Year-to-year variation in attack rates could result in underpowered respiratory syncytial virus vaccine efficacy trials

Journal article

Objectives: Year-to-year variation in respiratory viruses may result in lower attack rates than expected. We aimed to illustrate the impact of year-to-year variation in attack rates on the likelihood of demonstrating vaccine efficacy (VE). Study Design and Setting: We considered an individually randomized maternal vaccine trial against respiratory syncytial virus (RSV)-associated hospitalizations. For 10 RSV-associated hospitalizations per 1,000 infants, sample size to have 80% power for true VE of 50% and 70% was 9,846 and 4,424 participants. We reported power to show VE for varying attack rates, selected to reflect realistic year-to-year variation using observational studies. Eight scenarios including varying number of countries and seasons were developed to assess the influence of these trial parameters. Results: Including up to three seasons decreased the width of the interquartile range for power. Including more seasons concentrated statistical power closer to 80%. Least powered trials had higher statistical power with more seasons. In all scenarios, at least half of the trials had <80% power. For three-season trials, increasing the sample size by 10% reduced the percentage of underpowered trials to less than one-quarter of trials. Conclusion: Year-to-year variation in RSV attack rates should be accounted for during trial design. Mitigation strategies include recruiting over more seasons, or adaptive trial designs.

Authors: Billard, MN; Wildenbeest, J; Bont, LJ; Nair, H; McCracken, JP

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Journal of Clinical Epidemiology
• Volume: 147
• Pages: 11-20
• Publication date: 2022-02-23
• Acceptance date: 2022-02-16
• DOI: 10.1016/j.jclinepi.2022.02.003
• EISSN: 1878-5921
• ISSN: 0895-4356
• Pmid: 35217153
• Language: English
• Keywords: RSV; seasonality; FFR; attack rate; sample size; statistical power; incidence