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Optimizing Clinical Trial Design to Maximize Evidence Generation in Pediatric HIV

Ford, D; Turner, R; Turkova, A; Penazzato, M; Musiime, V; Bwakura-Dangarembizi, M; Violari, A; ... Gibb, DM; + view all (2018) Optimizing Clinical Trial Design to Maximize Evidence Generation in Pediatric HIV. Journal of Acquired Immune Deficiency Syndromes , 78 (Sup) S40-S48. 10.1097/QAI.0000000000001748. Green open access

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Abstract

For HIV-infected children, formulation development, pharmacokinetic (PK) data, and evaluation of early toxicity are critical for licensing new antiretroviral drugs; direct evidence of efficacy in children may not be needed if acceptable safety and PK parameters are demonstrated in children. However, it is important to address questions where adult trial data cannot be extrapolated to children. In this fast-moving area, interventions need to be tailored to resource-limited settings where most HIV-infected children live and take account of decreasing numbers of younger HIV-infected children after successful prevention of mother-to-child HIV transmission. Innovative randomized controlled trial (RCT) designs enable several questions relevant to children's treatment and care to be answered within the same study. We reflect on key considerations, and, with examples, discuss the relative merits of different RCT designs for addressing multiple scientific questions including parallel multi-arm RCTs, factorial RCTs, and cross-over RCTs. We discuss inclusion of several populations (eg, untreated and pretreated children; children and adults) in "basket" trials; incorporation of secondary randomizations after enrollment and use of nested substudies (particularly PK and formulation acceptability) within large RCTs. We review the literature on trial designs across other disease areas in pediatrics and rare diseases and discuss their relevance for addressing questions relevant to HIV-infected children; we provide an example of a Bayesian trial design in prevention of mother-to-child HIV transmission and consider this approach for future pediatric trials. Finally, we discuss the relevance of these approaches to other areas, in particular, childhood tuberculosis and hepatitis.

Type: Article
Title: Optimizing Clinical Trial Design to Maximize Evidence Generation in Pediatric HIV
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/QAI.0000000000001748
Publisher version: http://dx.doi.org/10.1097/QAI.0000000000001748
Language: English
Additional information: Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution 3.0 IGO license (CC BY 3.0 IGO), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. The work cannot be changed in any way or used commercially without permission from the journal (http:// creativecommons.org/licenses/by/3.0/igo/legalcode)
Keywords: clinical trial design, pediatric clinical trials, pediatric HIV
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/10053365
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