Real-world evidence (RWE) has become central to evaluating therapies, medical products, and health interventions—providing insight into how they perform outside controlled clinical trials. As healthcare systems seek more timely, representative, and cost-effective approaches to evidence generation, real-world data (RWD) is increasingly used to inform regulatory decisions, guide clinical practice, and shape health policy.
As RWE gains traction, fundamental questions remain: How do we ensure it’s reliable? How do we define quality? And how do we use it consistently across systems that were never built for it? The industry agrees on RWE’s importance—but not yet on how to evaluate or integrate it.
In 2025, RWE stands at a crossroads. The infrastructure to support it is growing, but the rules of engagement—especially across international borders—remain in flux. Healthcare systems and regulators must resolve key challenges around standards, governance, and data integration to realize its full value.
Regulatory definitions still lack global consistency.
One of the most pressing issues is the lack of harmonized regulatory standards for RWE. A recent Duke-Margolis Institute for Health Policy report assessed how major regulators define three foundational pillars: Relevance, Reliability, and Quality. Only four—the FDA, EMA, Taiwan FDA, and Brazil’s ANVISA—have issued formal definitions for at least two of these concepts. Even where terms are defined, meanings differ. For instance, relevance may refer to data’s applicability to a regulatory context in one jurisdiction and a research question in another. This lack of global consistency in regulatory definitions is a significant barrier that urgently needs to be addressed.
Such differences create obstacles for healthcare systems and life sciences companies operating globally. Submitting real-world evidence across jurisdictions can mean navigating varying expectations for data integrity, representativeness, and completeness. This variability slows evidence generation and creates uncertainty about whether data will be accepted for regulatory or reimbursement purposes.
To clarify this landscape, the Duke-Margolis team developed a dashboard tracking regulatory definitions and opportunities for alignment. But dashboards alone are not solutions. Moving toward consensus will require a coordinated effort, transparent dialogue, and international frameworks that elevate RWE from a national asset to a global resource.
Europe sets strategy with EMANS 2028
In March 2025, the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) jointly adopted the European Medicines Agencies Network Strategy to 2028 (EMANS 2028)—a roadmap to improve regulatory agility, expand access to medicines, and strengthen Europe’s global competitiveness. A central theme of the strategy is the integration of digital technologies, including real-world data, into the regulatory ecosystem—while keeping patient privacy and data security at the forefront.
The European Health Data Space (EHDS) is a key enabler of this vision, aiming to support cross-border data exchange under consistent, trusted standards. Yet, as with any policy, the true challenge lies in execution. Success will depend on whether health systems can build the infrastructure, governance, and analytic capacity needed to generate and share evidence at scale—without compromising data protection or public trust.
COVID-19 response offers a model for rapid evidence generation
The COVID-19 pandemic provided a real-time case study of how to use RWE rapidly and responsibly. A collaboration between Aetion and the FDA produced a framework for evidence generation that balanced urgency with methodological rigor. The process relied on standardized data assessments, pre-specified protocols, and secure, blinded data exploration to validate feasibility and ensure data quality.
This model is now being adopted beyond the pandemic response. The experience demonstrated that speed need not come at the expense of quality—provided there are agreed-upon processes for evaluating data relevance and reliability. As real-world studies expand in areas such as oncology and gene therapy, the lessons from COVID-19 remain highly relevant: structure and transparency are prerequisites for evidence that can inform high-stakes decisions.
Secure data linkage remains a significant challenge
Even as data sources proliferate, securely linking them remains a challenge. Healthcare systems are rich in patient data but often lack the tools—or legal clarity—to share it across networks. Privacy concerns, regulatory restrictions, and technical incompatibilities hinder comprehensive, longitudinal patient views.
Platforms like Aetion Generate support this goal, offering risk-based de-identification and regulatory-aligned evidence generation within secure, auditable environments. These tools help enable broader collaboration while upholding global privacy standards and protecting data integrity.
Still, technology alone won’t resolve the trust deficit. Ensuring that data is used ethically, securely, and transparently will require precise governance models—and a willingness among stakeholders to prioritize collective value over individual data silos.
Integration, not expansion, will define the next phase of RWE
RWE is no longer a niche capability or an optional supplement to clinical trials. It is now arguably necessary to understand real-world effectiveness, patient experience, and long-term outcomes. But the challenge now is not about expanding RWE use—it’s about integrating it meaningfully into clinical, regulatory, and policy decision-making.
This expanded usage means investing in data quality assurance, building internal analytic capacity, and collaborating across sectors for healthcare systems. For regulators, it means aligning standards, clarifying expectations, and accepting that RWE, like any form of evidence, will always come with limitations that must be managed, not avoided.
Ultimately, the value of RWE will not be measured by the volume of data collected but by the quality of decisions it informs. In a field that has long celebrated innovation, the real test now is integration—and whether the healthcare ecosystem can make real-world evidence work for patients, not just on paper, but in practice.
About Natalie Schibell
Natalie Schibell is Vice President of Market Strategy and Communications at Aetion, where she oversees enterprise market intelligence, competitive insights, and strategic positioning across healthcare and life sciences sectors. Previously, she held multiple leadership roles at Forrester, including Vice President, Research Director and Vice President, Principal Analyst. She was also a Public Health Analyst at the Centers for Disease Control and Prevention’s National Center for Emerging and Zoonotic Infectious Diseases. A former Lieutenant Commander in the United States Navy Medical Service Corps, Schibell is a recognized author and speaker specializing in healthcare innovation and strategic market insights.
