LAUSR

Objectives To assess the sources of publicly available evidence supporting withdrawal, revocation or suspension of marketing authorisations (‘regulatory actions’) due to safety reasons in the EU since 2012 and to investigate the time taken since initial marketing authorisation to reach these regulatory decisions. Setting This investigation examined the sources of evidence supporting 18 identified prescription medicinal products which underwent regulatory action due to safety reasons within the EU in the period 1 July 2012 to 31 December 2016. Results Eighteen single or combined active substances (‘medicinal products’) withdrawn, revoked or suspended within the EU for safety reasons between 2012 and 2016 met the inclusion criteria. Case reports were most commonly cited, supporting 94.4% of regulatory actions (n=17), followed by randomised controlled trial, meta-analyses, animal and in vitro, ex vivo or in silico study designs, each cited in 72.2% of regulatory actions (n=13). 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 was the most common adverse drug reaction leading 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 found to be 204.5 days (143, 535 days) and decreased across the study period. Duration of marketing prior to regulatory action, from the medicinal product’s authorisation date, increased across the period 2012–2016. Conclusions The sources of evidence supporting pharmacovigilance regulatory activities appear to have changed since implementation of Directive 2010/84/EU and Regulation (EU) No. 1235/2010. This, together with a small improvement in regulatory efficiency, suggests progress towards more rapid regulatory decisions based on more robust evidence. Future research should continue to monitor sources of evidence supporting regulatory decisions and the time taken to reach these decisions over time.