Considerations for master protocols using external controls

• DOI: 10.1080/10543406.2024.2311248
• Publication Date: 2024-02-16T18:35:40Z
• Authors: Jie Chen; Xiaoyun (Nicole) Li; Chengxing (Cindy) Lu; Sammy Yuan; Godwin Yung; Jingjing Ye; Hong Tian; Jianchang Lin

There has been an increasing use of master protocols in oncology clinical trials because its efficiency to accelerate cancer drug development and flexibility accommodate multiple substudies. Depending on the study objective design, a protocol trial can be basket trial, umbrella platform or any other form which investigational products and/or subpopulations are studied under single protocol. Master external data evidence (e.g. controls) for treatment effect estimation, further improve trials. This paper provides overview different types controls their unique features when used protocols. Some key considerations with discussed including construction estimands, assessment fit-for-use real-world data, Similarities differences between regular randomized controlled using discussed. A targeted learning-based causal roadmap is presented constitutes three steps: (1) define target statistical estimand that aligns objective, (2) efficient estimator estimate uncertainty, (3) evaluate impact assumptions conclusion by performing sensitivity analyses. Two illustrative examples merits possible improvement estimation.