FDA’s New Clinical Trial Guidance Allows you to Streamline!

On May 2, 2023, FDA published a draft guidance for Decentralized Clinical Trials for Drugs, Biological Products, and Devices – Guidance for Industry, Investigators and Other StakeHolders.

In this draft guidance, the FDA states that “regulatory requirements for investigations of medical products are the same for DCTs and traditional site-based clinical trials”, however provides recommendations for the use of DCTs to support drug and device development, but these recommendations are not legally enforceable.

The FDA recommendations for the implementation of DCTs for both hybrid and fully decentralized trials as appropriate for different trial activities, some of which are already in implementation such as Laboratory Facilities or Digital Health Technologies (DHT), and for different Investigational Products (IP) based on the safety profile and risk of the IP and study.

These DCT recommendations refer to:

1. DCT design, advising on the variability and precision of the data which may differ than the traditional trials, challenging the non-inferiority margin calculation
2. Remote trial visits, which should consider and be clearly specified in the protocol:
   • Telehealth visits,
   • In-Person visits at home or preferred locations,
   • Who will conduct the visits, HCPs, MDs, RNs, Investigators who should have detailed knowledge of the protocol and IP,
   • Confirmation of the participant’s identity,
   • How data and other documents are completed and collected,
   • How the adverse events are identified remotely.
3. Digital Health Technologies, which points to the earlier FDA draft guidance Digital Health Technologies for Remote Data Acquisition in Clinical Investigations. Other considerations should be the availability and suitability of DHT for all trial participants.
4. Roles and Responsibilities, which are defined separately for Sponsors and Investigators.
   • Sponsor considerations:
     • Proper coordination of contracted services for those conducted decentralized
     • Diversity and inclusiveness by proper outreach to local health care facilities, to reduce participant travel and improved engagement, recruitment and retention.
     • Accounting for multiple sources of data collection which should be detailed in the Data Management Plan (DMP), and to identify where the data came from
     • IP delivery process and accountability
     • Safety monitoring and management of adverse events
   • Investigator considerations:
     • The extent of use of telehealth, trial personnel working remotely, local HCPs
     • Technologies used for videoconferencing and others to oversee the personnel activities at participant locations
     • Enrollment should be done as appropriately able to oversee and manage remotely with adequate supervision

All facilities and local HCPs are expected to be listed on 1572 for drugs trials or on the task log for device trials.

DEVICE Investigators are expected to have a signed agreement with the Sponsors, and the local HCPs involved in the trial should be kept on a task log, with the assigned tasks, dates and locations, and signed by the Investigator. This list will be required to be included in the FDA submissions for clearance or approval.

5. Informed Consent and IRB, for DCT an eConsent is allowed to be obtained at the remote location and a central IRB is recommended to efficiently expedite protocol review and relevant information.
6. IP for Medical Devices,
   • Device suited for home use and does not pose risks to participants may be adequate for use without direct Investigator Oversight.
   • Device not intended for self-use or with significant risks should be used/administered by qualified personnel.
7. Packaging and Distribution for DCT should be described clearly in the protocol, including stability of the IP during shipment, documentation of handling, shipping and tracking , should be done preferably form a central location, as well as return or disposition.
8. Safety Monitoring Plan, should defined how the adverse events are captured remotely and address appropriately and if telehealth or in-person visits are used and when, who schedules them as well as how unscheduled visits are done.
9. Software Used in conducting DCTs, states that Sponsors have support of multiple platforms such as: eConsent, capturing and storing monitoring reports, managing data eCRFs, scheduling visits and tracking IP. However, appropriate training to all involved parties is required on all software used. All DCT software used is subject to 21 CFR Part 11.

For more details, please see FDA draft guidance https://www.fda.gov/media/167696/download