{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:55:59Z","timestamp":1780671359727,"version":"3.54.1"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>The purpose of this study was to evaluate the effectiveness of the risk minimisation measures (RMMs) implemented in Europe in 2014 for valproate\u2010containing products to mitigate their risk during pregnancy and to characterise valproate prescribing patterns in women of childbearing potential (WCBP) before and after implementation of RMMs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A multinational cohort study based on existing data sources using a pre\u2010\/post\u2010 design was performed in five European countries (France, Germany, Spain, Sweden, UK) in an outpatient setting. Effectiveness of RMMs was assessed by comparing the proportion of valproate initiations as second (or subsequent) line therapy before and after implementation of RMMs (primary outcome) with an increase in this proportion indicating success of RMMs. Overall use of valproate and incidence of pregnancies in WCBP were also examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The proportion of valproate initiations as second line therapy increased after implementation of RMMs in incident female users in Sweden (from 81.1%, 95% CI 79.9%\u201082.3% to 84.5%, 95% CI 83.5%\u201085.5%) and the UK (from 66.4%, 95% CI 64.5%\u201068.3% to 72.4%, 95% CI 70.0%\u201074.9%), it remained the same in Germany and Spain and decreased in France from 48.7% (95% CI 45.6%\u201051.9%) to 40.6% (95% CI 37.6%\u201043.7%). In Sweden and the UK, the incidence of pregnancies exposed to valproate decreased in the post\u2010implementation period: 8.0 vs 9.5 and 10.9 vs 16.9 per 1000 person\u2010years, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results on primary outcome of this study suggest limited effectiveness of the RMMs. Additional RMMs were implemented in 2018.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5166","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T19:36:08Z","timestamp":1603827368000},"page":"292-303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Effectiveness of risk minimisation measures for valproate: A drug utilisation study in Europe"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6780-0676","authenticated-orcid":false,"given":"Massoud","family":"Toussi","sequence":"first","affiliation":[{"name":"Department Real World Solutions IQVIA  La D\u00e9fense Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4238-1759","authenticated-orcid":false,"given":"Margarita","family":"Shlaen","sequence":"additional","affiliation":[{"name":"Department Real World Solutions IQVIA  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Coste","sequence":"additional","affiliation":[{"name":"Department Epidemiology and Risk\u2010Benefit Sanofi Aventis R&amp;D  Chilly Mazarin France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanka","family":"de Voogd","sequence":"additional","affiliation":[{"name":"Department Global Clinical Research Mylan  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilis","family":"Dimos","sequence":"additional","affiliation":[{"name":"Department Pharmacovigilance (medical section) Demo S.A.  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3352-8480","authenticated-orcid":false,"given":"Sigal","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department Pharmacoepidemiology Teva Pharmaceutical Industries Ltd  Netanya Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2008.04.022"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2009.04.026"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000339399.64213.1a"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01376.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2009.176990"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70323-X"},{"key":"e_1_2_9_8_1","first-page":"CD010236","article-title":"Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child","volume":"10","author":"Bromley R","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2011.06.014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2270"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2013.08.001"},{"key":"e_1_2_9_12_1","unstructured":"European Medicines Agency. Assessment report \u2010 Procedure under Article 31 of Directive 2001\/83\/EC resulting from pharmacovigilance data. Substances related to valproate.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Referrals_document\/Valproate_and_related_substances_31\/Recommendation_provided_by_Pharmacovigilance_Risk_Assessment_Committee\/WC500177352.pdf.2014. Accessed May 21 2019."},{"key":"e_1_2_9_13_1","unstructured":"European Medicines Agency: PRAC recommends strengthening the restrictions on the use of valproate in women and girls. Women to be better informed of the risks of valproate use during pregnancy.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Referrals_document\/Valproate_and_related_substances_31\/Recommendation_provided_by_Pharmacovigilance_Risk_Assessment_Committee\/WC500175214.pdf. 2014. Accessed May 21 2019."},{"key":"e_1_2_9_14_1","unstructured":"European Medicines Agency. Guideline on good pharmacovigilance practices (GVP) Module XVI\u2014risk minimisation measures: selection of tools and effectiveness indicators (Rev 1).http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2014\/02\/WC500162051.pdf. 2014. Accessed May 21 2019."},{"key":"e_1_2_9_15_1","unstructured":"European Medicines Agency. Annex IV Conditions to the marketing authorisations.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Referrals_document\/Valproate_and_related_substances_31\/Position_provided_by_CMDh\/WC500181294.pdf. 2014. Accessed May 21 2019."},{"key":"e_1_2_9_16_1","unstructured":"European Medicines Agency. Notification of a Referral under Article 31 of Directive 2001\/83\/EC.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Referrals_document\/Valproate_and_related_substances_31\/Procedure_started\/WC500151966.pdf. 2013. 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European Congress of Epidemiology \u201cCrises, epidemiological transitions and the role of epidemiologists\u201d","volume":"66","author":"Degremont A","year":"2018","journal-title":"Revue d'\u00c9pid\u00e9miologie et de Sant\u00e9 Publique"},{"issue":"3","key":"e_1_2_9_21_1","first-page":"311","article-title":"Usage of valproate in women in the UK. 32nd International Conference on Pharmacoepidemiology and Therapeutic Risk Management. Ireland","volume":"25","author":"Quinn DDK","year":"2016","journal-title":"Pharmacoepidemiol Drug"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-317368"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12228"},{"key":"e_1_2_9_24_1","unstructured":"European Medicines Agency. New measures to avoid valproate exposure in pregnancy endorsed. 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