Abstract

In this article, we illustrate the method of designing a group-sequential randomized clinical trial based on the difference in restricted mean survival time (RMST). The procedure is based on theoretical formulations of Murray and Tsiatis. We also present a numerical example in designing a cardiology surgical trial. Various practical considerations are discussed. R codes are provided in the supplementary materials. We conclude that the group-sequential design for RMST is a viable option in practice. A simulation study is performed to compare the proposed method to the Max-Combo and conventional log-rank tests. The simulation result shows that when there is a delayed treatment benefit and the proportional hazards assumption is untrue, the sequential design based on the RMST can be more efficient than that based on the log-rank test but less efficient than that based on the Max-Combo test. Compared with Max-Combo test, the RMST-based study design yield coherent estimand, statistical inference and result interpretation.

摘要

在本文中，我们说明了基于受限平均生存时间 (RMST) 的差异设计组序贯随机临床试验的方法。该程序基于 Murray 和 Tsiatis 的理论公式。我们还提供了一个设计心脏病手术试验的数值示例。讨论了各种实际考虑。R 代码在补充材料中提供。我们得出结论，RMST 的群序设计在实践中是一个可行的选择。进行模拟研究以将所提出的方法与 Max-Combo 和传统的对数秩检验进行比较。模拟结果表明，当存在延迟治疗收益且比例风险假设不成立时，基于 RMST 的序列设计可以比基于对数秩检验的顺序设计更有效，但比基于 Max-Combo 检验的效率低。与 Max-Combo 检验相比，基于 RMST 的研究设计产生了一致的估计、统计推断和结果解释。