A hybrid procedure for detecting global treatment effects in multivariate clinical trials: theory and applications to fMRI studies.
A hybrid procedure for detecting global treatment effects in multivariate clinical trials: theory and applications to fMRI studies.
复制标题
用于检测多变量临床试验中整体治疗效果的混合程序：功能磁共振成像研究的理论和应用。
DOI：
10.1002/sim.4395
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发表时间：
2012
影响因子：
2
通讯作者：
Minas G
中科院分区：
文献类型：
--
作者：
Minas G
在多变量临床试验中，一个关键的研究终点是确定候选治疗是否比已确定的替代方案更有效。这一全球终点对于研究（例如神经影像学研究）显然具有很高的实用价值，这些研究的结局维度不仅众多，而且高度相关，可用样本量通常较小。在本文中，我们开发了一个两阶段的程序来检验治疗效果之间的全局等效性的零假设，并展示了其在分析II期神经影像学试验中的应用。将诸如历史数据的适当统计或适当引出的专家临床意见之类的先验信息与从试验的第一阶段收集的数据相结合，以学习一组最佳权重。我们将这些权重应用于第二阶段响应的结果维度，以形成线性组合检验统计量，同时控制检验的假阳性率。我们表明，所提出的测试具有理想的渐近性质和在广泛的条件下，他们的幂函数。特别是，通过比较的权力提出的测试与霍特林的T2，我们证明了他们的优势时，样本量接近的多变量结果的尺寸。我们将我们的方法应用于fMRI研究，我们发现，对于治疗效果的足够精确的第一阶段估计，标准单阶段测试程序优于标准单阶段测试程序。版权所有© 2011约翰威利父子有限公司.
In multivariate clinical trials, a key research endpoint is ascertaining whether a candidate treatment is more efficacious than an established alternative. This global endpoint is clearly of high practical value for studies, such as those arising from neuroimaging, where the outcome dimensions are not only numerous but they are also highly correlated and the available sample sizes are typically small. In this paper, we develop a two‐stage procedure testing the null hypothesis of global equivalence between treatments effects and demonstrate its application to analysing phase II neuroimaging trials. Prior information such as suitable statistics of historical data or suitably elicited expert clinical opinions are combined with data collected from the first stage of the trial to learn a set of optimal weights. We apply these weights to the outcome dimensions of the second‐stage responses to form the linear combinationzandttests statistics while controlling the test's false positive rate. We show that the proposed tests hold desirable asymptotic properties and characterise their power functions under wide conditions. In particular, by comparing the power of the proposed tests with that of Hotelling'sT2, we demonstrate their advantages when sample sizes are close to the dimension of the multivariate outcome. We apply our methods to fMRI studies, where we find that, for sufficiently precise first stage estimates of the treatment effect, standard single‐stage testing procedures are outperformed. Copyright © 2011 John Wiley & Sons, Ltd.