Non-Interventional retrospective longitudinal study in the United Kingdom and France to investigate the therapeutic strategies after discontinuation of valproate and related substances in clinical practice (VALSE study - VALNAC09344)

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/48865
• EU PAS number:
  EUPAS37438
• Study ID:
  48865
• Official title and acronym:
  Non-Interventional retrospective longitudinal study in the United Kingdom and France to investigate the therapeutic strategies after discontinuation of valproate and related substances in clinical practice (VALSE study - VALNAC09344)
• DARWIN EU® study:
  No
• Study countries:
  France

  United Kingdom
• Study description:
  In Europe, valproate and related substances have been licensed to treat epilepsy and bipolar disorder. Following the identification of an increased risk of malformations and neurodevelopmental disorders in children exposed to valproate in utero, in 2018 the Pharmacovigilance Risk Assessment Committee (PRAC) recommended restrictions on the use of valproate for the treatment of woman of child-bearing potential (WCBP) and pregnant woman. Recommendations on switching or discontinuation of valproate remained poorly defined. The PRAC requested the consortium of Marketed Authorization Holders to conduct an observational study aimed to evaluate and identify the best practices for switching of valproate in clinical practice. The primary study objective is (i) to determine the clusters of patients that are the most likely to reflect a success in epilepsy/ bipolar disorder management after valproate discontinuation based on: (i) the description of the overall treatment patterns in the year following valproate discontinuation, (ii) the categorization of patients according to their treatment patterns (clusters), and (iii) the description of patients’ and treatment characteristics at baseline, and clinical relapse occurrence, pregnancy occurrence, and other healthcare resources in the follow-up period in each of these clusters. The secondary study objective is to identify the baseline factors (e.g., patients’, Epilepsy/BD treatments, disease characteristics) associated with the potential successful / unsuccessful clusters. The objectives will be split for each indication of valproate (epilepsy or bipolar disorder). This is a cohort study conducted with secondary data from the UK electronic medical records database (Clinical Practice Research Datalink) and the French claims database (Système National des Données de Santé) which will include women aged 13 to 49 years, who have discontinued valproate from 2014 to 2017 and followed for 1 year.
• Study status:
  Finalised

Research institutions and networks

Institutions

Bordeaux PharmacoEpi, University of Bordeaux

France

Sanofi Winthrop Industrie, France

Study timelines

Date when funding contract was signed

Actual: 08/04/2019

Study start date

Planned: 01/01/2021

Actual: 29/03/2021

Data analysis start date

Planned: 01/01/2021

Actual: 29/03/2021

Date of interim report, if expected

Planned: 31/01/2023

Actual: 14/12/2022

Date of final study report

Planned: 31/07/2023

Actual: 05/07/2023

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

A Consortium of Marketing Authorization Holders for valproate and related substances

Study protocol

Initial protocol

VALSE_Protocol v8.0_08NOV2022-clean

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  EU RMP category 1 (imposed as condition of marketing authorisation)
• Regulatory procedure number:
  EMEA/H/A-31/1454