Abstract
Annual reformulation and approval of seasonal influenza vaccines necessitate yearly evaluation of their effectiveness. Regulatory agencies, including the European Medicines Agency (EMA), rely on timely, real-world evidence to inform product-specific benefit-risk assessments. We explored the feasibility of conducting annual, brand-specific influenza vaccine effectiveness studies in Denmark, Finland and Sweden, starting with the 2024/25 season. These countries maintain population-wide vaccination, clinical and laboratory registers, linkable via personal identification numbers and updated in near real-time. We discuss suitable study designs and document that cohort studies using a target trial emulation (TTE) framework are feasible in all three countries; register-based test-negative case-control design (TND) studies are currently only feasible in Denmark. Supplementary methods, including regression discontinuity and negative control outcome analyses, can address residual bias. This Nordic collaboration has proven capacity for large-scale register-based studies and its infrastructure is able to address EMA's requirements for timely, robust post-authorisation evidence to guide public health and regulatory decisions.