TY - JOUR
T1 - Year-to-year variation in attack rates could result in underpowered respiratory syncytial virus vaccine efficacy trials
AU - Billard, Marie-Noëlle
AU - Wildenbeest, Joanne
AU - Bont, Louis J
AU - Nair, Harish
AU - McCracken, John P
AU - Oude Rengerink, Katrien
AU - RESCEU Investigators
A2 - Fischer, Thea Kølsen
N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2022/2/23
Y1 - 2022/2/23
N2 - 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.
AB - 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.
KW - Attack rate
KW - Incidence
KW - RSV
KW - Sample size
KW - Seasonality
KW - Statistical power
UR - http://www.scopus.com/inward/record.url?scp=85127529392&partnerID=8YFLogxK
U2 - 10.1016/j.jclinepi.2022.02.003
DO - 10.1016/j.jclinepi.2022.02.003
M3 - Journal article
C2 - 35217153
SN - 0895-4356
VL - 147
SP - 11
EP - 20
JO - Journal of Clinical Epidemiology
JF - Journal of Clinical Epidemiology
ER -