A European multicentre drug utilisation study of the impact of regulatory measures on prescribing of codeine for pain in children

Abstract

Purpose In June 2013, following recommendations from the World Health Organization (WHO) and Food and Drug Administration (FDA), the European Medicines Agency agreed updates to the codeine product information regarding use for pain in children younger than 12 years and children undergoing tonsillectomy or adenoidectomy (TA) for obstructive sleep apnoea. This study was conducted to (a) assess effectiveness of these measures on codeine prescribing in the “real‐world” setting and (b) test feasibility of a study using a common protocol by regulators with access to databases. Methods The study was performed using BIFAP (Spain), CPRD (UK), and IMS® Disease Analyzer (France and Germany) databases. Prescribers included general practitioners (GPs) (France and UK), GPs and paediatricians together (Spain), and GPs, paediatricians, and ear, nose, and throat (ENT) specialists separately (Germany). Between January 2010 and June 2015, prevalence of codeine prescribing was obtained every 6 months, and a time series analysis (joinpoint) was performed. Codeine prescribing within ±30 days of TA was also identified. Furthermore, doses, durations, and prior prescribing of other analgesics were investigated. Results Over the 5‐year period, codeine prescribing decreased in children younger than 12 years (by 84% in France and Spain, 44% in GP practices in Germany, and 33% in the United Kingdom). The temporal pattern was compatible with the regulatory intervention in France and the United Kingdom, whereas a decrease throughout the study period was seen in Germany and Spain. Decreased prescribing associated with TA was suggested in ENT practices in Germany. Conclusions Codeine prescribing for children decreased in line with introduced regulatory measures. Multidatabase studies assessing impact of measures by EU regulators are feasible.

Impact of medicines regulatory risk communications in the UK on prescribing and clinical outcomes: Systematic review, time series analysis and meta‐analysis

“…Regulatory risk communication is likely to have variable effects because it is a complex intervention in a complex system and the wider health service context may modify the effect of regulatory risk communications that can occur between countries . Antipsychotic prescribing in dementia is an example of this, where, in England, antipsychotic prescribing also declined in 2007 in the absence of any risk communication, shortly after the publication of National Institute of Health and Care Excellence guidance for England and Wales in late 2006 .…”

“…because it is a complex intervention in a complex system and the wider health service context may modify the effect of regulatory risk communications that can occur between countries. 55 57 The decision for how certain types of information are communicated are made by committees and can be complex, being made by the MHRA for nationally authorised medicines or the EMA for centrally authorised and some nationally authorised medicines. These could be based upon the strength of evidence, the perceived importance of the safety concern, and how likely…”

Ability of Primary Care Health Databases to Assess Medicinal Products Discussed by the European Union Pharmacovigilance Risk Assessment Committee

“…The EMA supports medicines evaluation by analyzing data for products or groups of products, particularly where it is hard to identify a single marketing authorization holder from three commercially available electronic primary care health databases (primary EHDs) that it accesses to assess drug utilization, risks of medicines, and effectiveness of risk minimization measures. [3][4][5][6][7][8][9] These primary EHDs include routinely collected patient data from a network or a sample of mainly general practitioners (GPs) practices. Primary EHDs represent an optimal data source for medicines evaluation by capturing detailed information on patients' health status, drugs prescribed, and medical outcomes.…”

Can We Rely on Results From IQVIA Medical Research Data UK Converted to the Observational Medical Outcome Partnership Common Data Model?

“…CPRD was one of the databases used in the Hedenmalm et al . study . The results of the CPRD study, compared with those found in this study on IMRD‐UK, not only revealed a lower prevalence in the prescribing of codeine but, more remarkably, an absence of seasonality ( Figure ).…”

“…This current study aimed to replicate the Hedenmalm et al study but with the main objective to compare the prescribing of codeine for the treatment of pain in children in the OMOP CDM converted database against results in the original IMRD‐UK source database. The specific objective was to explore any potential loss of information and inaccuracy resulting from the conversion and, if so, whether these changes would have impacted on the interpretation of study results and lead to a different conclusion.…”