Simultaneous Group Sequential Analysis of Rank-Based and Weighted Kaplan–Meier Tests for Paired Censored Survival Data

ABSTRACT

Summary .   This research sequentially monitors paired survival differences using a new class of nonparametric tests based on functionals of standardized paired weighted log-rank (PWLR) and standardized paired weighted Kaplan–Meier (PWKM) tests. During a trial, these tests may alternately assume the role of the more extreme statistic. By monitoring PEMAX, the maximum between the absolute values of the standardized PWLR and PWKM, one combines advantages of rank-based (RB) and non-RB paired testing paradigms. Simulations show that monitoring treatment differences using PEMAX maintains type I error and is nearly as powerful as using the more advantageous of the two tests in proportional hazards (PH) as well as non-PH situations. Hence, PEMAX preserves power more robustly than individually monitored PWLR and PWKM, while maintaining a reasonably simple approach to design and analysis of results. An example from the Early Treatment Diabetic Retinopathy Study (ETDRS) is given.