On September 12 and 13th, the Regan-Udall Foundation for the FDA held a public meeting on Good Clinical Practice: Considerations for Trials with Pragmatic or Decentralized Features. The purpose of the foundation, an independent 501(c)(3) organization created by Congress, is to advance the mission of the Food and Drug Administration to modernize product development, accelerate innovation, and enhance product safety. The session was hosted by Khair El Zarrad, PhD, MPH, Director, Office of Medical Policy, at the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA).
Today’s session started at the unholy hour of 7:30 a.m. Eastern (4:30 for those of us on the west coast!) So grab a cup of coffee and let’s dive in.
Decentralized trials, per FDA’s recent draft guidance, are trials where some or all activities occur at locations other than traditional clinical trial sites. Thus, trials are “decentralized” in terms of the clinical site, the traditional “center,” but re-centered on the participants. (One webinar participant offered the term “Participant-Centered Research” as an alternative.) The term “pragmatic” was also used, which refers to use of real-world data in trials. Dr. El Zarrad encouraged webinar participants to think of “decentralization” and “pragmatism” as elements of clinical trials, per the webinar title.
The first speaker, Eric Lenze, MD, Professor, Head of Psychiatry and Director, Healthy Mind Lab, Washington University School of Medicine, St. Louis, made the case for conducting decentralized trials (DCT) to improve participant recruitment, diversity, speed, and quality. As he described it, it’s a numbers game: it’s more efficient to recruit a small number of sites to enroll a large number of participants than the reverse, and those sites gain experience with each participant that improves quality of study conduct. He also promoted the use of decentralized health technology (DHT) tools to collect more frequent assessments, which increases their accuracy.
Craig Lipset, MPH, Co-Chair, Decentralized Trials and Research Alliance, spoke next. Dr. Lipset is also an Adjunct Professor at Rutgers; VP, Foundation for Sarcoidosis Research; and Managing Partner at Clinical Innovation Partners. In addition to diversity, Dr. Lipset cited sustainability and business continuity in the face of health emergencies, war, and weather upsets as drivers for decentralized trials. He traced the progress from “DCT 1.0,” a response to the pandemic, where the focus was on moving clinic visits to the home, adopting technology, and shipping drug to home, to “DCT 2.0,” which expands the scope of locations beyond the home and looks to “connect” existing technologies, such as the participant’s existing medical record, to collect data.
Kenichi Nakamura, MD, PHD, MBA, Director, Department of Clinical Development and Chief Management Officer, Clinical Support Office, National Cancer Center (NCC) Hospital in Tokyo, Japan, spoke last with two case studies of decentralized oncology trials. For the first example, the NCC team recruits participants from a wide geographic area, then identifies and qualifies a “partner site” to support the participant’s enrollment. The NCC consents the patient remotely and performs other assessments via a telemedicine portal, while the “partner site” supports patient care and conducts basic physical exams. The “partner site,” which is not considered a research site and does not require separate IRB review, shares source data with the NCC, which enters data into the EDC system. The NCC is also collaborating with Thailand on a cross-country DCT, which required Japanese investigators to obtain temporary Thai medical licenses.
While the speakers limned the future of decentralized trials, participants were busily entering questions about logistics into the chat: How are adverse events collected in DCTs? How is IMP accountability maintained? How is participant privacy protected? How is site monitoring performed? What are best practices for biospecimen collection in DCT? How is the delegation log completed?
During the Q&A, panelists emphasized that challenges with decentralized trials, including control of IMP, use of digital technologies, and safety, are also common to “traditional” trials. In theory, the increase and specificity of assessments enabled by decentralized trials should improve safety. Panelists acknowledged that additional controls are warranted to protect participant privacy in cases where trials extend to participants’ homes. They acknowledged that reliance on technology may actually be an obstacle to recruiting participants in rural areas and noted that plans must include provisioning of technology and connectivity for participants who need it.
Stay tuned for a summary of part 2 of this meeting.
