Decentralized clinical trials and digital health technologies are gaining momentum in medical research, allowing research participants to partake in trials remotely using state-of-the-art digital health technologies. We speak to Leonard Sacks, MD, associate director for clinical methodology in CDER’s Office of Medical Policy, about the benefits as well as implementation challenges.

What are decentralized clinical trials and digital health technologies?

In a decentralized clinical trial (DCT), some or all of a clinical trial’s activities occur at locations other than a traditional clinical trial site. These alternate locations can include the participant’s home, a local health care facility, or a nearby laboratory.

DCTs often incorporate digital health technologies (DHTs), which are systems that capture health care information for the clinical trials directly from individuals. Many DHTS are portable instruments such as activity trackers, glucose monitors, blood pressure monitors, or spirometers (devices that measure lung function). These sensors can be wearable, implantable, or ingestible. DHTs also include interactive mobile applications where participants can rate their quality of life, pain, depression, daily functioning, or perform tests of functional performance such as cognition, coordination, and vision.  

Why are DCTs and DHTs becoming a larger component of the clinical trial landscape?

DCTs and DHTs are gaining traction for many reasons. Technologies are improving, making it easier to collect, transfer, and store electronic data. Patients and providers are becoming much more tech savvy and comfortable with telemedicine.

We have seen the impact of the COVID-19 pandemic. Travel restrictions, physical distancing precautions, and so forth made it very difficult to start clinical trials at traditional research sites. Sponsors were motivated to begin facilitating more trial elements remotely, such as informed consent agreements, data collection, and patient monitoring using telemedicine.

And to no surprise, we are finding that many clinical trial participants like to receive treatments at home or at their local clinic, rather than to travel far distances to a traditional clinical trial site. It can be easier to recruit people and keep them enrolled if they don’t have the burden of travel. In addition to convenience, DHTs can collect data much more frequently than scheduled trial visits, sometimes even continuously. These technologies also capture information during participants’ routine activities, providing insight into the effectiveness and safety of the treatment in “real life.”     

On a practical level, DCTs can reduce time and expenses in the long term, limiting or eliminating the need for the resources associated with a traditional site. However, there may be upfront technology and training costs.

We hear a lot about the underrepresentation of racial and ethnic minority populations in clinical research. How might DCTs and DHTs be part of the answer?

Clinical trials provide evidence for evaluating whether a treatment is safe and effective. Despite researchers’ efforts to recruit people of diverse backgrounds, members of minority groups are generally underrepresented in clinical research. This underrepresentation can have real-world consequences, as people of different ages, biological sexes, races, and ethnicities may have a range of responses to treatments that the clinical trial may not fully capture.

DCTs and DHTs may help make clinical trials more inclusive because they can reduce barriers to participation. For example, older individuals and people with disabilities may find it physically exerting to travel to a traditional clinical trial site but could participate in a clinical trial from their home or a nearby clinic. People with household and childcare responsibilities may also find it difficult to meet prescribed timeframes for clinical site visits. Individuals from racial and ethnic minority groups may disproportionately live in areas without clinical research facilities, and DCTs may open access to research for them.

We’ve discussed the benefits of DHTs and DCTs. What are the challenges?

Yes, there are implementation challenges that we need to consider as we transition to a more digital clinical trial space. For example, for DCTs, sponsors need to store electronic data securely, transport treatments safely (e.g., refrigerated if necessary), and allow participants to report adverse events. Participants and the clinical research staff must understand how to use the technologies correctly and safely. Research subjects may also need to learn how to take the experimental treatment at home. Collecting data from multiple remote sources may require strong data management skills and data management platforms.

While DCTs and DHTs can reduce barriers to clinical trial participation, they also introduce technical hurdles. People uncomfortable with wearable sensors, those without access to technology, and those who are unfamiliar with electronic instruments like cell phones and smart watches may opt out of participating. As a result, the clinical trial participants may be younger and more tech savvy than the actual patient population.

What is FDA doing to address these challenges and continue the conversation about DCTs and DHTs?

Aware of both the promise and challenges of DCTs and DHTs, FDA has been working on resources for sponsors, patients, health care providers, and the broader community. These resources include the FDA DHT for Drug Development website and new opportunities for stakeholder engagement with FDA to address the development of novel DHTs and their use in medical product development.

We are working on electronic methods to track drug application submissions containing DHT-derived data. We are asking sponsors to use the updated versions of FDA forms 1571 and 356h to indicate when they include DHT data in submissions. This will help us understand the changing landscape of DHT utilization, and the trends, challenges, and opportunities for implementation. If drug sponsors have questions about DHT-derived data, please reach out to us at [email protected].

The agency has issued guidances on this topic, including a guidance on DCTs that we published today. Earlier this month, the agency issued a draft guidance on using electronic systems, electronic records and electronic signatures in clinical investigations, which revises a 2017 guidance. We also issued a draft guidance in December 2021 that discusses how to use DHTs for remote data acquisition in clinical trials to ensure that they are reliable.

In addition to guidance development, FDA has created a framework that includes workshops, demonstration projects, stakeholder engagement, a website, internal processes to evaluate DHTs, and other initiatives. Plus, FDA has established a steering committee that may provide advice on the general use or feasibility of DHTs and the implementation of DCTs not associated with a specific drug development program. The steering committee includes senior staff from CDER, the Center for Biologics Evaluation and Research (CBER), and Center for Devices and Radiological Health, including the Digital Health Center of Excellence, as well as the Oncology Center of Excellence and the Office of Clinical Policy and Programs.

In March, FDA hosted the first in a series of five public workshops on issues related to DHTs in regulatory decision-making. The March workshop discussed their potential to increase clinical trial accessibility and diversity, and to expand the type of data and clinical outcome measures that we can capture in clinical trials.

On the legislative front, the Food and Drug Omnibus Reform Act of 2022 includes new requirements to advance the use of DHTs and DCTS. Under the Prescription Drug User Fee Amendments (PDUFA) VII, CDER and CBER have committed to activities to enhance the use of DHTs to support drug development and review.

How do we expect DCTs and DHTs to evolve?

This area will continue to grow as technology advances and people become even more comfortable with DHTs and remote medicine. However, I don’t see all clinical trials moving to an entirely remote setting; people will need to go to a clinical trial site at times. I think hybrid models will be more common, where some trial activities will take place at clinical trial sites and others at patients’ homes or other convenient locations.