DARWIN EU® – Proof-of-concept: Preparedness for annual seasonal influenza vaccine effectiveness studies - Vaccine coverage and incidence of influenza-related outcomes

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Validation of study variables (exposure outcome covariate)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  INFLUENZA VACCINE
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BB) Influenza vaccines

  Influenza vaccines

Population studied

• Short description of the study population:
  Objective 1: Population-level drug utilisation on influenza vaccine ; Inclusion criteria; • All individuals present in each influenza season (1st October-30th April) during the study period of 01/10/2015 to 30/04/2024 (or the latest available date); Exclusion criteria; • Individuals with missing information on sex and age ; ; Objective 2: Patient-level characterisation on use and type of influenza vaccine; Inclusion criteria; • All individuals receiving influenza vaccine in each influenza season during the period of 01/10/2015 to 30/04/2024 (or the latest available date); Exclusion criteria; • Individuals with missing information on sex and age ; Objective 3: Patient-level characterisation of influenza vaccine recipients; Inclusion criteria; • All individuals receiving influenza vaccine in each influenza season during the period of 01/10/2015 to 30/04/2024 (or the latest available date); • Minimum 365 days of available history before index date; Exclusion criteria; • Individuals with missing information in sex and age ; ; Objective 4: Population-level descriptive epidemiology of influenza-related outcomes ; Inclusion criteria; • All individuals with at least one of the defined influenza-related outcomes in each influenza season during the period of 01/10/2015 to 30/04/2024 (or the latest available date); Exclusion criteria; • Individuals with missing information in sex and age;

Study design details

• Study design:
  A cohort study will be conducted using routinely collected health data from six databases from six countries across Europe and in five EU member states
• Main study objective:
  1. To estimate the period prevalence of influenza vaccination in the general population for each influenza season from 2015/16 to 2023/24, overall and stratified by age group and sex. ; 2. To characterise influenza vaccine use within each influenza season by month of vaccination, vaccine brand, and route of administration, stratified by age group and sex. ; 3. To describe the baseline demographic characteristics, comorbidities, immunocompromised status, and receipt of other vaccinations of individuals receiving any influenza vaccine in each influenza season. ; 4. To describe the background incidence rates of influenza-related clinical outcomes, hospitalisations, and deaths in the general population, and crude incidence rates of influenza-related clinical outcomes, hospitalisations, and deaths in the vaccinated and unvaccinated populations, overall and stratified by age group and sex in each influenza season.
• Data analysis plan:
  Period prevalence of influenza vaccines will be estimated in the general population for each influenza season from October to April, overall and stratified by age group and sex. The statistical analyses will be performed based on OMOP CDM mapped data using IncidencePrevalence R package. A minimum cell counts of 5 will be used when reporting results, with any smaller count reported as “<5”.
• Summary results:
  CONCLUSION ; This multi-data source characterisation demonstrated generally slightly increasing or stable trends in influenza vaccination prevalence from 2015 to 2019, followed by a notable rise during 2020–2022 coinciding with the COVID-19 pandemic, and a subsequent slight decline. Prevalence was consistently highest among older adults and higher in females, and between-country variation largely reflected differences in national influenza vaccination policies. From a data-preparedness perspective, detailed vaccine brand information was available only in DK-DHR and FinOMOP-THL, and detailed route information was available in these two data sources as well as in NAJS. Symptom-based outcomes (ARI) were generally captured more frequently than diagnosis-based outcomes (acute respiratory infection (broad definition), influenza). Certain data considerations, such as the absence of hospitalisation data in CPRD GOLD, the temporary gap in hospital records in NAJS and SIDIAP, and occasional code-mapping inconsistencies, should be considered when selecting data sources and refining phenotypes for future analyses. For future IVE studies, several considerations may help strengthen study design and optimise the use of these data sources. Data sources with more complete information on vaccine brand, route of administration, or with hospital linkage may be particularly valuable for analyses requiring brand stratification or severe outcomes. Continued refinement and validation of phenotypes, building on the work undertaken in this study, together with harmonised outcome definitions across data partners are crucial to ensure consistency and comparability. Symptom-based outcomes may help mitigate this variability, given their reduced dependence on clinical judgement and coding compared to diagnosis-based outcomes. Taken together, these considerations, alongside attention to country-specific vaccination campaign timing, may enhance the ability of these data sources to contribute reliabl