Generic protocol for COVID-19 vaccine effectiveness studies at long-term care facilities in the EU/EEA : version 1.0

The end of 2019 saw the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). By early August 2022, over 160 million cases and over one million deaths had been reported in the European Union/European Economic Area (EU/EEA). During 2021, first the variant of concern (VOC) Alpha and then the VOC Delta became the dominant viruses in circulation across the EU/EEA. At the beginning of December 2021, the Omicron VOC was introduced into the EU/EEA which then rapidly replaced SARS-CoV-2 Delta in most European Union/European Economic Area (EU/EEA) countries. More recently, SARS-CoV-2 Omicron sub-lineages have also emerged. As of 16 August 2022, six vaccines have been authorised by the European Medicines Agency (EMA) for use in the European Union (EU), and many others are under development. Post marketing authorisation monitoring of vaccine effectiveness is an essential tool to document how COVID-19 vaccines perform in real life. These studies are the key to generating adequate evidence to support continuous assessment of the benefits and risks of the vaccines and informing decision-making on their use in national and regional vaccination strategies for different populations. This protocol outlines the methods for a prospective cohort study in long-term care facilities (LTCFs) to evaluate the effectiveness of COVID-19 vaccines in preventing laboratory-confirmed SARS-CoV-2 symptomatic infection in LTCF residents. Given the priority assigned to older population groups for COVID-19 vaccination programmes, and the vulnerability seen for LTCF residents during the pandemic, ECDC encourages the active endorsement and implementation of this protocol to strengthen the evidence base for future policy decisions. The document is a ready-to-use tool to support establishment of studies with the primary objective of measuring product-specific COVID-19 vaccine effectiveness in residents of LTCFs. Additional secondary objectives are also proposed, which could be included as additional primary objectives depending on the circumstances. The document is broken down into several key sections including the outline of a protocol; definitions to use; a template for a protocol; laboratory methods; limitations and ethical considerations. In addition, the annexes provide templates of questionnaires for use at different points in time, an informed consent form and an outline for an analysis plan.