Decentralized clinical trials (DCTs) are evolving and gaining momentum within medical research as they increasingly incorporate state-of-the-art digital health technologies (DHTs). Indeed by way of DHTs, useful data for clinical trials can be collected, exchanged, transferred, and stored electronically and in a more efficient manner. In order to stay aligned with the momentum, regulatory agencies are also revising guidelines to provide recommendations for sponsors and key stakeholders in implementing DCTs with the aim to improve the research and development of pharmaceutical products.
The U.S. Food and Drug Administration (FDA) published a preliminary guidance document on May 2, 2023, outlining its regulatory approach to decentralized clinical trials (DCTs) for drugs, devices, and biological products. This draft guidance builds upon previous recommendations made during the COVID-19 pandemic, which aimed to enable trial decentralization in response to quarantine measures, site closures, and travel limitations. The FDA intends to provide recommendations in this guidance for the design and implementation of DCTs while incorporating digital health technologies (DHTs) into the trial process.
Advantages and Background of DCTs
The FDA recognizes the numerous benefits associated with DCTs, including enhanced convenience for participants, reduced caregiver burden, improved trial efficiencies, expanded access to diverse populations, and facilitation of advancement on rare diseases. These trials involve conducting trial-related activities at locations other than traditional clinical trial sites, such as participants’ homes or local health care facilities. The COVID-19 pandemic has accelerated the adoption of DCTs due to disruptions in traditional clinical trial operations.
The Key Provisions of the Draft Guidance
Nine essential DCT implementation components are recommended in the proposed guidance:
1. DCT Design
The FDA advises sponsors considering non-inferiority studies in a DCT environment to speak with the agency due to potential challenges in calculating the non-inferiority margin. The guidance also emphasizes the need for a central physical location where trial-related records are accessible for inspection.
2. Remote Clinical Trial-Related Activities and Clinical Trial Visits
Telehealth appointments are deemed suitable for DCTs as long as there is no need for face-to-face interaction. Certain trial-related tasks that do not necessitate a deep understanding of the investigational product or study protocol can be carried out by local healthcare professionals who are not directly involved in the trial.
3. Use of Digital Health Technologies
DHTs facilitate the gathering of data from trial participants who are located remotely. It is crucial for investigators and sponsors to ensure that the DHTs employed in DCTs are appropriate for every participant. If the trial permits participants to utilize their personal devices, sponsors should supply the necessary DHTs.
4. Roles and Responsibilities of Investigators and Sponsors
The regulatory requirements for DCTs are the same as those for traditional site-based trials. Sponsors should coordinate and oversee decentralized activities and describe the DCT’s operating aspects in the trial protocol. Investigators may require additional training and coordination due to the use of telehealth, local healthcare professionals, and DHTs.
5. IRB Oversight and Obtaining Informed Consent
Informed consent may be obtained electronically from trial participants at remote locations. The draft guidance recommends the use of a central institutional review board (IRB) for efficient review of the protocol, informed consent, and trial-related information.
6. Investigational Products in DCTs
Whether administration can take place outside of a clinical trial site depends on the characteristics of the investigational product. If the administration procedures are complicated or if there are significant safety risks involved, it may be necessary to have in-person supervision. On the other hand, certain devices can be used at home or self-administered, as long as trial personnel provide oversight.
7. Packaging and Shipping of Investigational Products
Direct distribution of these products to participants may be possible with DCTs. Clear instructions on how to handle, store, and return any unused product components should be included in the shipment packages.
8. Safety Monitoring Plans
DCT sponsors must implement a safety monitoring plan considering the decentralized nature of the trial. Adverse events should be appropriately captured and addressed, and the plan should describe how DHTs will be used to monitor participant safety.
9. Software Used in Conducting DCTs
Training should be provided to all parties involved in using software for DCT
Conclusion
The FDA’s draft guidance on decentralized clinical trials (DCTs) is a significant step in modernizing clinical research regulation. DCTs offer advantages like convenience, improved efficiency, and broader participant access. The guidance covers trial design, remote visits, digital health technologies, roles/responsibilities, consent, safety monitoring, and more. It emphasizes proper coordination, training, and data management to ensure consistency. Digital health technologies are encouraged, with a focus on inclusivity. The FDA aims to promote innovation, efficiency, and patient-centricity through this guidance, inviting stakeholder feedback to shape the future of DCTs.
For references and further reading:
FDA. Decentralized Clinical Trials for Drugs, Biological Products, and Devices. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/decentralized-clinical-trials-drugs-biological-products-and-devices. U.S. Food and Drug Administration. 2023