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Using biomarkers to allocate patients in a response-adaptive clinical trial

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posted on 25.11.2021, 12:00 by H. Jackson, S. Bowen, T. Jaki

In this paper, we discuss a response adaptive randomization method, and why it should be used in clinical trials for rare diseases compared to a randomized controlled trial with equal fixed randomization. The developed method uses a patient’s biomarkers to alter the allocation probability to each treatment, in order to emphasize the benefit to the trial population. The method starts with an initial burn-in period of a small number of patients, who with equal probability, are allocated to each treatment. We then use a regression method to predict the best outcome of the next patient, using their biomarkers and the information from the previous patients. This estimated best treatment is assigned to the next patient with high probability. A completed clinical trial for the effect of catumaxomab on the survival of cancer patients is used as an example to demonstrate the use of the method and the differences to a controlled trial with equal allocation. Different regression procedures are investigated and compared to a randomized controlled trial, using efficacy and ethical measures.


T Jaki received funding from UK Medical Research Council (MC_UU_00002/14). This report is independent research arising in part from Prof Jaki’s Senior Research Fellowship (NIHR-SRF-2015-08-001) supported by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care (DHCS). H Jackson is grateful for the support of the Engineering and Physical Sciences Research Council (Grant Number EP/L015692/1). The authors also acknowledge Quanticate for financial support and are grateful to Sarah Bowen and Karen Ooms in Quanticate for helpful discussions.