Increasing the use of RWE: Key European initiatives for 2025
Introduction
The use of real-world data (RWD) and real-world evidence (RWE) to support pharmaceutical decision making has been a dominant trend over the last decade (ranking as the #1 ISPOR HEOR trend for the last 3 years! [1]). RWE is now routinely used to support some regulatory, access and pricing decisions however, scepticism remains, and there is still a feeling that RWE is still underutilised.
2025 is likely to see a large change to the pharmaceutical industry in the European Union (EU). Alongside the on-going European wide pharmaceutical strategy, it will see the culmination of the European Medicines Agency’s (EMA) ambitious 5-year strategy to develop a best-in-class regulatory environment [2,3] as well as the phased roll out of the long-awaited European Health Technology assessment regulation (EUHTAR)[4]. These key initiatives are expected to transform multiple aspects of the pharmaceutical industry and here we discuss the possible impact on the utilisation of RWE.
EMA initiatives
A key part of the EMA’s strategy was to establish a framework to enable the use and demonstrate the value of RWE for its decision making. RWE is already widely used for pharmacovigilance but has historically been underutilised in the earlier stages of medicine development. Last year (2024), the EMA published a framework outlining several use cases for RWE across its decision-making including the planning of studies (design, feasibility, representativeness) and understanding the clinical context (epidemiology, clinical management, utilisation) as well as effectiveness and safety [5]. With the establishment of these use cases, several initiatives are expected to increase the EMA’s use of RWD/RWE in 2025:
Expansion of DARWIN EU®: The Data Analysis and Real-World Interrogation Network (DARWIN EU®) is a pivotal programme that includes a catalogue of databases from which the EMA can carry out high quality RWE studies [6]. The programme is planning a large expansion in 2025 and is expected to deliver >140 studies to support the above use cases this year [6].
Release of formal guidance: The EMA continues to publish guidance documents on the use of RWD/RWE to increase confidence and reduce scepticism in its evaluators. Alongside reflections on the use of RWD in registry led (2021 [7]) and non-interventional (2024 [8]) studies, 2025 will also see a public consultation on a data quality framework specifically for RWD [9].
Continued progress on the Big Data Workplan: The Big Data Steering Group (BDSG) workplan, which runs until 2025, includes both DARWIN EU® and the data quality framework as well as several other initiatives that aims to integrate RWD/RWE into the EMA’s regulatory system [10].
Leveraging the European Health Data Space (EHDS): The EHDS is a health specific ecosystem that will allow a single market for electronic healthcare records and was officially adopted by the EU Council in January 2025 [11]. The EHDS aims to enhance the availability of healthcare data which alongside DARWIN EU® should increase the access and use of RWD/RWE to the EMA.
The high priority of RWE in the EMAs strategic vision and the recent framework around RWE to support EU regulatory decision-making are positive signals however, they also highlight key challenges with access to data, earlier identification of research questions and the need to build capacity and capabilities amongst all stakeholders.
EUHTAR
The EUHTAR has been developed to harmonise the EU’s approach to health technology assessments (HTAs) and has the potential to increase the use of RWD/RWE across member states [4]. Harmonised evidence generation frameworks could increase the trust in RWE and collaborative working will allow member states who have historically underutilised RWE to build their capabilities. The EUHTAR may also lead to the increase of RWE across a product’s lifecycle. Specifically, parallel EMA and joint clinical assessment (JCA) processes mean that early stakeholder engagement and coordinated evidence generation planning are expected to be key success factors [12,13]. Market access and HEOR teams regularly utilise RWD/RWE for HTA assessments so early engagement of these teams may lead to RWE playing an earlier role in evidence generation plans.
Recent JCA guidance has given positive signals that RWE will be reviewed and evaluated as part of the JCA dossier [14,15]. Specifically, guidance on the validity of clinical studies states that RWE can be accepted for various questions and although, clear limitations are outlined, as a source for indirect treatment comparisons (ITCs) [14,15]. Importantly, although randomised clinical trials (RCTs) are preferred, single arms trials could be accepted (at least theoretically) if they are coupled with an external control arm that may be sourced from RWD [14]. Similarly, another guidance states that outcomes outside of a clinical setting will be accepted (for example those collected from digital health technologies) [16].
However, although this guidance is a positive sign, how RWD/RWE will be accepted in JCA evaluations and thus translated to country HTA body decisions remains to be seen. The guidance also highlights limitations with RWE including a “high risk of confounding bias” for ITCs [14,15] and scepticism around its validity found in current HTA agencies (e.g. GB-A) is likely to remain.
Conclusions
2025 will see a large transformation to the pharmaceutical industry with the culmination of several key strategic initiatives as well as the roll out of the EUHTAR. RWE will need to be considered much earlier in medicine development to capitalise on the EMAs initiatives and as a key success factor for JCAs. However, progress is likely to be slow and how these initiatives will translate into the collection, integration and evaluation of RWD/RWE remains to be seen.
Staying ahead of these changes and leveraging our expertise ensures we can help clients turns these challenges into opportunities, ensuring successful market access in an evolving environment.
Written by Rosa Willock
Decisive Dialogue 12th February 2025
Have questions or need RWD/RWE support? Please get in touch with us via: enquiries@decisiveconsulting.co.uk
References
1. ISPOR (2024) ISPOR 2024-2025 Top 10 HEOR Trends Report. Available from: ISPOR - Top 10 HEOR Trends
2. EMA (2020). EMA Regulatory Science to 2025. Available at: EMA Regulatory Science to 2025
3. EMA (2020). European medicines agencies network strategy to 2025. Available at: European medicines agencies network strategy to 2025 - Protecting public health at a time of rapid change
4. EC (2021) Regulation (EU) 2021/2282 of the European Parliament and of the Council of 15 December 2021 on health technology assessment and amending Directive 2011/24/EU. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32021R2282
5. EMA (2024). Real-world evidence provided by EMA. Available at: Real-world evidence provided by EMA
6. EMA (2024). DARWIN EU®: Making health data count. Available from: DARWIN EU®: Making health data count
7. EMA (2021). Guideline on registry-based studies. Available from: Guideline on registry-based studies
8. EMA (2024). Reflection paper on use of real-world data in non-interventional studies to generate real-world evidence. Available from: RWE Reflection paper - draft for public consultation
9. EMA (2024). Data Quality Framework for EU medicines regulation: application to Real-World Data. Available from: Data Quality Framework for EU medicines regulation: application to Real-World Data
10. EMA/HMA (2024). Big Data Workplan 2023-2025. Available from: PowerPoint Presentation
11. EU (2022). Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL on the European Health Data Space. Available from: EUR-Lex - 52022PC0197 - EN - EUR-Lex
12. Regulatory Rapporteur (2024). A key role for the European Medicines Agency in the European Union’s Health Technology Assessment Regulation. Available from: A key role for the European Medicines Agency in the European Union’s Health Technology Assessment Regulation | Journal | Regulatory Rapporteur
13. EC (2024) Commission Implementing Regulation (EU) 2024/1381 of 23 May 2024 laying down, pursuant to Regulation (EU) 2021/2282 on health technology assessment, procedural rules for the interaction during, exchange of information on, and participation in, the preparation and update of joint clinical assessments of medicinal products for human use at Union level, as well as templates for those joint clinical assessments. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=OJ:L_202401381
14. HTACG (2024). Guidance on Validity of Clinical Studies. Available from: Styles
15. HTACG (2024). Methodological Guideline for Quantitative Evidence Synthesis: Direct and Indirect Comparisons. Available from: 4ec8288e-6d15-49c5-a490-d8ad7748578f_en
16. HTACG (2024). Guidance on outcomes for joint clinical assessments. Available from: Styles