Woman Testing Glucose Level With Continuous Glucose Monitor; fda decentralized trials concept

The FDA’s Newest Guidance on Decentralized Trials: 5 Things to Know

In May 2023, the Food and Drug Administration (FDA) issued updated guidance on conducting decentralized trials.

Clinical researchers in the United States had been expecting this guidance for several months, and they had hoped it would resolve some brewing issues with the tools and processes researchers around the world use to collect trial participant data remotely.

Below are five things clinical researchers should know about the FDA’s updated guidance.

1. The FDA Wants Researchers to Be Mindful of Trial Design

A major focus of the guidance is clinical trial design, and whether externally controlled (i.e. remote and decentralized) trial design is the right option in certain scenarios.

“Whether the trial can be conducted entirely using remote visits or a hybrid trial design is appropriate depends on the types of assessments and procedures needed to collect endpoints and monitor safety,” the FDA writes. “The decentralized features of the trial may necessitate additional training, coordination, and standard operating procedures to ensure consistent implementation.”

Annalee Armstrong at FierceBiotech has a great analysis of the guidance. Armstrong reports that even in a decentralized trial, “the FDA urges investigators to have a physical location where all clinical trial-related records for the participants are held, even if trial activities will occur somewhere other than traditional trial sites.”

Further, Armstrong notes how the guidance defines more clearly the roles and responsibilities of all involved in the research, especially when it comes to using remote monitoring or telehealth technologies to track participant data.

Old woman in bed looking at screen of laptop and consulting with a doctor online at home; fda decentralized trials concept

2. Factors Impacting the Superiority or Inferiority of Trials

COVID-19 continues to impact how clinical trials are conducted today.

Craig Lipset, cofounder and co-chair of Decentralized Trials & Research Alliance, tells Urtė Fultinavičiūtė at Clinical Trials Arena that researchers had to quickly adopt decentralized clinical trial designs and processes during the height of the pandemic.

However, since the quick inception of DCTs, questions and doubts have since arisen about their risks and best practices. Many CROs have been hesitant about how to proceed.

This new guidance reflects that hesitation in its discussion of trial design. “Remote assessments may differ from on-site assessments, particularly when trial participants are responsible for performing their own physiological tests (e.g., home spirometry),” the FDA writes.

“Assessments performed by local HCPs as part of routine clinical practice (e.g., evaluation of symptoms) may also be more variable and less precise than assessments conducted by dedicated trial personnel. In non-inferiority trials, when the effect size of an active control drug, for example, has only been determined in a traditional site-based clinical trial, it may not be reasonable to assume that the same effect size would be seen for the active control drug in a DCT.

“This may present challenges in calculating a non-inferiority margin. FDA review divisions should be consulted when planning a non-inferiority trial in a DCT setting.”

3. Previous Guidance Focused on Data Collection Tools

In December 2021, the FDA released guidance called “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations” that could provide a glimpse into what we can expect in forthcoming guidance.

The guidance focused on the tools researchers might use to gather clinical trial data, and whether those technologies and processes met the rigorous standards of medical research.

POLITICO regulatory reporter ​​Alexander Gaffney wrote about this at the time. Gaffney used the example of consumer step-counting devices in the context of the FDA’s concern that some devices might not be “fit-for-purpose.”

“As noted by the FDA, an algorithm used to measure step counts in healthy persons may not be accurate in persons with a health condition which causes an irregular gait pattern,” Gaffney wrote.

Again, the pattern seems to reveal that the FDA sees real opportunities in decentralized trial designs; it just wants to ensure the supporting infrastructure is up to the task.

woman talking to medic on video call to receive medical advice; fda decentralized trials concept

4. A Wider Perspective on Decentralized Trials

There’s plenty of evidence to suggest that the FDA is thinking about decentralized trials in a big-picture sense.

Rather than asking “How can we optimize decentralized trials?” the FDA is wondering “How can optimal decentralized trial designs fit into a larger research context?”

“[W]e’re likely to see some emphasis put into previous documents that have not been rigidly enforced,” writes Jane Myles, chairperson of the strategic advisory board at Curebase and program director at the Decentralized Trials Research Alliance.

“Unfortunately, a lot of trial sponsors aren’t thinking about these guidance documents in a holistic manner; rather, they are treating them in silos. And that’s a mistake because the FDA isn’t treating these guidances as checklists. Rather, the agency’s goal is to spur a macro shift in clinical trials.”

In December 2022, FDA Associate Director for Oncology Endpoint Development Nicole Gormley told attendees at the American Society of Hematology Annual Meeting and Exposition that a hybrid model of on-site and remote research is emerging that can lower hurdles to trial participation.

“It’s important to keep in mind that decentralized clinical trials don’t have to be an all or nothing endeavor,” Gormley said. “What’s much more common is a hybrid approach, where some aspects are done at the central location and other aspects are conducted remotely.”

5. The FDA Wants to See Consistent, Non-Fragmented Trial Data

In the May 2023 guidance, the FDA writes that trial sponsors have a responsibility to consider what medical devices are being used in the investigation, how it will be used, its instructions, and whether its use creates significant or insignificant risk to the trial.

“Medical devices suitable for home use (i.e., over-the-counter devices) that do not pose significant risks to trial participants may be appropriate for use by trial participants without the investigator’s direct oversight,” the FDA writes.

“The use of medical devices that are not intended for self-use (i.e., devices used in hospital or ambulatory care settings) or that pose significant risks to trial participants should be used or administered by qualified trial personnel with investigator oversight.”

In December 2022, Applied Clinical Trials’ Moe Alsumidaie reported on the second annual meeting of the Decentralized Trials and Research Alliance, which brought together regulators from the FDA and governing bodies from other countries to discuss decentralized trials.

A concern that Alsumidaie noted from that event was data quality and consistency. For example, the FDA’s Leonard Sacks, the acting deputy director office of medical policy at the Center for Drugs Evaluation and Research, expressed concern that without some kind of supervisor or supervisory mechanism, inconsistencies in trial participant data would appear.

Regulators worry about this happening at the device level, too. Bradley Merrill Thompson, an attorney at Epstein Becker Green and chief data scientist at EBG Advisors, Inc., tells Regulatory Focus that medical device manufacturers are likely frustrated by inconsistent device policies among the different FDA centers.

If the Center for Drugs Evaluation and Research and the Center for Devices and Radiological Health develop policies independently, Thompson says, they leave room for contradictions to emerge. This leaves industry participants uncertain of how to proceed.

Look for a digital health technologies (DHT) steering committee to “help coordinate different working groups across the Centers and make policy recommendations impacting the use of DHT-based measurements in clinical drug trials,” Foley & Lardner LLP attorneys Alexandra B. Maulden and Kyle Y. Faget write.

“… [The] FDA also plans to upgrade its technical expertise and training, leverage its statistical expertise to analyze endpoints derived from DHT data, and upgrade its IT capabilities to allow for large-scale analysis of DHT-generated data.”

Learn More

The FDA released its “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” guidance document with a 90-day comment period. That means researchers and clinical trial professionals have until August 1, 2023, to submit their comments on this draft of the guidance.

Clinical trial data capture and analysis is at the core of what our team does. In February, we wrote about the future of decentralized trials. To learn more about solutions that help you manage clinical trial data, request a demo today.

Images used under license from Shutterstock.com.

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