Decentralized clinical trials: FDA guidance and the ‘new modus operandi’

Key takeaways:

• FDA issued guidance on decentralized elements of clinical trials last fall.
• Investigators need to balance using decentralized elements and limiting data variability.

The COVID-19 pandemic forced investigators conducting clinical trials to use decentralized elements, such as telehealth, to continue their research.

The FDA provided recommendations to investigators during the pandemic about how to integrate decentralized elements into clinical trials. Last fall, the agency issued guidance for the continued use of these elements, ensuring their role in trials for the foreseeable future.

“It’s hard to tell everybody to reverse course, especially because of the benefits that they bring to patients and sites who are conducting the trial,” Joseph M. Unger, PhD, MS, associate professor at Fred Hutch Cancer Center, told Healio. “There may be some modifications that occur along the way, and people are going to learn about what works best and what doesn’t; but as far as the general strategy, I think decentralized clinical trials are the new modus operandi of clinical research.”

FDA guidance

The FDA’s guidance on decentralized elements included insight on clinical trial design and conduct, remote visitations, digital health technologies, and the roles of both sponsors and investigators.

Notable components of the guidance include:

• Trials can be designed so patients can be seen in their own home with telehealth or in-person visits, at mobile research units or at local health care facilities. Telehealth can be used when no in-person contact is necessary.
• Clinical trial design should aim to limit data variability through detailed instructions, education, training and supervision.
• Investigators should ensure privacy when conducting telehealth assessments or in-person visits.
• Investigators should keep records on where and how visits with patients occurred in a trial, whether by telehealth, at a health care facility or at the investigative site..
• Trial protocols should detail how adverse events are collected and monitored from remote locations or during telehealth visits
• Investigators should carefully monitor assessments from health care professionals at local facilities
• Decentralized elements can open enrollment to more individuals, but investigators should only enroll the number of people they can properly manage.

“For an investigator, [this guidance] gives them the ability to expand the breadth of their reach for participants,” Keith S. Usiskin, MD, FACP, an endocrinologist and industry-experienced clinical researcher in New Jersey for more than 30 years, told Healio. “One of the biggest challenges that many investigators have is recruitment and retention. This is a problem in almost every therapeutic area. Incorporating decentralized elements into the clinical trial plan helps a lot. It helps because it increases the catchment area for patient recruitment. It helps because it increases the ability to use new technology that might not be available at the main investigative site.”

However, Usiskin cautioned investigators must make sure they can gather verifiable data.

“The biggest risk would be data variability and inconsistent results because of a lack of uniformity of data collected at different locations and under different circumstance. Even equipment differences at offsite locations may contribute to variability,” he said.

Pharmaceutical Research and Manufacturers of America (PhRMA) responded to the FDA’s draft guidance on decentralized elements in August 2023.

Organization leaders emphasized decentralized trials should have the same standards as traditional trials. They also highlighted the opportunities created by use of digital health technologies, as well as the need for oversight of health care providers and nurses who may contribute to a study but who do not have clinical trial experience.

“We support FDA’s efforts to provide additional details regarding its expectations for the design and conduct of decentralized clinical trials and agree that decentralized clinical trials have the potential to reduce the burden on patients, caregivers and medical providers involved in clinical trials,” they wrote to the FDA. “We further agree with FDA that decentralized clinical trials have the potential to expand access to more diverse patient populations by making use of decentralized elements.”

‘This is a process’

Unger recently chaired a taskforce with ASCO and Friends of Cancer Research that evaluated whether decentralized elements impacted data quality and the conduct of clinical research during the pandemic. They are in the process of submitting their quantitative-based paper for publication in a peer-reviewed journal.

“At that time, clinical trial enrollment plummeted,” Unger said. “The guidance put forth by both the NCI and the FDA said that, among other measures, you can go ahead and very widely employ the idea of remote consent to trials. A patient could — from their home — discuss the trial with a clinical research associate or a physician and consent remotely without having to come into the clinic.”

Some investigators may worry about missing something over a teleconference that they normally would see in person, Unger said.

“But you can also flip that around,” he added. “It’s not uncommon for patients to miss visits to clinics, in which case everything is lost in terms of what’s going on with the patient at that time. If you allow a remote visit, maybe then the patient actually engages in that monitoring assessment.”

Not all trials will or should have decentralized elements, Unger said.

Phase 1 or phase 2 trials may work best at research institutions when investigators are still evaluating new therapies, he said. Phase 3 trials, on the other hand, could use decentralized elements because safety profiles of treatments being investigated would be better understood.

“This is a process,” Unger said. “It may not be a one-size-fits-all strategy. On a study-specific basis, there will be some determinations about what’s best in terms of procedures that can be adopted, and what kind of things may not be best for that individual study. I think there is going to be room for discretion.”

More research into data quality should be conducted, Unger said.

“That cannot be considered in isolation because it’s not just the potential adverse consequences,” Unger said. “It’s the trade-offs in terms of, is the adoption of decentralized elements to clinical trials making trials easier for patients in general? Is it improving enrollment in general? Is it making trials more diverse because it allows patients with a more diverse background, patients who may be clinically or socioeconomically vulnerable or those who might not otherwise participate in trials to participate more readily? These are the kinds of questions that I think are really important.

“It is so interesting to me personally how, in the midst of all the tragedy of COVID, there was potentially something good that came out of it in terms of making clinical research better,” he added. “It forced the sudden adoption of all of these procedures and, in my view, I think that their adoption is going to have a net positive impact on the entire system.”

References:

For more information:

Joseph M. Unger, PhD, MS, can be reached at junger@fredhutch.org.

Keith S. Usiskin, MD, FACP, can be reached at kusiskin@gmail.com.

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Sources/Disclosures

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Disclosures:
Unger reports consulting fees for Eli Lilly & Co. Usiskin reports no relevant financial disclosures.

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