Valproate has been authorised for several decades across the EU for the treatment of epilepsy and bipolar disorders. Recently, a safety concern arose with the use of valproate medicines in pregnant women specifically, a potential risk of malformations and developmental problems was identified in children exposed to valproate in the womb. A decision was made by the European Medicines Agency to recommend restricting the use of valproate to treat epilepsy or bipolar disorder in girls and in women who are pregnant or who can become pregnant unless other treatments are not effective or not tolerated. In addition to these recommendations, targeted educational material surrounding these risks is being sent to prescribers and to women prescribed valproate in the UK.
This study is being conducted to assess if there are demonstrable differences in prescribing practices in the UK since the introduction of these measures, by looking at practices before and after their introduction, in women overall and in subpopulations of interest (pregnant women and women of child bearing potential). This will then be used to inform the EMA as to the effectiveness of such measures or whether further measures may be required to ensure safe prescribing of this medicine.
An assessment of the impact of dissemination of risk minimisation measures (i.e. educational materials and Dear Healthcare Professional Communication) and an assessment of these measures is planned. To meet the primary study objective, a main analysis will be performed on two 3-year periods before and after the implementation of risk minimisation measures, by subgroup of population (girls and women of childbearing potential). The main analysis will be descriptive and will provide information on demographics; medical history; valproate indication, dosage and duration; usage of medications related to any of the valproate indications; concomitant medications prescribed; hormonal contraceptives and IUD; co-morbidities; pregnancies.
Interim reports will be conducted every 6 months until the final report. An interrupted time series report will be considered for the final report if conditions are met in which data are evaluated at multiple time points before and after an intervention in order to detect whether or not an intervention had a significantly greater effect than any underlying trend. Regression analysis will be used to define the trends of each proportion in pre- and post implementation periods. The angle between the trends will be calculated for the two periods to provide insights into the impact of the implementation.
Health Outcomes to be Measured:
The main analysis will compare the prescribing patterns of valproate during the pre- and post- implementation periods in females to meet the study objective. The analysis will be descriptive in nature. Descriptive statistics will be provided for the patients, treatments and diagnosis characteristics.