Wheeler, GM;
(2016)
Incoherent dose-escalation in phase I trials using the escalation with overdose control approach.
Statistical Papers
pp. 1-11.
10.1007/s00362-016-0790-7.
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Abstract
A desirable property of any dose-escalation strategy for phase I oncology trials is coherence: if the previous patient experienced a toxicity, a higher dose is not recommended for the next patient; similarly, if the previous patient did not experience a toxicity, a lower dose is not recommended for the next patient. The escalation with overdose control (EWOC) approach is a model-based design that has been applied in practice, under which the dose assigned to the next patient is the one that, given all available data, has a posterior probability of exceeding the maximum tolerated dose equal to a pre-specified value known as the feasibility bound. Several methodological and applied publications have considered the EWOC approach with both feasibility bounds fixed and increasing throughout the trial. Whilst the EWOC approach with fixed feasibility bound has been proven to be coherent, some proposed methods of increasing the feasibility bound regardless of toxicity outcomes of patients can lead to incoherent dose-escalation. This paper formalises a proof that incoherent dose-escalation can occur if the feasibility bound is increased without consideration of preceding toxicity outcomes, and shows via simulation studies that only small increases in the feasibility bound are required for incoherent dose-escalations to occur.
Type: | Article |
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Title: | Incoherent dose-escalation in phase I trials using the escalation with overdose control approach |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1007/s00362-016-0790-7 |
Publisher version: | http://dx.dpo.org/10.1007/s00362-016-0790-7 |
Language: | English |
Additional information: | © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
Keywords: | Bayesian statistics, Dose-escalation, Adaptive designs, Maximum tolerated dose, Phase I trials, Coherence |
UCL classification: | UCL 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: | https://discovery.ucl.ac.uk/id/eprint/1516718 |
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