Clinical Researcher—October 2024 (Volume 38, Issue 5)

RULES & REGULATIONS

Pamela Tenaerts, MD

 

 

 

One of the first things that struck me about the U.S. Food and Drug Administration’s (FDA’s) newly finalized guidance on decentralized clinical trials (DCTs) was the title: “Conducting Clinical Trials with Decentralized Elements.”

Historically, the clinical research industry has referred to a decentralized model as a DCT or hybrid trial. Now, the FDA is reframing it to simply be what it is—a clinical trial with decentralized elements, such as telehealth visits, electronic informed consent, and digital health technologies (i.e., wearable devices).

In this linguistic edit, the FDA has done two important things. First, the agency has made it clear that a clinical trial is a clinical trial and, as such, subject to all applicable laws and regulations regardless of how it is designed or what technology tools are leveraged. Second, the FDA has emphasized one of the greatest advantages of a decentralized model: Flexibility, in that trial sponsors can pick and choose decentralized elements á la carte style, so trials are designed to be fit-for-purpose, fit for the patient population.

Here’s a look at additional changes for the better.

Data Oversight: Minimizing Data Variability

To account for multiple sources of data collection (via the site, provider, home health visit, sensors), the guidance suggests a data flow diagram should be available to show:

• Data origin
• Data flow
• Data transfer pathways
• Methods and technologies used, including service providers for data collection, handling, and management
• Transmission of reports

Study records should capture the visit type (i.e., telehealth or in person); the visit location (i.e., participant’s home, local health care facility, traditional clinical trial site); the date of the visit; and the data originator.

PI Oversight: A Bit More Clarified, But Questions Remain

Clinical trial investigators should evaluate reports from local healthcare providers (HCPs) for abnormal signs or symptoms detected at in-person visits and follow up with participants as appropriate. Televisits can be used for principal investigator (PI) to supervise trial personnel, and the FDA no longer requires an HCP log compared to the draft guidance, but just names and dates of contacts need to be in records. PIs will need to review HCP reports for trial data quality, and questions remain how this will be operationalized.

Clinical Trial Visits

Remote visits can include telehealth visits, participant visits to local HCPs, or in-person visits by trial personnel or local HCPs to participants’ homes. The schedule of events should clearly indicate which visits will always be at the site and which will be remote (the latter can be left up to the participants’ choice). The trial team must address privacy for in-home assessments, whether telehealth or in person.

In addition, data collection can be done by nearby HCPs and ideally by a participant’s treating physicians, if they do not differ from those the HCPs are qualified to perform. Therefore, no detailed trial knowledge is required as activities are not considered critical and essential to the trial. However, trial activities unique to the trial need to be performed by qualified personnel (PIs, sub-investigators, and other trial personnel) who are appropriately trained and well-versed on the protocol and investigator’s brochure.

Informed Consent

The FDA guidance says that informed consent should not be done by local HCPs, as they are not required to have protocol knowledge or specific clinical trial training. The consent forms should indicate if HCPs will be used in a trial and what trial activities will be done where—for example, at the site, at the participants’ homes, or elsewhere. Who will have access to the participants’ personal health information will also need to be further specified.

Safety Monitoring

Generally, adverse events should be captured during scheduled visits with investigators or trial personnel. Local HCPs performing trial-related activities may become aware of a concerning sign, symptom, or clinical event. The safety monitoring plan should describe how local HCPs will be instructed to report such findings, as well as what information will be collected via a digital health technology, how it will be used and monitored, and actions trial participants or personnel should take in response to abnormal findings or electronic alerts. Trial participants should also be able to arrange for an unscheduled visit with trial personnel using telehealth or an in-person visit, as appropriate.

Electronic Systems

Electronic systems can be used to perform multiple functions to manage DCT operations, including:

• Managing electronic informed consent (e.g., maintaining approved versions of informed consent, documenting institutional review board approval, archiving signed forms
• Capturing and storing reports from remote trial personnel, local HCPs, and local clinical laboratory facilities
• Managing electronic case report forms (eCRFs)
• Scheduling trial visits and other trial activities
• Tracking IPs that are shipped directly to trial participants
• Syncing information recorded by digital health technologies
• Serving as communication tools between trial personnel and trial participants

In all cases, the FDA says training should be provided to sites and participants. Real-time videos and audio interactions are a live exchange of information between trial personnel and participants, but the FDA does not consider these systems to be electronic systems specific for clinical trial purposes, so they are not subject to 21 CFR Part 11 in the Code of Federal Regulations (but they may be subject to local telehealth laws).

The Perfect Menu for Flexible Trial Design

Building a fit-for-purpose trial should always be top priority, but in all the recent hype around the potential of digital technologies, researchers may not have always deployed technology in ways that benefitted the trial design or patients. In some cases, the industry deployed technology for technology’s sake—experimenting with innovations in hopes of operational improvement. After all, this is an industry rooted in experimentation to find new cures. Now with emerging data on DCT impacts and the FDA’s re-characterization, we can confidently return to trial design fundamentals but with the option to leverage modern technologies á la carte style if—and when—they benefit the trial.

No more fixed menus…being able to choose what is optimum for individual trials is the ultimate flexibility for the ultimate outcomes.

Pamela Tenaerts, MD, (pamela.tenaerts@medable.com) is Medable’s Chief Scientific Officer, and aims to drive advancement of decentralized research methodologies with evidence-based best practices. She brings more than two decades of clinical research experience, having previously served as Executive Director of the Clinical Trials Transformation Initiative (CTTI), Director of Clinical Programs at Coaxia, and Director of the Clinical Research Center at Sarasota Memorial Hospital, among various other research positions.