Toward a better understanding of the relationship between influenza vaccine efficacy against specific and non-specific endpoints and vaccine efficacy against influenza infection

Jozef Nauta,Walter Ep Beyer,Erna Pja Kimp

doi:10.2427/12367

Jozef Nauta, Walter Ep Beyer + Show 1 more

Open Access

https://doi.org/10.2427/12367

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Abstract

In influenza vaccination studies assessing vaccine efficacy (VE), both specific and non-specific endpoints (outcomes) are used. We present a formula for the relationship between VE against influenza-related outcomes (VEO), 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 VEO estimates. With the full form of the formula it can be shown that, contrary to popular believe, VEO may be greater than VEI. We argue that interpreting VEO 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.

Highlights

Influenza vaccine effectiveness field studies are conducted to assess vaccine effectiveness, i.e. to assess how well vaccinated subjects are protected against influenza infection in the “real world”
We present a formula for the relationship between vaccine effectiveness (VE) against influenza-related outcomes (VEE), specific and non-specific, and that against influenza infection (VEI)
We hope that our formula will help investigators and health care workers to better understand influenza vaccine effectiveness against other endpoints than influenza infection

Summary

INTRODUCTION

Influenza vaccine effectiveness field studies are conducted to assess vaccine effectiveness, i.e. to assess how well vaccinated subjects are protected against influenza infection in the “real world”. A non-specific endpoint as surrogate for influenza infection will, as is generally assumed, underestimate VEI The reason for this is that there may be endpoint cases due to other causes than influenza infection, cases that cannot be prevented by influenza vaccination [2]. It may not be possible to collect all specimens within a few days of symptoms onset and the laboratory test may be done too late, after viral shedding has stopped, causing a number of influenza cases to be missed and VEI to be underestimated. This is why specific endpoint are generally more difficult to identify than non-specific ones. We will show that these estimates can vary considerably between seasons and require a different interpretation than estimates of influenza vaccine effectiveness against infection

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