An Observational Study to Evaluate the Utilisation Patterns and Long-term Effects of Lumacaftor and Ivacaftor Combination Therapy in Patients With Cystic Fibrosis

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

  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Observational retrospective study

Study drug and medical condition

• Name of medicine:
  ORKAMBI
• Medical condition to be studied:
  Cystic fibrosis

Population studied

• Short description of the study population:
  The study population involved cystic fibrosis (CF) patients reported in the US and UK CF registries.
• 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)
      • 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:
  Hepatic impaired

  Immunocompromised

  Other

  Pregnant women

  Renal impaired
• Special population of interest, other:
  Patients with cystic fibrosis
• Estimated number of subjects:
  11529

Study design details

• Main study objective:
  To evaluate: 1. Safety outcomes in CF patients ?6 years, homozygous for F508del, and treated with Orkambi, 2. Frequency and outcome of pregnancies in female patients ?14 years, homozygous for F508del, and treated with Orkambi, 3. Disease progression in CF patients ?6 years, homozygous for F508del, and treated with Orkambi, 4. Drug utilisation / potential off-label use of Orkambi
• Outcomes:
  Safety analyses: risks of death, organ transplant, hospitalizations, pulmonary exacerbations, CF complications, respiratory microbiology, liver function tests. Pregnancy analyses: pregnancy outcome, gestational age (US and UK), congenital anomalies (UK only). Disease progression analyses: Percent predicted FEV1, clinical signs of CF disease progression. Drug utilization analyses: Orkambi use.
• Data analysis plan:
  Data will be analyzed separately for each registry for 5 years. The results of the annual analyses will be combined in a single study report for each year. Each annual report will include the patient data collected during the previous calendar year. Descriptive statistics will be presented for all study endpoints. All safety, pregnancy, and CF disease progression endpoints (Objectives 1, 2, and 3, respectively) will be compared between the respective Orkambi and Comparator Cohorts. Risks, as well as crude relative risks with 95% confidence intervals will be calculated for safety outcomes for each of the analyses years. Analyses will be stratified by patient age, percent predicted FEV1, and other variables as appropriate. Multivariate modeling and sensitivity analysis may be performed for outcomes deserving further investigation if sufficient data are available. Off-label use definition will be adjusted for each annual analysis as necessary if labeled indications change.