A Non-Interventional Post-Authorization Safety Study of Pfizer-BioNTech Bivalent COVID-19 Vaccine in the United States (US)

Study type

• Study topic:
  Human 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

• Name of medicine:
  COMIRNATY
• 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
• Medical condition to be studied:
  Pregnancy

Population studied

• Short description of the study population:
  Individuals will be eligible for the analysis of general safety events if they are aged ≥ 6 months during the study period and have continuous medical and pharmacy insurance coverage for at least 12 months before their vaccination date or from birth until the vaccination date (for children aged younger than 12 months on the vaccination date). Women will be eligible for inclusion in analyses of pregnancy and birth outcomes if they are aged between 12 and 55 years, had a pregnancy outcome recorded during the study period, and had continuous medical and pharmacy coverage from at least 12 months before the vaccination date until the end of pregnancy. Eligibility criteria is outlined in further detail in the study protocol.
• Age groups:
  Paediatric Population (< 18 years)

  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adults (18 to < 65 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  20000

Study design details

• Study design:
  This study is a post-authorization observational cohort study based in the US.
• Main study objective:
  Primary objectives:; 1. To estimate the relative risk of safety events of interest (including myocarditis/pericarditis) in a post-vaccination risk interval, compared with a self-matched post-vaccination control interval, among individuals in the overall population who have received Pfizer-BioNTech bivalent COVID-19 Vaccine.; 2. To estimate the relative risk of pregnancy outcomes (including spontaneous abortion, stillbirth, and preterm birth) following receipt of Pfizer-BioNTech bivalent COVID-19 Vaccine during pregnancy compared with no receipt of any COVID-19 vaccine during pregnancy.; 3. To estimate the POR of birth outcomes (including major congenital malformations and small size for gestational age) in infants born to women who were exposed to PfizerBioNTech bivalent COVID-19 Vaccine during pregnancy compared with that in infants born to women who were not exposed to any COVID-19 vaccine during pregnancy.; ; Secondary objectives:; 1. To estimate the relative risk of safety events of interest (including myocarditis/pericarditis) in a post-vaccination risk interval, compared with a self-matched post-vaccination control interval, among individuals who have received Pfizer-BioNTech bivalent COVID-19 Vaccine for the following subgroups: pregnant women, immunocompromised individuals, individuals with a recorded history of severe COVID-19, and subgroups defined by age (as appropriate for the outcome).; 2. To estimate the relative risk of pregnancy outcomes (including spontaneous abortion, stillbirth, and preterm birth) following receipt of Pfizer-BioNTech bivalent COVID-19 Vaccine during pregnancy compared with no receipt of any COVID-19 vaccine during pregnancy by subgroups of maternal age.; 3. To estimate the POR of birth outcomes (including major congenital malformations and small size for gestational age) in infants born to women who were exposed to Pfizer-BioNTech bivalent COVID-19 Vaccine during pregnancy compared with that in infants born to women who were not exposed to any COVID-19 vaccine during pregnancy by subgroups of maternal age.
• Setting:
  The source population will be health plan enrollees from data Research Partners (RPs) that contribute data from claims and electronic health records to the US FDA Sentinel System.
• Outcomes:
  This study aims to assess general safety events as well as pregnancy and birth outcomes.; ; General safety events:; - Myocarditis/pericarditis; - Acute myocardial infarction; - Acute disseminated encephalomyelitis; - Bell’s palsy; - Convulsions; - Encephalomyelitis/encephalitis; - Guillain-Barré syndrome; - Transverse myelitis; - Deep vein thrombosis; - Disseminated intravascular coagulation; - Immune hemolytic anemia; - Immune thrombocytopenia; - Pulmonary embolism; - Thromboembolic events associated with thrombocytopenia; - Thrombotic thrombocytopenic purpura; - Venous thromboembolism; - Hemorrhagic stroke; - Ischemic stroke; - Acute respiratory distress syndrome; - Anaphylaxis; - Appendicitis; - Kawasaki disease; - Multisystem inflammatory syndrome ; - Multisystem inflammatory syndrome in children; ; Pregnancy outcomes and birth outcomes:; - Spontaneous abortion; - Stillbirth; - Preterm birth; - Major congenital malformations; - Small size for gestational age
• Data analysis plan:
  Analyses will initially be conducted separately using data from each RP. RP–specific aggregated results will be sent to the study coordinating center, which will combine aggregated results across the RPs for reporting. Pooled analysis of incidence rate ratios, HRs, and odds ratio estimates from all RPs will be conducted using privacy-preserving summary-level data sets (eg, risk set–level data sets) or another appropriate method. Detailed methodology for summary and statistical analyses of data collected in this study will be documented in the SAP.