Practical Considerations and Recommendations for Master Protocol Framework: Basket, Umbrella and Platform Trials

Lu, Chengxing (Cindy); Li, Xiaoyun (Nicole); Broglio, Kristine; Bycott, Paul; Jiang, Qi; Li, Xiaoming; McGlothlin, Anna; Tian, Hong; Ye, Jingjing

Master protocol, categorized as basket trial, umbrella trial or platform trial, is an innovative clinical trial framework that aims to expedite clinical drug development, enhance trial efficiency, and eventually bring medicines to patients faster. Despite a clear uptake on the advantages in the concepts and designs, master protocols are still yet to be widely used. Part of that may be due to the fact that the master protocol framework comes with the need for new statistical designs and considerations for analyses and operational challenges. In this article, we provide an overview of the master protocol framework, unify the definitions with some examples, review the statistical methods for the designs and analyses, and focus our discussions on some practical considerations and recommendations of master protocols to help practitioners better design and implement such studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43441-021-00315-7.