Dmitrienko Alex, Millen Brian A, Brechenmacher Thomas, Paux Gautier
Eli Lilly and Company, Indianapolis, IN 46285, USA.
Biom J. 2011 Nov;53(6):875-93. doi: 10.1002/bimj.201100036.
This paper discusses multiplicity issues arising in confirmatory clinical trials with hierarchically ordered multiple objectives. In order to protect the overall type I error rate, multiple objectives are analyzed using multiple testing procedures. When the objectives are ordered and grouped in multiple families (e.g. families of primary and secondary endpoints), gatekeeping procedures are employed to account for this hierarchical structure. We discuss considerations arising in the process of building gatekeeping procedures, including proper use of relevant trial-specific information and criteria for selecting gatekeeping procedures. The methods and principles discussed in this paper are illustrated using a clinical trial in patients with type II diabetes mellitus.
本文讨论了在具有分层排序多目标的验证性临床试验中出现的多重性问题。为了保护总体I型错误率，使用多重检验程序对多个目标进行分析。当目标按顺序排列并分组为多个族（例如主要和次要终点的族）时，采用把关程序来考虑这种层次结构。我们讨论了构建把关程序过程中出现的考虑因素，包括相关试验特定信息的正确使用以及选择把关程序的标准。本文所讨论的方法和原则通过一项II型糖尿病患者的临床试验进行了说明。
