Biostatistics and Methodology Unit, Institut Paoli-Calmettes, Marseille, France.
INSERM, IRD, SESSTIM, Aix Marseille Univ, Marseille, France.
Stat Methods Med Res. 2024 Jul;33(7):1137-1151. doi: 10.1177/09622802241254211. Epub 2024 Jun 5.
Despite the widespread use of Cox regression for modeling treatment effects in clinical trials, in immunotherapy oncology trials and other settings therapeutic benefits are not immediately realized thereby violating the proportional hazards assumption. Weighted logrank tests and the so-called Maxcombo test involving the combination of multiple logrank test statistics have been advocated to increase power for detecting effects in these and other settings where hazards are nonproportional. We describe a testing framework based on supremum logrank statistics created by successively analyzing and excluding early events, or obtained using a moving time window. We then describe how such tests can be conducted in a group sequential trial with interim analyses conducted for potential early stopping of benefit. The crossing boundaries for the interim test statistics are determined using an easy-to-implement Monte Carlo algorithm. Numerical studies illustrate the good frequency properties of the proposed group sequential methods.
尽管 Cox 回归在临床试验中被广泛用于建模治疗效果，但在肿瘤免疫治疗试验和其他情况下，治疗益处不会立即显现，从而违反了比例风险假设。加权对数秩检验和所谓的 Maxcombo 检验（涉及多个对数秩检验统计量的组合）已被提倡用于增加在这些和其他情况下检测效果的功效，这些情况下风险是非比例的。我们描述了一种基于通过连续分析和排除早期事件或使用移动时间窗口获得的极大对数秩统计量的检验框架。然后，我们描述了如何在具有中期分析以潜在提前停止获益的分组序贯试验中进行此类检验。使用易于实现的蒙特卡罗算法确定中期检验统计量的边界。数值研究说明了所提出的分组序贯方法的良好频率特性。
