Safety and Incidence of Side Effects in a Cohort of Postmenopausal Women Prescribed Ospemifene Relative to Patients Diagnosed with but not Treated for Vulvar and Vaginal Atrophy (VVA) and Patients on Selective Oestrogen Receptor Modulators (SERMs) for Oestrogen-deficiency Conditions or Breast Cancer Prevention – A Post-Authorisation Safety Study

Study type

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

  Disease epidemiology

  Drug utilisation

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (G03XC05) ospemifene

  ospemifene
• Medical condition to be studied:
  Dyspareunia

Population studied

• Age groups:
  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  35115

Study design details

• Main study objective:
  a) Compare the incidence of VTE, among postmenopausal women who are newly prescribed ospemifene to that among patients diagnosed with but not treated for VVA.b) Compare the incidence of VTE, among postmenopausal women who are newly prescribed ospemifene to that among postmenopausal women newly prescribed other SERM therapies being utilised for oestrogen-deficiency conditions.
• Outcomes:
  The primary outcome of the study is the first occurrence of the following events during the follow-up period:• Venous thromboembolic events(VTE), including deep vein thrombosis (DVT), pulmonary embolism, and retinal vein thrombosis, First occurrence of the following events (time to event): Cerebrovascular events, Endometrial hyperplasia, Endometrial cancer, Pelvic organ prolapse, Urinary incontinence, Gall bladder events, Atrial fibrillation, Renal failure, Renal carcinoma, Renal adenoma, Liver tumours, Thymic epithelial tumours, Increased triglycerides, uterine diagnostic tests and procedures, off-label usage of ospemifene.
• Data analysis plan:
  Descriptive statistics will summarise patient demographics, proportion of patients with VTE, proportion of patients prescribed medications related to VTE. Hazard ratios and their 95% confidence intervals will be calculated and appropriate analyses will be conducted for the events of interest. A Cox regression model with time-dependent predictors will be used for the main comparison analysis. The analyses will be carried out separately to compare ospemifene to treatment with SERM and to untreated patients. The analyses would rely on time-dependent indicators to track changes in treatments. The Cox proportional hazard models will be adjusted for confounding factors using fully covariate adjusted models (implemented through inclusion of covariates in the model).As a secondary analysis, marginal structural models using inverse probability of treatment weighting in time-varying Cox models will be used to compare the risk of each outcome (VTE and stroke) between the treatment cohorts.