EMA reports significant growth in use of real-world evidence for medicines regulation

The European Medicines Agency (EMA) has released its third annual report on the use of real-world evidence (RWE) in medicines regulation, covering the period from February 2024 to February 2025. The report highlights significant progress in embedding RWE into regulatory decision-making, with 59 studies conducted, almost 48% more than the previous year. Of these studies, 33 were completed and 26 are ongoing, supporting a wide range of safety, utilization, and epidemiological assessments.

A key development this year was the increased role of DARWIN EU®, EMA’s federated network for real-world data (RWD) generation. Now in its third year, the initiative is expanding its capacity to support regulatory decision-making by delivering high-quality, timely evidence from across Europe. With 25 completed studies, nearly triple the previous figure, DARWIN EU® has become the agency’s primary pathway for RWE generation. The network now includes 30 data partners across 16 European countries, providing access to data from around 180 million patients. With a median turnaround of 4 months per study, the network enables timely evidence generation aligned with regulatory timelines.

The majority of studies focused on drug utilization (42%), safety (24%), and disease epidemiology (24%), reflecting regulatory priorities across the product lifecycle. Study requests were submitted by a diverse group of stakeholders, including EMA scientific committees, national competent authorities, the European Commission, the European Centre for Disease Prevention and Control (ECDC), and health technology assessment (HTA) bodies.

According to Peter Arlett, Head of Data Analytics and Methods Task Force at EMA,

“Excellent clinical evidence is at the heart of a successful marketing authorization for a medicine. While clinical trials remain the core of demonstrating efficacy and safety, real world evidence complements clinical trial results. Furthermore RWE may play a critical role in understanding disease epidemiology and current treatment pathways, in extrapolating efficacy results to under-represented populations.”

He added that the report, “charts how RWE is being enabled, particularly through DARWIN EU, and how its value is being established, use case by use case, through the product lifecycle.”

Several studies from this reporting period illustrate the regulatory impact of RWE. A study on the antibiotic doxycycline helped the Pharmacovigilance Risk Assessment Committee (PRAC) rule out a link to suicidality, while another study assessed safety signals for anti-migraine CGRP antagonists. The latter evaluated reports of insomnia, erectile dysfunction, and high blood pressure, ultimately finding no need for regulatory action. A third study on respiratory syncytial virus (RSV) helped demonstrate unmet medical need in vulnerable populations, such as infants and older adults, and will inform vaccine effectiveness planning.

RWE also played a role in addressing medicine shortages. The Medicines Shortages Steering Group (MSSG) used studies to monitor trends in GLP-1 receptor agonists and ADHD medicines, supporting planning and mitigation efforts as demand continues to rise.

Feasibility assessments also improved significantly. Across all RWE pathways, 78% of proposed studies were deemed feasible, up from 60% in the previous cycle. Within DARWIN EU specifically, feasibility rose to 76% (from 63%). This progress was driven by enhanced phenotype libraries, standardized study templates, and improved data quality checks. To support low-feasibility areas such as pediatrics, the National Neonatal Research Database (UK) was added to the DARWIN EU network. The report highlights that:

“The largest change between the period covered by the second and third reports was the reduction in research topics deemed unfeasible due to inadequate capture of the outcomes of interest.”

In parallel, EMA expanded its methodological support. Between February 2024 and January 2025, the RWE team contributed to 26 scientific advice procedures and 10 portfolio and technology meetings, offering guidance on the appropriate use of RWD in regulatory submissions. Topics included the use of historical data as clinical benchmarks, external comparators, target trial emulation, and the application of AI and machine learning in evidence generation. As the report highlights, this methodological advice, “supports EMA committees/working parties in their evaluation of regulatory applications through peer-review processes.”

Transparency also improved with the launch of the HMA-EMA Catalogues of RWD sources and studies in February 2024. Replacing earlier systems, the catalogues now provide access to over 3000 studies and 247 data sources, with study protocols and results published shortly after approval. These efforts support the broader European Medicines Regulatory Network (EMRN) strategy to 2028.

Further stakeholder engagement was delivered through the Real-World Academy event series and the rollout of new curriculum modules from the Big Data Steering Group. In addition, the EMA created a dedicated RWD-focused special interest area within the Methodology European Specialised Expert Community (ESEC), offering a platform for knowledge exchange across the EU regulatory network.

Looking ahead, the EMA will continue to expand DARWIN EU with a final wave of data partners focusing on oncology, cardiometabolic disease, and pediatric populations. As the report notes,

“We will also explore large data sources in countries outside EU and Europe, if relevant, representative enough, and adding incremental value to the existing network.”

Additional guidance on data quality, study design, and fit-for-purpose assessments is also expected, further embedding RWE within the EU regulatory framework.