Lane S, Lynn E and Shakir S.

Background

Major updates to the European Union (EU) pharmacovigilance (PV) legislation were implemented in July 2012. One objective of the update was “rapid and robust assessment of issues related to the safety of medicines.”(1) Since PV legislation updates were applied there have been no studies investigating sources of evidence and time to reach regulatory decision for products withdrawn, revoked, or suspended from EU market (“regulatory actions”). This study builds on previous DSRU research for 1999-2001 and 2002-2011.(2, 3)

Objectives

To assess sources of publicly available evidence supporting regulatory actions due to safety reasons in the EU since 2012. To investigate time taken from authorisation to reach each regulatory decision.

Methods

Types of publicly available evidence, time to decision and duration of marketing for each identified product were examined. We considered prescription products subject to regulatory action in the EU market (plus Norway, Iceland and Liechtenstein) for safety reasons between 1 July 2012 and 31 December 2016 for inclusion. Evidence supporting each regulatory action was identified and categorised; frequencies and proportions were calculated. Median time to regulatory decision and duration of marketing prior to regulatory action were calculated. ANOVA was performed for time to regulatory decision.

Results

18 medicinal products withdrawn, revoked or suspended in the EU for safety reasons between 2012 and 2016 met our inclusion criteria. Case reports most frequently supported regulatory actions (n=17, 94.4%). Epidemiological study designs were least commonly cited (n=8, 44.4%). Multiple sources of evidence contributed to 94.4% of regulatory decisions (n=17). Death most commonly led to regulatory action (n=5; 27.8%), with four of these related to medication error or overdose. Median (IQR) time taken to reach a decision from the start of regulatory review was 204.5 days (143, 535 days) and fell across the study period (p=0.87). Duration of marketing prior to regulatory action from each authorisation date increased between 2012 and 2016.

Conclusion

Sources of evidence supporting PV regulatory activities appear to have changed since implementation of updated EU PV legislation, particularly in favour of multiple supporting study designs. Case reports remain a common evidence source in regulatory decision-making, while epidemiological designs were least frequently cited. A small drop in time to reach regulatory decisions suggests better regulatory efficiency.