(15) Contribution of Real-World Evidence to Support Efficacy Claims in Centralised Marketing Authorisation Applications Submitted to EMA in 2018-2019

Publication Number: 346

Background: Real-world evidence (RWE) has the potential to provide insightful information on the clinical effects of medicines to guide regulatory decisions. Whilst its contribution has been recognised for safety monitoring and disease epidemiology across medicines’ life cycle, the use of RWE to demonstrate efficacy requires further evaluation.

Objectives: 1) To characterize RWE used by applicants to support efficacy claims on medicines as part of initial marketing authorisation applications (MAAs) and extension of indications applications (EoIs) and 2) to analyse the contribution of RWE to regulatory decision-making on medicines’ benefit-risk profile.

Methods: From the Flynn et al. (2022) study, we selected the sample of MAAs and EoIs submitted to the European Medicines Agency (EMA) in 2018-2019 that contained RWE to support efficacy claims. We reviewed the factual contribution of RWE (e.g., submitted pre- or post-authorisation, within main or supportive studies, purpose and data sources) to medicines’ benefit-risk evaluation using assessment reports available at EMA.

Results: Preliminary results show that RWE was included to support pre-authorisation or monitor post-authorisation medicines’ efficacy in 32 of the 63 MAAs and 18 of 28 EoIs identified by Flynn et al. (2022). RWE generated pre-authorisation was submitted in 16 MAAs (16/32) and 10 EoIs (10/18), mainly to serve as complementary efficacy data (13/16 MAAs; 8/10 EoIs) or to contribute as an external comparator (5/16 MAAs; 3/10 EoIs). RWE was considered contributory to the benefit-risk assessment in five MAAs (5/16) and five EoIs (5/10), not adequate in seven MAAs (7/16) and five EoIs (5/10), and was not addressed in the assessment of four MAAs (4/16). Justifications on RWE non-adequacy included that data were too limited and subject to bias, lacked representativeness to serve as comparator, lacked a pre-defined analysis plan, or lacked access to individual data.

Conclusions: Due to differences in purpose and data source of the RWD in applications, the appraisal of RWD still requires a case-by-case analysis. We identified several challenges around methodologies and data sources where RWE was not considered adequate for benefit-risk evaluation. These may be addressed through early interactions with regulators to explore available options and identify solutions.