A Revisit of Sample Size Decisions in Confirmatory Trials
A Revisit of Sample Size Decisions in Confirmatory Trials
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DOI：
10.1198/sbr.2009.0073
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发表时间：
2010-05-01
影响因子：
1.8
通讯作者：
Yang, Ruoyong
中科院分区：
文献类型：
--
作者：
Chuang-Stein, Christy;Yang, Ruoyong
在设计III期优势试验时，我们经常计算样本量，以检测在先前试验中观察到的治疗效果。在这篇文章中，我们建议考虑到围绕估计的治疗效果和患者反应的估计变异性的不确定性。我们认为，将验证性试验的样本量决定建立在试验将产生积极结果的概率上将比传统的统计权力更好。我们表明，在传统方法下计算的样本量往往太小，无法产生理想的成功概率。我们将这一论点扩展到“条件概率”概念，该概念通常是自适应设计中无效性判定和样本量重新估计的基础。我们认为，在后一种情况下，预测力的概念可能会为审判的前景提供更现实的衡量标准。在我们看来，无论是在设计阶段还是在临时样本量重估决策点，当基于阳性试验机会的确证试验所需的样本量大大高于传统方法计算的样本量时，试验者应予以关注。
When designing a phase III superiority trial, we often compute the sample size to detect a treatment effect observed in a previous trial. In this article, we propose to take into account uncertainties around the estimated treatment effect and the estimated variability in patients' responses jointly. We argue that it will be better to base the sample size decision for a confirmatory trial on the probability that the trial will produce a positive outcome than the traditional statistical power. We show that sample sizes computed under the traditional method are often too small to yield a desirable success probability. We extend this argument to the "conditional probability" concept that is often the basis for futility decision and sample size reestimation in an adaptive design. We argue that in the latter case, the concept of predictive power is likely to provide a more realistic measure on the prospect of the trial. In our opinion, a trialist should be concerned when the required sample size for a confirmatory trial based on the chance of a positive trial is substantially higher than that calculated under the traditional approach, either at the design stage or at the interim sample size reestimation decision point.