(013) Effectiveness of additional risk minimisation measures for valproate among healthcare professionals and patients: a cross-sectional survey in six European countries

Background: Valproate (VPA) indicated for the treatment of epilepsy and bipolar disorder can be harmful to unborn children if taken during pregnancy. The European authorities approved prescribing restrictions and additional risk minimisation measures (aRMMs) in 2018 regarding the use of VPA in women of childbearing potential (WCBP) and during pregnancy. The aRMMs consisted of a pregnancy prevention program (PPP) that included the use of educational materials (EMs) for healthcare professionals (HCPs) and patients, and appropriate counselling regarding contraception and pregnancy.

Objectives: To assess the impact of the aRMMs issued in Europe in 2018, regarding the use of VPA in WCBP and during pregnancy.

Methods: A cross-sectional, multinational, non-interventional survey was conducted among 1982 HCPs and 779 WCBP treated with VPA for epilepsy, bipolar disorder or other indications, in France, United Kingdom, Sweden, Poland, Germany and Spain. Three categories of HCPs were targeted: prescribing physicians, gynaecologists and pharmacists. Three dimensions, awareness, knowledge and behaviour, were assessed. Awareness score was assessed based on the percentage of HCPs and WCBP who answered they had received and read each of the relevant EMs. Knowledge and behaviour dimensions scores were assessed as the proportion of HCPs and WCBP with correct answers to the relevant questions. Stringent criteria were defined for success in each dimension (correct answers to ≥80% of questions) and overall success: ≥90%/80% successful HCPs/ WCBP respectively, in the behaviour dimension and one of the two other dimensions.

Results: Overall, HCPs and WCBP did not meet the stringent individual dimension or overall success criteria. Of note, some questions had confusing phrasing. Highest success rates were in the behaviour dimension for gynaecologists (71.7%), pharmacists (49.7%) and WCBP (51.2%), and in the awareness dimension for prescribing physicians (23.6%). HCPs reported being unfamiliar with some EMs and lacked knowledge of detailed prescribing conditions for VPA and the need for contraception regardless of sexual activity. More than 50% of WCBP were aware of the relevant EMs and knew about the teratogenic risks of VPA.

Conclusions: Despite gaps in awareness of some educational materials and knowledge of detailed prescribing conditions for VPA, HCPs and WCBP followed many of the aRMMs in their clinical practice/behaviour. As the ultimate goal of the aRMMs is to change clinical practice, to optimize the safe and effective use of a medicinal product, and protect patients, these results are encouraging. Still, further investigation is needed to understand the barriers and reasons why certain measures of the PPP are not followed in clinical practice.