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

Area of Science:

• Clinical Trials Methodology
• Biostatistics
• Medical Research Design

Background:

• Response-adaptive randomization (RAR) dynamically adjusts patient allocation in clinical trials using accumulating response data.
• RAR offers benefits including enhanced statistical efficiency, improved ethical treatment allocation, and robust parameter estimation.
• Despite growing interest and regulatory support, real-world implementation of RAR remains limited.

Purpose of the Study:

• To review the practical application of RAR in clinical trials from 2015 to 2024.
• To identify and address key challenges hindering RAR implementation.
• To provide practical solutions and insights for clinical trial practitioners and advance RAR methodology.

Main Methods:

• Systematic review of RAR applications in clinical practice (2015-2024).
• Identification and categorization of common challenges (e.g., diverse outcomes, repeated measures, missing data).
• Proposal of practical solutions and discussion of existing RAR methods.

Main Results:

• Key challenges in RAR implementation were identified, including managing diverse patient outcomes, incorporating repeated measurements, and handling missing data.
• Various RAR methods were categorized, and practical solutions were proposed to overcome identified challenges.
• Insights and references were provided for clinical trial practitioners.

Conclusions:

• Bridging the gap between RAR theory and practice is crucial for broader adoption.
• Addressing implementation challenges can promote the wider use of RAR in clinical trials.
• Further research is needed to advance RAR methodology and overcome existing limitations.