Informing randomized clinical trials of respiratory syncytial virus vaccination during pregnancy to prevent recurrent childhood wheezing: A sample size analysis
for the WHO Technical Working Group on Respiratory Syncytial Virus Vaccination During Pregnancy to Prevent Recurrent Childhood Wheezing
(2018) Vaccine, volume 36, issue 52, pp. 8100 - 8109
(Article)
Abstract
Background: Early RSV illness is associated with wheeze-associated disorders in childhood. Candidate respiratory syncytial virus (RSV) vaccines may prevent acute RSV illness in infants. We investigated the feasibility of maternal RSV vaccine trials to demonstrate reductions in recurrent childhood wheezing in general paediatric populations. Methods: We calculated vaccine trial effect
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sizes that depended on vaccine efficacy, allocation ratio, rate of early severe RSV illness, risk of recurrent wheezing at age 3, and increased risk of RSV infection on recurrent wheezing. Model inputs came from systematic reviews and meta-analyses. For each combination of inputs, we estimated the sample size required to detect the effect of vaccination on recurrent wheezing. Results: There were 81 scenarios with 1:1 allocation ratio. Risk ratios between vaccination and recurrent wheezing ranged from 0.9 to 1.0 for 70% of the scenarios. Among the 57 more plausible scenarios, the lowest sample size required to detect significant reductions in recurrent wheezing was 6196 mother-infant pairs per trial arm; however, 75% and 47% of plausible scenarios required >31,060 and >100,000 mother-infant pairs per trial arm, respectively. Studies with asthma endpoints at age 5 will likely need to be larger. Discussion: Clinical efficacy trials of candidate maternal RSV vaccines undertaken for licensure are unlikely to demonstrate an effect on recurrent wheezing illness due to the large sample sizes likely needed to demonstrate a significant effect. Further efforts are needed to plan for alternative study designs to estimate the impact of maternal RSV vaccine programs on recurrent childhood wheezing in general populations.
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Keywords: Asthma, Global health, Pregnant, Respiratory syncytial virus, Vaccine, Wheeze, Molecular Medicine, General Immunology and Microbiology, General Veterinary, Public Health, Environmental and Occupational Health, Infectious Diseases
ISSN: 0264-410X
Publisher: Elsevier BV
Note: Funding Information: Dr. Riddell reports personal fees from WHO Initiative for Vaccine Research during the conduct of the study. Dr. Dupont reports grants from NIH, during the conduct of the study. Dr. Hartert reports grants from NIH, outside the submitted work. Dr. Karron reports grants from National Institutes of Health, outside the submitted work. .Dr. Nair reports grants from Bill and Melinda Gates Foundation, grants and personal fees from Sanofi Pasteur, grants from Innovative Medicines Initiative / Horizon 2020, outside the submitted work. Funding Information: This work was supported by the Bill & Melinda Gates Foundation ( OPP1114766 ), which provides financial support to the World Health Organization Initiative for Vaccine Research . The funder had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Funding Information: Dr. Stein reports personal fees from Regeneron, personal fees from Janssen, outside the submitted work. Dr. Zar reports grants from Medimmune, grants from Novavax, grants from Bill & Melinda Gates Foundation, outside the submitted work. Dr. Ortiz reports grants from Bill & Melinda Gates Foundation, grants from World Health Organization Initiative for Vaccine Research and during the conduct of the study. All other authors have nothing to disclose. Funding Information: We wish to acknowledge Marc Perut and Erin Sparrow from WHO for their help coordinating aspects of the project. We also wish to acknowledge the following persons for their technical advice on this project: Filip Dubovski (Medimmune), Lynn Finelli (Merck), and Alexander Schmidt (GSK). CAR acknowledges salary support from McGill University’s Department of Epidemiology, Biostatistics, and Occupational Health . Funding Information: This work was supported by the Bill & Melinda Gates Foundation (OPP1114766), which provides financial support to the World Health Organization Initiative for Vaccine Research. The funder had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Publisher Copyright: © 2018 The Author(s)
(Peer reviewed)
