OP4-2 - Review of studies evaluating the effectiveness of risk minimization measures assessed by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency during 2016-2021

Background: The European Medicines Agency (EMA) monitors safe and effective use of medicines throughout the product life cycle by, amongst others, implementation of risk minimization measures (RMMs). Through post-authorization safety studies (PASS) marketing authorization holders are required to monitor effectiveness of RMMs in the European Union. Limited information is available on factors associated with effective RMM.

Objectives: To assess and characterize industry funded PASS evaluating RMM effectiveness assessed by the Pharmacovigilance Risk Assessment Committee (PRAC) during 2016-2021.

Methods: All PASS assessment reports finalized by PRAC between 1^st of January 2016 and 31^st of December 2021 were identified from PRAC minutes and compiled from non-public EMA databases (i.e., Documents Records Electronic Archive Management System and the European Review System for electronic Common Technical Documents). Data on PASS characteristics were extracted including: PASS design, analytical methods, outcome measures, type of RMMs evaluated, conclusion on RMM effectiveness, and definition of effectiveness. Extracted variables were analyzed using descriptive statistics.  

Results:

The study cohort consisted of 94 PASS of which 59.6% rendered a conclusion on RMM effectiveness. RMM were evaluated as effective in 80.4% and ineffective in 19.6% of the conclusive PASS. The majority of PASS (64.9%) aimed to measure health care professional’s (HCPs) awareness, knowledge and behavior regarding RMM. Primary data collection was used in 68.1% of the PASS, 23.4% of PASS used secondary data and 8.5% used both. A cross-sectional study design was most frequently observed (76.6%), followed by a cohort study design (27.7%). Additional RMM (aRMM) were evaluated in 60.6% of the PASS, routine RMM in 8.5%, and a combination of both in 30.9%. Amongst those PASS that evaluated effectiveness of aRMM, 84.9% evaluated educational materials (e.g., guides, checklists, patient cards). Half of the included PASS used predefined effectiveness criteria for the evaluation of RMM effectiveness.

PASS characteristics stratified by outcome (i.e., effective RMM, ineffective RMM, no conclusion on RMM effectiveness) showed minor differences. A higher proportion of PASS aimed at measuring patterns of use in clinical practice were inconclusive (44.7%), where conclusive PASS more frequently measured, for instance, risk awareness and knowledge (64.4% of PASS with effective RMM conclusion, 72.7% of PASS with ineffective RMM conclusion).

Of the 47 PASS for which effectiveness criteria were defined a priori, half of the studies concluded that RMM were effective (50.0 %).

Conclusion:

In 40.4% of 94 industry sponsored PASS PRAC considered that the PASS did not allow to conclude on the effectiveness of RMMs. Only minor differences were seen in PASS characteristics between effective, ineffective and inconclusive PASS. Defining RMM effectiveness criteria a priori was more often seen for PASS with a conclusion on RMM effectiveness compared to inconclusive PASS, which highlights the need for early determination of how effectiveness will be measured.