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Response-adaptive randomization in clinical trials: from myths to practical considerations.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Robertson, David S 
Lee, Kim May 
López-Kolkovska, Boryana C 
Villar, Sofía S 

Abstract

Response-Adaptive Randomization (RAR) is part of a wider class of data-dependent sampling algorithms, for which clinical trials are typically used as a motivating application. In that context, patient allocation to treatments is determined by randomization probabilities that change based on the accrued response data in order to achieve experimental goals. RAR has received abundant theoretical attention from the biostatistical literature since the 1930's and has been the subject of numerous debates. In the last decade, it has received renewed consideration from the applied and methodological communities, driven by well-known practical examples and its widespread use in machine learning. Papers on the subject present different views on its usefulness, and these are not easy to reconcile. This work aims to address this gap by providing a unified, broad and fresh review of methodological and practical issues to consider when debating the use of RAR in clinical trials.

Description

Keywords

ethics, patient allocation, power, sample size imbalance, time trends, type I error control

Journal Title

Stat Sci

Conference Name

Journal ISSN

0883-4237
2168-8745

Volume Title

Publisher

Institute of Mathematical Statistics
Sponsorship
Biometrika Trust (Unknown)
Medical Research Council (MR/N028171/1)
Medical Research Council (MC_UU_00002/14)
National Institute for Health and Care Research (IS-BRC-1215-20014)
The authors acknowledge funding and support from the UK Medical Research Council (grants MC UU 00002/15 (SSV), MC UU 00002/3 (BCL-K), MC UU 00002/14 (DSR), MR/N028171/1 (KML)), the Biometrika Trust (DSR) and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) (DSR, KML, BCLK, SSV).