Abstract

BackgroundRoutine influenza vaccine effectiveness (VE) surveillance networks use frequentist methods to estimate VE. With data from more than a decade of VE surveillance from diverse global populations now available, using Bayesian methods to explicitly account for this knowledge may be beneficial. This study explores differences between Bayesian vs. frequentist inference in multiple seasons with varying VE.MethodsWe used data from the United States Influenza Vaccine Effectiveness (US Flu VE) Network. Ambulatory care patients with acute respiratory illness were enrolled during seasons of varying observed VE based on traditional frequentist methods. We estimated VE against A(H1N1)pdm in 2015/16, dominated by A(H1N1)pdm; against A(H3N2) in 2017/18, dominated by A(H3N2); and compared VE for live attenuated influenza vaccine (LAIV) vs. inactivated influenza vaccine (IIV) among children aged 2–17 years in 2013/14, also dominated by A(H1N1)pdm. VE was estimated using both frequentist and Bayesian methods using the test-negative design. For the Bayesian estimates, prior VE distributions were based on data from all published test-negative studies of the same influenza type/subtype available prior to the season of interest.ResultsAcross the three seasons, 16,342 subjects were included in the analyses. For 2015/16, frequentist and Bayesian VE estimates were essentially identical (41% each). For 2017/18, frequentist and Bayesian estimates of VE against A(H3N2) viruses were also nearly identical (26% vs. 23%, respectively), even though the presence of apparent antigenic match could potentially have pulled Bayesian estimates upward. Precision of estimates was similar between methods in both seasons. Frequentist and Bayesian estimates diverged for children in 2013/14. Under the frequentist approach, LAIV effectiveness was 62 percentage points lower than IIV, while LAIV was only 27 percentage points lower than IIV under the Bayesian approach.ConclusionBayesian estimates of influenza VE can differ from frequentist estimates to a clinically meaningful degree when VE diverges substantially from previous seasons.

Highlights

  • Routine influenza vaccine effectiveness (VE) surveillance networks use frequentist methods to estimate VE

  • Subjects provide paired nasal and oropharyngeal swab specimens, which are tested for influenza via real-time reverse transcriptase polymerase chain reaction (RT-PCR)

  • Effectiveness of live attenuated influenza vaccine (LAIV) against A(H1N1)pdm in children aged 2–17 years during the 2013/14 season, which was unexpectedly lower than effectiveness of inactivated influenza vaccines (IIV) that season [12]

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Summary

Introduction

Routine influenza vaccine effectiveness (VE) surveillance networks use frequentist methods to estimate VE. A number of surveillance networks provide annual estimates of influenza vaccine effectiveness (VE) against laboratory-confirmed influenza disease diagnosed in ambulatory or inpatient settings [1,2,3,4,5]. These networks aim to estimate VE both overall and stratified by various factors including age, virus subtype/lineage, and vaccine type. The influenza research community collectively has more than a decade’s worth of influenza VE estimates drawn from diverse populations worldwide These studies inform our expectations about influenza VE before annual estimates are computed. Incorporating data from previous studies may enable us to more precisely estimate VE with smaller sample sizes, which would be useful both for providing early-season VE estimates and for estimating VE among sub-groups

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