DARWIN EU® - Assessing the feasibility of conducting a causal study on the potential association between beta-blockers and breast cancer

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Population studied

• Short description of the study population:
  Study population: ; Objectives 1, 2, and 4: Newly initiating an index treatment during the study period (At least 1 prescription/dispensation of an index treatment; when both are available, prescription data will be prioritised).; Inclusion criteria; • Female individuals aged ≥18 years; • ≥365 days of prior observation; • Hypertension diagnosis on or before the index date[JN1.1]; Exclusion criteria; • Breast cancer diagnosis (including in situ breast cancer) or bilateral preventive mastectomy any time before the index date.; Washout: Infinite washout [-inf, -1] will be applied for prior use of the index treatment class. For any beta-blocker cohorts, washout will be applied across all beta-blockers. For any CCBs cohorts, washout will be applied across all CCBs; ; For objective 3, a different cohort (general female population) will be defined: ; Inclusion criteria; • Female individuals aged ≥18 years; • ≥365 days of prior observation; Exclusion criteria; • Breast cancer diagnosis (including in situ) or bilateral preventive mastectomy any time before index date.;
• 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)

Study design details

• Study design:
  A cohort study will be conducted using routinely collected health data from 5 data sources from 5 countries across Europe and in 3 European Union (EU) member states.
• Main study objective:
  1. To describe baseline demographic, clinical characteristics, the potential indications, as well as previous and baseline antihypertensive medication use in female individuals newly initiating the following distinct antihypertensive classes: Β1-selective beta-blockers, non-selective beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), non-dihydropyridines calcium channel blockers (CCBs), dihydropyridines CCBs.; 2. To describe the number, proportion, and time-to-event distribution of the following events among female individuals newly initiating Β1-selective beta-blockers, non-selective beta-blockers, ACE inhibitors, ARBs, non-dihydropyridines CCBs, dihydropyridines CCBs during 5 and 10 years of follow-up: 1) all cause death, 2) loss to follow-up, and 3) discontinuation of index treatment.; 3. To estimate the yearly incidence of primary breast cancer in the general adult (≥18 years) female population overall and by age group (18–40, 41–50, >50 years).; 4. Based on the size of each cohort, assess whether the study size provides adequate precision to support a causal analysis.