Sample size determination and re‐estimation for matched pair designs with multiple binary endpoints
Sample size determination and re‐estimation for matched pair designs with multiple binary endpoints
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DOI：
10.1002/bimj.201100231
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发表时间：
2013-05
影响因子：
1.7
通讯作者：
Jin Xu;Menggang Yu
中科院分区：
文献类型：
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作者：
Jin Xu;Menggang Yu
最近的症状管理试验的动机，同时评估癌症化疗的多个二元终点，我们扩展了单变量McNemar检验多变量的情况下，双盲临床试验配对。我们提出了一个通用的方法来测试非劣效性或等效性。该方法采用边际得分统计量的交并原理来获得渐近α水平检验。把握度公式和样本量计算通过一种简单的数值方法提供，该方法考虑了终点之间的相关性结构。我们进一步考虑通过内部初步研究重新估计样本量。为了避免双盲试验的揭盲，我们还提出了一种盲法的滋扰参数估计。仿真研究表明了所提出的方法的有效性。癌症化疗试验的应用举例说明。
Motivated by a recent symptom management trial to simultaneously assess multiple binary endpoints for cancer chemotherapy, we extend the univariate McNemar test to multivariate cases for doubly blinded clinical trials with matched pairs. We propose a general method to test noninferiority or equivalence. The method employs the intersection‐union principle on the marginal score statistics to obtain an asymptotic α‐level test. Power formula and sample size calculation are provided by a simple numerical method that accounts for the correlation structure among the endpoints. We further consider sample size re‐estimation through internal pilot study. To avoid the need of unblinding for doubly blinded trials, we also propose a blinded approach for nuisance parameter estimation. The effectiveness of the proposed methods is demonstrated by simulation studies. Application to the cancer chemotherapy trial is illustrated.