Pooling Different Placebos as a Control Group in a Randomized Platform Trial: Benefits and Challenges From Experience in the ACTIV-2 COVID-19 Trial.

Autor:	Moser CB; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Chew KW; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA., Ritz J; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Newell M; Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA., Javan AC; Division of AIDS/National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA., Eron JJ; Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA., Daar ES; Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA., Wohl DA; Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA., Currier JS; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA., Smith DM; Department of Medicine, University of California, San Diego, La Jolla, California, USA., Hughes MD; Department of Biostatistics and Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2023 Aug 31; Vol. 228 (Suppl 2), pp. S92-S100.
DOI:	10.1093/infdis/jiad209
Abstrakt:	Adaptive platform trials were implemented during the coronavirus disease 2019 (COVID-19) pandemic to rapidly evaluate therapeutics, including the placebo-controlled phase 2/3 ACTIV-2 trial, which studied 7 investigational agents with diverse routes of administration. For each agent, safety and efficacy outcomes were compared to a pooled placebo control group, which included participants who received a placebo for that agent or for other agents in concurrent evaluation. A 2-step randomization framework was implemented to facilitate this. Over the study duration, the pooled placebo design achieved a reduction in sample size of 6% versus a trial involving distinct placebo control groups for evaluating each agent. However, a 26% reduction was achieved during the period when multiple agents were in parallel phase 2 evaluation. We discuss some of the complexities implementing the pooled placebo design versus a design involving nonoverlapping control groups, with the aim of informing the design of future platform trials. Clinical Trials Registration. NCT04518410. Competing Interests: Potential conflicts of interest. C. B. M. participated on a data safety monitoring board for the BONE STAR study. K. W. C. has received research funding to the institution from Merck Sharp & Dohme; and is a consultant for Pardes Biosciences. E. S. D. receives consulting fees from Gilead Sciences, Merck, and GSK/ViiV; and research support through the institution from Gilead Sciences and GSK/ViiV. D. A. W. has received funding to the institution to support research and honoraria for advisory boards and consulting from Gilead Sciences. J. S. C. has consulted for Merck and Company. J. J. E. is an ad hoc consultant to GSK/VIR; and data monitoring committee chair for Adagio phase 3 studies. D. M. S. has consulted for Evidera, Fluxergy, Kiadis, Linear Therapies, Matrix BioMed, Arena Pharmaceuticals, VxBiosciences, Model Medicines, Bayer Pharmaceuticals, Signant Health, and Brio Clinical. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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