FDA draft guidance paves way for more real-world, point-of-care clinical trials

The US Food and Drug Administration (FDA) on Tuesday issued a draft guidance that’s intended to pave the way for using data from research carried out during routine clinical practice to support drug approvals.

FDA explained that during routine clinical practice, additional information is often gathered to support a wide range of purposes, for example in employment medical exams and travel visa applications, not to mention exams or procedures needed to inform standard randomized clinical trials (RCTs). Data from routine clinical practice has also sometimes been used to support the approval of new indications for approved drugs, as seen with FDA’s 2020 nod of tocilizumab (Genentech’s rheumatoid arthritis drug Actemra) for treatment of hospitalized COVID-19 patients, based on UK clinical practice data.

Trials that blend research data collection with routine clinical practice are sometimes called “point-of-care” or “simple trials,” the agency noted. This approach can improve convenience and access to new interventions for patients, while at the same time producing results that are more representative of a real-world population.

“Leveraging established healthcare institutions and existing clinical expertise in the medical community can reduce startup times and speed up enrollment,” the agency wrote.

Which drugs are eligible?

Trials in routine clinical practice are particularly appropriate for testing new indications of drugs that are already FDA-approved and have a good safety track record. For these drugs, sponsors might need to only collect certain safety data – like severe adverse events – from real-world trials in new indications, the agency wrote.

“Sponsors should consult with the relevant FDA review division to determine whether a selective approach to safety data collection would be appropriate,” the guidance states. “FDA-approved drugs may still need a more robust safety evaluation if there are new concerns raised by their use in a novel combination or use in a new population or indication.”

But the agency also opened the door to using clinical practice trials to test drugs that are not FDA-approved.

“In some cases, it may be possible to study unapproved drugs with well-understood safety profiles in clinical practice environments (e.g., those that are members of an existing class, those where safety is already well characterized from prior trials),” the agency wrote. “Sponsors should consult with the FDA review division to determine if a particular practice environment is suitable for trials with these types of drugs.”

Real-world efficiencies, growing interest

The guidance on clinical practice trials is part of FDA’s broader program promoting the use of real-world evidence (RWE) in drug development, approvals, and post-marketing surveillance. (RELATED: FDA finalizes guidance on real-world evidence in drug approvals, Regulatory Focus 31 August 2023)

In addition to the new clinical practice document, the agency also just published final guidance on decentralized clinical trials. (RELATED: FDA’s final guidance on DCTs adds clarity on HCP task log, inspection requirements, data variability, Regulatory Focus 17 September 2024)

“There has been increasing interest in the use of real-world data acquired during routine clinical practice to support drug development,” the agency explained. “Advances in information technology and widespread use of electronic health records (EHRs) have facilitated access to real-world data obtained during routine clinical care and provided new opportunities for the integration of clinical research and clinical care.”

Data gathered in randomized controlled trials could be collected in EHRs and combined with clinical data from routine practice, the agency suggested.

“Experience with trials conducted in clinical practice settings has demonstrated the potential value of this approach for drug development in certain circumstances,” FDA wrote. “Such trials with simplified data collection have allowed for rapid enrollment and evidence generation.”

Guidance on feasibility, trial protocols

FDA’s draft guidance explains the situations where sponsors could consider conducting trials in routine clinical practice, what personnel are involved, and key aspects of protocol design.

Clinical trial investigators don’t need to be employed at the site where the clinical practice trial is being conducted. Responsibilities of healthcare institutions and employees should be documented in sponsor agreements.

Clinical practice trials are appropriate in scenarios where the necessary data and exams are routinely collected and performed in regular office visits.

“Sponsors should consider the complexity of trial requirements, the need for standardization of trial-related activities, and the need for research-specific expertise when deciding on the feasibility of trials in a practice setting,” FDA guided. “The integration of RCTs into clinical practice should not interfere with the appropriate delivery or administration of patient care.”

It’s best to use a quality by design (QdB) approach in order to meet scientific objectives and comply with the usual regulatory requirements for clinical trials, FDA advised.

“In designing protocols using a QbD approach, sponsors may wish to engage FDA, clinicians, patients, and other interested parties early to discuss trial design, data quality considerations, and operational issues,” FDA wrote.

Trials should be randomized, and blinding is advised, if possible, but if not, sponsors should identify and control for potential areas of bias, the agency said. As for endpoints, sponsors may use lab measures as biomarkers and track major events that lead to acute care and poor clinical outcomes, such as strokes, heart attacks, and fractures. They should be aware of acute care taking place outside the trial site(s) and obtain medical records as needed, the agency suggested.

FDA draft guidance paves way for more real-world, point-of-care clinical trials

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