Benefit-Risk Re-Assessment of Pharmaceuticals: A Retrospective Analysis of Safety-Related Referral Procedures in the European Union in the Period 2001 - 2012
Background: As the benefit-‐risk profile of a medicinal product is often not fully established at the granting of the Marketing Authorisation (MA), unexpected safety issues may emerge once a medicine is widely used by larger populations. Such safety issues are referred to the European Medicines Agency (EMA) for benefit risk re-‐ assessment to gain an Opinion on whether the MA should be maintained, changed, suspended or withdrawn across the European Union. There is a call for more transparency and for a switch from implicit towards a well-‐balanced decision-‐making procedure. The understanding of the determinants relevant to the re-‐assessment procedures may help to improve the transparency and may elicit some points for improvement in the process. Objective: The aim of this study is to determine the triggers, outcomes and timing within the product life cycle of referral procedures for both centrally and non-‐centrally authorised medicines and to investigate the attributes that contribute to the EMA’s Opinion. Methods: A retrospective study of all available documentation issued by the EMA was performed including all safety-‐related referral procedures concluded during 2001-‐2012 included. The elapsed time between the year that the first Marketing Authorisation was issued and the year a referral procedure was initiated was determined. Characteristics of the product and safety issue under suspicion were identified and reviewed. Results: A total of 113 safety-‐related referral procedures were concluded in 2001-‐2012 included, concerning 106 active ingredients, or 119 product-‐safety issue combinations. In 9% of the procedures the EMA Opinion recommended withdrawal of the product, in 10% a suspension and in 72% to change the Marketing Authorisation. Only in 6% of the cases the recommendation was to maintain the Marketing Authorisation unchanged. Referral procedures were initiated in all phases of the product life cycle, and in a broad variety of product classes. The Member states are key in notifying safety concerns, triggered most often by spontaneous case reports (31%) or clinical studies (37%). Conclusions: The seriousness of the adverse event under suspicion was the strongest if not the sole determinant in the decision-‐making procedure. (Relative) effectiveness played a role in only a minority of procedures, and re-‐assessments due to a safety-‐ related referral procedure are more a unilateral risk-‐assessment rather than a benefit- risk assessment.
|benefit risk, reanalysis, referral procedures, drug safety|
|Master Health Economics, Policy and Law|
|Organisation||Erasmus School of Health Policy & Management|
Huinink, L.K. (2013, August 28). Benefit-Risk Re-Assessment of Pharmaceuticals: A Retrospective Analysis of Safety-Related Referral Procedures in the European Union in the Period 2001 - 2012. Master Health Economics, Policy and Law. Retrieved from http://hdl.handle.net/2105/16007