Background: The novel coronavirus SARS-CoV-2 caused a pandemic and subsequently brought about a mass vaccination campaign involving several vaccines. The scale and speed of this campaign necessitated unprecedented collaboration to overcome challenges for large scale European multinational post-authorization studies of vaccines.
Objectives: To explore optimal approaches to harmonize multinational observational studies of adverse events of special interest (AESIs) in vaccinees of mRNA-1273 in Europe.
Methods: This study, conducted by the Vaccine monitoring Collaboration for Europe (VAC4EU) association, relies on secondary routinely collected data from 5 countries selected based on availability of specific data elements. The databases included national registers (Denmark and Norway), regional administrative databases (Italy’s Agenzia Regionale di Sanita’ della Toscana [ARS]; Spain’s Sistema d’Informació per al Desenvolupament de la Investigació en Atenció Primaria [IDIAP]), and the Clinical Practice Research Datalink (CPRD), in the UK.
Source data was extracted and transformed into the standardized format of the ConcepTION common data model, consisting of semantically harmonized tables of persons, observation periods, vaccines, drugs, and diagnoses. AESI-defining algorithms, based on diagnoses and/or drug proxies, were developed using cross-mapping with the automated tool Codemapper, published algorithms, and clinical expertise.
We created scripts to define study variables and populations and perform prespecified analyses. Results from the analyses were output aggregated data, enabling their transfer to a cloud-based centralized Digital Research Environment where the report tables are generated, while preserving data privacy.
Results: We programmed 127 scripts which aimed at ultimately generating 23 report tables covering population selection, population description, and results from seven different epidemiological designs spanning 5 countries and 38 AESIs. Our federated approach identified 4.7M people who received at least one dose of mRNA-1273. Over 2.1M individuals met the eligibility criteria for the statistical analyses.
Conclusions: Combining heterogeneous data sources from 5 European countries, this project used and further developed a successful analysis pipeline, serving as a model for conducting multinational post-authorization observational studies of vaccine safety. Comparing and harmonizing outcomes of interest without violating privacy regulations, our solution automates documentation to ensure reproducibility.