Abstract 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.

中文翻译：

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当测试基于加权对数秩统计时，灵活监控组序贯生存试验

摘要 我们考虑使用加权对数秩统计对具有随时间变化的治疗效果的生存终点进行重复的组序贯测试。本文的重点是在信息增长是非线性的情况下监控此统计数据。我们建议使用约束边界方法来维持组顺序设计的计划操作特性。提出了一个模拟研究来证明该方法的操作特性，并通过一个案例研究来说明该过程。我们表明，在监测加权对数秩统计时，需要在中期分析中估计进入和生存分布。