title: Estimation and interpretation of heterogeneous vaccine efficacy against recurrent infections.
abstract: Vaccine-induced protection may not be homogeneous across individuals. It is possible that a vaccine gives complete protection for a portion of individuals, while the rest acquire only incomplete (leaky) protection of varying magnitude. If vaccine efficacy is estimated under wrong assumptions about such individual level heterogeneity, the resulting estimates may be difficult to interpret. For instance, population-level predictions based on such estimates may be biased. We consider the problem of estimating heterogeneous vaccine efficacy against an infection that can be acquired multiple times (susceptible-infected-susceptible model). The estimation is based on a limited number of repeated measurements of the current status of each individual, a situation commonly encountered in practice. We investigate how the placement of consecutive samples affects the estimability and efficiency of vaccine efficacy parameters. The same sampling frequency may not be optimal for efficient estimation of all components of heterogeneous vaccine protection. However, we suggest practical guidelines allowing estimation of all components. For situations in which the estimability of individual components fails, we suggest to use summary measures of vaccine efficacy.
authors.affiliation: Department of Health Protection, National Institute for Health and Welfare, Helsinki, Finland. juha.mehtala@gmail.com.
authors.forename: Juha
authors.initials: J
authors.lastname: Mehtälä
authors.affiliation: Pediatric Infectious Disease Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Dagan
authors.affiliation: Department of Health Protection, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Auranen
mesh_terms: D015982:Bias; D006801:Humans; D007239:Infections / Q000473:pathology / Q000628:therapy*; D015233:Models, Statistical; D012008:Recurrence; D016896:Treatment Outcome; D014612:Vaccines / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014612:Vaccines
keywords: All-or-nothing vaccine; Discrete-time data; Heterogeneity; Leaky vaccine; SIS model; Vaccine efficacy