The costs and effects of post-authorisation safety studies for new active substances

Abstract

Objectives: At market entry, there usually is uncertainty regarding a new medicine's benefit-risk profile. Therefore, regulatory authorities may request additional pharmacovigilance (PhV) activities. Regulatory Authorities can request a Post- Authorisation Safety Study (PASS) such as a registry, database study, survey, or clinical trial to reduce the uncertainty regarding certain safety risks. We aimed to assess the costs and effects of PASS for centrally approved new active substances (NAS) in Europe in 2007. Methods: We compared two scenarios for all NAS (n= 47): (1) Full regulation: routine PhV activities (spontaneous adverse drug reaction (ADR) reporting) with additional PASSs for some NAS; (2) Limited regulation: only routine PhV activities. For a follow-up period of six years after marketing we assessed the safety-related labeling changes for NAS and identified the source of these changes (PASS, spontaneous ADR reporting or other). Data on labeling changes was extracted from the European Medicines Agency's website. A survey among pharmaceutical companies was used to estimate the costs of all requested PASSs. Results: For 23 of the 47 NAS, at least one PASS (33 PASS in total) was requested in 2007. After six years, on average 8.1 safety-related labeling changes were identified per NAS. Requested PASS were the source of ∼4% of all cases of new safety information identified. The total estimated costs of the 33 requested PASS were between € 50 and € 150 million. Conclusions: For the 2007 cohort of NAS approved in Europe, the total costs of all requested PASS were substantial and yet these PASS contributed to the identification of only 4% of all new safety information identified post-marketing for NAS. However, PASS primarily aim to reduce uncertainty regarding safety risks and the (societal) value of this uncertainty reduction might not fully be captured by assessing health effects alone.