Post-Authorization Safety Study (PASS) of conjugated estrogens/bazedoxifene (CE/BZA) in the United States

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Post Authorization Safety Study (PASS)

Study drug and medical condition

• Name of medicine, other:
  Duavee
• Medical condition to be studied:
  Menopausal symptoms

Population studied

• Short description of the study population:
  Study subjects are all patients identified in each database with minimal exclusion criteria applied. This broad subject eligibility will ensure that the study is representative of the actual ‘real-world’ use of the product in a clinical setting.; ; Inclusion Criteria; All patients who have received a prescription for Duavee or E+P HT since May 2014 (date of; first commercial availability in the US) and have a baseline period of at least 12 months prior; to their first dispensing of a study medicine will be eligible for inclusion.; Primary Analyses;  To be included in the primary analyses, patients need to be new initiators of Duavee or E+P HT, as evidenced by a minimum 12 month baseline period with no prior use of either Duavee or E+P HT (including non-study estrogens).; Secondary Analyses;  To be included in the secondary analyses, patients will have use of either (1) single-entity estrogens or progestins (non-study drugs) or (2) unopposed estrogen; (single-entity estrogen without evidence of any progestin dispensing) in their baseline period.; ; Exclusion Criteria; Patients meeting any of the following criteria will be excluded from the study:;  Patients with <12 months of continuous enrollment prior to their dispensing of a study medication. This baseline period is necessary to determine if the patient is a new initiator of Duavee or E+P HT without a history of unopposed estrogen use, and to ascertain baseline covariates and medical history;;  Patients without a uterus, ie, males, or women for whom evidence of hysterectomy is identified prior to initiation of Duavee or comparator E+P HT; or;  Patients with a diagnosis or history of any cancer during their baseline period;;  Patients for whom Duavee, comparator E+P HT or unopposed estrogen are identified during the baseline period will be excluded from the primary analyses and will be evaluated in separate secondary analyses;;  Patients for whom cardiovascular outcomes are identified in the six months prior to the index date will be excluded from the analyses of cardiovascular outcomes.
• 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)
• Estimated number of subjects:
  13698

Study design details

• Main study objective:
  The overall aim of this PASS is to monitor the safety profile of Duavee in comparison to estrogen + progestin (E+P) combination hormone replacement therapies (HRT) in the US.
• Outcomes:
  Endometrial hyperplasia and Endometrial cancer, VTE, CHD, stroke, breast cancer, ovarian cancer, thyroid cancer, renal cancer, renal adenoma, gastrointestinal tract cancers, all cancers, and all-cause mortality
• Data analysis plan:
  Analyses will focus on the comparison between women initiating either Duavee or E+P HRT. Baseline characteristics will be compared across the two cohorts of new users to assess potential confounding variables. For each safety endpoint (venous thromboembolism VTE, stroke, coronary heart disease CHD, breast cancer, ovarian cancer, endometrial hyperplasia, and endometrial cancer, etc.), univariate and adjusted HRs will be estimated that compare incidence of the first occurrence of each safety event between Duavee and E+P HRT users.