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

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.