Covariate-Adaptive Biased Coin Randomization for Master Protocols with Multiple Interventions and Biomarker-Stratified Allocation

Abstract

In a multi-arm trial with predefined subgroups for each intervention to target, it is often desirable to enrich assignment to an intervention by enrolling more biomarker-positive participants to the intervention. We describe how to implement a biased coin design to achieve desired allocation ratios among interventions and between the number of biomarker-positive and biomarker-negative participants assigned to each intervention. We illustrate the proposed method with the randomization algorithm implemented in the Precision Interventions for Severe and/or Exacerbation-prone Asthma (PrecISE) trial.

KEYWORDS:

• Biased coin design
• Biomarker-positive subgroup
• Covariate-adaptive randomization
• Enrichment

Acknowledgments

The authors thank the guest editors and anonymous reviewers for their helpful comments.

Disclosure Statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work is supported in part by the National Heart, Lung, and Blood Institute, National Institutes of Health, grant U24 HL138998.