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A Bayesian model‐free approach to combination therapy phase I trials using censored time‐to‐toxicity data

Wheeler, GM; Sweeting, M; Mander, A; (2019) A Bayesian model‐free approach to combination therapy phase I trials using censored time‐to‐toxicity data. Journal of the Royal Statistical Society: Series C (Applied Statistics) , 68 (2) pp. 309-329. 10.1111/rssc.12323. Green open access

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Abstract

The product of independent beta probabilities escalation design for dual agent phase I dose escalation trials is a Bayesian model‐free approach for identifying multiple maximum tolerated dose combinations of novel combination therapies. Despite only being published in 2015, the design has been implemented in at least two oncology trials. However, these trials require patients to have completed follow‐up before clinicians can make dose escalation decisions. For trials of radiotherapy or advanced therapeutics, this may lead to impractically long trial durations due to late‐onset treatment‐related toxicities. We extend the product of independent probabilities escalation design to use censored time‐to‐event toxicity outcomes for making dose escalation decisions. We show via comprehensive simulation studies and sensitivity analyses that trial duration can be reduced by up to 35%, particularly when recruitment is faster than expected, without compromising on other operating characteristics.

Type: Article
Title: A Bayesian model‐free approach to combination therapy phase I trials using censored time‐to‐toxicity data
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/rssc.12323
Publisher version: https://doi.org/10.1111/rssc.12323
Language: English
Additional information: © 2018 The Authors Journal of the Royal Statistical Society: Series C (Applied Statistics) Published by John Wiley & Sons Ltd on behalf of the Royal Statistical Society. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Adaptive designs, Bayesian methods, Clinical trials, Dose escalation, Model‐free approach, Model‐free approach
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
URI: http://discovery.ucl.ac.uk/id/eprint/10058098
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