VAC4EU Postauthorisation Safety Study of BIMERVAX® Vaccine in Europe

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-only

  Cohort

Study drug and medical condition

• Name of medicine:
  BIMERVAX (--) - EMULSION FOR INJECTION
• Study drug International non-proprietary name (INN) or common name:
  COVID-19 VACCINE (RECOMBINANT, ADJUVANTED)
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BN04) covid-19, protein subunit

  covid-19, protein subunit
• Medical condition to be studied:
  COVID-19

Population studied

• Short description of the study population:
  The eligible population for the vaccine utilisation study will be all individuals actively enrolled in each of the selected European health data sources for at least 12 months before receiving a booster dose of the BIMERVAX® vaccine within the study period. For the comparative safety studies, the main eligibility criterion will be having received a COVID-19 vaccine in the past. The study period will be from the date of availability of BIMERVAX® vaccine in each participant country to 2 to 3 years past that date (4 years for pregnancy outcomes), pending the timing and potential seasonality of booster administration campaigns.
• Age groups:
  All

  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)

  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)
• Special population of interest:
  Frail population

  Immunocompromised

  Pregnant women

Study design details

• Study design:
  The study will comprise a vaccine utilisation study component consisting of a cohort that will be described using standard statistics. The study will also comprise a comparative safety component, consisting of both a cohort and a self-controlled risk interval design.
• Main study objective:
  Primary objectives:; •To characterise recipients of BIMERVAX® in relation to demographics and clinical characteristics at the time of vaccination, including the following: pregnancy status, age of childbearing potential, immunocompromised status, comorbidities, presence of autoimmune and inflammatory disorders, and interaction with other vaccines (influenza).; •To estimate the risk ratio and risk difference of prespecified AESIs comparing recipients of BIMERVAX® with recipients of other COVID-19 vaccines authorised for the booster indication, using a cohort design.; •To estimate the incidence rate ratio of selected AESIs comparing a prespecified risk period following BIMERVAX® vaccination with a later post-risk interval, using a self controlled risk interval (SCRI) design.
• Setting:
  The population studied is that described in section 13. The study period will start on the first date of launch of BIMERVAX® in each country where the participating data sources are located and will end 36 months later (48 months later for pregnancy outcomes) or on the date of the latest data availability. The contributing data sources are from Spain.
• Comparators:
  The cohort study will compare the following two vaccination strategies:; • Receive 1 dose of BIMERVAX® vaccine. Individuals can subsequently receive other COVID-19 vaccinations as per local policies; • Receive 1 dose of another COVID-19 vaccine authorised for booster use. Individuals subsequently can receive other COVID-19 vaccinations as per local policies, using any brand but BIMERVAX.; The SCRI study will compare a risk period following receipt of BIMERVAX® with a post-risk control interval when it is assumed that BIMERVAX® has no effect.
• Outcomes:
  Safety outcomes (AESIs) include: ; • Guillain-Barré syndrome; • Acute disseminated encephalomyelitis; • Transverse myelitis; • Encephalopathy; • Aseptic meningitis, meningoencephalitis; • Generalised convulsion (seizures); • Facial nerve palsy, Bell’s palsy; • Narcolepsy; • Anosmia, ageusia; • Anaphylaxis; • Multisystem inflammatory syndrome ; • Acute aseptic arthritis; • Subacute thyroiditis; • Diabetes mellitus (type 1) c; • Diabetes mellitus (any type); • Acute cardiac injury (including microangiopathy, heart failure, stress cardiomyopathy, coronary artery disease, arrhythmia, myocarditis/pericarditis) ; • Coagulation disorders (including DVT, pulmonary embolus, cerebrovascular stroke, limb ischaemia, cerebral venous sinus thrombosis, haemorrhagic disease); • Disseminated intravascular coagulation; • Thrombocytopenia; • Immune thrombocytopenia, thrombosis with thrombocytopenia syndrome; • Single organ cutaneous vasculitis; • Erythema multiforme; • Chilblain-like lesions; • Acute respiratory distress syndrome; • Acute kidney injury; • Acute liver injury; • Acute pancreatitis; • Appendicitis; • Rhabdomyolysis; • Death (any causes); • Sudden death; • Spontaneous abortion, stillbirth; • Foetal growth restriction; • Preterm birth; • Major congenital anomalies; • Microcephaly; • Neonatal death; • Gestational diabetes; • Preeclampsia; • Maternal death; • Menstrual disorder
• Data analysis plan:
  The vaccine utilisation study will summarise the variables of interest at the time of vaccination using standard measures of central tendency and of dispersion for continuous variables as well as counts and percentages for categorical variables.; The comparative safety cohort study will use matching and inverse probability weighting to adjust for the measured baseline confounders. Outcomes will be treated as time-to-event variables and will be analysed accordingly. Effect estimates will be provided as risk ratios and as risk differences scales.; The SCRI study will compare the risk of each AESI during a prespecified period following the index date (the “risk interval” during which there is a hypothesised increased risk of the outcome) with that of a self-matched “control interval,” used to assess the baseline risk of the outcome.