title: Risk management plans as a tool for proactive pharmacovigilance: a cohort study of newly approved drugs in Europe.
abstract: Risk Management Plans (RMPs) have become a cornerstone in the pharmacovigilance of new drugs in Europe. The RMP was introduced in 2005 to support a proactive approach in gaining knowledge on safety concerns through early planning of pharmacovigilance activities. However, the rate at which uncertainties in the safety profile are resolved through this proactive approach is unknown. We therefore examined the evolution of safety concerns in the RMP after initial approval for a selected cohort of 48 drugs, to provide insight into the knowledge gain over time. We found that 20.7% of the uncertainties existing at approval had been resolved 5 years after approval. Because new uncertainties were included in the RMP at a similar rate, the overall number of uncertainties remained approximately equal. The relatively modest accrual of knowledge, as demonstrated in this study through resolution of uncertainties, suggests that opportunities for optimization exist while ensuring feasible and risk-proportionate pharmacovigilance planning.
authors.affiliation: 1] Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands [2] Medicines Evaluation Board, Utrecht, The Netherlands.
authors.forename: N S
authors.initials: NS
authors.lastname: Vermeer
authors.affiliation: 1] Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands [2] Medicines Evaluation Board, Utrecht, The Netherlands.
authors.forename: R G
authors.initials: RG
authors.lastname: Duijnhoven
authors.affiliation: 1] Medicines Evaluation Board, Utrecht, The Netherlands [2] Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: S M J M
authors.initials: SM
authors.lastname: Straus
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: A K
authors.initials: AK
authors.lastname: Mantel-Teeuwisse
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: P R
authors.initials: PR
authors.lastname: Arlett
authors.affiliation: 1] Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands [2] Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: A C G
authors.initials: AC
authors.lastname: Egberts
authors.affiliation: 1] Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands [2] Medicines Evaluation Board, Utrecht, The Netherlands.
authors.forename: H G M
authors.initials: HG
authors.lastname: Leufkens
authors.affiliation: 1] Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands [2] Medicines Evaluation Board, Utrecht, The Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: De Bruin
mesh_terms: D015331:Cohort Studies; D017277:Drug Approval; D005060:Europe; D006801:Humans; D060735:Pharmacovigilance; D012308:Risk Management