Study identification

PURI

https://redirect.ema.europa.eu/resource/50599

EU PAS number

EUPAS34201

Study ID

50599

Official title and acronym

A post-authorization safety study (PASS) to evaluate the paternal exposure to valproate and the risk of neurodevelopmental disorders including autism spectrum disorders as well as congenital abnormalities in offspring - a population-based retrospective study

DARWIN EU® study

No

Study countries

Denmark
Norway
Sweden

Study description

This population-based retrospective cohort study using secondary data from national registries within Norway, Denmark and Sweden aims to examine the association between paternal exposure to valproate at conception and the risk of Neurodevelopmental disorders (NDD), including Autism spectrum disorder (ASD), as well as Congenital Malformations (CM) in offspring. The primary objective is to investigate the risk of NDD, including ASD, in offspring paternally exposed to valproate (monotherapy), compared to lamotrigine or levetiracetam (composite monotherapy) treatment at the time of conception. Secondary objectives are to 1) investige the risk of CM in live and non-live offspring paternally exposed to valproate (monotherapy), compared to lamotrigine or levetiracetam (composite monotherapy) treatment at the time of conception, in Norway and Denmark, 2) describe the anti-epileptic drug (AED) exposure (posology and duration) data and health characteristics of male patients prescribed AEDs (including valproate and lamotrigine/levetiracetam) in treatment of epilepsy and other indications at the time of conception of their offspring, both for NDD and CM cohort, and 3) identify potentially important risk factors for outcomes of interest, in offspring paternally exposed to valproate (monotherapy) or lamotrigine or levetiracetam (composite monotherapy) at the time of conception, by examining AED exposure and health characteristics of the offspring and their mothers. Additional exploratory and sensitivity analyses apply (such as narrow case definition for primary outcome with a focus on ASD). Separate cohorts for analysis will be created where medical record linkage between offspring (<12 years), mother and father is available, the NDD cohort will consist of live births and the CM cohort will consist of live births, stillbirths and spontaneous abortions during gestation (2nd or 3rd trimester) for Norway and Denmark, and live births only for Sweden.

Study status

Ongoing
Research institution and networks

Institutions

IQVIA
United Kingdom
First published:
22/04/2024
Institution
Non-Pharmaceutical companyENCePP partner

Contact details

Florent Richy

Primary lead investigator
Study timelines

Date when funding contract was signed

Actual:

Study start date

Planned:
Actual:

Data analysis start date

Planned:

Date of interim report, if expected

Planned:
Actual:

Date of final study report

Planned:
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

Valproate_PASS_Protocol_V7.0.PDF

English (4.09 MB - PDF)View document
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