To what extent is response-adaptive randomization used in clinical trials? A systematic review using Cortellis Regulatory Intelligence database.

Abstract

Background: There is emerging evidence of the increasing uptake of response-adaptive randomization (RAR) in clinical trials. However, a systematic review of RAR trials, their context of use, characteristics, and stakeholder acceptance has been lacking. Methods: We performed a systematic review of clinical trials that utilized elements of RAR, identified via the Cortellis Regulatory Intelligence database following a pre-specified selection process. We report a summary of relevant characteristics of the identified trials. Results: Out of 170 records, 39 RAR trials were identified (22 completed, 17 ongoing as of October 2024). The majority were Phase 2-focused studies (phases 1/2, 2, 2b, and 2/3), academically sponsored, and concentrated in oncology, neurology, and infectious diseases. Small molecules and biologics were the most common investigational products. Among the 22 completed trials, seven reported positive outcomes. Notably, two of these trials provided pivotal data that informed the further development and subsequent regulatory approval of the investigational compounds. Conclusion: Over the past two decades, RAR has been increasingly utilized in complex adaptive trials across diverse therapeutic areas and clinical research phases. This systematic review provides a critical "baseline" for tracing the dynamics of RAR applications and should help the clinical research community recognize RAR as a valuable methodology for optimizing future trial designs.