We have reviewed the final 2024 FDA guidance on Conducting Clinical Trials with Decentralized Elements (DCTs). While the general concepts are not new, the guidance clarifies many key points that impact the clinical trial experiences for sponsors, investigators, clinical trial industry supporters, and participants. The guidance provides recommendations and best practices for integrating decentralized elements in clinical trials, while ensuring regulatory compliance, maintaining data quality, and supporting participant safety.
The final 2024 guidance updates the Agency’s prior guidances on decentralized clinical trials and digital health technologies (DHTs), clarifying considerations for designing DCTs based on appropriateness of telehealth or in-person visits for trial participants, investigational products, medical conditions of the trial population, and use of DHTs. The current guidance maintains the focus on two overarching principles, participant safety and data integrity by incorporating responsibilities specifically related to DCTs for sponsors, investigators and participants.
The use of decentralized components, such as telehealth or home visits in a clinical trial reinforces prior FDA guidance on patient-focused drug development (PFDD), by allowing trial activities to occur in places where it is convenient for participants. This benefits both participants and trials by reducing participant burden, improving accessibility, and improving retention.
The guidance references participants use of their own digital health technology, often referred to as ‘Bring Your Own Device’ (BYOD), with the caveat that sponsors make provisioned devices available to participants who do not have their own, to ensure that participation is accessible for all potential participants. At times in the past, sponsors have questioned whether the FDA would accept data collected via BYOD when considering regulatory approval. By describing use of a participant’s own DHT in the final guidance, it is clear that the FDA considers data collected via BYOD acceptable (see also the 2023 FDA guidance on Digital Health Technologies for Remote Data Acquisition in Clinical Investigations).
While recognizing that DCTs may risk increased data variability compared to traditional site-based trials, the guidance highlights the need for a strong risk-based monitoring plan to maintain data quality. In a DCT, data integrity can be supported through robust remote trial monitoring plans to ensure compliance with study protocol conventions and best practices for data collection. This may include use of video to supervise remote visits and real-time access to study data and standardized reports/dashboards. While audio/video telehealth interactions do not need to be 21 CFR Part 11 compliant, all study data captured during the virtual visit must conform to these guidelines (Section J). In addition, site and de-identified participant access details (date/time, etc.) should be captured in a robust audit trail (Section J). Critically, participant data privacy and security must be ensured during remote visits/events in decentralized settings.
The guidance also states that training participants on study guidelines is an important element for successful DCT and may be provided by site staff or within the application (Sections A, B, C, D, and J). Furthermore, to improve data consistency and limit variability, protocols for DCTs should include specific instructions for where and how trial activities are to be performed.
Participants must adhere to recommended safety procedures when health/safety issues occur to document potential Adverse Events (AEs) when they are not at the study site. However, the guidance advises that it is helpful to collect real-time information from participants when event-triggering thresholds are exceeded. Safety monitoring plans should ensure that AEs, including those that are identified remotely, are documented, assessed, and addressed. The safety monitoring plan should also detail the type of information specifically collected using DHTs, how it will be monitored, what actions participants should take if something concerning occurs and how trial personnel should respond to electronic alerts (Sections B and I).
The implications for sponsors and vendors have expanded beyond the delivery of enabling technology to include a serious focus on staff training, all quality assurance processes and foundational quality management systems. These are areas where we have focused our attention to ensure compliance not just for audit but for successful trial execution.
Authored on behalf of Clinical ink by Yamamoto, R, Anderson, D, Bowen, C, & Barrasso, B
