A practical review of response-adaptive randomization: Under-explored challenges and potential directions

Response-adaptive randomization (RAR) dynamically adjusts allocation probabilities of sequentially enrolled patients based on accumulating response information. It has gained increasing attention in clinical trials for its ability to enhance statistical efficiency by accelerating estimation of treatment effects, improve ethical allocation by favoring superior interventions, and maintain robust parameter estimation (e.g. via variance or uncertainty reduction) while accounting for adaptive modifications. While both regulatory agencies and the broader clinical research community are making efforts to promote the application of RAR, its real-world implementation remains limited. In this article, we review the application of RAR in clinical practice from 2015 to 2024, identifying key challenges such as managing diverse patient outcome types, incorporating repeated measurements, and addressing missing data. We categorize various RAR methods and propose practical solutions to these challenges, providing insights and practical references for clinical trial practitioners. Additionally, we discuss the limitations of existing RAR methods and outline potential future research directions. Our review aims to bridge the gap between theory and practice, promoting the broader adoption of RAR in clinical trials while advancing the development of RAR theory and methodology.