Royston Patrick
MRC Clinical Trials Unit, University College London, London, UK.
Stata J. 2017 Apr;17(2):405-421.
Most randomized controlled trials with a time-to-event outcome are designed and analyzed assuming proportional hazards of the treatment effect. The sample-size calculation is based on a log-rank test or the equivalent Cox test. Nonproportional hazards are seen increasingly in trials and are recognized as a potential threat to the power of the log-rank test. To address the issue, Royston and Parmar (2016, 16: 16) devised a new "combined test" of the global null hypothesis of identical survival curves in each trial arm. The test, which combines the conventional Cox test with a new formulation, is based on the maximal standardized difference in restricted mean survival time (rmst) between the arms. The test statistic is based on evaluations of rmst over several preselected time points. The combined test involves the minimum -value across the Cox and rmst-based tests, appropriately standardized to have the correct null distribution. In this article, I outline the combined test and introduce a command, stctest, that implements the combined test. I point the way to additional tools currently under development for power and sample-size calculation for the combined test.
大多数具有事件发生时间结局的随机对照试验在设计和分析时都假定治疗效果的风险比例恒定。样本量计算基于对数秩检验或等效的Cox检验。在试验中，非比例风险越来越常见，并被认为是对数秩检验效能的潜在威胁。为解决这一问题，Royston和Parmar（2016年，第16卷，第16期）设计了一种新的“联合检验”，用于检验每个试验组中生存曲线相同这一全局零假设。该检验将传统的Cox检验与一种新的公式相结合，基于两组间受限平均生存时间（rmst）的最大标准化差异。检验统计量基于在几个预先选定的时间点对rmst的评估。联合检验涉及Cox检验和基于rmst的检验中的最小值，并进行适当标准化以使其具有正确的零分布。在本文中，我概述了联合检验，并介绍了一个实现联合检验的命令stctest。我还指出了目前正在开发的用于联合检验效能和样本量计算的其他工具。
