# A protocol for high-dose quadrivalent influenza vaccine effectiveness in the community and long-term care facilities using electronic health records

## TL;DR

This study aims to estimate the effectiveness of a high-dose influenza vaccine in elderly individuals and those in long-term care facilities using electronic health records.

## Contribution

The study introduces a protocol for assessing high-dose influenza vaccine effectiveness in new populations using electronic health records.

## Key findings

- The study will estimate both relative and absolute influenza vaccine effectiveness in two distinct subgroups.
- Electronic health records will be used to monitor hospital admissions and assess vaccination outcomes.
- The protocol addresses limitations like data constraints and reporting bias while leveraging routinely collected data.

## Abstract

Since the 2022–2023 season in Portugal, a high-dose quadrivalent influenza vaccine is freely available for individuals living in long-term care facilities (LTCF). In 2024–2025, vaccination was extended to community-dwelling individuals aged ≥85 years. Given the scarcity of reported high-dose influenza vaccine effectiveness (IVE) estimates for this population, this study aims to estimate the high-dose relative and absolute IVE. A retrospective cohort study using data from electronic health records databases (EHR) will be implemented, using two cohorts, one of individuals vaccinated with influenza vaccine (to estimate relative IVE) and another of individuals eligible for the high-dose quadrivalent influenza vaccine (to estimate absolute IVE). We will consider two subgroups for both cohorts: individuals living in LTCF and community-dwelling individuals aged ≥85. We will use a fixed cohort approach, defining the eligible population by age at the vaccination campaign(s) start and living status. The outcomes are based on the primary cause of hospital admission. The reference population database will be defined by linking EHR on vaccination, comorbidities, and hospitalisations using a unique identifier through a deterministic data linkage procedure, and influenza vaccination status will be assessed retrospectively. We will use Cox proportional hazards regression models to estimate the hazard ratio (HR), considering as event the first hospitalisation due to influenza-like-illness and as exposure the vaccination status. IVE will be estimated as one minus the confounder-adjusted HR of vaccinated with the high-dose quadrivalent influenza vaccine vs vaccinated with standard dose (to estimate relative IVE) or unvaccinated (to estimate absolute IVE). While challenges such as EHR constraints and potential reporting bias pose limitations, using routinely collected data has successfully estimated COVID-19 VE and enables precise monitoring of VE with higher representativeness. The results of this study will inform the Health Ministry on the future influenza vaccine programme in Portugal.