FDA Advises When to Do or Not Do Decentralized Clinical Trials
(Thursday, May 4, 2023)
During the pandemic, completely or partially decentralized clinical trials (DCTs) became the only way clinical trials could be conducted reasonably, where possible. Although the dire necessity for DCTs is no longer there, their utility in increasing trial accessibility to a wider patient pool cannot be denied. FDA described eight considerations for DCTs which could determine if a trial could benefit from being conducted virtually, and where such operations are not practical. A DCT is characterized by conducting trial operations at patients’ homes, collecting source data remotely, and using local health care providers (HCPs) and labs that are closer to the patient with the ultimate goal of reducing physical visits to the trial sites. DCTs can increase accessibility for patients who live far from trial sites thereby increasing recruitment and potentially reducing the time to complete a given trial. However, there are challenges with ensuring data reliability, integrity, and inspection. DCTs involve coordination of trial activities with individuals and facilities in multiple locations that may be new to clinical trials, data collected from multiple sources with varying formats that need reconciliation and relying on patients/participants being properly trained and able to use the technology used to collect trial data. DCTs require specific plans for the use of local health care facilities, local HCPs, and local clinical laboratories, visits to trial participants’ homes; and direct distribution of the investigational product (IP) to trial participants at their locations. DCTs require CROs (contract research organizations) and other vendors that have experience with assessing feasibility, design, and implementation of such operations. The FDA guidance lists eight considerations for DCTs based on the experiences collected, not just over the pandemic years but over the last decade. First, sponsors must verify that variability and precision of the data obtained from diverse locations does not affect its validity. Superiority trials are better suited for DCTs than non-inferiority trials. All locations involved in the trial operations should be listed on the 1572 forms so FDA can audit them if necessary. Second, do a risk-assessment of the use of telehealth, in-person visits by trial personnel at patients’ homes, training of local HCPs in trial procedures, patient identity checks, study documents, and remote adverse event monitoring. Third, evaluate remote data collection using Digital Health Technologies (DHTs). Fourth, define delegation/distribution of responsibilities for all personnel and locations participating in the DCT. Fifth, consider remote informed consent. Sixth, evaluate shipping of the IP directly to participants and instructing for self-administration, packaging, and shipping of the IP to the participants, particularly for blinded studies. Seventh, ensure adequate safety monitoring using local HCPs and self-reporting by participants. And eighth, evaluate technologies for documentation generation and transmittal to a centralized location so all the data is available for monitoring and inspection. DCTs are practical where the investigational product is “simple to administer or use, have well-characterized safety profiles, and do not require complex medical assessments.” FDA advises use of “Hybrid DCT” where some trial activities involve in-person visits by trial participants to traditional clinical trial sites, and other activities are conducted at locations other than traditional clinical trial sites, such as participants’ homes. Hybrid DCTs may be more appropriate in cases where the administration of an IP or a complex medical assessment needs to be performed at a clinical trial site and some follow-up assessments could be performed remotely through online patient-reported outcome measures, via telehealth or in-home visits, or by local HCPs, as appropriate. Specific issues related to the feasibility, design, implementation, or analysis of a DCT should be discussed early with the relevant FDA review divisions. Appropriate training, oversight, and up-front risk assessment and management will be key to implementing a DCT successfully. The Guidance reads as a compilation of all the experiences FDA has collected over the last decade in reviewing the various issues encountered and addressed by sponsors of DCTs and should be a good primer for anyone interested in exploring DCTs.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC