title: Regression approaches in the test-negative study design for assessment of influenza vaccine effectiveness.
abstract: Influenza vaccination is the most practical means available for preventing influenza virus infection and is widely used in many countries. Because vaccine components and circulating strains frequently change, it is important to continually monitor vaccine effectiveness (VE). The test-negative design is frequently used to estimate VE. In this design, patients meeting the same clinical case definition are recruited and tested for influenza; those who test positive are the cases and those who test negative form the comparison group. When determining VE in these studies, the typical approach has been to use logistic regression, adjusting for potential confounders. Because vaccine coverage and influenza incidence change throughout the season, time is included among these confounders. While most studies use unconditional logistic regression, adjusting for time, an alternative approach is to use conditional logistic regression, matching on time. Here, we used simulation data to examine the potential for both regression approaches to permit accurate and robust estimates of VE. In situations where vaccine coverage changed during the influenza season, the conditional model and unconditional models adjusting for categorical week and using a spline function for week provided more accurate estimates. We illustrated the two approaches on data from a test-negative study of influenza VE against hospitalization in children in Hong Kong which resulted in the conditional logistic regression model providing the best fit to the data.
authors.affiliation: WHO Collaborating Centre for Infectious Disease Epidemiology and Control,School of Public Health,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong Special Administrative Region,China.
authors.forename: H S
authors.initials: HS
authors.lastname: Bond
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity,Melbourne,Australia.
authors.forename: S G
authors.initials: SG
authors.lastname: Sullivan
authors.affiliation: WHO Collaborating Centre for Infectious Disease Epidemiology and Control,School of Public Health,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong Special Administrative Region,China.
authors.forename: B J
authors.initials: BJ
authors.lastname: Cowling
mesh_terms: D002675:Child, Preschool; D003198:Computer Simulation; D004812:Epidemiologic Methods; D005260:Female; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000517:prevention & control*; D008297:Male; D015233:Models, Statistical; D016896:Treatment Outcome
chemical_list: D007252:Influenza Vaccines
keywords: Epidemiology; influenza; influenza vaccines; statistics