Pragmatic Clinical Trials: On the Way from Niche to Necessity

Over the past decade, the number of U.S. trials labeled “pragmatic” has increased significantly. Once viewed as an approach with limited applicability, pragmatic trials are being looked at as an opportunity to expand access to trials, and an efficient way to answer regulatory questions. Introducing pragmatic elements such as simplified procedures and expanding eligibility criteria make it possible to collect data at the point of care that can answer questions important to regulators while also informing clinical care decisions at the bedside. 

While pragmatic trials still represent a small proportion of total studies, they are steadily moving from niche applications toward a more essential role in the research ecosystem.

Positioning Pragmatic Trials for Broader Adoption

Several forces are converging to make this a pivotal moment for pragmatic trials:

• Maturing of electronic health record systems: Electronic health records (EHRs) are widely embedded across healthcare. Cooperation among policy makers, healthcare systems, and sponsors will be required to be able to integrate research into care at scale.
• Pandemic lessons: The COVID-19 era demonstrated that large studies, such as the RECOVERY trial in the UK, could deliver reliable results quickly when pragmatic elements were embraced. 
• Comparative effectiveness: Public health agencies need evidence that goes beyond “does it work in ideal circumstances?” to “how does it perform compared to alternatives, in the patients we actually serve?” Pragmatic designs are uniquely suited to answer those questions.
• Access and representation: By reducing eligibility restrictions and bringing trials closer to where care is delivered, pragmatic designs expand participation to populations who often have difficulty accessing traditional randomized controlled trials (RCTs).

Regulatory and Operational Considerations

Embedding research in care is not as simple as plugging trials into EHRs. The shift toward pragmatic designs requires new approaches to ensuring evidence is reliable, ethical standards are upheld, and regulatory expectations are met.

Based on both real-world experiences and TransCelerate’s recent tabletop exercise with the FDA’s CDER Center for Clinical Trial Innovation (C3TI), several considerations stand out:

• Fit-for-purpose oversight: Physicians and nurses may be eager to support research, but they need not meet the same documentation and monitoring demands as formal investigators. Activities such as performing an exam or drawing blood do not require them to be protocol experts. Data generated in the course of providing routine care can be valid for answering research questions without qualifying the care team as an investigator. Sponsors and regulators must agree on alternative quality-assurance methods like proportional monitoring or computational checks that protect patients and satisfy inspectors without overwhelming frontline staff.
• Endpoint alignment: Clear, agreed-upon endpoint definitions are essential when introducing pragmatic designs. Early engagement with regulators can prevent downstream concerns over data reliability and acceptability of critical design features.
• Cross-agency input: Within agencies like the FDA, progress depends on alignment across review divisions, policy groups, quality functions, and inspection teams so expectations are consistent and clear. At the same time, important gaps remain for other government agencies to address—particularly around infrastructure and data privacy law—which are critical enablers for pragmatic trial adoption.
• Privacy: Data use must comply with region-specific privacy requirements, and solutions to ensure data quality and validity (e.g., computational verification approaches, use of metadata) are needed to protect patients, investigators and sponsors.

One barrier remains cultural: Many sponsors hesitate to use pragmatic designs for fear that regulators won’t accept them for labeling claims. That caution is understandable, but it also slows progress. Collaborative exercises with agencies can help assuage those fears and create the assurance needed to try new approaches.

De-Risking Innovation Through STEP

A key accelerant is the FDA’s Streamlined Trials Embedded in clinical Practice (STEP) Demonstration Project. STEP provides a structured way for sponsors to test pragmatic approaches with FDA input across multiple functions. It essentially creates a “learning lab” where new ideas can be piloted, de-risked, and refined before being scaled.

Collaboration here works like a feedback loop: Sponsors test ideas with confidence, regulators get insights into what works in practice, and both sides feed those lessons back into the system. Together, those gains translate into better evidence, smarter guidance, and a research model that keeps evolving.

Standards That Enable Scale

Standards and interoperability may not sound headline-grabbing, but they are the foundation of pragmatic trial adoption.

In the short term, shared infrastructure reduces friction by making it easier to extract, curate, and analyze EHR data across diverse health systems. In the longer term, it enables innovations such as modeled or external control arms built from existing data, and real-time decision-making. Without baseline standards, every trial would require bespoke integrations—unsustainable at scale.

Think about digital photography: Once JPEG became the common standard, any device or app could open the same image. That foundation made sharing easier, and it also enabled whole new categories of tools. Pragmatic trials need a similar base: shared data standards that make today’s work easier and tomorrow’s innovations possible.

A Resource for Getting Started

To support adoption, TransCelerate created Getting Started with Embedded Pragmatic Trials: A Resource Guide, a single reference that consolidates definitions, design tools, regulatory considerations, and case examples.

Instead of chasing down answers across dozens of sources, sponsors can now have access to them in one streamlined guide. The aim is to inform and equip sponsors with an opportunity to take ideas from concept to implementation.

Consider it less of a rulebook and more of a curated “wiki”—a practical, evolving resource to help teams learn from what has been tried before and to make pragmatic choices that fit their own context.

Moving Closer to Mainstream Adoption

Pragmatic trials are not a cure-all, and not every research question is suited to them. They do, however, represent a powerful complement to traditional RCTs, especially when the goal is to understand how an intervention performs in real-world settings and with highly representative patient populations. Likewise, it could be an efficient avenue to label expansion and a method for meeting the requirements of a confirmatory trial.

The opportunity is to identify the sweet spots—questions where pragmatic elements add the most value—and then refine those elements until they become routine. With initiatives like STEP, collaborative workshops with regulators, and resources that consolidate shared learning, the field is well-positioned to expand the role of pragmatic approaches over time. 

For patients, that means trials that are easier to join, more representative of the patients they are intended to treat, and more directly connected to everyday care. For regulators, it means evidence that better supports access and decision-making. And for sponsors, it means the chance to generate faster, more relevant data, while helping to reshape clinical research for the future.