RWD real-time monitoring of COVID-19 vaccine effectiveness using health registries: ECDC pilot protocol

ECDC has published a pilot protocol for real-time monitoring of COVID-19 vaccine effectiveness in EU/EEA populations using RWD from health registries, in order to detect any reduction in vaccine performance that requires further investigation and public health action.

In September 2022 the European Centre for Disease Prevention and Control (ECDC) published version 1.0 of their Pilot protocol for a COVID-19 vaccine effectiveness study using data health registries. The methodology presented is being used in a pilot phase to assess the feasibility of using vaccination status and COVID-19 outcome data routinely collected in health registries to monitor COVID-19 vaccines’ effectiveness (VE) in community-dwelling resident populations across several countries in the EU/EEA, and to explore the validity of pooled estimates at country and European level.

As of 22 July 2022, six COVID-19 vaccines had been given conditional marketing authorization within the European Union/ European Economic Area (EU/EEA) by the European Commission (EC), based on the scientific opinion of the European Medicines Agency (EMA). Five are spike protein based: Comirnaty, Spikevax, Vaxzevria, Jcovden, Nuvaxovid, and one non-spike protein based (inactivated, adjuvanted) Valneva.

In 2020, the EC emphasized the importance of continuously monitoring the safety and effectiveness of vaccines and called on the ECDC and EMA to develop a structured post-authorization monitoring platform for vaccines, prioritizing COVID-19 vaccines. The EC then proposed creation of a European Health Union, empowering the EMA and ECDC to jointly coordinate independent vaccine monitoring studies.

ECDC utilized lessons learned from other vaccine effectiveness (VE) studies (e.g., influenza vaccine) to design their COVID-19 VE studies. Their ongoing aim is to build an infrastructure capable of regularly monitoring various aspects of vaccine performance, such as incidence of severe disease, moderate disease, or transmission, in different settings and populations (e.g., healthcare workers), using a range of routinely available or ad hoc data sources and data linkage. The initial pilot study is based upon four countries (Denmark, Spain, Norway and Portugal), with data gathered over a 6-month study period (January to June 2022) and focused on the resident community-dwelling populations (i.e., excluding those living in closed institutions such as nursing homes and prisons). Outcomes include laboratory-confirmed SARS-CoV-2 infection (either symptomatic or asymptomatic) or COVID-19-related hospital admission (either all wards or intensive care units) or death, in people aged 65 years and above (with results stratified by age group, 65–79 and 80+ years). Other data collected include sociodemographic (age, sex), clinical (comorbidities, previous history of SARS-CoV-2 infection) and COVID-19 vaccination variables (brand, number, and dates of doses). The analyses will produce hazard ratios or rate ratios of outcomes of interest.

ECDC encourages use of this protocol as a basis for conduction of further COVID-19 VE studies in countries not currently planning to participate in ECDC-funded studies. The use of consistent protocols will facilitate the comparability of results across study sites/studies.