In influenza vaccination studies assessing vaccine effectiveness (VE), both specific and non-specific endpoints (outcomes) are used. We present a formula for the relationship between VE against influenza-related outcomes (VEE), specific and non-specific, and that against influenza infection (VEI). In its simplest form, the formula comprises two additional parameters: the influenza attack rate among unvaccinated subjects, and the relative risk of the outcome for influenza infected subjects versus non-infected subjects. Both parameters may show large between-seasonal variation, which translates to a large between-seasonal variation of VEE estimates. With the full form of the formula it can be shown that, contrary to popular believe, VEE may be greater than VEI. We argue that interpreting VEE estimates in terms of “low” or “high” is not possible without taking the costs of an outcome case into account. We conclude that the decision to use a non-specific endpoint as surrogate for influenza infection should be taken in the awareness of these limitations.

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Epidemiology Biostatistics and Public Health
Department of Virology

Nauta, J., Beyer, W., & Kimp, E.P.J.A. (Erna P. J. A.). (2017). Toward a better understanding of the relationship between influenza vaccine effectiveness against specific and non-specific endpoints and vaccine effectiveness against influenza infection. Epidemiology Biostatistics and Public Health, 14(4), e12367‐1–e12367‐5. doi:10.2427/12367