Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials.
Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials.
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DOI：
10.1371/journal.pone.0146465
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Posch M
中科院分区：
文献类型：
--
作者：
Magirr D;Jaki T;Koenig F;Posch M
在验证性临床试验中，研究中期设计修改越来越被接受，只要应用适当的方法，控制错误率。因此，不幸的是，标准理论不容易处理事件发生时间终点的重要情况。我们分析了当前的方法，允许设计修改是基于完整的中期数据，即，不仅包括观察到的事件时间，还包括尚未发生事件的患者的次要终点和安全性数据。我们发现，最终的检验统计量可能会忽略一个重要的子集所观察到的事件时间。一个替代的测试，将所有事件的时间，必须作出保守的假设，以保证I型错误控制。我们使用比较两种癌症疗法的临床试验的例子来检查这种方法的功效。
Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of time-to-event endpoints is not easily handled by the standard theory. We analyze current methods that allow design modifications to be based on the full interim data, i.e., not only the observed event times but also secondary endpoint and safety data from patients who are yet to have an event. We show that the final test statistic may ignore a substantial subset of the observed event times. An alternative test incorporating all event times is found, where a conservative assumption must be made in order to guarantee type I error control. We examine the power of this approach using the example of a clinical trial comparing two cancer therapies.