Effect of regulatory interventions on agomelatine use in Spain: A multiple intervention time-series analysis in a nationwide electronic healthcare record database.

BACKGROUND: Liver injury is an important identified risk for agomelatine and several measures were put in place to prevent and minimize such risk. The study aims to assess the impact of four interventions on the incidence of agomelatine use, particularly among patients aged ≥75 in Spain between 2011 and 2018. METHODS: Quasi-experimental interrupted time-series analysis to examine data from a nationwide electronic healthcare record database (BIFAP). Quarterly cumulative incidence of agomelatine use per 100 000 patients was calculated and the impact of four regulatory interventions was quantified. RESULTS: The incidence of agomelatine use decreased by 85% and 87% from first quarter 2011 to last quarter 2018 in patients below and above 75 years old, respectively. Regulatory actions taken were not associated with an immediate and significant falling level of use or slope. The incidence was less than expected 6 months after the first and third intervention for patients below and above 75 years old, and more than expected after the second and fourth intervention for both populations, though these analyses were underpowered to observe significant results. The downward trend became less pronounced, reaching a residual level of use, which remained stable in the last segment of the study period. CONCLUSION: New users of agomelatine decreased throughout the study period, starting before interventions took place. The effect of specific interventions might be masked by the progressive decrease tendency, constant over the study period. The effects of external factors that might overlap, unintended consequences, and issues concerning statistical modeling in situations where rates are already falling, should be considered when interpreting the results.

Drug utilization study on immediate release Fentanyl in Spain. Prevalence, incidence, and indication.

PURPOSE: We aimed to characterize the trends of immediate release fentanyl (IRF) use in Spain between 2012 and 2017 and indication for its use. IRF drugs are rapid-acting opioids approved to treat breakthrough cancer pain (BTCP) in patients already receiving maintenance opioid therapy for chronic cancer pain. A substantial increase in consumption of IRF has been observed with emerging cases of abuse and dependence, most of them in noncancer patients. METHODS: An ecological descriptive consumption study with aggregated data from drug dispensed by community pharmacies and reimbursed by the National Health System in which Defined Daily Doses per 10 000 inhabitants (DID) were calculated and a retrospective cohort study using data from the Spanish Database for Pharmacoepidemiological Research in Primary Care in which participants entered the cohort study after 1 year with the Primary Care Practitioners were performed. Annual prevalence and incidence rate of IRF use were estimated by sex and calendar year. Potential indication was also assessed. RESULTS: IRF use in Spain increased from 2.1 DID in 2012 to 3.8 DID in 2017. The incidence rate and prevalence increased in 53% and 74%, respectively. Patients without previous cancer or BCTP diagnosis represented 27% of incident users, predominantly women. Half of patients with noncancer-related diagnosis had a musculoskeletal disorder linked to the first IRF prescription. CONCLUSIONS: National consumption and new IRF users in Spain increased over the study period and one quarter of patients did not have a BTCP or cancer diagnosis registered in their clinical record.

Correction to: Safety Communication Tools and Healthcare Professionals' Awareness of Specific Drug Safety Issues in Europe: A Survey Study.

In the original publication of the article, the headings of columns 3 and 4 in the data table.

Safety Communication Tools and Healthcare Professionals' Awareness of Specific Drug Safety Issues in Europe: A Survey Study.

INTRODUCTION: National competent authorities (NCAs) use Direct Healthcare Professional Communications (DHPCs) to communicate new drug safety issues to healthcare professionals (HCPs). More knowledge is needed about the effectiveness of DHPCs and the extent to which they raise awareness of new safety issues among HCPs. OBJECTIVE: The objective was to assess and compare general practitioners' (GPs'), cardiologists', and pharmacists' familiarity with DHPCs as communication tools, their awareness of specific drug safety issues, and the sources through which they had become aware of the specific issues. METHODS: GPs, cardiologists, and pharmacists from nine European countries (Croatia, Denmark, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, and the UK) completed a web-based survey. The survey was conducted in the context of the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action. Respondents were asked about their familiarity with DHPCs in general and their awareness of safety issues that had recently been communicated and involved the following drugs: combined hormonal contraceptives, diclofenac, valproate, and ivabradine. Those HCPs who were aware of the specific safety issues were subsequently asked to indicate the source through which they had become aware of them. Differences between professions in familiarity with DHPCs and awareness were tested using a Pearson χ2 test per country and post hoc Pearson χ2 tests in the case of statistically significant differences. RESULTS: Of the 3288 included respondents, 54% were GPs, 40% were pharmacists, and 7% were cardiologists. The number of respondents ranged from 67 in Denmark to 916 in Spain. Most respondents (92%) were familiar with DHPCs, with one significant difference between the professions: pharmacists were more familiar than GPs in Italy (99 vs 90%, P = 0.004). GPs' awareness ranged from 96% for the diclofenac issue to 70% for the ivabradine issue. A similar pattern was shown for pharmacists (91% aware of the diclofenac issue to 66% of the ivabradine issue). Cardiologists' awareness ranged from 91% for the ivabradine issue to 34% for the valproate issue. Overall, DHPCs were a common source through which GPs (range: 45% of those aware of the contraceptives issue to 60% of those aware of the valproate issue), cardiologists (range: 33% for the contraceptives issue to 61% for the valproate issue), and pharmacists (range: 41% for the contraceptives issue to 51% for the ivabradine issue) had become aware of the specific safety issues, followed by information on websites or in newsletters. CONCLUSIONS: GPs, cardiologists, and pharmacists were to a similar extent (highly) familiar with DHPCs, but they differed in awareness levels of specific safety issues. Cardiologists were less aware of safety issues associated with non-cardiology drugs even if these had cardiovascular safety concerns. This implies that additional strategies may be needed to reach specialists when communicating safety issues regarding drugs outside their therapeutic area but with risks related to their field of specialisation. DHPCs were an important source for the different professions to become aware of specific safety issues, but other sources were also often used. NCAs should consider the use of a range of sources when communicating important safety issues to HCPs.