The public health impact of suspending cyproterone acetate/ ethinylestradiol (Diane-35 and generics) in France: A predictive modelling technique

Purpose : To predict the public health impact of marketing authorisation suspension of cyproterone acetate/ ethinylestradiol (Diane-35 and its generics) in France using a novel modelling technique, and to critique the model. Methods : Cyproterone acetate/ ethinylestradiol exposures in primary care were estimated using IQVIA’s IMS-France electronic health records database. Systematic review identified quantitative research with event data for exposed participants. The main outcome measure was prevented thromboembolic events as a result of marketing authorisation suspension. Results : At the time of marketing authorisation suspension, 4,325,863 active female patients of childbearing potential (aged 10-49 years) were in the IMS-France database. Between 12 months pre- and 12 months post-suspension, average monthly exposure to Diane-35 and its generics decreased by 78.79%, from 8.49 to 1.80 per 100,000 female patients aged 10-49 years. Absolute risk, calculated from event data from three observational studies, was estimated at 53.9%. Approximately 147 cases of thromboembolism would be prevented as a result of the eight-month suspension within exposed IMS-France patients (female, aged 10-49 years). A sensitivity analysis with risk estimates from the Summary of Product Characteristics suggested that less than one case would be prevented during the eight-month suspension. Conclusions : The predictive modelling technique is heavily reliant on the accuracy of utilisation and absolute risk data, as the risk of thromboembolic events differed when event data was estimated from published research or the Summary of Product Characteristics. Nonetheless, this model has wide applicability in other settings where a measurable change in drug utilisation may be obtained, such as withdrawal of marketing authorisation or restriction of prescribing.