Challenges in the Implementation of EU Risk Minimisation Measures for Medicinal Products in Clinical Practice Guidelines: Mixed Methods Multi-Case Study

Mathias Møllebæk*, Helga Gardarsdottir, Alexia Georgia Bikou, Ana Kodrič, Ana Marta Silva, Armin Andersen, Christos Kontogiorgis, Elita Poplavska, Fariba Ahmadizar, Foteini Dermiki-Gkana, Ieva Rutkovska, Inês Ribeiro Vaz, Mitja Kos, Paula Barão, Renske Grupstra, Teresa Leonardo Alves, Anna Birna Almarsdóttir

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Introduction
Risk minimisation measures (RMMs) aim to ensure safe use of medicines, but their implementation in clinical practice is complicated by the diversity of stakeholders whose clinical decision making they seek to inform. Clinical practice guidelines (CPGs) are considered integral in clinical decision making.

Objectives
To determine the extent to which RMMs are included in the relevant CPGs and to describe factors that determine RMM inclusion.

Methods
A multi-case study design using quantitative document analysis of CPGs combined with qualitative interviews with informants from organisations that issue CPGs. Cases from five therapeutic areas (TAs) with a regulatory requirement for further RMMs were studied individually in six EU member states (Denmark, Greece, Latvia, Netherlands, Portugal and Slovenia). Clinical practice guidelines were analysed using pre-defined coding frameworks. Interviewees were sampled purposively for experience and knowledge about CPG development and RMM inclusion. Verbatim interview transcripts were analysed inductively.

Results
In total, 136 CPGs were analysed, and RMM information about TAs was included in 25% of CPGs. Based on 71 interviews we found that factors that determine RMM inclusion in CPGs include clinicians’ low awareness of RMMs despite awareness of RMMs’ safety concern, low expectation of RMMs’ clinical utility, and unfamiliarity with pharmacovigilance data supporting RMMs and perceived incompatibility of CPGs’ scope and purpose and RMM information.

Conclusions
The inclusion of RMM information in relevant CPGs is remarkably limited. It may be explained by characteristics of CPGs and of RMMs as well as lack of connection between national regulators and organisations and authors developing CPGs. More collaboration between stakeholders, national regulators and the EMA may advance implementation.
Original languageEnglish
JournalDrug Safety
ISSN0114-5916
DOIs
Publication statusE-pub ahead of print - 2024

Bibliographical note

Funding Information:
Open access funding provided by Copenhagen University. The research leading to these results was conducted as part of the activities of the EU PE&PV (Pharmacoepidemiology and Pharmacovigilance) Research Network, which is a public academic partnership coordinated by the Utrecht University, The Netherlands. The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2020/46/TDA/L4.02. This document expresses the opinion of the authors of the paper, and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its committees or working parties.

Publisher Copyright:
© The Author(s) 2024.

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