Nested case-control study evaluating effectiveness of immunization of girls and women of childbearing potential with GARDASIL(TM)/GARDASIL(TM) 9 against juvenile-onset recurrent respiratory papillomatosis (JoRRP) in Sweden, Denmark, and Norway (V503-095)

Study type

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

Non-interventional study

• Non-interventional study design:
  Case-control

  Other
• Non-interventional study design, other:
  Population-based nested case-control

Study drug and medical condition

• Name of medicine:
  GARDASIL

  GARDASIL 9
• Name of medicine, other:
  Gardasil 4
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BM01) papillomavirus (human types 6, 11, 16, 18)

  papillomavirus (human types 6, 11, 16, 18)

  (J07BM03) papillomavirus (human types 6, 11, 16, 18, 31, 33, 45, 52, 58)

  papillomavirus (human types 6, 11, 16, 18, 31, 33, 45, 52, 58)
• Medical condition to be studied:
  Respiratory papilloma
• Additional medical condition(s):
  juvenile-onset recurrent respiratory papillomatosis

Population studied

• Short description of the study population:
  Inclusion Criteria: ; ; -Birth cohorts 2008 to 2020; - The study subject (child) must be born and resident in Sweden, Denmark or Norway as defined through the Total Population Registry for their entire life. ; - The study subject must be between 0 to 9 years of age; - The child's mother had the opportunity to be fully vaccinated with GARDASIL/GARDASIL 9 at least one year prior to delivery.; ; Exclusion Criteria: ; - Children whose mother immigrated to Sweden, Denmark, or Norway both after 2006 and after age 9 years; - Adopted children, as the vaccination status of the actual, biological mother will be missing.; - Children whose mother received the bivalent vaccine Cervarix, since it provides no effectiveness against the causative HPV types (6 and 11) in RRP.; - Any child (case or control subject) who previously received any HPV vaccine
• Age groups:
  Paediatric Population (< 18 years)
• Estimated number of subjects:
  200

Study design details

• Study design:
  Population-based nested case-control study
• Main study objective:
  To assess if the odds of juvenile-onset recurrent respiratory papillomatosis (JoRRP) are lower among children whose biologic mothers were fully vaccinated with GARDASIL/GARDASIL 9 at least one year prior to delivery versus unvaccinated mothers.
• Setting:
  Nordic population, patient, and vaccine registries.
• Comparators:
  Random selection of up to 100 controls per case from the underlying population at risk, using incidence density sampling procedures. Matching criteria will be age of mother (+/- 1 year), sex of child, calendar year of case diagnosis, and region where case was diagnosed.
• Outcomes:
  A subject will be defined as having JoRRP if he/she has > or =1 hospitalization or outpatient record with diagnosis registered as D14.1, with appropriate topography/morphology codes (where possible to obtain from pathology/cancer registry), between 0-9 years of age
• Data analysis plan:
  Conditional logistic regression will be used for estimation of odds ratios (ORs) and corresponding 95% confidence intervals in the pooled analysis using 1-step approach, with adjustment for clustering and adjustment for relevant covariates; all measured with similar high accuracy in each country.