Optimising trial designs to identify appropriate antibiotic treatment durations

<p><strong>Background</strong></p> <p>For many infectious conditions, the optimal antibiotic course length remains unclear. The estimation of course length must consider the important trade-off between maximising short- and long-term efficacy and minimising antibiotic r...

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Asıl Yazarlar: Pouwels, K, Yin, M, Butler, C, Cooper, B, Wordsworth, S, Walker, A, Robotham, J
Materyal Türü: Journal article
Baskı/Yayın Bilgisi: BioMed Central 2019
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author Pouwels, K
Yin, M
Butler, C
Cooper, B
Wordsworth, S
Walker, A
Robotham, J
author_facet Pouwels, K
Yin, M
Butler, C
Cooper, B
Wordsworth, S
Walker, A
Robotham, J
author_sort Pouwels, K
collection OXFORD
description <p><strong>Background</strong></p> <p>For many infectious conditions, the optimal antibiotic course length remains unclear. The estimation of course length must consider the important trade-off between maximising short- and long-term efficacy and minimising antibiotic resistance and toxicity.</p> <p><strong>Main body</strong></p> <p>Evidence on optimal treatment durations should come from randomised controlled trials. However, most antibiotic randomised controlled trials 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 the 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.</p> <p><strong>Conclusion</strong></p> <p>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.</p>
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spelling oxford-uuid:ba3a2182-f3de-42a4-a23b-0806cbf8bd4b2022-03-27T05:08:22ZOptimising trial designs to identify appropriate antibiotic treatment durationsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ba3a2182-f3de-42a4-a23b-0806cbf8bd4bSymplectic Elements at OxfordBioMed Central2019Pouwels, KYin, MButler, CCooper, BWordsworth, SWalker, ARobotham, J<p><strong>Background</strong></p> <p>For many infectious conditions, the optimal antibiotic course length remains unclear. The estimation of course length must consider the important trade-off between maximising short- and long-term efficacy and minimising antibiotic resistance and toxicity.</p> <p><strong>Main body</strong></p> <p>Evidence on optimal treatment durations should come from randomised controlled trials. However, most antibiotic randomised controlled trials 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 the 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.</p> <p><strong>Conclusion</strong></p> <p>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.</p>
spellingShingle Pouwels, K
Yin, M
Butler, C
Cooper, B
Wordsworth, S
Walker, A
Robotham, J
Optimising trial designs to identify appropriate antibiotic treatment durations
title Optimising trial designs to identify appropriate antibiotic treatment durations
title_full Optimising trial designs to identify appropriate antibiotic treatment durations
title_fullStr Optimising trial designs to identify appropriate antibiotic treatment durations
title_full_unstemmed Optimising trial designs to identify appropriate antibiotic treatment durations
title_short Optimising trial designs to identify appropriate antibiotic treatment durations
title_sort optimising trial designs to identify appropriate antibiotic treatment durations
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