Post-licensure observational safety study after meningococcal B vaccine 4CMenB (Bexsero®) vaccination in routine UK care

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Self-controlled case series

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (J07AH09) meningococcus B, multicomponent vaccine

  meningococcus B, multicomponent vaccine
• Medical condition to be studied:
  Seizure

  Febrile convulsion

  Acute disseminated encephalomyelitis

  Guillain-Barre syndrome

  Anaphylactic reaction

  Kawasaki's disease

Population studied

• Short description of the study population:
  The baseline population will be those children permanently registered at a UK primary care practice which contributes data to The Health Information Network (THIN) database between a start date and an end date (observation period). The start date for each child will be the most recent of 1st May 2015 (earliest data included), date of birth plus one month, or transfer from another practice plus three months. The first month of life is not included as part of this time is usually spent in secondary care. The three months after transfer in is not included so that prevalent events recorded at a registration visit during this period are not mistaken for incident episodes. The end date will be the earliest of date of birth plus 18 months, transfer out of the practice, last data collection or the study end.; There are no exclusion criteria. ; ; Descriptive analysis – The study population will be all children in the baseline population who receive one or more vaccination with 4CMenB in their observation period.; SCCS – For both primary outcomes the study population will be children in the baseline population who had a diagnosis of that outcome and had received at least one dose of 4CMenB vaccine.
• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
• Estimated number of subjects:
  70000

Study design details

• Main study objective:
  The objective is to assess the safety of 4CMenB vaccination within the UK National Immunisation program.
• Outcomes:
  Seizures (all and febrile seizures) and Kawasaki disease. Acute disseminated encephalomyelitis, Guillain-Barré syndrome, and anaphylaxis
• Data analysis plan:
  A post-exposure risk period has been assigned for each outcome as the time following vaccination during which an outcome would be expected to occur if it were caused by the vaccination. The incidence of each outcome in the post-exposure risk periods will be estimated for all vaccination doses and each dose. Plots will be produced for outcomes with at least one event to show the temporal distribution around exposure. Age-sex distributions will be reported. The self-controlled case series will analyse the primary outcomes of seizures and KD (first episodes). GBS, ADEM and anaphylaxis will be analysed if sufficient events are observed in the risk period to provide 80% power, relative incidence of 10. All exposures to 4CMenB will be treated as equivalent risk periods. Outcomes and person-time during pre-defined pre-exposure periods will be excluded from baseline and analysed as a separate risk window.SCCS subgroup and sensitivity analyses have been outlined in a Statistical Analysis Plan.