Real-world evidence reported for clinical efficacy evaluation in European Public Assessment Reports of authorised targeted therapies for solid malignancies: a comprehensive review (2018-2022)

Background The role of real-world evidence (RWE) for clinical efficacy regulatory evaluation remains unclear. We aimed to assess and describe the reported use of RWE for clinical efficacy evaluation of authorised targeted therapies for treatment of solid malignancies in Europe. Design We studied all authorised indications of targeted therapies for the treatment of solid malignancies granted by the European Medicines Agency between 2018 and 2022. Data were retrieved in March 2023 from European Public Assessment Reports (EPARs). We evaluated the frequency of RWE use for clinical efficacy evaluation and its role based on the reported information in the EPAR, and assessed characteristics and risk of bias of published studies. Results Out of 75 authorised indications identified, most related to the treatment of patients with lung (21.3%) or breast (20.0%) cacer, and to advanced settings (89.3%). The use of RWE for clinical efficacy evaluation was reported in the EPAR of 16 (21.3%) indications, tending to increase overtime (15.0%-35.7% in 2018-2022). RWE was more frequently considered in lung (37.5%) and breast (33.3%) cancer indications, for antibody–drug conjugates (60.0%), and conditional approvals (46.7%). We classified RWE’s role as ‘supportive’ confirmatory evidence in 12 of 16 (75.0%) indications. RWE studies were mostly analytical (57.1%), non-international (92.9%), retrospective cohort studies (57.1%), and originated from the United States (78.6%). High or serious risk of bias was identified in different domains of most studies assessed. Conclusions RWE was reported to be used for clinical efficacy regulatory evaluation in 21% of targeted therapy indications for solid malignancies, with an increasing trend over time.