Hasler Mario
Int J Biostat. 2014;10(1):17-28. doi: 10.1515/ijb-2012-0015.
This article describes an extension of multiple contrast tests to the case of multiple, correlated endpoints. These endpoints are assumed to be normally distributed with different scales and variances. Unlike in previous articles, the covariance matrices are also assumed to be unequal for the treatment groups. Approximate multivariate t-distributions are used to obtain multiplicity-adjusted p-values and quantiles for test decisions or simultaneous confidence intervals. Simulation results show that this approach controls the family-wise error type I over both the comparisons and the endpoints in an admissible range. The approach will be applied to a semi-synthetic example data set of a randomized, placebo-controlled phase IIb dose-finding study of a novel anti-muscarinic agent for five continuous endpoints. A related R package is available.
本文描述了将多重对比检验扩展到多个相关终点的情况。这些终点被假定为具有不同尺度和方差的正态分布。与先前的文章不同，还假定治疗组的协方差矩阵不相等。使用近似多元t分布来获得用于检验决策或同时置信区间的多重性调整p值和分位数。模拟结果表明，该方法将I型家族性错误在比较和终点方面都控制在可接受范围内。该方法将应用于一种新型抗毒蕈碱药物的随机、安慰剂对照IIb期剂量探索研究的半合成示例数据集，该研究有五个连续终点。有一个相关的R包可供使用。
