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Status: Finalised First registered on: 24/01/2020

Last updated on: 21/04/2021

1. Study identification

EU PAS Register NumberEUPAS32405

Official titleImpact of EU label changes and pregnancy prevention programme for medicinal products containing valproate and related substances: risk awareness and adherence

Study title acronymValproateRiskAware

Study typeOther: Cross-sectional

Brief description of the studyThis is a multi-country study in eight European countries: Belgium, Denmark, Greece, Latvia, Portugal, The Netherlands, Slovenia and Spain. In each country a web-based questionnaire will be conducted among users and former users of valproate and related products, and among health care professionals. An electronic survey including questions on the influence of regulatory recommendations on HCP awareness about the teratogenic and neurodevelopment effects of valproate and related substances will be used to gauge their perspective and to assess effects on knowledge, attitudes and practices. Similary a patient questionnaire will measure awareness about regulatory recommendations as well as uptake of pregnancy prevention measures, and investigate their effect on valproate use. Data from the survey and questionnaire will be anonymised and analysed for differences between countries. Determinants for adherence to the measures implemented per country will be analysed. Additionally, in two countries (Netherlands and Portugal) semi-structured telephone interviews will be held with 6-8 patients with a range in age and varied educational background.

Was this study requested by a regulator?Yes: EMA

Is the study required by a Risk Management Plan (RMP)? Not applicable

Regulatory procedure number (RMP Category 1 and 2 studies only)

Other study registration identification numbers and URLs as applicable

2. Research centres and Investigator details

Coordinating study entity

Centre to which the investigator belongsUtrecht University Pharmacoepidemiology Center

Department/Research groupDivision of Pharmacoepidemiology & Clinical Pharmacology

Organisation/affiliationUtrecht Institute for Pharmaceutical Sciences

Website/Homepagewww.uu.nl/pecp

Details of (Primary) lead investigator

Title Dr

Last name Klungel

First name Olaf

Is this study being carried out with the collaboration of a research network?

Yes

Pharmacoepidemiology and Pharmacovigilance Network

Other centres where this study is being conducted

Multiple centres

In total how many centres are involved in this Study?9

Utrecht University Pharmacoepidemiology Center

Laboratory of Hygiene and Environmental Protection

UFPorto

The Institute of Public Health of Riga Stradins University, Riga, Latvia

University of Copenhagen, Faculty of Health and Medical Sciences, Department of Pharmacy (Social and Clinical Pharmacy), Copenhagen, Denmark

Sección de Innovación y Organización, Servicio Navarro de Salud, Pamplona, Spain

Pharmaceutical Care Unit – Ghent University, Ghent, Belgium

Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, Netherlands

Countries in which this study is being conducted

International study

Belgium

Denmark

Greece

Latvia

Netherlands

Portugal

Slovenia

Spain

3. Study timelines: initial administrative steps, progress reports and final report

PlannedActual

Date when funding contract was signed25/02/201925/02/2019

Start date of data collection25/10/201925/10/2019

Start date of data analysis25/12/2019

Date of interim report, if expected24/07/2020

Date of final study report28/08/202001/04/2021

4. Sources of funding

Please provide estimates of the percentage of funding by source for this study

Names(s)Approximate % funding

Pharmaceutical companies

Charities

Government body

Research councils

EU funding scheme

OtherEuropean Medicines Agency100

5. Contact details for enquiries

Scientific Enquiries

Title Dr

Last name Leonardo Alves

First name Teresa

Address line 1National Institute for Public Health and the Environment (RIVM)

Address line 2Centre for Health Protection (GZB)

Address line 3P.O.Box 1,

CityBilthoven

Postcode3720 BA

CountryNetherlands

Phone number (incl. country code)31-30-2743238

Alternative phone number

Fax number (incl. country code)

Email address teresa.leonardo.alves@rivm.nl

Public Enquiries

Title Dr

Last name Leonardo Alves

First name Teresa

Address line 1National Institute for Public Health and the Environment (RIVM

Address line 2Centre for Health Protection (GZB)

Address line 3P.O.Box 1,

CityBilthoven

Postcode3720 BA

CountryNetherlands

Phone number (incl. country code)31-30-2743238

Alternative phone number

Fax number (incl. country code)

Email address teresa.leonardo.alves@rivm.nl

11. Scope of the study

What is the scope of the study?

Risk assessment

Drug utilisation study

Effectiveness evaluation

Primary scope : Risk assessment

12. Main objective(s)

What is the main objective of the study?

1) To assess the extent of the influence of recommendations from regulatory authorities on patients’, prescribers’ and pharmacists’ awareness about the risk of adverse teratogenic effects and neurodevelopmental disorders to children of women exposed to valproate and related substances during pregnancy, and to investigate whether knowledge, attitudes and practices have been affected.

Are there primary outcomes?No

Are there secondary outcomes?No

13. Study design

What is the design of the study?

Cross-sectional study

14. Follow-up of patients

Will patients be followed up?Not applicable/no follow-up

15. Data analysis plan

Please provide a brief summary of the analysis method

The surveys will generate descriptive statistics, describing the distribution of characteristics of patients and HCPs for the variables included in the questionnaires. Univariate and bivariate analyses will be conducted according to stratifying variables, including HCP characteristics (age, gender, country, specialism, years of experience) and patient characteristics (age, diagnosis, past use of valproate and related products, type of prescriber, country) For the qualitative data, the analysis involves an inductive content analysis based on a close line-by-line reading of the responses and developing a conceptual coding scheme based on the major themes in the interview guides. Transcripts will be categorized individually by two coders in each country in native languages. Coders from all countries will meet prior to the analysis to predefine categories and codes to be used. They meet again to evaluate the categories identified and to write up the results using illustrative quotes.