On the Fleming-Harrington test for late effects in prevention randomized controlled trials
On the Fleming-Harrington test for late effects in prevention randomized controlled trials
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DOI：
10.1080/15598608.2017.1295889
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发表时间：
2017-01-01
影响因子：
0.6
通讯作者：
Savy, Nicolas
中科院分区：
文献类型：
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作者：
Gares, Valerie;Andrieu, Sandrine;Savy, Nicolas
加权对数秩检验是检测临床试验中后期效应的常用工具。权重决定了测试最佳的替代假设。因此，选择特定的权重是实践中的一个关键问题。 Harrington 和 Fleming 于 1982 年提出了一种常见的重量。相应的测试是在标准统计软件包中实现的。然而，在随机对照临床试验中使用该测试提出了两个尚未解决的主要困难。首先，权重取决于在收集数据之前必须设置的参数 q。其次，必要的样本量取决于这个 q。本文解决了这些困难。我们提供了备择假设的明确形式，在该备择假设下，后期效应的 Fleming-Harrington 检验在 Pitman 渐近相对效率方面是最佳的。通过模拟，我们研究了 Fleming-Harrington 检验的后期效应的各个方面，例如功率特性和对 q 值的敏感性。我们还研究了 q 与 Fleming-Harrington 检验所需样本量之间的关系。基于这些结果，我们建议 q = 3 作为测试后期效应的一般选择。我们用痴呆症领域预防试验产生的数据集来说明我们的方法。
Weighted logrank tests are the usual tool for detecting late effects in clinical trials. Weights determine the alternative hypotheses against which the tests are optimal. Choosing a specific weight is thus a crucial issue in practice. One common weight was introduced in 1982 by Harrington and Fleming. The corresponding test is implemented in standard statistical softwares packages. However, using this test in randomized controlled clinical trials raises two major and still unsolved difficulties. First, the weight depends on a parameter q that has to be set before collecting the data. Second, the necessary sample size depends on this q. This article addresses these difficulties. We provide the explicit form of the alternative hypothesis under which the Fleming-Harrington test for late effects is optimal in terms of Pitman's asymptotic relative efficiency. Using simulations, we investigate various aspects of the Fleming-Harrington test for late effects, such as power properties and sensitivity to the value of q. We also investigate the relation between q and the necessary sample size for the Fleming-Harrington test. Based on these results, we propose q = 3 as a general choice for testing late effects. We illustrate our methodology on a data set arising from a prevention trial in the field of dementia.