Sample size recalculation for binary data in internal pilot study designs
Sample size recalculation for binary data in internal pilot study designs
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DOI：
10.1002/pst.140
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发表时间：
2004-10-01
影响因子：
1.5
通讯作者：
Kieser, M
中科院分区：
文献类型：
--
作者：
Friede, T;Kieser, M
对于二元终点，所需的样本量不仅取决于显著性水平、把握度和临床相关差异的已知值，还取决于总体事件发生率。然而，研究之间的整体事件率可能会有很大差异，因此，在规划阶段对这一滋扰参数所做的假设在很大程度上是不确定的。内部试点研究设计是处理这一问题的一个有吸引力的策略。在此，根据两个治疗组的汇总数据，在正在进行的试验期间估计总体事件概率，如有必要，相应调整样本量。从监管的角度来看，除了保留盲性外，还需要解释1型错误率的最终后果。我们提出了分析计算的实际类型1错误率的内部试点研究设计与二进制端点，并将其与卡方检验的实际水平的固定样本量设计。给出了一种方法，该方法允许在盲态样本量重新计算下控制卡方检验的指定显著性水平。此外，还评估了该程序在功效和预期样本量方面的特性。在整个论文中，每个组的样本量相等的情况下，和分配比例不等的考虑。该方法是说明与应用程序在抑郁症的临床试验。版权所有（C）2004约翰威利父子有限公司。
For binary endpoints, the required sample size depends not only on the known values of significance level, power and clinically relevant difference but also on the overall event rate. However, the overall event rate may vary considerably between studies and, as a consequence, the assumptions made in the planning phase on this nuisance parameter are to a great extent uncertain. The internal pilot study design is an appealing strategy to deal with this problem. Here, the overall event probability is estimated during the ongoing trial based on the pooled data of both treatment groups and, if necessary, the sample size is adjusted accordingly. From a regulatory viewpoint, besides preserving blindness it is required that eventual consequences for the Type 1 error rate should be explained. We present analytical computations of the actual Type 1 error rate for the internal pilot study design with binary endpoints and compare them with the actual level of the chi-square test for the fixed sample size design. A method is given that permits control of the specified significance level for the chi-square test under blinded sample size recalculation. Furthermore, the properties of the procedure with respect to power and expected sample size are assessed. Throughout the paper, both the situation of equal sample size per group and unequal allocation ratio are considered. The method is illustrated with application to a clinical trial in depression. Copyright (C) 2004 John Wiley Sons Ltd.