Effect of European Medicines Agency's restrictions on trimetazidine utilization in Portugal.

PURPOSE: Following safety concerns regarding trimetazidine, the European Medicines Agency (EMA) recommended restrictions on its use. Our objective was to determine the impact of regulatory actions on trimetazidine utilization in Portugal. METHODS: Retrospective interrupted time-series analysis of monthly ambulatory pharmacy reimbursement records for the Portuguese National Health Service between January 2006 and December 2015. Regulatory actions were identified by searching the EMA, Portuguese Medicines Authority, and European Commission's websites. Concurrent factors in the same period were also identified. The main outcome was the dispensing of trimetazidine-containing products per month in Portugal. RESULTS: Two interruption periods were defined in the series: May 2011, when EMA announced it would review trimetazidine safety, and June 2012 to January 2013, when EMA announced it had reached a final opinion recommending restrictions; the European Commission approved EMA's recommendation; the Portuguese Medicines Authority issued safety alerts, changed the summary of product characteristics, and approved a direct health-care professional letter; and a regional bulletin was issued. Interruption 1 had no effect on trimetazidine use, but interruption 2 resulted in decreases in level and trend-from 8.3 million defined daily doses in 2010 to 2.8 million in 2015. After interruption 2, trimetazidine use tended towards a lower steady state. CONCLUSIONS: There was a significant decrease in trimetazidine use in Portugal following a complex intervention that included safety alerts, changes to the summary of product characteristics, a direct health-care professional letter, and a regional drug bulletin. No effect was seen when EMA announced its review of trimetazidine safety.

Effectiveness of educational outreach visits compared with usual guideline dissemination to improve family physician prescribing-an 18-month open cluster-randomized trial.

BACKGROUND: Educational outreach visits are meant to improve the practice of health professionals by promoting face-to-face visits to deliver educational contents. They have been shown to change prescription behavior, but long-term effects are still uncertain. This trial aimed to determine if they improve family physician prescribing compared with passive guideline dissemination. METHODS: Parallel, open, superiority, and cluster-randomized trial. National Health Service primary care practices (clusters) were recruited in the Lisbon region-Portugal between March 2013 and January 2014. They could enter if they had at least four family physicians willing to participate and not planning to retire in the follow-up period. Three national guidelines were chosen for dissemination: acid secretion modifiers, non-steroidal anti-inflammatory drugs, and antiplatelets. Physicians in the intervention group received one 15 to 20 min educational outreach visit at their workplace for each guideline. Physicians in the control group had access to guidelines through the Directorate-General for Health's website (passive dissemination). Primary outcomes were the proportion of COX-2 inhibitors prescribed within the NSAID class and the proportion of omeprazole within the PPI class at 18 months after the intervention. A cost-benefit analysis was performed. Practices were randomized by minimization. Data analyses were done at individual physician level using generalized mixed-effects regression models. Participants could not be blinded. RESULTS: Thirty-eight practices with 239 physicians were randomized (120 to intervention and 119 to control). Of 360 planned visits, 322 were delivered. No differences were found between physicians in the intervention and control groups regarding the proportion of omeprazole prescribed among PPIs 18 months after the visit (46.28 vs 47.15%, p = 0.971) or the proportion of COX-2 inhibitors among NSAIDs (12.07 vs 13.08%, p = 0.085). All secondary outcome comparisons showed no effect. There was no difference in cumulative drug costs at 18 months (3223.50€/1000 patients in the intervention group and 3143.92€/1000 patients in the control group, p = 0.848). CONCLUSIONS: Educational outreach visits were unsuccessful in improving compliance with guideline recommendations among Portuguese family physicians. No effects were observed at 1, 6, and 18 months after the intervention, and there were no associated cost savings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01984034 . Registered 7 November 2013.

An open cluster-randomized, 18-month trial to compare the effectiveness of educational outreach visits with usual guideline dissemination to improve family physician prescribing.

BACKGROUND: The Portuguese National Health Directorate has issued clinical practice guidelines on prescription of anti-inflammatory drugs, acid suppressive therapy, and antiplatelets. However, their effectiveness in changing actual practice is unknown. METHODS: The study will compare the effectiveness of educational outreach visits regarding the improvement of compliance with clinical guidelines in primary care against usual dissemination strategies. A cost-benefit analysis will also be conducted. We will carry out a parallel, open, superiority, randomized trial directed to primary care physicians. Physicians will be recruited and allocated at a cluster-level (primary care unit) by minimization. Data will be analyzed at the physician level. Primary care units will be eligible if they use electronic prescribing and have at least four physicians willing to participate. Physicians in intervention units will be offered individual educational outreach visits (one for each guideline) at their workplace during a six-month period. Physicians in the control group will be offered a single unrelated group training session. Primary outcomes will be the proportion of cyclooxygenase-2 inhibitors prescribed in the anti-inflammatory class, and the proportion of omeprazole in the proton pump inhibitors class at 18 months post-intervention. Prescription data will be collected from the regional pharmacy claims database. We estimated a sample size of 110 physicians in each group, corresponding to 19 clusters with a mean size of 6 physicians. Outcome collection and data analysis will be blinded to allocation, but due to the nature of the intervention, physicians and detailers cannot be blinded. DISCUSSION: This trial will attempt to address unresolved issues in the literature, namely, long term persistence of effect, the importance of sequential visits in an outreach program, and cost issues. If successful, this trial may be the cornerstone for deploying large scale educational outreach programs within the Portuguese National Health Service. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01984034.