Practice and Consideration of Master Protocol in Clinical Trials

Abstract

There is great interest in accelerating late-stage therapy development by efficiently performing a trial design with multiple therapies or multiple subpopulations simultaneously under a single protocol. The master protocols are termed to describe the design of such trials, with a variety of terms such as umbrella, basket, or platform describing specific designs, which are, in contrast to the traditional trial designs, full of complexity. What should we consider in designing a trial ensuring the safety of human subjects and demonstrating the efficacy of new therapy? This paper overviews the master protocol framework, comprehensively unifies the definitions and illustrates essential design elements of representative example trials conducted in drugs and medical devices. Besides, to understand the master protocols deeply, it is also a need to summarize the commonly-used types of master protocols in various disease and treatment fields, along with the reasons for these phenomena by analyzing the characteristics of the diseases, the mechanism of therapeutic products, and the principles of various types of master protocols. Finally, we also propose practical considerations, including the design, ethical, statistics, and funding considerations that arise from implementing complex master protocols to help practitioners better design and identify potential valuable therapies.