The implementation of risk minimization measures to prevent teratogenic pregnancy outcomes related to oral retinoid and valproate use in Belgium

ABSTRACT

Introduction

Both oral retinoid and valproate containing medicines are highly teratogenic. Their use by women of childbearing age is controlled by risk minimization measures (RMMs) introduced by the European Medicine Agency, including the pregnancy prevention programme (PPP). In 2018, the RMMs were revised as previous measures were insufficient to prevent the use of these medicines during pregnancies.

Aim & Methods

A cross-sectional survey was conducted among patients, physicians and pharmacists to evaluate the implementation of the revised RMMs in Belgium. The primary outcome was compliance with key aspects of the PPP. Differences in compliance between oral retinoid and valproate stakeholders were investigated. The relationship between potential determinants (population characteristics and RMM usage) and compliance was studied via multiple logistic regression.

Results

A total of 317 eligible patients, physicians and pharmacists participated. The majority of the studied patients fail to comply with the PPP, mainly driven by poor implementation of pregnancy testing. A large number of healthcare providers is unaware of the available educational materials.

Conclusion

It is likely that a substantial part of Belgian women of childbearing age using oral retinoids or valproate insufficiently meet the PPP requirements. We propose to better inform healthcare providers about the mandatory PPPs and available educational materials as well as to support them with the implementation of such programmes to improve the safe use of these teratogenic medicines.

KEYWORDS:

• Valproate
• oral retinoids
• pregnancy prevention
• risk minimization measures
• drug safety

Acknowledgments

We would like to thank all patients, physicians, and pharmacists explicitly for their time in filling in the questionnaire.

Authors’ contributions

Conceptualization: Xander Bertels, Lies Lahousse, Koen Boussery; Methodology: Xander Bertels, Lies Lahousse; Formal analysis and investigation: Xander Bertels; Writing - original draft preparation: Xander Bertels; Writing - review and editing: Lies Lahousse, Koen Boussery, Els Mehuys; Funding acquisition: Lies Lahousse; Resources: Lies Lahousse; Supervision: Lies Lahousse. All authors read and approved the final manuscript.

Availability of data and material

For access to the datasets generated during this study we refer to the European Pharmacoepidemiology and Pharmacovigilance Research Network (EU PE&PV). The subset of data used for the analyses within this manuscript are directly available from the corresponding author upon reasonable request and with permission of EU PE&PV.

Code availability

The scripts used for the analysis of the current study are not publicly available but are available from the corresponding author on reasonable request.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

All individual participants consented with publication of this article.

Disclosure statement

The authors (Xander Bertels, Lies Lahousse, Koen Boussery and Els Mehuys) report no declarations of interest.

Ethics approval

The questionnaires and methodology for the current study were approved by the Ghent University Hospital Medical Ethics Committee (B670202043088).

Geolocation information

The questionnaire was filled in online by Dutch-speaking Belgian stakeholders (Flemish Region and Brussels-Capital Region) and analysed at the Pharmaceutical Care Unit, located in Ghent, Belgium.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work (EUPAS32408 & EUPAS32405) was supported by the European Medicines Agency through the EU PE&PV Research Network led by Utrecht University under contracts EMA/2018/18/PE SC01 & SC02.