Time-to-event endpoints show an increasing popularity in phase II cancer trials. The standard statistical tool for such one-armed survival trials is the one-sample log-rank test. Its distributional properties are commonly derived in the large sample limit. It is however known from the literature, that the asymptotical approximations suffer when sample size is small. There have already been several attempts to address this problem. While some approaches do not allow easy power and sample size calculations, others lack a clear theoretical motivation and require further considerations. The problem itself can partly be attributed to the dependence of the compensated counting process and its variance estimator. For this purpose, we suggest a variance estimator which is uncorrelated to the compensated counting process. Moreover, this and other present approaches to variance estimation are covered as special cases by our general framework. For practical application, we provide sample size and power calculations for any approach fitting into this framework. Finally, we use simulations and real world data to study the empirical type I error and power performance of our methodology as compared to standard approaches.
翻译:时间到活动终点在第二阶段癌症试验中越来越受欢迎。这种单臂生存试验的标准统计工具是一模一样的日志测试。其分布特性通常取自大抽样限值。然而,据文献所知,当抽样规模小时,静脉近似值会受到影响。已经尝试过几次解决这一问题。虽然有些方法不易进行权力和抽样规模计算,但另一些方法缺乏明确的理论动机,需要进一步考虑。问题本身部分可归因于补偿性计数过程的依赖性及其差异估计。为此目的,我们建议一个与补偿性计数过程无关的差异估计值。此外,总框架将这一差异估计方法和其他现行方法作为特例包括在内。关于实际应用,我们为任何适合这一框架的方法提供抽样规模和权力计算。最后,我们利用模拟和真实世界数据来研究与标准方法相比,我们方法的经验型I错误和权力表现。