The U.S. Food & Drug Administration (FDA) issued final guidance on September 18, 2024, titled “Conducting Clinical Trials With Decentralized Elements, Guidance for Industry, Investigators, and Other Interested Parties.” This guidance builds upon a prior draft and provides insights into decentralized clinical trials (DCTs), underscoring the benefits they offer to trial participants, industry members, and healthcare consumers.
Understanding Decentralized Clinical Trials
A DCT is defined as a clinical trial that includes decentralized elements where trial-related activities occur at locations other than traditional clinical trial sites. DCTs can be fully decentralized, with all activity taking place remotely, or partially decentralized (hybrid), where some activity occurs at nontraditional sites, such as a participant’s home or a local healthcare facility.
A DCT offers a more participant-centric approach, bringing the trial to the participant rather than requiring the participant to come to the trial site. While not every trial is suited for decentralization, a well-designed DCT can enhance participant convenience, improve enrollment, diversity, and retention, and generate more targeted data. Challenges include coordinating activities across multiple locations, overseeing remote activity, and ensuring data integrity.
DCT Design and Implementation
DCTs achieve decentralization by using local healthcare providers (HCPs), local labs, conducting activities at participants’ homes, and utilizing digital health technologies (DHTs) to gather and transmit data remotely. The guidance advises sponsors to implement decentralized elements through specific protocol instructions to mitigate potential variability or bias.
Protocols should specify which visits will be conducted remotely, the types of remote visits permissible (telehealth, local HCP), and the remote data collection activity to be performed by participants. Sponsors can design trials creatively with decentralized elements, provided they adhere to regulatory requirements and research needs. Flexibility can be built into protocols to allow investigators to adapt to individual participant needs. Consultation with the FDA is advised when planning a DCT.
Increasing Diversity and Generating Meaningful Data
Improving inclusion and diversity in clinical research is increasingly recognized as important. The FDA has identified clinical trial diversity as a key to advancing health equity and emphasizes the role DCTs can play in improving accessibility and mitigating barriers to participation.
The guidance identifies remote trial activities that can promote broader participation, such as telehealth visits, in-person visits at the subject’s home, and visits conducted by HCPs near the participant’s home. The use of local HCPs can improve engagement, recruitment, and retention of a more representative population and reduce cultural or linguistic barriers.
DHTs, which use computer platforms, connectivity, software, and sensors to gather and transmit data, are also crucial. Examples include spirometers with smart connectivity, glucose monitoring devices, and mobile applications. DHTs can transmit data remotely and securely, collect data more frequently, and facilitate more comprehensive data sets.
By broadening participation, DCTs can generate more useful data. The clinical trial population should reflect the intended patient population, including race, ethnicity, age, sex, and geographic location. Enrolling subjects who better represent the target population can lead to more relevant and powerful data for FDA approval and a better understanding of a product’s post-market safety profile.
Regulatory Considerations
Regulatory requirements for DCTs are the same as those for traditional trials. The FDA will conduct oversight through regulatory inspections and remote assessments. Sponsors are responsible for ensuring proper monitoring and conduct of DCTs, including coordination of decentralized elements and oversight of contracted services like local HCPs and third-party labs.
The guidance advises sponsors to implement plans addressing decentralized elements, such as a monitoring plan using a risk-based approach and a data management plan tracking data origin and flow. A safety monitoring plan should also account for the decentralized nature of the trial to ensure adverse events are appropriately addressed.
Contract research organizations (CROs) can assist sponsors with DCT implementation, oversight, and monitoring. Clinical trial agreements (CTAs) between sponsors and CROs should clearly define responsibilities for decentralized elements.
Institutional review boards (IRBs) must review and approve DCT research. The guidance recommends using a central IRB rather than local IRBs. Obtaining informed consent from remote participants requires IRB oversight to ensure the process is adequate.
Investigators are responsible for the conduct of DCTs and protecting the rights, safety, and welfare of subjects. They are also responsible for the work of local HCPs, ensuring activities are conducted according to the protocol and regulations, and for adequate supervision and data review.
Conclusion
The FDA continues to focus on clinical trial decentralization. The CTDE guidance provides insight into the FDA’s current thinking on DCTs and reflects the momentum they continue to build. While DCTs pose regulatory challenges, their use is expected to grow and provide significant benefits to stakeholders.
