(008) Comparing regulatory guidance on risk mitigation (or RMM) studies and the Reporting recommendation Intended for pharmaceutical Risk Minimization Evaluation Studies (RIMES) checklist

Background: The RIMES checklist (2017) is a useful guide to assess the design, implementation, and effectiveness of risk mitigation strategies or risk minimization measures (RMM). Apart from RIMES, the EMA and FDA provide guidance on planning, conducting, and reporting of risk mitigation strategies or RMM assessments. However, the availability of corresponding specific regulatory guidance from other countries, and the alignment between these guidance and the RIMES recommendations is less well known.

Objectives: To (1) identify the latest regulatory guidance/recommendations for assessing the effectiveness of risk mitigation strategies/RMM, and to (2) describe their alignment with the recommended RIMES checklist items.

Methods: The websites of regulatory bodies were searched for the latest guidance/recommendations for assessing the effectiveness of risk mitigation strategies/RMM, in the countries with most likelihood of having one: EU, US, Canada, China, Japan, Australia and South Africa. When no specific document was available, information on risk management plans (RMP) was explored. Documents in non-English languages were auto translated. The presence of the 17 RIMES checklist items (4 areas: study design, measures, analysis, reporting results) in the regulatory guidance was reported descriptively.

Results: Specific guidance existed for the EU (EMA’s GVP module XVI, 2021), and the US (FDA’s REMS guidance, 2019). In other geographies no specific guidance existed, therefore, RMP and Pharmaco-Vigilance (PV) guidance published in 2012 (Japan), 2021 (China), and 2022 (Canada and South Africa) were used. The EMA and the FDA guidance provided information on 35% (n=6) and 59% (n=10) of the 17 RIMES checklist items, respectively. In the FDA guidance, the RIMES checklist items were frequently present in the categories measures (100%) and reporting results (67%). The regulators in Canada and Australia recommended using EMA/FDA guidelines and using the ICH E2E guideline in Japan and South Africa. In China, general recommendations were incorporated in the PV guidance.

Conclusions: There was lack of specific guidance in some countries for assessing the effectiveness of risk mitigation strategies/RMM. Also, there was limited alignment between the regulatory guidance and the RIMES checklist. The recommendations in the RMP/PV regulatory guidance were heterogenous across countries, which may limit planning and conducting of such studies, particularly if requirements must be met in different countries. The RIMES checklist could be used to further develop and harmonize the regulatory agencies efforts to reduce known and potential safety risks in the post-approval settings.