Estimands for Continuous Longitudinal Outcomes in the Presence of Treatment Discontinuation?A Simulation Study in Hyperkalemia Treatments
Estimands for Continuous Longitudinal Outcomes in the Presence of Treatment Discontinuation?A Simulation Study in Hyperkalemia Treatments
复制标题
治疗中断时连续纵向结果的估计？高钾血症治疗的模拟研究
DOI：
10.1080/19466315.2022.2050289
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发表时间：
2022
影响因子：
1.8
通讯作者：
Sakamaki Kentaro
中科院分区：
文献类型：
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作者：
Tsuchikawa Masaru;Sakamaki Kentaro
ICH-E9（R1）附录指南要求精确描述关注的治疗效果，称为“被估量”，反映每种特定治疗环境中试验目的提出的临床问题。在评价维持治疗（如高钾血症治疗）的临床试验中，其中一个并发事件是由于异常实验室检查值（超出可接受范围）而计划停止治疗。在使用纵向数据进行评价时，经常使用重复测量、应答者分析和生存分析的混合模型来处理并发事件。在复合变量或假设策略下，也可以考虑优先的复合结果或最后一个等级结转。在这项研究中，我们提出了一个优先的复合结果在临床试验中评估维持治疗与治疗中断。此外，定义了每项分析的被估量，并评价了操作特性。模拟研究表明，使用复合变量策略的优先复合结果和使用假设策略的重复测量的混合模型的有用性。
The ICH-E9 (R1) addendum guideline requires a precise description of the treatment effect of interest, named “estimand,” reflecting the clinical question posed by the trial objective, in each specific therapeutic setting. In clinical trials evaluating maintenance treatments, such as hyperkalemia treatments, one of the intercurrent events is planned treatment discontinuation due to abnormal laboratory values (outside the acceptable range). When using longitudinal data for evaluation, the mixed model for repeated measures, responder analysis, and survival analysis are often used to deal with intercurrent events. Under composite variable or hypothetical strategies, prioritized composite outcome or the last rank carried forward can also be considered. In this study, we propose a prioritized composite outcome in clinical trials evaluating maintenance treatments with treatment discontinuation. In addition, the estimand for each analysis was defined, and operating characteristics were evaluated. Simulation studies indicate the usefulness of the prioritized composite outcome using the composite variable strategy and the mixed model for repeated measures using the hypothetical strategy.