Contributed Commentary by Gary Zammit

February 17, 2021 | 2020 will go down as a miserable year, but beyond the heartache, some developments may represent bright spots that light the way to the future. One of these is the growth of Decentralized Clinical Trials (DCTs).

DCTs are virtual trials that integrate remote assessments with modern digital health technologies, including remote rating apps, wearable monitoring devices, and online social engagement platforms into study design and execution. They were already growing in popularity prior to COVID-19, thanks to regulatory acceptance, trends in clinical practice and the operational/cost efficiencies afforded by remotely conducting “siteless” trials with patients remaining at home.

But the ongoing global pandemic has accelerated the implementation of DCTs, bringing us to a tipping point. At a time when the face-to-face interaction of patients and clinicians at brick-and-mortar trial sites is sometimes considered unsafe or largely restricted, it appears that the age of telehealth and telemedicine would offer the perfect circumstance for remotely executing DCTs, as long as the technology can ensure patient safety, data integrity and compliance with FDA standards and regulations.  

We are likely to see a sharp increase in DCTs in 2021 in a wide-ranging effort to meet not only the patients but also the investigators where they are. It should all work fine, but thoughtful construction of DCT protocols and integration of functional tools will be essential. There are a few road maps and a lot of learning to be done. 

Site, Investigator selection

​DCT sites should be determined by the availability of investigators who are able to utilize in-clinic, remote, and hybrid subject assessments. The site should, of course, have access to patient populations who meet inclusion/exclusion criteria and are likely to be compliant. However, success keys on the availability of clinical trial staff and supplies, and appropriate procedures in place to minimize risk of COVID-19 infection to the staff and subjects.

While pre-qualification visits to prospective trial sites are traditionally conducted on site, the hybrid approach allows for remote site assessments. A virtual tour of and overview of the site can cover a protocol review with principal investigators and staff, as well as assessment of capabilities (experience, subject database, recruiting, staffing), safety and compliance, facilities (diagnostic, lab, pharmacy), technology and telemedicine capabilities, and IT infrastructure.  

Investigators can be onboarded efficiently in virtual environments. Virtual pre-qualification visits, site selection visits, and investigator meetings can be conducted on platforms like MS Teams or Zoom, which are now common and have several advantages over in-person meetings. Virtual meetings eliminate travel, reduce cost and the investigator’s time away from clinical practice, and improve engagement through the use of videoconference tools and multimedia. 

Telemedicine Offers A Practical Alternative To In-Person Assessment​ 

Trial subjects can be pre-screened, screened, and consented effectively in virtual environments. Online questionnaires provide an entry threshold, and real-time video interactions with screeners provide a live exchange of information between trial personnel and trial participants. Factors important to CNS research such as eye contact, facial expression, empathic gestures, voice and attentiveness can be effectively communicated in a telemedicine encounter.  

E-consent

E-consent tools allow investigator sites to obtain remote informed consent from patients through electronic signatures or even image or video capture. Witness confirmation is possible. E-consent helps to avoid the common pitfalls of paper documentation, such as consent form versioning. E-consent may offer electronic communication pathways (video, e-mail, or text) when patients have questions or concerns.

Electronic patient engagement

Many studies have shown that virtual clinical trials recruit faster, improve retention, and increase participation with lower dropout rates. Patients can be accessed via electronic media, including social networking sites, which offer an ample breadth and diversity of the subject sample (especially racial or ethnic diversity, which have become critically important to understanding trial outcomes). Patients find this digital approach more convenient to their participation as it reduces their burden, including time required for clinic visits and travel to study sites.   

Logistical considerations 

When assessing a DCT patient virtually, it’s obviously important that the patient be facile with videoconference methods. While advanced age can be a factor, we’ve found that participants with a mean age of 65-75 have shown good performance in videoconference settings. One must take care to ensure patient confidentiality and protection of privacy by using HIPAA-compliant telemedicine applications and/or encrypted, password-protected videoconferencing applications. It also is important to confirm that the audio-visual connectivity is sufficient to accurately assess the patient.  

Unique central nervous system (CNS) challenges

The remote assessment of a patient in a CNS trial may bring unique challenges. With a cognitive assessment for example, the patient may have sensorimotor limitations, distractions, potential access to aids such as clocks, calendars or notes, or sideline assistance from family members or caregivers. In some cases, cognitive telehealth assessments may not be appropriate substitutes for standardized neurocognitive assessments. 

On the other hand, wearables can be extremely useful in the telemedicine assessment of a CNS patient. A multitude of wearables are relevant to CNS trials, measuring everything from sleep/wakefulness and step count to ECG, body temperature, and blood pressure.  

DCTs are a patient-centric, disruptive technology that fit right into the FDA’s long-standing interest in the modernization of clinical trials and its agency-wide priority, pre-dating COVID-19, to advance ways for the public to gain earlier access to important new therapeutic options. 

However, the model can’t work for everyone. Some patients will always need to be in a clinic or hospital setting for certain trials, and digital technologies can only go so far. Questions remain about how telehealth monitoring—talking to patients via video and smartphone—can replace one-to-one contact, and how well older patients in trials can navigate modern tech. But with all the advantages piling up in the plus column here—patients staying at home, reduced travel and costs, enhanced COVID-era safety and the boost in recruitment and retention—it would appear that the future of clinical research trials is “virtually” here, and it’s DCT.    

Gary Zammit, PhD, is the President & CEO of Clinilabs Drug Development Corporation, a full-service CRO that provides clinical drug development to industry, focusing on CNS therapeutics. He also is an Associate Clinical Professor of Psychiatry, Icahn School of Medicine at Mount Sinai (New York, NY). Dr. Zammit is widely sought for his expertise in neuropsychiatric drug development. He has authored two books and over 230 articles and abstracts that have appeared in medical journals. He can be reached at gzammit@clinilabs.com.