Sample size required to detect the effect of RSV vaccination on recurrent wheezing

Riddell CA, Bhat N, Bont LJ, Dupont WD, Feikin DR, Fell DB, Gebretsadik T, Hartert TV, Hutcheon JA, Karron RA, Nair H, Reiner RC Jr, Shi T, Sly PD, Stein RT, Wu P, Zar HJ, Ortiz JR; WHO Technical Working Group on Respiratory Syncytial Virus Vaccination During Pregnancy to Prevent Recurrent Childhood Wheezing.Vaccine. 2018 Dec 18;36(52):8100-8109. doi: 10.1016/j.vaccine.2018.10.041. Epub 2018 Nov 22.

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


Riddell and colleagues investigated the feasibility of utilizing maternal RSV vaccine trials to detect the effect of RSV vaccine on childhood recurrent wheezing. The model inputs came from systematic reviews and meta-analyses, including the following parameters: 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. The result showed that among the plausible scenarios the lowest sample size required was 6196 mother-infant pairs per trial arm, and 75% and 47% of plausible scenarios required more (>31,060 and >100,000). Unfortunately all these scenarios exceed the size of the only current phase III trial of RSV vaccination in pregnant women, which indicated the impossibility of demonstrating an effect on recurrent wheezing. Further efforts are needed to plan for post-licensure studies to inform the impact of RSV vaccines given during pregnancy on long term respiratory illness.

Abstract on PubMed