Group Sequential Sample Size for Comparing Two Survival Probabilities at a Specific Time Point.

Abstract

We propose a novel method that simultaneously determines the sample size for testing two survival probabilities at a pre-specified time while guaranteeing Type I error control in both fixed and group-sequential trial designs. Simulations across varying hypothesized differences, failure distributions, censoring proportions, and nominal powers demonstrate consistent performance, while interim analyses highlight maintained nominal Type I error control and increased power at each look relative to the standard binomial approach, regardless of the underlying failure time distribution or spending function. Importantly, our method is especially useful for evaluating survival outcomes at a fixed time in randomized trials where one treatment arm includes neoadjuvant therapy prior to surgery while the other involves surgery alone. Furthermore, it is advantageous when the proportional hazards assumption is not satisfied, as often occurs in immunotherapy trials with delayed or time-varying treatment effects or crossing survival curves. The method is also applicable to randomized Phase II trials, where smaller sample sizes and the use of intermediate or surrogate time-to-event endpoints demand efficient data use and robust error control. We illustrate the approach with motivating examples in renal and prostate cancer. An accompanying R Shiny application enables investigators to compute sample sizes interactively, facilitating practical trial planning in diverse settings.