When the FDA last month published long-awaited draft guidance on decentralized clinical trials the agency cemented the research approach as not just a pandemic-era necessity, but a long-term term antidote to improve accessibility and diversity in drug R&D.
While the document has been heralded as a major game-changer that provides much needed clarity on how the regulator will review decentralized trial designs, it also raised a slew of questions about how the industry should navigate a patchwork of telemedicine laws that have previously stymied the adoption of DCTs.
“Having the FDA come out and give a draft guidance on this topic is real validation for industry that this is real, this is here to stay, this is the future of clinical trials,” said Kyle Faget, a partner with the law firm Foley & Lardner. “Everyone's really been wondering, ‘How do we do this? How do we comply with the FDA’s regulatory requirements for the conduct of clinical trials?’”
And although the FDA notes in the guidance that the regulatory requirements for DCTs remain the same as for traditional clinical trials, Faget argues that the protocols are actually “much more nuanced.”
“A huge shift is that when conducting clinical trials utilizing telemedicine, there's an entire geographic patchwork of practice standards that all of a sudden clinicians need to concern themselves with, whereas in the traditional local clinical trial context you already know that the investigator and academic medical center is licensed to practice medicine there and knows the appropriate practice standards,” she said.
The FDA’s guidance warns that both sponsors and investigators must be cognizant of the local standard of care and telemedicine practice standards for each location where trial participants reside. But because these laws differ in each state, sponsors and investigators may have to traverse a complex set of trial protocols, she said.
Fundamental questions remain about whether an investigator may need to be licensed in each state where a trial takes place to provide meaningful oversight of the trial. And unless the FDA provides further clarification about how to navigate these kinds of issues in its final guidance, which is slated for publication by the end of the year, Faget warns that the industry will need to design for an array of new challenges.
Creating cross-state protocols
Telehealth is the bread and butter of decentralized trials, as it allows clinicians in a central location to communicate and potentially provide clinical care to patients anywhere in the world.
In its guidance, the FDA contends that reducing these physical barriers to trial participation with telemedicine could “increase the breadth and diversity of participants in clinical trials and improve accessibility for those with rare diseases or mobility challenges.”
To that end, it recommends that investigators “consider telehealth visits instead of in-person visits with trial participants if no in-person interaction is needed” and notes that the trial protocol should “specify when a telehealth visit with a trial participant is appropriate.”
But implementing telehealth visits in trials and then specifying when they will be held is easier said than done, Faget argues. One challenge to consider is the need to develop a protocol that addresses the varying state laws governing telehealth practice standards.
“Having the FDA come out and give a draft guidance on this topic is real validation for industry that this is real, this is here to stay, this is the future of clinical trials."
Partner, Foley and Lardner
In Texas, for example, clinical research is considered a practice of medicine, and telehealth providers who are conducting that research must be licensed to practice in the state. For trials conducting telehealth visits from a centralized location, an added layer of due diligence is needed to ensure that all personnel are licensed where the trial participants are located.
Several other states have laws that prohibit internet prescribing, which may prevent a patient receiving telehealth care from receiving medication in the trial through a “soley asynchronous modality,” Faget warned.
“If you're a clinician and you send a (patient a) questionnaire, and the answers to that questionnaire are the only communication you have with the patient, then that could be considered internet prescribing in many, many states and be illegal,” she said.
Faget recommends sponsors carefully investigate “what can be done in the specific geography utilizing telemedicine and what can't be done. And then if utilizing telemedicine, what the appropriate modality is.”
To compound the problem, Faget said many states don’t define under their standard of care laws what types of care can be conducted via telehealth and instead leave it up to the clinician to decide. And that complicates the ability of sponsors and investigators to define, under the FDA’s guidance, when telehealth care will be given, as it may ultimately be up to the clinician’s discretion.
“This is where this model gets really gray,” Faget said. “The FDA probably wants to be very careful not to opine on how clinicians practice medicine, but at the same time, (provide guidance on) how you meet regulatory requirements like investigator oversight appropriately.”
A finalized FDA guidance will likely need to “drill down on this issue a little bit and in doing so leave it more open ended so that sponsors can leave as optional whether or not certain parts of the protocol can be done virtually or can be in office subject to the clinicians judgment,” she added.
The FDA is legally obligated under the 2022 Omnibus law to publish the finalized guidance by this December and will accept comments on the draft until August. For companies moving forward with decentralized trials now, Faget said she recommends following the guidance closely and keeping in constant contact with the agency over the trial design.
They should include information on how adverse events will be reported, data will be managed, patients will be monitored, and variability in data handled in their trial design and should have a physical location where clinical trial records and personnel can be accessible.
“These are the kinds of things that sponsors are going to have to grapple with that they never did before,” she said.