Post-Approval Observational Cohort Study to Evaluate the Safety of the COMIRNATY 2023-2024 Formula in the United States

Study type

• Study topic:
  Disease /health condition

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

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  COVID-19 MRNA VACCINE (NUCLEOSIDE-MODIFIED)
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BN01) covid-19, RNA-based vaccine

  covid-19, RNA-based vaccine

Population studied

• Age groups:
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Estimated number of subjects:
  160000

Study design details

• Study design:
  This is a non-interventional observational study utilizing an administrative claims database in the US. Phase 1 will utilize a self-controlled risk interval (SCRI) design, and Phase 2 will utilize a matched comparative safety cohort design
• Main study objective:
  To estimate the incidence of pre-specified safety events of interest following vaccination with the COMIRNATY 2023-2024 Formula compared to the incidence of these events during a control window (i.e. expected rates of these events).
• Setting:
  The source population for this study will consist of all individuals with at least one medical or pharmacy claim from 11 September 2023 through 31 March 2024. The end date of 31 March 2024 was chosen based on the assumption that vaccine uptake will be similar to uptake during the 2022-2023 season. During the 2022-2023 COVID-19 season, the end of March reflected the time when uptake of the bivalent booster was no longer increasing (i.e., ; most individuals who received the bivalent booster dose had done so prior to March 2023), and COVID-19 cases declined substantially from their peak (CDC, 2020).
• Outcomes:
  The pre-specified safety outcomes of interest include the following: acute disseminated encephalomyelitis (ADEM), anaphylaxis, Bell’s palsy, cerebral venous sinus thrombosis (CVST), convulsions/seizures (non-febrile), encephalomyelitis, glomerulonephritis, Guillain-Barré syndrome, herpes zoster, immune-mediated myositis, ; immune thrombocytopenia, Kawasaki disease, multi inflammatory syndrome (in children and adults), multiple sclerosis (MS), myocardial infarction (MI), myocarditis/pericarditis, pulmonary embolism (PE), hemorrhagic stroke, ischemic stroke, and transverse myelitis. Study outcomes will be identified through claims indicators using published validated claims-based algorithms with high performance when available.
• Data analysis plan:
  For the phase 1 SCRI design, the observed incidence rates of the pre-specified safety outcomes of interest will be estimated in the risk window and the control window. Among individuals who experience an outcome of interest, an exact conditional Poisson regression model with the natural logarithm of the person-time as the offset will be used to calculate the rate ratio and corresponding 95% confidence interval (CI) of events occurring during the risk period relative to the control period. The results from the SCRI utilizing the Optum pre-adjudicated claims database will be presented in the interim report, while results utilizing the ORD 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.