Informing randomized clinical trials of respiratory syncytial virus vaccination during pregnancy to prevent recurrent childhood wheezing: A sample size analysis

被引:16
作者
Riddell, Corinne A. [1 ]
Bhat, Niranjan [2 ]
Bont, Louis J. [3 ,4 ]
Dupont, William D. [5 ]
Feikin, Daniel R. [6 ]
Fell, Deshayne B. [7 ]
Gebretsadik, Tebeb [8 ]
Hartert, Tina V. [9 ]
Hutcheon, Jennifer A. [10 ]
Karron, Ruth A. [11 ]
Nair, Harish [12 ]
Reiner, Robert C., Jr. [13 ]
Shi, Ting [12 ]
Sly, Peter D. [14 ]
Stein, Renato T. [15 ]
Wu, Pingsheng [16 ]
Zar, Heather J. [17 ,18 ]
Ortiz, Justin R. [19 ]
机构
[1] Univ Calif Berkeley, Div Epidemiol & Biostat, 2121 Berkeley Way,Suite 5404, Berkeley, CA 94720 USA
[2] PATH, Ctr Vaccine Innovat & Access, 2201 Westlake Ave, Seattle, WA USA
[3] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Paediat, Lundlaan 6, Utrecht, Netherlands
[4] ReSViNET Fdn, Zeist, Netherlands
[5] Vanderbilt Univ, Sch Med, Dept Biostat, Suite 1100,Room 11119,2525 West End Ave, Nashville, TN 37203 USA
[6] WHO, Initiat Vaccine Res, 20 Ave Appia, Geneva, Switzerland
[7] Univ Ottawa, Sch Epidemiol & Publ Hlth, Res Inst, CHEO,CPCR, 401 Smyth Rd,Room L-1154, Ottawa, ON K1H 8L1, Canada
[8] Vanderbilt Univ, Dept Biostat, Ctr Asthma Res, Sch Med, 2525 West End Ave,Suite 11000, Nashville, TN 37203 USA
[9] Vanderbilt Univ, Ctr Asthma Res Allergy Pulm & Crit Care Med, Sch Med, 2525 West End Ave,Suite 450, Nashville, TN 37203 USA
[10] Univ British Columbia, British Columbia Childrens & Womens Hosp, Dept Obstet & Gynaecol, Shaughnessy C408A,4500 Oak St, Vancouver, BC V6H 3N1, Canada
[11] Johns Hopkins Univ, Ctr Immunizat Res, 624 N Broadway,Suite 217, Baltimore, MD 21205 USA
[12] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Med Sch, Ctr Global Hlth Res, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland
[13] Univ Washington, Dept Global Hlth, 2301 5th Ave,Suite 600, Seattle, WA 98102 USA
[14] Univ Queensland, Child Hlth Res Ctr, 62 Graham St, South Brisbane, Qld 4101, Australia
[15] Pontificia Univ Catolica RS, Pediat Pulm Unit, Av Ipiranga 6690-420, Porto Alegre, RS, Brazil
[16] Vanderbilt Univ, Med Ctr, Div Allergy Pulm & Crit Care Med, 2525 West End Ave,Suite 1130, Nashville, TN USA
[17] Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Cape Town, South Africa
[18] Univ Cape Town, SA Med Res Council, Unit Child & Adolescent Hlth, 5th Floor,ICH Bldg,Klipfontein Rd, Cape Town, South Africa
[19] Univ Maryland, Sch Med, Ctr Vaccine Dev, 685 W Baltimore St,Suite 480, Baltimore, MD 21201 USA
基金
比尔及梅琳达.盖茨基金会;
关键词
Respiratory syncytial virus; Vaccine; Wheeze; Asthma; Global health; Pregnant; INFLUENZA VACCINATION; YOUNG-CHILDREN; ASTHMA; INFECTION; BURDEN; PREVALENCE; INFANTS; PHASE-3; DISEASE; RISK;
D O I
10.1016/j.vaccine.2018.10.041
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 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. (C) 2018 The Author(s). Published by Elsevier Ltd.
引用
收藏
页码:8100 / 8109
页数:10
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