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Optimising trial designs for identifying appropriate antibiotic treatment durations

Pouwels, K; Yin, M; Butler, C; Cooper, B; Wordsworth, S; Walker, A; Robotham, JV; (2019) Optimising trial designs for identifying appropriate antibiotic treatment durations. BMC Medicine , 17 , Article 115. 10.1186/s12916-019-1348-z. Green open access

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Abstract

Background: For many infectious conditions, the optimal antibiotic course length is unclear. There is an important trade-off between maximising short- and long-term efficacy and minimising antibiotic resistance and toxicity. Main Body: Evidence on optimal treatment durations should come from randomised controlled trials (RCTs). However, most antibiotic RCTs compare two arbitrarily chosen durations. We argue that alternative trial designs, which allow allocation of patients to multiple different treatment durations, are needed to better identify optimal antibiotic durations. There are important considerations when deciding which design is most useful in identifying optimal treatment durations, including the ability to model duration-response relationship (or duration-response ‘curve’), the risk of allocation concealment bias, statistical efficiency, the possibility to rapidly drop arms that are clearly inferior, and the possibility of modelling the trade-off between multiple competing outcomes. Conclusion: Multi-arm designs modelling duration-response curves with the possibility to drop inferior arms during the trial could provide more information about the optimal duration of antibiotic therapies than traditional head-to-head comparisons of limited numbers of durations, while minimising the probability of assigning trial participants to an ineffective treatment regimen.

Type: Article
Title: Optimising trial designs for identifying appropriate antibiotic treatment durations
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12916-019-1348-z
Publisher version: https://doi.org/10.1186/s12916-019-1348-z
Language: English
Additional information: © The Author(s). 2019 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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: antimicrobial resistance; design; randomised trial; duration of therapy; antibiotics; Bayesian; frequentist
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10073689
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