The FDA Recognizes the Importance of Adopting Decentralized Trial Elements

In its Final Guidance on Decentralized Clinical Trials, the FDA provides recommendations for trial sponsors incorporating virtual elements into clinical research.

Author: Irena Lambridis, Vice President, Head of Quality Assurance & Compliance, Science 37

Recognizing the growing importance of decentralized clinical trial (DCT) elements to research sponsors seeking new efficiencies in recruiting and retaining representative participant populations, the U.S. Food and Drug Administration (FDA) released its final guidance on DCTs in September 2024.  
 

In the guidance, the FDA acknowledges that the emergence of DCTs holds far-reaching implications as new patient populations are able to participate in clinical research for the first time and how this shift can help reshape drug development and improve data quality. But to realize these benefits, careful planning and coordination need to be exercised in the lead-up to and throughout trial execution.
 

As with the previous DCT draft guidance, the FDA encourages sponsors to work with experienced vendors who can help navigate the complexities of DCTs, while enabling participant safety from adverse events and the integrity of the trial data being collected within this novel approach.
 

Areas Covered by FDA Guidance

Organized into a detailed set of recommendations across a wide range of DCT implementation topics, the FDA guidance covers:
 

• DCT Design and Conduct
• Remote Visits
• Digital Health Technologies
• Sponsor and Investigator Roles and Responsibilities
• FDA Oversight
• Informed Consent and IRB Oversight
• Safety Monitoring
• Electronic Systems Use
   

Important Benefits for Participants

The widespread adoption and proper implementation of DCT elements promises to expand trial access to a variety of traditionally underserved populations. These participant groups will:
 

• Gain greater access to trials due to reduced geographic restrictions and relief of participation burdens
• Enjoy more convenient options for remote study conduct, such as telehealth, local health care provider (HCP) visits, and in-home visits, to make participation more attractive and in turn, reduce attrition

The DCT model can reach specific patient populations, including participants in rural areas and those in medically underserved situations. Patients with rare diseases are another highlighted population that will benefit from not having to travel great distances to be study participants. In addition, the reduction of burden on caregivers reaches all participants in all therapeutic areas.
 

Important Benefits for Non-Participant Stakeholders

For clinical research sponsors and other non-participant stakeholders, the benefits of DCT implementation in accordance with FDA guidance can positively impact study participation in a variety of ways.
 

• Research sponsors have increased ability to be creative in their trial design/conduct,    providing new pathways to recruitment, retention, and study conduct efficiencies
• Research sponsors may consider the use of telehealth visits when appropriate, potentially reducing costs and enhancing participant convenience
• Local HCPs may be used for activities that they are qualified to perform (routine in their   clinical practice) without being considered trial personnel/sub-investigators, simplifying study conduct and expanding HCP opportunities to participate in clinical research
• Medical Healthcare Practitioners (MHPs) without research infrastructure will also have better opportunities to participate in clinical research
   

Roles and Responsibilities of Clinical Research Stakeholders

In terms of stakeholder impacts, the Agency’s updated guidance identifies many of the roles and responsibilities associated with DCT implementation in order to comply with FDA recommendations.
 

Research Sponsors

• Maintain ultimate responsibility for coordinating the decentralized aspects of their trials
• Establish a protocol to clearly outline how DCTs will be used in the trial
  o   Scheduled vs unscheduled visits
  o   Trial site personnel vs local HCP activities
  o   Sharing of e-data across organizations
  o   IP management
  o   Safety monitoring/planning (including how HCPs will fit into the matrix)
• Maintain a centralized Data Management Plan with data flow maps to depict data from inception/data origin to archive, including methods and technologies used
• Protect data integrity by ensuring that only secure/compliant electronic systems are used and that these systems allow real-time oversight
• Provide appropriate remote visit oversight, especially regarding the use of local MHPs
• Establish clear protocols describing how Adverse Events (AEs) will be managed in remote settings
• Make digital health technologies available to all trial participants and ensure that they are suitable for all participants
• Maintain a trial monitoring plan to ensure proper study oversight
   

Sites and Investigators

• Take measures to protect participant privacy whether the participant is in the home or at alternative locations for study assessments. Collection and sharing of data will be restricted to appropriately delegated stakeholders only
• Help ensure that participants are informed of what data is being collected and why, and establish guardrails for all information obtained during study participation
• Maintain a log of local HCPs being used to perform authorized activities (routine in their clinical practice)
• Provide clear and specific instructions to HCPs to ensure consistency and completeness and limit variability
• Provide clear oversight of any HCP being used by sites/Principal Investigators (PIs)
• Ensure that any trial-related activities unique to the research study are not delegated to HCPs, but performed by appropriately trained study personnel 
• Capture details specific to how study visits occur (e.g. where, when, by whom, and in-person, remotely, or at a brick-and-mortar site location)
• Provide mandatory PI oversight of DCT participants in a well-structured, manageable manner
• Ensure the privacy and security of all real-time video and audio interactions, which are considered a live exchange of information but not subject to 21 CFR Part 11

Not coincidentally, Science 37’s pioneering DCT approach to executing clinical research aligns uniformly with the latest FDA recommendations. This is particularly true in the areas of patient recruitment and enrollment, where properly deployed decentralized capabilities are demonstrating a remarkable ability to impact full enrollment timelines.

For research sponsors ready to take their first or next big step into the world of DCT, compliance with FDA recommendations becomes seamless when partnering with experts who not only have successfully undergone FDA inspection but also have a proven track record of excellence in executing clinical trials using this cutting-edge approach to research.