Key Takeaways:

1. Decentralized clinical trials (DCTs) are recommended for promoting diversity and inclusion, which can be achieved by conducting trial-related activities at participants’ homes and using local healthcare providers.
2. The Food and Drug Administration (FDA) supports utilizing non-trial personnel and facilities, such as local health care providers and clinical laboratories, to perform routine clinical tasks that are part of the trial protocol.
3. Telehealth can be used for monitoring trial personnel and conducting remote trial visits and remote consents processes can be used for recruitment.

On May 2nd, the FDA published draft guidance regarding the use of DCTs to support the development of drugs, biological products and devices. In contrast to traditional site-based clinical trials, DCTs are characterized by their reliance on telehealth, digital health technologies (DHTs), local healthcare providers and other innovations to perform trial-related procedures remotely. DCTs are considered a valuable mechanism in the effort to promote diversity and increase access to clinical trial participation. Guidance on how to implement DCTs within the confines of regulations centered on site-based trials has been lacking.

In this guidance, the FDA makes novel recommendations for DCTs to provide clarity on compliant implementation, including the following highlights:

• Telehealth
  • Investigators may use videoconferencing to monitor trial personnel as they perform trial activities at participants’ locations. Such monitoring is not required for routine activities.
  • Investigators should verify the identity of a trial participant when conducting a remote trial visit.
• Diversity and Inclusion
  • Sponsors should strive to recruit diverse cohorts of trial participants. Performing trial-related activities at participants’ homes and using local pharmacies, clinics and other community healthcare providers may increase recruitment and retention of diverse participants.
  • In trials where participants may use their personal DHTs, sponsors should provide DHTs to any participant who cannot afford them.
• Use of Third-Party Healthcare Providers for Remote Clinical Trial Activities
  • Certain trial-related activities may be conducted by local healthcare providers who are not trial personnel but are more accessible to participants. The activities should be commensurate with their clinical qualifications, and they should not require detailed knowledge of the trial protocol or the investigational product being studied.
• Form FDA 1572 and IDE Applications; Task Logs
  • The physical location where study records are maintained and trial personnel may be interviewed must be identified on Form FDA 1572 or the IDE application.
  • Form FDA 1572 must be completed by all investigators.
  • Local healthcare providers who provide trial-related services that are routine clinical practice only do not need to be listed on Form FDA 1572. The local providers should be included in the task log along with additional specified information.
• Task Log of Local Healthcare Providers
  • Investigators must maintain a task log of local healthcare providers who perform trial-related activities. The task log should include (1) the providers’ names and affiliations, (2) descriptions of their assigned roles and tasks, (3) the dates they were added to the log and (4) the locations where they performed trial-related activities. The log should be signed and dated by the investigator when initially created.
• Use of Local Clinical Laboratory Facilities
  • When a trial requires the use of clinical laboratory facilities to conduct routine, standardized tests, local clinical laboratories may be used. Otherwise, designated clinical laboratories are preferred to minimize variability.
• Safety Monitoring Plans
  • Sponsors should implement a plan to monitor the safety of DCT participants. This plan should prespecify whether safety data will be collected by trial personnel or local healthcare providers in person or remotely, and it should describe how participants are expected to respond to and report adverse events.
• Data Management Plans
  • For DCTs involving remote data collection sources, sponsors should create a data management plan (DMP). The DMP should detail the origins of the remote data, the methods by which the data are obtained, and a list of all vendors used to collect, handle and manage the data.
• Applicability of 21 CFR Part 11
  • Software programs that produce and process trial records must satisfy the requirements of 21 CFR Part 11. However, telehealth visits and other real-time video interactions are not subject to 21 CFR Part 11 because they are live interactions – not electronic records.
• Data Variability and Precision in Non-Inferiority Clinical Trials
  • Using DCT models for non-inferiority trials may affect the validity of trial findings. DCTs often involve procedures that increase variability and diminish precision (e.g., trial participants performing at-home tests), which may in turn impede comparisons between the experimental drug and the active control drug.

For additional information, see the FDA’s press release. The comment period for this draft guidance ends on Aug. 1.