EMA’s vision for clinical evidence prioritizes patients, data, and real-world evidence

A new article in Clinical Pharmacology & Therapeutics by authors from the European Medicines Regulatory Network (EMRN) explores the future of clinical evidence generation, highlighting a patient-centered, data-driven approach that integrates real-world evidence (RWE) and regulatory collaboration to enhance research and improve access to treatments.

In 2021, the European Medicines Agency (EMA) set a goal that “by 2025 the use of real-world evidence will have been enabled and the value will have been established across the spectrum of regulatory use cases.” With progress towards this goal fully underway, authors from the EMA and other regulatory agencies within the EMRN have outlined a new vision focused on achieving "excellence of clinical evidence.” In a recently published article in Clinical Pharmacology & Therapeutics, they propose that by 2030 clinical evidence generation should be guided by six key principles, stating:

"Building on existing practices, our vision is that by 2030, clinical evidence generation will be further guided by the patient voice and informed by existing data and knowledge; study design will be driven by research questions to be addressed; clinical trials will be more efficient and impactful; real-world evidence will be enabled and its value fully established; and trust will be built through transparency."

Global regulatory cooperation plays a critical role in shaping this future. As highlighted in a recent article from The Evidence Base, the International Coalition of Medicines Regulatory Authorities (ICMRA) has emphasized the importance of RWE in regulatory decision-making. The pandemic accelerated collaboration between regulators worldwide, strengthening the use of real-world data (RWD) to support evidence generation. These lessons are now informing policy initiatives and frameworks that will continue to drive innovation and efficiency in clinical research.

Six guiding principles for clinical evidence generation

1. Patients are at the center of clinical evidence generation and guide every step

This principle ensures that evidence is generated with a clear focus on patients' needs and public health. By actively involving patients in healthcare decisions, particularly in evaluating the benefit–risk of medicines, the process integrates their insights, experiences, and priorities. This patient-centered approach enhances the relevance and impact of clinical evidence. Additionally, ongoing efforts should aim to refine the collection and use of patient experience data to inform medicine development and regulatory decision-making, with multi-stakeholder collaboration playing a key role in advancing these initiatives.

2. Existing data and knowledge are leveraged to inform the identification of gaps, generation of clinical evidence, and healthcare decisions

Clinical evidence generation must be guided by purpose, data, and expertise. As the authors note:

"When formulating research questions and designing clinical evidence programs, existing data, information, and knowledge should be leveraged."

To foster a more informed approach, open access to study protocols, regulatory assessments, and adverse reaction reports should be prioritized. Greater transparency in data sharing and multi-stakeholder collaboration at the planning stage will facilitate informed decision-making and ensure a feedback loop that integrates past learnings and minimizes unnecessary duplication.

3. Evidence gaps are formulated in clear research questions that drive the choice of evidence generation

Within this principle, the authors recommend a "research question"-driven approach to strengthen clinical evidence generation by ensuring study design aligns with clear, well-defined research objectives.

"Clearly articulating one or several research questions strengthens clinical evidence generation through optimal study design, particularly if supported by scientific advice that involves different stakeholder voices."

They recommend enhancing regulatory support for R&D and using frameworks like PICOT (Population-Intervention-Comparator-Outcome-Time) and Target Trial Emulation, and Estimand to refine research questions. These tools help ensure studies are well-structured, evidence gaps are addressed, and clinical research is more effective.

4. The full spectrum of data and methods is embraced, with better, smarter, and faster clinical trials remaining at the core of clinical evidence, complemented by real-world evidence for which evidentiary value is established across the full spectrum of research questions

A research question-driven approach ensures the systematic consideration of all evidence in decision-making. While randomized clinical trials remain central, they must be optimized for efficiency through initiatives like Accelerating Clinical Trials in the EU (ACT EU), which enhances trial design and integration into European health systems. Real-world data (RWD) must be validated across research contexts, supported by initiatives like DARWIN EU® and EHDEN, which address data standardization and quality. The authors emphasize the need for ongoing stakeholder training, international collaboration, such as with the International Council for Harmonization (ICH), and regulatory alignment, including the Big Data Steering Group’s workplan on the data quality framework and data discoverability through RWD catalogues and sources. Artificial intelligence, validated through rigorous frameworks, is another key enabler. Legislative advancements, such as the EHDS and EU pharmaceutical reform, further support improved access to high-quality clinical evidence.

5. The generation of clinical evidence is planned earlier and collaboratively across healthcare stakeholders, allowing them to fully leverage the totality of evidence

This principle emphasizes the importance of early and integrated planning in clinical evidence generation to ensure stakeholders can leverage comprehensive evidence for decision-making. The authors highlight collaboration to align on identifying unmet medical needs, translating them into R&D plans, and refining those plans through scientific advice from regulators and health technology assessment (HTA) bodies. Joint scientific advice procedures have proven successful and widely valued, while DARWIN EU® facilitates post-licensing evidence generation pilots. Additionally, pharmacovigilance must incorporate smarter adverse reaction reporting, leveraging RWE to assess on-market medicine performance and optimize risk minimization measures through enhanced stakeholder engagement.

6. High levels of transparency underpin societal trust

Underpinning these principles, the authors emphasize the importance of transparency and collaboration in reinforcing trust and engagement among all stakeholders, particularly patients and healthcare professionals. This will ensure that:

"Clinical evidence then becomes a trusted, powerful, and efficient instrument for bringing better medicines to patients faster."