Title: Group Sequential Design for Non-Proportional Hazards: Logrank, Weighted Logrank, and MaxCombo Methods Show Chinese title

Title: 非比例风险的组序设计：对数秩检验、加权对数秩检验和MaxCombo方法

Abstract: Non-proportional hazards (NPH) are often observed in clinical trials with time-to-event endpoints. A common example is a long-term clinical trial with a delayed treatment effect in immunotherapy for cancer. When designing clinical trials with time-to-event endpoints, it is crucial to consider NPH scenarios to gain a complete understanding of design operating characteristics. In this paper, we focus on group sequential design for three NPH methods: the average hazard ratio, the weighted logrank test, and the MaxCombo combination test. For each of these approaches, we provide analytic forms of design characteristics that facilitate sample size calculation and bound derivation for group sequential designs. Examples are provided to illustrate the proposed methods. To facilitate statisticians in designing and comparing group sequential designs under NPH, we have implemented the group sequential design methodology in the gsDesign2 R package at https://cran.r-project.org/web/packages/gsDesign2/. Show Chinese abstract

Abstract: 非比例风险（NPH）在具有事件时间终点的临床试验中经常被观察到。 一个常见的例子是癌症免疫治疗中具有延迟治疗效果的长期临床试验。 在设计具有事件时间终点的临床试验时，考虑NPH情景至关重要，以全面了解设计的操作特性。 本文重点研究三种NPH方法的组序设计：平均风险比、加权对数秩检验和MaxCombo组合检验。 对于每种方法，我们提供了设计特性的解析形式，以促进组序设计的样本量计算和边界推导。 提供了示例来说明所提出的方法。 为了便于统计学家在NPH下设计和比较组序设计，我们已在gsDesign2 R包中实现了组序设计方法，网址为https://cran.r-project.org/web/packages/gsDesign2/。