries approach to maintain the planned operating characteristics of a group sequential design. A simulation study is presented to demonstrate the operating characteristics of the method together with a case study to illustrate the procedure. We show that when monitoring a weighted logrank statistic, the entry and survival distribution needs to be estimated at interim analyses.