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Embracing model-based designs for dose-finding trials

Love, SB; Brown, S; Weir, CJ; Harbron, C; Yap, C; Gaschler-Markefski, B; Matcham, J; ... Cornelius, V; + view all (2017) Embracing model-based designs for dose-finding trials. British Journal of Cancer , 117 (3) pp. 332-339. 10.1038/bjc.2017.186. Green open access

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BACKGROUND: Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM). METHODS: We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. RESULTS: We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators' preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. CONCLUSIONS: There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for dose-finding trials in academia.

Type: Article
Title: Embracing model-based designs for dose-finding trials
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/bjc.2017.186
Publisher version: https://doi.org/10.1038/bjc.2017.186
Language: English
Additional information: This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Attitude, Clinical Trials, Phase I as Topic, Dose-Response Relationship, Drug, Humans, Maximum Tolerated Dose, Models, Statistical, Professional Competence, Research Personnel, Software, Surveys and Questionnaires, Time Factors
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 Population Health Sciences > Inst of Clinical Trials and Methodology
URI: https://discovery.ucl.ac.uk/id/eprint/10059964
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