Risk Minimisation Evaluation with Process Indicators and Behavioural or Health Outcomes in Europe: Systematic Review.

BACKGROUND European Pharmacovigilance regulatory guidance recommends the evaluation of additional risk minimisation measures (aRMMs) with process indicators and outcomes. Evaluation of both measures within the same evaluation helps to establish the relationship between the implementation of aRMMs (across process indicators) and the impact on drug safety-related outcomes. The term risk minimisation evaluation (RMEv) was used to describe a study or group of studies that assesses the effectiveness of aRMMs for one specific product. OBJECTIVES The objective of this systematic review was to describe the characteristics and results of RMEv that include both process indicators and outcomes as well as those of studies that conform the RMEv in Europe. METHODS We conducted a systematic search in the European Union Register of Post-Authorization Studies, PubMed and grey literature (Google and abstracts of the International Conference on Pharmacoepidemiology and Therapeutic Risk Management) to identify studies that assessed the effectiveness of aRMMs including at least one European country, from 1 January, 2011 to 12 October, 2019. Identified studies linked to one product were considered part of the product RMEv. Only RMEv that included both process indicators and outcomes (behavioural and/or health/safety outcomes) were eligible. Data were abstracted from reports, manuscripts and abstracts. RESULTS Eighteen of 102 (18%) RMEv had both process indicators and outcomes, and were included in this review. Of the 18 RMEv, ten consisted of one study only, five of two studies, and three of three or more studies. A total of 30 studies were included within the 18 RMEv. The designs of the studies were: 19 (63%) cross-sectional surveys (47% targeted patients and 89% healthcare professionals), 17 (57%) retrospective studies (47% using pre/post approach) and 3 (10%) prospective studies. Nineteen studies included process indicators that were receipt (n = 14), use (n = 12), knowledge (n = 17) and self-reported behaviour (n = 15). Regarding outcomes, 67% of the 18 RMEv evaluated behavioural outcomes and 50% health/safety outcomes. Three of the 18 RMEv evaluated both behavioural and health/safety outcomes. For five RMEv, correlations between process indicators and outcomes were performed, two at the patient level. Results were available for 14 of the 18 RMEv. In healthcare professional surveys, the median percentage was 57% for receipt, 92% for reading, 80% for use, 77% for knowledge and 74% for behaviour. In patient surveys, the median percentage was 56% for receipt, 87% for reading, 65% for use, 47% for knowledge and 69% for behaviour. Knowledge was better in healthcare professionals than patients (p < 0.05). Of the three RMEv with a correlation analysis, only one found a positive trend for a lower occurrence of outcomes as process indicators improved, though this was not statistically significant. CONCLUSIONS A minority of RMEv assessed both process indicators and outcomes. More RMEv require approaches that correlate process indicators and outcomes at the patient level to evaluate more comprehensively the implementation of aRMMs.