Inconsistencies among European Union pharmaceutical regulator safety communications: a cross-country comparison.

Jean-David Zeitoun,Nicholas Downing,Henri Bergeron,Jérémie H Lefèvre,Joseph S Ross

doi:10.1371/journal.pone.0109100

Abstract

BackgroundThe European Medicines Agency (EMA) and national regulators share the responsibility to communicate to healthcare providers postmarketing safety events but little is known about the consistency of this process. We aimed to compare public availability of safety-related communications and drug withdrawals from the EMA and European Union member countries for novel medicines.Methods and FindingsWe performed a cross-sectional analysis using public Dear Healthcare Professional Communications (DHPCs) for all novel medicines authorized between 2001 and 2010 by the EMA and available for use in France, Netherlands, Spain, and the United Kingdom. Between 2001 and 2010, the EMA approved 185 novel medicines. DHPCs could not be ascertained for the EMA. Among the 4 national regulators, as of April 30, 2013, at least one safety DHPC or withdrawal occurred for 53 (28.6%) medicines, totaling 90 DHPCs and 5 withdrawals. Among these 53 medicines, all 4 national agencies issued at least one communication for 17 (32.1%), three of the four for 25 (47.2%), two of the four for 6 (11.3%), and one of the four for 5 (9.4%). Five drugs were reported to be withdrawn, three by all four countries, one by three and one by two. Among the 95 DHPCs and withdrawals, 20 (21.1%) were issued by all 4 national regulators, 37 (38.9%) by 3 of the 4, 22 (23.2%) by 2 of the 4, and 16 (16.8%) by one. Consistency of making publicly available all identified safety DHPC or withdrawal across regulator pairs varied from 33% to 73% agreement.ConclusionsSafety communications were not made publicly available by the EMA. Among the 4 European member countries with national regulators that make DHPCs publicly available since at least 2001, there were substantial inconsistencies in safety communications for novel medicines. The impact of those inconsistencies in terms of public health remains to be determined.

Highlights

The use of most medical therapies carries both the potential for patient benefit and risk, and this is especially true for pharmaceutical products
In Europe, the European Medicines Agency (EMA) is responsible for approving the vast majority of drugs but post-marketing safety surveillance is performed by both the EMA and national regulatory agencies
Novel Therapeutic Sample For purposes of studying consistency in safety communications across multiple European regulatory agencies, we studied a sample of novel therapeutic agents approved by the EMA between January 1, 2001 and December 31, 2010, by the Centralized Authorization Procedure of the EMA, that had been developed for prior work [5]

Summary

Introduction

The use of most medical therapies carries both the potential for patient benefit and risk, and this is especially true for pharmaceutical products. The so called ‘‘life-cycle approach’’ to drug evaluation, wherein benefits and risks are assessed during the pre-market drug development period, and throughout the post-market ‘‘life’’ of the drug, is currently being championed by leading regulators such as the U.S Food and Drug Administration (FDA) [1,2] and the European Medicines Agency (EMA) [3]. This emerging paradigm is contingent on an effective post-marketing surveillance and communication system for safety signals, so that physicians and patients are updated with relevant contemporary information. We aimed to compare public availability of safety-related communications and drug withdrawals from the EMA and European Union member countries for novel medicines

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