Protocol for COVID-19 vaccine effectiveness multi-country study (VEBIS) using health data registries : version 3.0

This protocol presents an updated common methodology for estimating COVID-19 vaccine effectiveness (VE) using established health data registries in participating European Union (EU) and European Economic Area (EEA) Member States. This work is performed within the Vaccine Effectiveness, Burden and Impact Studies (VEBIS) project. The first objective of the study is to prospectively monitor COVID-19 VE via pooled estimates produced monthly as part of a multi-country network [1-8]. The present master protocol (version 3.0) intends to update the methods [2,3] previously used to monitor COVID-19 VE, adapting them to the context of autumn 2024 vaccine campaigns in the EU/EEA. The proposed study design is a multicentre retrospective cohort design using data collected routinely from electronic health record (EHR) databases. The analysis included data from the resident community-dwelling population (i.e. excluding those living in nursing homes) ≥65 years of age and who belong to age-group for whom vaccination has been universally recommended at study enrolment (i.e. if vaccination with a booster was only recommended for individuals ≥80 years of age at a given month, VE corresponding to that month is only estimated in that group). Outcomes of interest include hospital admission due to COVID-19 and COVID-19-related death. Other data to be collected include socio-demographic (age, sex, region, country of birth, socioeconomic status), clinical (comorbidities) and COVID-19 vaccination (brand, number and dates of dose administration) variables. The protocol outlines the agreed methods for VE analyses using national databases, and includes a plan for the pooled analysis of all participating country VE estimates. In most participating countries, vaccination campaigns begin between September and October 2024, thus a first early estimate of VE will be produced from January 2025 covering the early phase of the rollout (October to November 2024) followed by mid-year estimates in March and June 2025, and end of year estimates in September 2025. This master protocol is primarily intended to guide the implementation of the ECDC-funded study in participating countries. However, ECDC encourages the conduct of VE studies, using this protocol as a basis, in countries that do not currently plan to participate in ECDC-funded studies. The use of common protocols will facilitate the comparability of results across studies, countries, sites, and time.