Systematising Pharmacovigilance Engagement of Patients, Healthcare Professionals and Regulators: A Practical Decision Guide Derived from the International Risk Governance Framework for Engagement Events and Discourse

Introduction: Input from patients and healthcare professionals to regulatory assessments is essential for benefit-risk management of medicines. How to best obtain input in different risk scenarios is uncertain.

Objectives: The objective of this study was to investigate whether the International Risk Governance Council (IRGC) Framework is applicable to pharmacovigilance and can guide selecting engagement mechanisms for optimising stakeholder input.

Methods: For proof-of-concept, classify 'iconic' cases of pharmacovigilance engagement at the European Medicines Agency (EMA) by IRGC risk scenario types and compare the engagement that happened with the engagement discourse recommended by the IRGC Framework for different risk scenarios. If the concept is proven, derive proposals for strengthening engagement.

Results: Six iconic cases were classified by risk scenario type at the respective time points when deciding on engagement: venous thromboembolism with combined hormonal contraceptives (complex risk); lipodystrophy with highly active antiretroviral therapy medicines, carcinogenicity with contaminated nelfinavir products (uncertain risks); teratogenicity with thalidomide, progressive multifocal leukoencephalopathy with natalizumab, teratogenicity and developmental disorders with valproate (ambiguous risks). The comparison of the engagement events with IRGC recommendations showed correspondence between the scope/outcomes of the events and the features of the recommended discourse.

Conclusions: The IRGC Framework appears applicable to pharmacovigilance. Proposals derived from the IRGC recommendations may be valuable for guiding regulators when selecting mechanisms for engagement with patients and healthcare professionals in given risk scenarios. The proposed decision guide aims at ensuring systematic and consistent engagement across regulatory assessments and providing for the most purposeful discourse, to effectively obtain real-world input for regulatory risk assessment, evaluation of risk minimisation measures and decision making.