Protocol for a COVID-19 vaccine effectiveness estimation using health data registries, VEBIS multi-country study - Version 2.0

This work is performed within the Vaccine Effectiveness, Burden and Impact Studies (VEBIS) project. The first objective of the study is to monitor COVID-19 VE in a prospective manner, with the production of VE monthly pooled estimates from up to eight countries, including Denmark, Spain (Navarre region only), Norway, Portugal, Belgium, and Luxembourg from October 2022, Italy from June 2023, and the Netherlands from October 2023, with retrospective contributions from the Netherlands and Italy since January and February 2023 respectively.

The present master protocol (version 2.0) intends to update the previously used methods [2] to monitor COVID-19 VE to reflect on the current SARS-CoV-2 testing strategies and 2023 autumn vaccination recommendations that now target specific age groups.

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 socioeconomic (age, sex, socioeconomic status), clinical (comorbidities) and COVID-19 vaccination variables (brand, number, and dates of dose administration).

The protocol outlines the agreed methods for data analysis of national databases and includes a plan for the pooled analysis of all participating country VE estimates. With the vaccination campaign being first deployed between September and October 2023 in most countries, a first early estimate of VE will be performed in January 2024 covering the early phase of the rollout (October–November 2023) eight-week follow-up period (consolidated data available in January of the following year, 2024) followed by mid-year estimates in March, June, and September 2024.

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.