FDA draft guidance aims to streamline trials and integrate research into real-world clinical practice

The FDA’s new draft guidance aims to support the conduct of randomized controlled trials by streamlining protocols and focusing on essential data collection, enabling the integration of research into routine clinical practice. Released as part of the FDA’s efforts to advance its Real-World Evidence Program, this guidance marks a significant step in making trials more accessible and efficient.

Building on its existing guidance for industry, the US Food and Drug Administration (FDA) has released a new draft guidance on integrating randomized controlled trials (RCTs) into routine clinical practice, sometimes referred to as point of care trials. The new draft guidance, titled “Integrating Randomized Controlled Trials for Drug and Biological Products Into Routine Clinical Practice,” aims to streamline drug development, making trials more accessible and efficient while maintaining data quality. By leveraging existing healthcare infrastructures, the FDA aims to reduce trial start-up times, expand trial populations, and use electronic health records (EHRs) to collect essential data. This draft guidance is part of the FDA’s broader Real-World Evidence (RWE) Program, mandated under the 21st Century Cures Act of 2016, which is designed to evaluate the use of real-world data (RWD) and RWE in supporting regulatory decisions.

Traditional RCTs often operate separately from real-world healthcare settings, creating logistical challenges and less representative populations. Both settings collect large amounts of overlapping patient data, such as demographic information or pharmacy data on prescriptions, particularly through EHR systems or other health records (see FDA issues final guidance clarifying role of real-world data from electronic health records or medical claims in regulatory decision-making). To address this duplication of efforts, the FDA’s draft guidance encourages using existing clinical data to meet trial requirements, reducing the need for dedicated trial sites and minimizing redundant data entry. This approach enhances trial accessibility, and by utilizing EHRs, smaller healthcare facilities – often underrepresented in FDA-regulated trials – can play a greater role in research.

The new guidance clearly defines the roles of sponsors, clinical investigators, and local healthcare providers, promoting the design of RCTs within existing clinical infrastructures to reduce the need for specialized trial sites and staff. It introduces streamlined protocols focusing on essential data collection and encourages a quality by design (QbD) approach to maintain data integrity and participant safety while simplifying processes. Additionally, the guidance supports a hybrid model where routine clinical data is supplemented by research-specific activities when necessary.

The research approach is suggested for studies involving FDA-approved drugs where new indications, populations, or uses are being explored, provided the drug’s safety profile is already established. For unapproved drugs with well-characterized safety profiles – such as those in an established drug class – the FDA may also consider trials integrated into routine clinical practice. The agency specifically notes that non-interventional studies are outscope the of the guidance. They also emphasizes the importance of consulting with the FDA before initiating any trial, in line with its standard recommendations to ensure compliance and proper trial design.

The draft guidance follows closely on the heels of the FDA’s final guidance on incorporating decentralized elements into clinical trials. Both highlight the agency’s shift towards modernizing the clinical trial process by integrating RWD and aligning research with everyday clinical practice. A recent commentary in Trials by Lindsay Kehoe (Clinical Trials Transformation Initiative, Duke University) and colleagues emphasizes the need for “a modern trial infrastructure for an improved evidence generation system,” highlighting the importance of streamlining clinical trials to better meet current regulatory and clinical demands.

“The time is now for a broad range of stakeholders, including patients, to build the clinical trial enterprise of the future and improve our evidence generation system. More reliable and higher-quality evidence can be generated with the creation of a sustainable system-wide infrastructure, simplified, quality by design trials that integrate with clinical care and reduce duplication of activities, regulatory clarity, and coordinated leadership.” Kehoe et al., Trials, 2024.

The FDA is actively seeking feedback from stakeholders to ensure that the final guidance addresses the practical needs of those involved in clinical trials and regulatory decision-making.