116239 - An observational cohort study to assess the risk of autoimmune diseases in adolescent and young adult women aged 9 to 25 years exposed to Cervarix® in the United Kingdom

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:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

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

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (J07BM02) papillomavirus (human types 16, 18)

  papillomavirus (human types 16, 18)
• Medical condition to be studied:
  Autoimmune disorder

Population studied

• Short description of the study population:
  Inclusion criteria for the exposed female cohort : Exposed females must satisfy ALL the following criteria at study entry; • Female aged from 9 to 25 years at the reference date (01 September 2008 through 31 August 2010); • Recorded in the CPRD GOLD for at least 12 months before the reference date; • The first dose of Cervarix received between 01 September 2008 through 31 August 2010, Full date (day/month/year) of Cervarix vaccination(s) available; • Subject defined as acceptable in CPRD GOLD; ; Inclusion criteria for the unexposed historical female cohort: Unexposed females must satisfy ALL the following criteria at study entry; • Female aged 9 to 25 years at the reference date (01 September 2005 through 31 August 2007); • Recorded in the CPRD GOLD for at least 12 months before the reference date; • Subject defined as acceptable in CPRD GOLD; ; Inclusion criteria for the unexposed concurrent male cohort: Unexposed concurrent males must satisfy ALL the following criteria at study entry; • Male aged 9 to 25 years at the reference date (01 September 2008 through 31 August 2010); • Recorded in the CPRD GOLD for at least 12 months before the reference date; • Subject defined as acceptable in CPRD GOLD; ; Inclusion criteria for the unexposed historical male cohort: Unexposed historical males must satisfy ALL the following criteria at study entry; • Male aged 9 to 25 years at the reference date (01 September 2005 through 31 August; 2007); • Recorded in the CPRD GOLD for at least 12 months before the reference date; • Subject defined as acceptable in CPRD GOLD
• Age groups:
  • Paediatric Population (< 18 years)

    • 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)
• Estimated number of subjects:
  1053

Study design details

• Main study objective:
  To assess the risk of neuroinflammatory/ophthalmic new onset of autoimmune disease(s) (NOAD) and other pre-specified NOAD within 12 months following the administration of the first dose of Cervarix.
• Outcomes:
  Occurrence of new onset of confirmed autoimmune disease during the period of one year following administration of the first dose of Cervarix (risk period) among an exposed cohort and during an equivalent time period in the unexposed cohorts for the following two co-primary composite endpoints:1 Neuroinflammatory/ophthalmic autoimmune diseases2 Other autoimmune diseases, Occurrence of new onset of individual confirmed autoimmune disease within 2 months (Guillain Barré syndrome and autoimmune haemolytic anaemia), within 6 months (idiopathic thrombocytopenic purpura) and within 1 year (e.g. multiple sclerosis, transverse myelitis, optic neuritis, other demyelinating diseases, auto-immune uveitis) following the administration of the first dose of Cervarix.
• Data analysis plan:
  Incidence rates for NOAD will be calculated as the number of cases divided by person-time. A Poisson regression model will estimate the exposed/unexposed risk ratio and its 95% confidence interval. The Poisson model will include the number of cases in each cohort as the dependent variable, the exposure status as a binary independent variable and the log-transformed total person-year as an offset. The same statistical model will be used to compare the two cohorts.The cases of NOAD in exposed subjects will be analysed using Self-control case-series (SCCS) methods.