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. 2019 Oct 28;9(10):e028133.
doi: 10.1136/bmjopen-2018-028133.

Use of real-world evidence in postmarketing medicines regulation in the European Union: a systematic assessment of European Medicines Agency referrals 2013-2017

Jeremy Philip Brown  1 , Kevin Wing  2 , Stephen J Evans  2 , Krishnan Bhaskaran  2 , Liam Smeeth  2 , Ian J Douglas  2
Affiliations

Use of real-world evidence in postmarketing medicines regulation in the European Union: a systematic assessment of European Medicines Agency referrals 2013-2017

Jeremy Philip Brown et al. BMJ Open. .

Abstract

Objectives: To assess the use, and evaluate the usefulness, of non-interventional studies and routinely collected healthcare data in postmarketing assessments conducted by the European Medicines Agency (EMA).

Design: We reviewed and systematically assessed all referrals to the EMA made due to safety or efficacy concerns that were evaluated between 1 January 2013 and 30 June 2017. We extracted information from the assessment report and the referral notification. Two reviewers independently assessed the contribution of non-interventional evidence to decision-making.

Results: The preliminary evidence leading to the assessment in 52 eligible referrals was mostly from spontaneous reports (cited in 26 of 52 referrals) and randomised trials (22/52). In contrast, many evidence types were used for the full assessment. Non-interventional studies were frequently used in the full assessment for the evaluation of product safety (31/52) and product efficacy (18/52). In particular, non-interventional studies were relied on for the evaluation of safety and efficacy in subgroups, the evaluation of safety relating to a rare adverse event, understanding product usage and misuse and for evaluation of the effectiveness of risk minimisation measures. The most common recommendations were changes to product information (43/52) and marketing authorisation withdrawal or suspension (12/52). In the majority of referrals, non-interventional evidence was judged to contribute to the decision made (30/52) and in three referrals it was the primary source of evidence.

Conclusions: European regulatory decision-making relies on multiple evidence types, particularly randomised trials, spontaneous reports and non-interventional studies. Non-interventional studies had an important role particularly for the characterisation and quantification of adverse events, the evaluation of product usage and for evaluating the effectiveness of regulatory action to minimise risk.

Keywords: medicines regulation; non-interventional studies; real world evidence.

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Conflict of interest statement

Competing interests: JPB had financial support from ABPI for the submitted work; IJD has received a grant from the ABPI for the study in question, financial support from GlaxoSmithKline for work unrelated to the study in question, has consulted for GlaxoSmithKline and Gilead, and holds stock in GlaxoSmithKline; SJE is an independent European Commission-appointed expert member of EMA’s Pharmacovigilance Risk Assessment Committee; LS reports personal fees from GSK outside the submitted work; there are no other relationships or activities that could appear to have influenced the submitted work. The views expressed in this article are personal views of the author and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its committees or working parties.

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