Impact of EU label changes and revised pregnancy prevention programme for medicinal products containing valproate: utilisation and prescribing trends

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cross-sectional

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (N03AG01) valproic acid

  valproic acid

  (N03AG02) valpromide

  valpromide

Population studied

• Short description of the study population:
  Female subjects of childbearing potential aged 12-55 years using valproate-containing medicinal products identified from the data sources of Netherlands, UK, Denmark, Italy and Spain between 01 January 2010 and 21 December 2020.
• Age groups:
  • Adolescents (12 to < 18 years)
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  8000000

Study design details

• Main study objective:
  This study will address the research question, “What was the effect of the EU label changes and the revised pregnancy prevention programme (2018) on utilization of valproate containing medicinal products and to what extent did prescribers and patients comply with recommendations?”.
• Outcomes:
  - valproate use (dispensing/prescription) (objective 1) - pregnancy test (objective 2) - contraceptive use (objective 2) - pregnancy (objective 3) - use of alternative medicines (objective 4), - reason for discontinuation of valproate (objective 1)
• Data analysis plan:
  1. Descriptive and hypothesis testing (objectives 1 and 4) - Incidence rates and quarter-year prevalences of outcomes will be calculated. - Interrupted time series analysis will be performed to test changes in outcomes before vs. after implementation of PRAC intervention. 2. Overall evaluation (objective 5) - The results of objectives 1-4 will be summarized qualitatively.