Uncertainties about the benefit-risk balance of oncology medicines assessed by the European Medicines Agency

Abstract

Background: Drug regulators assess and describe uncertainties regarding treatment outcomes and the benefit-risk balance of newly authorised medicines. We aimed to evaluate the type and number of uncertainties described in the benefit-risk assessment for initial marketing authorisations of oncology medicines assessed by the European Medicines Agency (EMA). We also aimed to develop a systematic classification of uncertainties to contribute to improved communication about uncertainties.

Materials and methods: We included all medicines containing a new active substance assessed by the EMA and granted an initial marketing authorisation by the European Commission in 2011-2022 for an oncology indication. We extracted characteristics of these oncology medicines and uncertainties described under the benefit-risk balance section of European public assessment reports. Uncertainties were categorised and their frequencies stratified according to time of marketing authorisation, and medicine and regulatory characteristics.

Results: In total, 121 oncology medicines were included for which 800 (median 6, range 0-23) uncertainties were identified. Uncertainties were classified into five categories: safety (n = 404, 51%), efficacy (n = 322, 40%), pharmacology (n = 58, 7%), use in clinical practice (n = 10, 1%), and quality (n = 6, 1%). Among 27 subcategories, most uncertainties were related to specific adverse events (n = 156, 20%), effect size (n = 155, 20%), safety in subpopulations (n = 124, 16%), or efficacy in subpopulations (n = 88, 11%). The type of medicine (P = 0.012), type of marketing authorisation (P = 0.001), and year of marketing authorisation (P = 0.007) were associated with the number of uncertainties per medicine, with the highest number observed for cell and gene therapies [8 (3-23)], medicines granted conditional marketing authorisation [7 (3-23)], and medicines authorised in 2019-2022 [7 (2-23)].

Conclusion: At the time of initial marketing authorisation of oncology medicines, uncertainties about their benefit-risk balance most often concerned safety aspects, followed by efficacy. The number of uncertainties was highest for cell and gene therapies, conditionally authorised medicines, and medicines authorised in recent years.

Keywords: European Medicines Agency; classification; oncology medicines; regulatory decision making; uncertainties.