Applications of covering principle to clinical trials with multiple objectives

Abstract

A novel covering principle was recently proposed to address the multiplicity issue in the multiple hypotheses testing with a hierarchical structure. In this article, a sieve method is proposed to decompose the family of hypotheses into subfamilies. A Shiny web app in R is developed which makes it easier for users to build the objective-tailored multiple testing procedure based on the covering principle by a smart phone or a tablet with a web browser. The proposed methods are applied to two real clinical trials, demonstrating the flexibility and greater power than the popular gate-keeping method.

KEYWORD:

• Closed testing principle
• Covering principle
• Dominance relation
• Familywise error rate
• Gate-keeping
• Graphical approach
• Multiple testing
• Shiny web app

Acknowledgments

We are very grateful to the editor and the referees for their valuable comments and suggestions in the improvement of the quality of our paper.