Post-Approval Safety Issues with Innovative Drugs: A European Cohort Study

PGM Mol, AH Arnardottir, D Motola, PJ Vrijlandt, Ruben Duijnhoven, FM Haaijer-Ruskamp, PA de Graeff, P Denig, Sabine Straus

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27 Citations (Scopus)


Background At time of approval, knowledge of the full benefit risk of any drug is limited, in particular with regards to safety. Post-approval surveillance of potential drug safety concerns is recognized as an important task of regulatory agencies. For innovative, often first-in-class drugs, safety knowledge at time of approval is often even less extensive and these may require tighter scrutiny post approval. Objective We evaluated whether more post-approval serious safety issues were identified for drugs with a higher level of innovation. Methods A cohort study was performed that included all new active substances approved under the European Centralized Procedure and for which serious safety issues were identified post-approval from 1 January 1999 to 1 January 2012. Serious safety issues were defined as issues requiring a Direct Healthcare Professional Communication to alert individual healthcare professionals of a new serious safety issue, or a safety-related drug withdrawal. Data were retrieved from publicly available websites Results In Europe, 279 new drugs were approved between 1999 and 2011. Fifty-nine (21 %) were graded as important, 63 (23 %) moderate, or 34 (12 %) modest innovations and 123 (44 %) as non-innovative (pharm/tech), while 15 (25 %), 13 (21 %), 8 (24 %) and 17 (14 %) had post-approval safety issues, respectively (p = 0.06, linear-by-linear test). Five drugs were withdrawn from the market. The Kaplan-Meier-derived probability for having a first serious safety issue was statistically significant, log- Conclusion A higher level of innovation was not clearly related to an increased risk of serious safety issues identified after approval.
Original languageUndefined/Unknown
Pages (from-to)1105-1115
Number of pages11
JournalDrug Safety
Issue number11
Publication statusPublished - 2013

Research programs

  • EMC NIHES-03-77-02

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