Flexibly Monitoring Group Sequential Survival Trials When Testing Is Based Upon a Weighted Log-Rank Statistic

We consider the repeated group sequential testing of a survival endpoint with a time-varying treatment effect using a weighted log-rank statistic. The emphasis of this article is on the monitoring of this statistic where information growth is nonlinear. 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 log-rank statistic, the entry and survival distribution needs to be estimated at interim analyses.