Post-authorization Safety Program Using the Swedish National Registers—A Validation Study of Cardiovascular and Neoplasm Events in Users of PharmacologicalTreatments for Overactive Bladder

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

  Other
• If ‘other’, further details on the scope of the study:
  Validation of the database Swedish Prescription and Inpatient National Databases for the study of CV and neoplasm events in users of treatments for overactive bladder
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Database validation study

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (G04BD04) oxybutynin

  oxybutynin

  (G04BD07) tolterodine

  tolterodine

  (G04BD08) solifenacin

  solifenacin

  (G04BD10) darifenacin

  darifenacin

  (G04BD11) fesoterodine

  fesoterodine
• Medical condition to be studied:
  Urinary incontinence

Population studied

• Short description of the study population:
  New users of any of the following medications for overactive bladder (OAB): oxybutynin, tolterodine, darifenacin, solifenacin, and fesoterodine.; ; Subjects in the program wiere required to meet all of the following inclusion criteria:;  Be a resident in Sweden for at least 12 months before the first dispensing of an OAB drug of interest (thereby providing medical and prescription history data).;  Have a first recorded dispensing for oxybutynin, tolterodine, darifenacin, solifenacin, or fesoterodine.;  Be aged 18 years or older at the time of first dispensing of a drug of interest.
• Age groups:
  • 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:
  Other
• Special population of interest, other:
  Overactive Bladder patients
• Estimated number of subjects:
  78000

Study design details

• Main study objective:
  Characterize users of OAB drugs.Describe patterns of usage of OAB drugs.Describe the availability of potential confounders in the database, to help in the design of the PASS studies of mirabegron.Estimate IRs of study endpoints in new users of OAB drugs.Estimate the IRRs of CV outcomes in users of OAB drugs compared with tolterodine.
• Outcomes:
  CV endpoints: AMI, stroke, CV mortality, all-cause mortality, major adverse cardiac events (MACE).Composite cancer endpoints: lung & bronchus, colon & rectum, melanoma of skin, urinary bladder, non-Hodgkin lymphoma, kidney & renal pelvis, pancreas, prostate (males), breast (females), corpus uteri (females)
• Data analysis plan:
  Summary statistics of the covariates will be generated. Characteristics of the users at cohort entry and the patterns of use of the study medications will be described.Users of OAB medications will be characterized with respect to selected covariates.Patterns of use of OAB drugs including dose, duration of treatment, drug switching, and use of drugs as add-on therapy will be described.The frequency of the different characteristics of the covariates and the degree of missing information will be described.3 types of incidence endpoints will be estimated:-IRs of 4 different CV events+all-cause mortality in new users of antimuscarinic drugs for the treatment of OAB.-IRR of 4 different CV outcomes+all-cause mortality in new users of each of the OAB drugs compared with tolterodine.-IRs of 2 sex-specific, multiple-cancer composite endpoints (1 for men/1 for women), during the first year after start of treatment and during subsequent years, among new users of antimuscarinic drugs