Alternative models and randomization techniques for Bayesian response-adaptive randomization with binary outcomes.

Background: Bayesian response-adaptive designs, which data adaptively alter the allocation ratio in favor of the better performing treatment, are often criticized for engendering a non-trivial probability of a subject imbalance in favor of the inferior treatment, inflating type I error rate, and inc...

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Published in:Clinical Trials Vol. 18; no. 4; pp. 417 - 427
Main Authors: Proper, Jennifer, Connett, John, Murray, Thomas
Format: equations & formulas research tables/charts Journal Article
Published: Sage Publications, Ltd. Aug2021
Online Access:View this record in EBSCOhost
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      dt: Aug2021
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      pub: Sage Publications, Ltd.
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        10.1177/17407745211010139
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        atl: Alternative models and randomization techniques for Bayesian response-adaptive randomization with binary outcomes.
      aug:
        au:
          Proper, Jennifer
          Connett, John
          Murray, Thomas
        affil: Division of Biostatistics, University of Minnesota Twin Cities, Minneapolis, MN, USA
      sug:
        subj:
          Clinical Trials Methods
          Random Assignment Methods
          Probability
          Models, Statistical
          Human
          Study Design
          Computer Simulation
          Random Sample Methods
          Logistic Regression
          Sample Size
          Sampling Error
      ab: Background: Bayesian response-adaptive designs, which data adaptively alter the allocation ratio in favor of the better performing treatment, are often criticized for engendering a non-trivial probability of a subject imbalance in favor of the inferior treatment, inflating type I error rate, and increasing sample size requirements. The implementation of these designs using the Thompson sampling methods has generally assumed a simple beta-binomial probability model in the literature; however, the effect of these choices on the resulting design operating characteristics relative to other reasonable alternatives has not been fully examined. Motivated by the Advanced R2 Eperfusion STrategies for Refractory Cardiac Arrest trial, we posit that a logistic probability model coupled with an urn or permuted block randomization method will alleviate some of the practical limitations engendered by the conventional implementation of a two-arm Bayesian response-adaptive design with binary outcomes. In this article, we discuss up to what extent this solution works and when it does not. Methods: A computer simulation study was performed to evaluate the relative merits of a Bayesian response-adaptive design for the Advanced R2 Eperfusion STrategies for Refractory Cardiac Arrest trial using the Thompson sampling methods based on a logistic regression probability model coupled with either an urn or permuted block randomization method that limits deviations from the evolving target allocation ratio. The different implementations of the response-adaptive design were evaluated for type I error rate control across various null response rates and power, among other performance metrics. Results: The logistic regression probability model engenders smaller average sample sizes with similar power, better control over type I error rate, and more favorable treatment arm sample size distributions than the conventional beta-binomial probability model, and designs using the alternative randomization methods have a negligible chance of a sample size imbalance in the wrong direction. Conclusion: Pairing the logistic regression probability model with either of the alternative randomization methods results in a much improved response-adaptive design in regard to important operating characteristics, including type I error rate control and the risk of a sample size imbalance in favor of the inferior treatment.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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