Non-Interventional Postmarketing Safety Study of the COMIRNATY 2025-2026 Formula (LP.8.1) in the United States

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  COMIRNATY
• Medicinal product name, other:
  COMIRNATY 2025-2026 Formula (LP.8.1)
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BN01) covid-19, RNA-based vaccine

  covid-19, RNA-based vaccine
• Medical condition to be studied:
  COVID-19 prophylaxis

Population studied

• Short description of the study population:
  The source population will be drawn from nationwide healthcare insurance claims databases. It will include individuals with at least one medical or pharmacy claim from 27 August 2025 (the date of product approval) through 31 March 2026. The end date of 31 March 2026 was chosen based on the assumption that the timing of vaccine uptake will be similar to the timing of uptake in previous vaccine seasons. During prior COVID-19 seasons, the end of March reflected the time when uptake of the COVID-19 vaccine was no longer increasing (ie, most individuals who received the COVID-19 vaccine had done so prior to March), and COVID-19 cases declined substantially from their fall/winter peak.; In Phase 1, individuals age ≥ 5 years will be eligible for inclusion if they receive at least one dose of the COMIRNATY 2025-2026 Formula from 27 August 2025 (the date of the COMIRNATY 2025-2026 US approval for marketed use) through 31 March 2026, have continuous medical and pharmacy insurance coverage in the 365 days prior to their vaccination date, experience a safety outcome of interest during a risk interval or control period, and do not experience the safety outcome of interest during the clean period prior to vaccination. ; In Phase 2, individuals age ≥ 5 years will be eligible for inclusion if they receive at least one dose of the COMIRNATY 2025-2026 Formula from 27 August 2025 (the date of the COMIRNATY 2025-2026 US approval for marketed use) through 31 March 2026, have continuous medical and pharmacy insurance coverage in the 365 days prior to their vaccination date.; Individuals aged ≥ 5 years will be eligible for inclusion in the unexposed cohort if they have a healthcare encounter (outpatient physician visit or receipt of a non-COVID-19 vaccine) from 27 August 2025 through 31 March 2026 and if they have continuous medical and pharmacy insurance coverage in the 365 days prior to their outpatient healthcare encounter. Individuals in the unexposed cohort will be matched to those in the exposed cohort if their outpatient healthcare encounter is within the same 14-day calendar period as the exposed individual’s vaccination date and if they are in the same age group;
• Age groups:
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
  • 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:
  This study will be conducted in two phases. Phase 1 will include a study of self-controlled risk interval (SCRI) design conducted using pre-adjudicated claims databases for the interim report. Phase 2 will be a comparative safety cohort design and will be included in the final report
• Main study objective:
  Primary Objective: To estimate the incidence of pre-specified AESIs among individuals who receive the COMIRNATY 2025-2026 Formula compared to the incidence among individuals with no recorded COVID-19 vaccination.; Secondary Objective: To estimate the incidence of pre-specified AESIs among individuals who receive the COMIRNATY 2025-2026 Formula compared to the incidence among individuals with no recorded COVID-10 vaccination within subgroups of individuals with prior SARS-CoV-2 infection; individuals with prior COVID-19 vaccination; individuals with administration of non-COVID-19 vaccines; children 5 through 17 years of age; adults 65 years of age and older; and individuals 5 years through 64 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19, if sample size permits.
• Data analysis plan:
  Phase 1: The observed incidence rates of the pre-specified AESIs will be estimated in the risk window and the control window. Among the individuals who experience an AESI in either the risk window or the control window (but not both), an exact conditional Poisson regression model with the natural logarithm of the person-time as the offset will be used to calculate the relative incidence (rate ratio) and corresponding 95% confidence interval (CI) of events occurring during the risk interval relative to the control period.; The results from the SCRI utilizing the Optum Pre-Adjudicated Claims Databases will be presented in the interim report, while results from the SCRI utilizing the Optum Research Database (ORD) and the Medicare Advantage and Medicare Part D (MA-PD) will be presented in the final report.; Please see the protocol for a description of the data analysis plan for the phase 2 cohort study.