A practical response adaptive block randomization (RABR) design with analytic type I error protection.

Statistics in Medicine
Tianyu ZhanIvan S F Chan

Abstract

Response adaptive randomization (RAR) is appealing from methodological, ethical, and pragmatic perspectives in the sense that subjects are more likely to be randomized to better performing treatment groups based on accumulating data. However, applications of RAR in confirmatory drug clinical trials with multiple active arms are limited largely due to its complexity, and lack of control of randomization ratios to different treatment groups. To address the aforementioned issues, we propose a Response Adaptive Block Randomization (RABR) design allowing arbitrarily prespecified randomization ratios for the control and high-performing groups to meet clinical trial objectives. We show the validity of the conventional unweighted test in RABR with a controlled type I error rate based on the weighted combination test for sample size adaptive design invoking no large sample approximation. The advantages of the proposed RABR in terms of robustly reaching target final sample size to meet regulatory requirements and increasing statistical power as compared with the popular Doubly Adaptive Biased Coin Design are demonstrated by statistical simulations and a practical clinical trial design example.

References

Sep 23, 2003·Controlled Clinical Trials·Theodore G KarrisonRick Chappell
Nov 21, 2007·Journal of Biopharmaceutical Statistics·Lin Wang, Lu Cui
Feb 12, 2009·Statistics in Medicine·Frank BretzMartin Posch
Feb 14, 2012·Pharmaceutical Statistics·Dominic Magirr
Jun 30, 2015·Journal of the American Statistical Association·Jianhua HuFeifang Hu
Sep 24, 2015·The New England Journal of Medicine·Michael P DiamondUNKNOWN NICHD Reproductive Medicine Network
Jun 28, 2017·JAMA : the Journal of the American Medical Association·Xiao-Ke WuUNKNOWN PCOSAct Study Group
Sep 24, 2018·Contemporary Clinical Trials·Kurt T BarnhartUNKNOWN NICHD Cooperative Reproductive Medicine Network

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