TARGET-EU: Effectiveness of BNT162b2 mRNA COVID-19 vaccine in healthy individuals or with stable pre-existing medical conditions against SARS-CoV-2 infection

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  COMIRNATY
• Study drug International non-proprietary name (INN) or common name:
  TOZINAMERAN
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BN01) covid-19, RNA-based vaccine

  covid-19, RNA-based vaccine
• Medical condition to be studied:
  SARS-CoV-2 test positive

Population studied

• Short description of the study population:
  The study population comprises individuals aged 16 years or older, drawn from the CPRD and VID linked population databases, who were continuously enrolled for at least six months prior to the index date. The cohort is designed to reflect a broadly healthy, immunocompetent population, including those with stable, well-managed chronic conditions, while excluding individuals with recent acute illness, defined as any hospitalisation within six weeks of the index date.; To ensure the cohort is appropriate for estimating the effectiveness of Comirnaty® (BNT162b2; tozinameran; ATC J07BN01) specifically, individuals with prior receipt of any other COVID-19 vaccine are excluded, preserving a vaccine-naïve unvaccinated comparator group. Additionally, individuals who received COVID-19 pre-exposure prophylaxis — including pemivibart or tixagevimab/cilgavimab (Evusheld) — are excluded, as these therapies may independently reduce infection risk and confound vaccine effectiveness estimates.; Individuals with immunocompromised status, identified through diagnostic codes or use of immunosuppressive therapies (ATC codes L04A, L01X, L01B, H02AB, P01BA) in the six months prior to the index date, are also excluded. This ensures that the study population reflects typical immune function, supporting the internal validity and generalisability of the vaccine effectiveness estimates to the broader immunocompetent population.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)

Study design details

• Study design:
  Matched cohort design to assess the real-world effectiveness of the BNT162b2 mRNA COVID-19 vaccine against SARS-CoV-2 infection involving two databases, that is CPRD and VID. We will estimate the incidence of SARS-CoV-2 infection after receipt of the Pfizer-BioNTech COVID-19 vaccine compared to not
• Main study objective:
  The overall aim is to assess whether BNT162b2 mRNA COVID-19 vaccine reduce the risk of SARS-CoV-2 infection compared to no COVID-19 vaccination in healthy individuals or with preexisting stable medical condition.
• Setting:
  The exposure assessment window is defined from December 1, 2020, to January 31, 2022. Additionally, to ensure sufficient baseline and follow-up data, individuals must have at least 6 months of available data prior to time zero (to capture covariates and prior health status) thus covering the start of the COVID-19 vaccine rollout through to the end of mass testing for both symptomatic and asymptomatic individuals in the UK. Consequently, the study period will be from 01 June 2020 to 30 April 2022 (i.e. source data range), with the latter date allowing for individuals enrolled on 31 January 2022 to enable 90 days of follow-up.
• Outcomes:
  Laboratory-confirmed SARS-CoV-2 infection or death from any cause.
• Data analysis plan:
  The BNT162b2 effectiveness in preventing the SARS-Cov-2 infection will be estimated as 1 - RR. Supplementary analyses including diagnostic and descriptive assessments to support the main analysis will be presented to contextualise data and results from the primary and sensitivity analyses. These will include number of infections per treatment group, crude incidence rates, covariate distributions of matched cohorts, number of individuals censored and censoring patterns (intercurrent events, loss to follow-up) as well as model diagnostics. An additional supplementary analysis will be produced whereby individuals in the control arm can contribute data multiple times to the control arm and also to the BNT162b2 arm after reception of the vaccine.; The results will be presented separately for each data source. In addition, we will explore the feasibility of combining the estimated Incidence Rate Ratios (IRR) from CPRD Aurum and VID using a random-effects meta-analysis of logarithmic transformation of the rate ratios. The combined IRRs and 95% CI will be calculated, and heterogeneity will be assessed using I2.
• Summary results:
  Not yet available.