The U.S. Food and Drug Administration (FDA) released its final guidance on "Conducting Clinical Trials With Decentralized Elements" on September 18, 2024, signaling a continued endorsement of decentralized clinical trials (DCTs). This guidance aims to provide clarity and support for implementing DCTs, which have the potential to improve participant enrollment, diversity, and data collection.
Decentralized Clinical Trial Design and Implementation
DCTs are defined as clinical trials where some or all activities occur at locations other than traditional clinical trial sites. This can include participants' homes, local healthcare facilities, or through digital health technologies. The FDA emphasizes that while DCTs offer numerous advantages, they also require careful design and implementation to ensure data integrity and patient safety.
To achieve decentralization, sponsors can use local healthcare providers (HCPs), local labs, and digital health technologies (DHTs). The guidance advises sponsors to implement decentralized elements through specific protocol instructions to minimize variability or bias. Protocols should specify which visits will be conducted remotely, the types of remote visits permissible (e.g., telehealth), and the remote data collection activities to be performed by participants.
Enhancing Diversity and Data Quality
The FDA recognizes the importance of improving diversity in clinical research and sees DCTs as a key tool in achieving this goal. By reducing geographic, logistical, and economic barriers, DCTs can broaden trial participation.
The guidance highlights various remote trial activities that can promote broader and more diverse participation, such as telehealth visits, in-home visits by trial personnel, and visits conducted by local HCPs near the participant's home. Digital health technologies (DHTs), including wearable devices and mobile applications, also play a crucial role by enabling remote data collection and transmission.
According to the FDA, a clinical trial population should reflect the intended patient population for the medical product being studied, including race, ethnicity, age, sex, and geographic location. Enrolling a more representative population can lead to more relevant and useful data, potentially improving the FDA approval process and post-market safety understanding.
Regulatory Oversight and Responsibilities
The FDA clarifies that the regulatory requirements for DCTs are the same as those for traditional site-based trials. Oversight will be conducted through regulatory inspections and remote assessments.
Sponsors are responsible for ensuring that DCTs are properly monitored and conducted according to the protocol. This includes coordinating decentralized elements and overseeing contracted services, such as local HCPs and third-party labs. Sponsors should develop monitoring, data management, and safety monitoring plans that address the unique aspects of DCTs.
While the guidance does not explicitly address contract research organizations (CROs), it acknowledges that sponsors may transfer clinical trial responsibilities to CROs. Institutional review boards (IRBs) are required to review and approve DCT research, with the guidance recommending the use of a central IRB.
Investigators remain responsible for the conduct of DCTs and the safety of participants. They must ensure that trial-related activities delegated to local HCPs are conducted according to the protocol and applicable regulations. The guidance notes that investigators are responsible for adequate supervision of HCPs and for reviewing their data to ensure quality.
Concerns and Considerations
Despite the positive outlook, some concerns remain regarding the implementation of DCTs. One major concern is the FDA's desire to have many DCT elements hardwired in the written protocol, potentially limiting the flexibility of site staff and trial participants. Experts hope that protocols will maximize participant flexibility and professional judgment to maintain patient centricity.
Another concern is the classification of HCPs involved in DCTs. Ambiguity remains over whether these individuals should be considered sub-investigators, leading to potential overreporting and increased costs. Clearer guidance is needed to alleviate these concerns and incentivize HCPs to participate in clinical trials.
Conclusion
The FDA's final guidance on DCTs underscores the growing importance of decentralized approaches in clinical research. While regulatory challenges exist, the guidance provides valuable insights for sponsors, investigators, and other stakeholders looking to leverage the benefits of DCTs. Thoughtful consideration of the investigational product, scope, participant population, and data objectives will be crucial for addressing regulatory issues and ensuring the success of decentralized trials.
