Abstract

Randomized clinical trials designed to establish noninferiority of an experimental therapy as compared to a standard (active-control) therapy as measured by binomial proportions are being widely used. Randomization is often stratified by prognostic factors. We propose a Mantel–Haenszel (MH) type test to demonstrate noninferiority in terms of the differences in success proportions and when the noninferiority margin is not necessarily uniform in all strata. It is assumed that the efficacy of the active control is documented in at least one earlier placebo-controlled trial. Derivation of the new test originates from Wittes and Wallenstein, who have discussed asymptotic unconditional power and sample size for the MH test. We provide an easy to calculate formula for sample size. We call the new test as W-square test. It may be an alternative to the one proposed by Yanagawa et al. Yanagawa’s Neriproct suppository data are analyzed using the W-square test. A SAS code that calculates the p-value is provided.

摘要

旨在确定与标准（主动对照）治疗相比，通过二项式比例测量的实验治疗的非劣效性的随机临床试验正在广泛使用。随机化通常根据预后因素进行分层。我们建议进行Mantel–Haenszel（MH）型测试，以证明成功率的差异以及非劣质性边缘不一定在所有阶层中均一的情况下的非劣质性。假设至少在一项较早的安慰剂对照试验中记录了主动对照的功效。新测试的派生来自Wittes和Wallenstein，他们讨论了MH测试的渐近无条件功效和样本量。我们提供了一个易于计算的样本量公式。我们称新测试为W方检验。它可以替代Yanagawa等人提出的方法。使用W方检验分析Yanagawa的Neriproct栓剂数据。提供了一个计算p值的SAS代码。