Post-Authorization Safety Program—Validation of the Clinical Practice Research Datalink for the Study of Cardiovascular and Neoplasm Events in Users of Treatments for Overactive Bladder

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Other
• If ‘other’, further details on the scope of the study:
  Validation of the CPRD database 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

Study drug and medical condition

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

  oxybutynin

  (G04BD07) tolterodine

  tolterodine

  (G04BD08) solifenacin

  solifenacin

  (G04BD09) trospium

  trospium

  (G04BD10) darifenacin

  darifenacin

  (G04BD11) fesoterodine

  fesoterodine
• Medical condition to be studied:
  Urinary incontinence

Population studied

• Short description of the study population:
  Patients in the study had at least 12 months of continuous enrollment in the database, followed by an index prescription for oxybutynin, tolterodine, darifenacin, solifenacin, trospium, or fesoterodine, provided that the agent was not prescribed during the previous 12 months; patients were aged 18 years or older at the time of the index prescription.; Subjects in the program will be required to meet all of the following inclusion criteria:; 1. Have at least 12 months of continuous enrollment in the database (thereby providing medical and prescription history data) before the first prescription or; dispensing of an OAB drug of interest.; 2. For most covariates (e.g., history of bilateral mastectomy, menopause status, use of hormone-replacement therapy), all available information without time; limitation will be used, although the 12-month period prior to the cohort entry date will be used to estimate measures of health care utilization.; 3. Have a first recorded prescription or dispensing for oxybutynin, tolterodine, darifenacin, solifenacin, trospium, or fesoterodine.; 4. Be aged 18 years or older at the time of first prescription of a drug of interest. ; Patients will be excluded if they meet any of the following criteria at any time prior to cohort entry:; 1. Had a diagnosis of cancer other than non-melanoma skin cancer.; 2. Had a diagnosis of human immunodeficiency virus (HIV) infection. These patients often receive health care through specialty clinics or separate health plans, and their health service use might not be fully captured in the data sources.
• 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:
  400000

Study design details

• Main study objective:
  Characterize users of OAB drugs. Describe patterns of usage of OAB drugs. Validate algorithms used for the diagnosis of study endpoints. Describe the availability of potential confounders in the CPRD, 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. The characteristics of the users at cohort entry and the patterns of use of the study medications will be described. CV cases will be classified as definite, probable, possible or noncases after patient profile review.A random sample of definite, probable and noncases will be selected for validation. GPs will be asked to review patients’ medical records and charts and complete a questionnaire. Based on this assessment, the PPV will be calculated for the definite, probable and possible cases.The screening and validation method of neoplasm endpoints will depend on whether the medical practice where the study subject is enrolled consented to have its information linked to other health care data within the NHS system. Characteristics of subjects in practices without and with data linkage will be compared. The concordance between diagnosis derived from the CPRD, the Hospital Episodes Statistics and the cancer registry will be described