FDA Policies Support Shift to Decentralized Clinical Trials

A notable benefit of using wearable devices and other innovative technology to collect patient data in real-time is to encourage the design and implementation of clinical trials conducted at the point of care. Such approaches can help biomedical research “become more agile and efficient” and reduce the cost of developing important new therapies, FDA commissioner Scott Gottlieb said in a January 2019 policy  speech designed to expand discussion and debate over how real-world data (RWD) and real-world evidence (RWE) can be utilized to support a range of drug development goals.

Decentralized, or virtual, or patient-centric clinical trials would facilitate recruiting, enrolling and retaining participants in clinical studies, a major challenge and cost for study sponsors. Such approaches promise to reduce administrative burdens on sponsors and investigators, while also permitting patients to receive treatments from community providers without compromising the quality of the study or the integrity of data. The clinical research community is looking at wearables, tele-health visits, online patient diaries, e-informed consent programs, patient apps and other tools that are easy to use and monitor, as well as reliable. Studies utilizing such innovations would also gain access to expanded sources of evidence from lab tests, insurance claims, and even media reports.

In addition to streamlining clinical research, greater use of RWD and RWE would continue to facilitate changes to product labeling by gathering evidence for adding or modifying indications to approved medicines. These approaches, moreover, could reduce the need for post-approval safety studies, which are often difficult to enroll and carry out. RWD may support more effective new dosing regimens and help develop and validate new surrogate endpoints or digital biomarkers to guide more efficient development programs. Expanded acceptance of RWE from registries, natural history studies, and chart reviews may help sponsors establish comparison arms in studies evaluating efficacy in new products, an important strategy for single arm trials in oncology and rare diseases affecting few patients.

Beyond boundaries

Moving forward in this area involves the “seamless integration” of digital technology in clinical trials, Gottlieb pointed out, to help “bring clinical trials to the patient.” This involves moving prospective data collection “outside the brick and mortar boundaries of traditional clinical research facilities,” instead of always requiring patients to travel to investigator sites. More accessible, decentralized clinical trials, moreover, would permit enrollment of more diverse patient populations within community settlings, which would generate information more representative of the real world to support more informed treatment decisions.

FDA has established a formal working group on decentralized trials that is charged with developing guidance further outlining these approaches. The agency also plans a stakeholder meeting to help develop a framework to advance this area. One goal is to utilize remote monitoring technologies to reduce the need for traditional on-site monitoring of each clinical site, while assuring the integrity of data needed to assess patient safety and  product efficacy.

These initiatives are particularly important in assessing new cancer treatments and rare disease therapies affecting small patient populations. FDA’s Oncology Center of Excellence (OCE) is working with Friends of Cancer Research, the National Cancer Institute and other stakeholders in assessing real world endpoints, such as time to treatment discontinuation. The project aims to harmonize reference standards for assessing tumor mutational burden, which will help identify cancer patients more likely to respond to immunotherapy. And it should improve the ability of FDA reviews and managers to evaluate products that incorporate advanced algorithms and novel tools. To support such internal efforts, FDA is launching a two-year fellowship program in artificial intelligence and machine learning that will bring in academic fellows to support these advances.

Expanded use of RWE in medical product development has been a main theme at FDA for several years, and most visibly since the agency was directed to develop a framework for defining data and uses by the 21^st Century Cures Act of 2016. FDA has held public workshops on defining RWD and on developing innovative medical devices for collecting this information. Decentralized clinical trials fit broader initiatives promoting patient centricity in clinical research. Gottlieb and other FDA officials have applauded efforts to collect and use RWD in previous policy statements and regard these approaches as key to modernizing drug development and regulatory oversight. FDA launched a new “digital tool” in November 2018 to promote collection of RWE via patients’ mobile devices, and the research community continues to advance this field.