FDA and NIH publish unified glossary to strengthen real-world evidence research

The FDA and NIH have jointly released a standardized glossary of real-world data (RWD) and real-world evidence (RWE) terms to improve communication and consistency across clinical studies involving innovative designs and data sources.

The US Food and Drug Administration (FDA) and the National Institutes of Health (NIH) have published a glossary of 40 clinical research terms aimed at promoting clarity and alignment across the clinical research community. Published in JAMA Network Open in June 2025, the glossary was developed to support the use of RWD and RWE in studies involving drugs, medical devices, and biological products.

Titled ‘Modernizing Research and Evidence Consensus Definitions: A Food and Drug Administration–National Institutes of Health Collaboration’, the glossary reflects a shared effort to modernize scientific communication and improve the consistent use of terminology in both interventional and noninterventional research. It was developed by the FDA-NIH Modernizing Research and Evidence (MoRE) Glossary Working Group, a multidisciplinary team of epidemiologists, clinicians, statisticians, pharmacologists, engineers, and policy experts from both agencies.

“The clear use of these terms is intended to allow for easier assessment and comparison of studies across the clinical research enterprise and improve communication about research opportunities,”

wrote lead author Donna Rivera (associate director for pharmacoepidemiology at the FDA Oncology Center of Excellence), and her co-authors.

The glossary addresses ongoing challenges in describing innovative clinical research designs, especially those that do not fit neatly into traditional regulatory categories. As Stuart McCully (Real-World Research Ltd) notes,

“The absence of a definition for "intervention" within most clinical trial regulations and guidelines often leads to confusion and challenges in categorizing studies correctly. We’ve all been there… it’s painful! These challenges (and pains) underscore the critical need for clarity and consensus in our real-world research (RWR) terms and definitions.”

Jeff Trotter, a pioneer in the RWE field, has similarly emphasized the importance of using the correct terminology when engaging regulators:

“Terminology and appropriate lexicon really helps ensure that the parties on both sides understand that you get it,” he said,

stressing that informed, early discussions with the FDA must reflect a shared understanding of terminology, reinforcing the glossary’s goal of facilitating clearer communication across researchers, sponsors, and regulatory authorities.

The glossary covers a broad spectrum of study designs, ranging from traditional randomized controlled trials to more innovative approaches such as pragmatic clinical trials, stepped-wedge trials, N-of-1 trials, and sequential multiple assignment randomized trials (SMART). These methodologies often involve complex features that can be challenging to describe consistently. As the authors observe, “misperceptions are common in the clinical research community,” underscoring the need for clear, standardized definitions to support shared understanding across stakeholders.

A pragmatic clinical trial, for example, is defined as, “a clinical trial designed to efficiently inform decision-making on the benefits, burdens, and risks of health interventions in representative populations by including pragmatic elements that are partially or fully integrated into routine clinical practice and/or streamline trial design and conduct.” The glossary also clarifies that RWD refers to the underlying data source, such as electronic health records (EHRs) or insurance claims, rather than a study design, and may be collected either prospectively or retrospectively.

To ensure the glossary reflected community needs, the agencies launched a public request for information (RFI) on May 6, 2024. Stakeholders were invited to comment on the clarity, relevance, and potential barriers to adopting the definitions. All comments were reviewed by the MoRE Working Group, with several suggestions incorporated.

“The feedback from the public comment period improved the definitions, provided an opportunity to add additional reference terms, and recommended ideas for potential future efforts,” the authors noted.

Existing terms already defined in FDA guidance were included in supplementary materials but were not revised.

The glossary supports a broader agenda to modernize evidence generation, aligned with recent legislative initiatives such as the 21st Century Cures Act and the Food and Drug Omnibus Reform Act of 2022. These policies encourage the integration of novel data sources and study designs into regulatory and scientific decision-making processes.

The authors emphasized that standardized terminology has the potential to enhance transparency and efficiency across the research lifecycle, from protocol development and regulatory submissions to peer-reviewed publications and postmarketing surveillance.

“Fostering accurate characterization of innovative interventional and noninterventional studies may improve evaluation of potential strengths and weaknesses of individual studies,” they wrote.

While the glossary is intended as a foundational resource, the authors acknowledge that terminology would need to evolve alongside scientific advances. They encourage continued collaboration across the clinical research ecosystem to define emerging terms and reassess foundational ones as needed.

“The clinical research community can continue to exercise diligence in defining emerging terms as well as where shared processes may be needed for re-evaluating these foundational current terms together as part of building an iterative practice to benefit greater shared understanding,” the article concluded.

The MoRE Consensus Definitions are available publicly through the NIH and are intended to serve as a resource for investigators, sponsors, regulators, and institutional review boards engaged in evidence generation and evaluation.