Informing randomized clinical trials of respiratory syncytial virus vaccination during pregnancy to prevent recurrent childhood wheezing: A sample size analysis
MetadataShow full item record
AbstractBackground: 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 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. Copyright 2018 The Author(s)
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85057047664&doi=10.1016%2fj.vaccine.2018.10.041&partnerID=40&md5=9326d6a028073d4bdbef707589dd655e; http://hdl.handle.net/10713/9720
- The preventive effect of vaccine prophylaxis on severe respiratory syncytial virus infection: A meta-analysis.
- Authors: Zhu T, Zhang C, Yu L, Chen J, Qiu H, Lyu W, Huang S
- Issue date: 2015 Oct
- Respiratory syncytial virus in infants: is maternal vaccination a realistic strategy?
- Authors: Munoz FM
- Issue date: 2015 Jun
- Assessing the strength of evidence for a causal effect of respiratory syncytial virus lower respiratory tract infections on subsequent wheezing illness: a systematic review and meta-analysis.
- Authors: Brunwasser SM, Snyder BM, Driscoll AJ, Fell DB, Savitz DA, Feikin DR, Skidmore B, Bhat N, Bont LJ, Dupont WD, Wu P, Gebretsadik T, Holt PG, Zar HJ, Ortiz JR, Hartert TV
- Issue date: 2020 Aug
- Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting.
- Authors: Driscoll AJ, Arshad SH, Bont L, Brunwasser SM, Cherian T, Englund JA, Fell DB, Hammitt LL, Hartert TV, Innis BL, Karron RA, Langley GE, Mulholland EK, Munywoki PK, Nair H, Ortiz JR, Savitz DA, Scheltema NM, Simões EAF, Smith PG, Were F, Zar HJ, Feikin DR
- Issue date: 2020 Mar 4
- Respiratory syncytial virus prophylaxis for prevention of recurrent childhood wheeze and asthma: a protocol for a systematic review.
- Authors: Quinn LA, Shields MD, Groves HE
- Issue date: 2019 Dec 19