Wiens Brian L
a Department of Biostatistics , Aquinox Pharmaceuticals Inc. , San Bruno , California.
J Biopharm Stat. 2018;28(1):52-62. doi: 10.1080/10543406.2017.1378667. Epub 2017 Oct 24.
We consider analysis of active control, non-inferiority clinical trials with multiple primary endpoints for assessing efficacy of an investigational treatment. Many of the issues with multiple endpoints for non-inferiority trials are similar to issues for superiority trials, but there are important differences. Because non-inferiority trials typically make decisions with confidence interval bounds instead of p-values, care must be taken in adjusting for multiple hypotheses. Composite endpoints are more difficult to interpret in non-inferiority trials due to difficulties in indirectly comparing the investigational treatment to placebo on each component. Otherwise many of the methods used in superiority trials (including sequential testing, graphical procedures and gatekeeping procedures) can be applied to non-inferiority trials with a little additional care. We focus on the differences between non-inferiority and superiority trials to provide guidance on application of recent regulatory guidance to non-inferiority trials.
我们考虑对采用多个主要终点的活性对照非劣效性临床试验进行分析，以评估一种试验性治疗的疗效。非劣效性试验中多个终点的许多问题与优效性试验的问题相似，但也存在重要差异。由于非劣效性试验通常根据置信区间界限而非p值做出决策，因此在进行多重假设调整时必须谨慎。由于在非劣效性试验中难以在每个组成部分上间接将试验性治疗与安慰剂进行比较，所以复合终点在非劣效性试验中更难解释。否则，优效性试验中使用的许多方法（包括序贯检验、图形程序和把关程序）稍作额外注意就可应用于非劣效性试验。我们着重探讨非劣效性试验与优效性试验之间的差异，以便为将最新监管指南应用于非劣效性试验提供指导。
