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On information fraction for Fleming‐Harrington type weighted log‐rank tests in a group‐sequential clinical trial design
Statistics in Medicine ( IF 2 ) Pub Date : 2021-02-24 , DOI: 10.1002/sim.8905
Madan G Kundu 1 , Jyotirmoy Sarkar 2
Affiliation  

When comparing survival times of treatment and control groups under a more realistic nonproportional hazards scenario, the standard log‐rank (SLR) test may be replaced by a more efficient weighted log‐rank (WLR) test, such as the Fleming‐Harrington (FH) test. Designing a group‐sequential clinical trial with one or more interim looks during which a FH test will be performed, necessitates correctly quantifying the information fraction (IF). For SLR test, IF is defined simply as the ratio of interim to final numbers of events; but for FH test, it can deviate substantially from this ratio. In this article, we separate the effect of weight function (of FH test) alone on IF from the effect of censoring. We have shown that, without considering the effect of censoring, IF can be derived analytically for FH test using information available at the design stage and the additional effect due to censoring is relatively smaller. This article intends to serve two major purposes: first, to emphasize and rationalize the deviation of IF in weighted log‐rank test from that of SLR test which is often overlooked (Jiménez, Stalbovskaya, and Jones); second, although it is impossible to predict IF for a weighted log‐rank test at the design stage, our decomposition of effects on IF provides a reasonable and practically feasible range of IF to work with. We illustrate our approach with an example and provide simulation results to evaluate operating characteristics.

中文翻译:

分组顺序临床试验设计中Fleming-Harrington型加权对数秩检验的信息分数

在比较现实的非比例危害情况下比较治疗组和对照组的生存时间时,标准对数秩(SLR)检验可以由更有效的加权对数秩(WLR)检验代替,例如Fleming-Harrington(FH) ) 测试。设计具有一个或多个临时外观的小组顺序临床试验,在此期间将进行FH测试,因此必须正确地量化信息分数(IF)。对于SLR测试,IF被简单定义为事件的临时数量与最终数量的比值;但是对于跳频测试,它可能会大大偏离该比率。在本文中,我们将权重函数(FH测试)对IF的影响与审查的影响分开。我们已经表明,不考虑审查的效果,可以使用设计阶段可用的信息通过分析得出用于FH测试的IF,并且由于检查而产生的附加影响相对较小。本文旨在达到两个主要目的:首先,强调并合理化加权对数秩检验中的IF与经常被忽略的SLR测试(Jiménez,Stalbovskaya和Jones)的偏差。其次,尽管在设计阶段无法通过加权对数秩检验来预测中频,但我们对中频影响的分解提供了一个合理且实际可行的中频范围。我们通过一个示例来说明我们的方法,并提供仿真结果以评估操作特性。强调并合理化加权对数秩检验中的IF与经常被忽略的SLR检验中的IF偏差(Jiménez,Stalbovskaya和Jones);其次,尽管在设计阶段无法通过加权对数秩检验来预测中频,但我们对中频影响的分解提供了一个合理且实际可行的中频范围。我们通过一个示例来说明我们的方法,并提供仿真结果以评估操作特性。强调并合理化加权对数秩检验中的IF与经常被忽略的SLR检验中的IF偏差(Jiménez,Stalbovskaya和Jones);其次,尽管在设计阶段无法通过加权对数秩检验来预测中频,但我们对中频影响的分解提供了一个合理且实际可行的中频范围。我们通过一个示例来说明我们的方法,并提供仿真结果以评估操作特性。
更新日期:2021-04-08
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