HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention.

The rigorous evaluation of the impact of combination HIV prevention packages at the population level will be critical for the future of HIV prevention. In this review, we discuss important considerations for the design and interpretation of cluster randomized controlled trials (C-RCTs) of combinatio...

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Main Authors: Marie-Claude Boily, Benoît Mâsse, Ramzi Alsallaq, Nancy S Padian, Jeffrey W Eaton, Juan F Vesga, Timothy B Hallett
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS Medicine
Online Access:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001250&type=printable
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author Marie-Claude Boily
Benoît Mâsse
Ramzi Alsallaq
Nancy S Padian
Jeffrey W Eaton
Juan F Vesga
Timothy B Hallett
author_facet Marie-Claude Boily
Benoît Mâsse
Ramzi Alsallaq
Nancy S Padian
Jeffrey W Eaton
Juan F Vesga
Timothy B Hallett
author_sort Marie-Claude Boily
collection DOAJ
description The rigorous evaluation of the impact of combination HIV prevention packages at the population level will be critical for the future of HIV prevention. In this review, we discuss important considerations for the design and interpretation of cluster randomized controlled trials (C-RCTs) of combination prevention interventions. We focus on three large C-RCTs that will start soon and are designed to test the hypothesis that combination prevention packages, including expanded access to antiretroviral therapy, can substantially reduce HIV incidence. Using a general framework to integrate mathematical modelling analysis into the design, conduct, and analysis of C-RCTs will complement traditional statistical analyses and strengthen the evaluation of the interventions. Importantly, even with combination interventions, it may be challenging to substantially reduce HIV incidence over the 2- to 3-y duration of a C-RCT, unless interventions are scaled up rapidly and key populations are reached. Thus, we propose the innovative use of mathematical modelling to conduct interim analyses, when interim HIV incidence data are not available, to allow the ongoing trials to be modified or adapted to reduce the likelihood of inconclusive outcomes. The preplanned, interactive use of mathematical models during C-RCTs will also provide a valuable opportunity to validate and refine model projections.
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spelling doaj-art-34b732f07a4546c0ba4a468eedc6b4e62025-08-20T02:22:37ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762012-01-0197e100125010.1371/journal.pmed.1001250HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention.Marie-Claude BoilyBenoît MâsseRamzi AlsallaqNancy S PadianJeffrey W EatonJuan F VesgaTimothy B HallettThe rigorous evaluation of the impact of combination HIV prevention packages at the population level will be critical for the future of HIV prevention. In this review, we discuss important considerations for the design and interpretation of cluster randomized controlled trials (C-RCTs) of combination prevention interventions. We focus on three large C-RCTs that will start soon and are designed to test the hypothesis that combination prevention packages, including expanded access to antiretroviral therapy, can substantially reduce HIV incidence. Using a general framework to integrate mathematical modelling analysis into the design, conduct, and analysis of C-RCTs will complement traditional statistical analyses and strengthen the evaluation of the interventions. Importantly, even with combination interventions, it may be challenging to substantially reduce HIV incidence over the 2- to 3-y duration of a C-RCT, unless interventions are scaled up rapidly and key populations are reached. Thus, we propose the innovative use of mathematical modelling to conduct interim analyses, when interim HIV incidence data are not available, to allow the ongoing trials to be modified or adapted to reduce the likelihood of inconclusive outcomes. The preplanned, interactive use of mathematical models during C-RCTs will also provide a valuable opportunity to validate and refine model projections.https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001250&type=printable
spellingShingle Marie-Claude Boily
Benoît Mâsse
Ramzi Alsallaq
Nancy S Padian
Jeffrey W Eaton
Juan F Vesga
Timothy B Hallett
HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention.
PLoS Medicine
title HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention.
title_full HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention.
title_fullStr HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention.
title_full_unstemmed HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention.
title_short HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention.
title_sort hiv treatment as prevention considerations in the design conduct and analysis of cluster randomized controlled trials of combination hiv prevention
url https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001250&type=printable
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