EVALUATION OF EXPERIMENTS WITH ADAPTIVE INTERIM ANALYSES
EVALUATION OF EXPERIMENTS WITH ADAPTIVE INTERIM ANALYSES
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DOI：
10.2307/2533441
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发表时间：
1994-12-01
期刊：
影响因子：
1.9
通讯作者：
KOHNE, K
中科院分区：
文献类型：
--
作者：
BAUER, P;KOHNE, K
提出了一种在具有自适应中期分析的实验中进行统计测试的通用方法。该方法基于在中期分析之前和之后观察到的不相交子样本的误差概率。形式上，通过将两个 p 值组合成全局检验统计量来检验各个原假设的交集。引入了费舍尔乘积标准在第一个子样本中 p 值的临界限值方面的停止规则，包括在缺失效应的情况下提前停止。考虑定性治疗阶段相互作用的控制。概述了三个阶段。在正态分布均值检验中，根据第一个子样本相对于总样本量的增加比例，计算使用乘积标准而不是对整个样本进行最佳经典检验时的功效损失。推导了由于提前停止而导致的功率损失的上限。给出了一个一般示例，并给出了评估试验第二阶段样本量的规则。讨论了解释问题和应用时应采取的注意事项。最后，描述了此类设计中估计偏差的来源。
A general method for statistical testing in experiments with an adaptive interim analysis is proposed. The method is based on the observed error probabilities from the disjoint subsamples before and after the interim analysis. Formally, an intersection of individual null hypotheses is tested by combining the two p-values into a global test statistic. Stopping rules for Fisher's product criterion in terms of critical limits for the p-value in the first subsample are introduced, including early stopping in the case of missing effects. The control of qualitative treatment-stage interactions is considered. A generalization to three stages is outlined.The loss of power when using the product criterion instead of the optimal classical test on the whole sample is calculated for the test of the mean of a normal distribution, depending on increasing proportions of the first subsample in relation to the total sample size. An upper bound on the loss of power due to early stopping is derived.A general example is presented and rules for assessing the sample size in the second stage of the trial are given. The problems of interpretation and precautions to be taken for applications are discussed. Finally, the sources of bias for estimation in such designs are described.