FDA Issues Final Guidance on DCTs and Decentralized Elements

Improving the strength and generalizability of evidence from decentralized clinical trials

Decentralized clinical trials (DCTs) have the potential to increase access to more representative patient populations and improve the efficiency of clinical trials. Towards this end, in September, the Food and Drug Administration issued a final guidance, "Conducting Clinical Trials With Decentralized Elements," providing recommendations for sponsors, investigators, and other interested parties regarding the implementation of decentralized elements in DCTs. 

This final guidance fulfills section 3606(a)(2) of the Consolidated Appropriations Act, 2023, directing FDA "to issue a final guidance that includes recommendations to clarify and advance the use of DCTs to support the development of drugs and devices." 

Integrating decentralized elements in clinical trials

Unlike traditional clinical trials, DCTs use decentralized elements like digital health technologies (DHTs), local healthcare office visits, direct shipping of investigational products to participants, etc. Because all or some of the elements of DCTs occur at locations convenient for trial participants and enable remote participation, they may, for example, facilitate research in rural or rare disease populations not usually included in clinical research, thus improving "the strength and generalizability of the evidence produced by the trial," according to the final guidance.

Challenges include coordinating trial activities with facilities and individuals at multiple locations, designing and implementing a feasible DCT, and establishing risk assessment and management strategies. 

The final guidance provides recommendations for establishing DCT design, conduct, and oversight; using local healthcare providers as well as remote clinical trial visits; implementing decentralized DHTs and software; and delineating the roles and responsibilities of sponsors and investigators.

Remote visits

The guidance highlights the important role of remote trial visits through means such as telehealth, home in-person visits, and local health care provider visits. Noted considerations in conducting these remote trial activities include protecting patient privacy, ensuring consistency in trial-related activities performed by local health care professionals, ensuring appropriate training of qualified staff for crucial research activities, documenting the manner in which data is collected, thorough consideration of adverse events monitoring in a remote setting, and ensuring adherence to applicable laws in telehealth data collection.

Digital health technologies

The new guidance builds on previous FDA guidance on using DHTs with a discussion of suitability of digital technologies for all participants and the ability of participants to use a bring-your-own device model of data collection. The guidance indicates that sponsors should make DHT and telecommunication options available to participants who would be excluded in the absence of sponsor-provided DHTs.

Roles and responsibilities 

The guidance reiterates that the study sponsor has the same responsibility for DCTs as for traditional site-based trials. It further emphasizes the need for proper oversight and coordination of DCT elements in data management plans, trial protocols, and other trial-related documents.

Informed consent and IRB Oversight

While informed consent may be obtained from participants in their remote location, the process is subject to all regulatory requirements and investigators maintain responsibility of obtaining informed consent, or delegating the responsibility to an appropriately trained individual. Accordingly, trials must meet 21 CFR part 50 and participants must have a designated contact for study questions. The guidance recommends using a central institutional review board (IRB) for DCTs following previously released guidance.

Investigational products

The guidance indicates that, whether evaluating drugs and biological products or medical devices, the study sponsor should thoroughly evaluate whether a DCT is appropriate given the risks and safety, indication or intended use, and instructions for use, providing detail on considerations and regulations that must be followed when making decisions. 

Packaging and shipping

The handling, packaging, shipping, and tracking of investigational products is the responsibility of the study investigator and requires detailed protocols, procedures, and documentation. In addition, investigators should consider the containers used for shipping, including provision of clear instructions, the physical integrity and stability of the investigational product during shipping, and ensuring that unused product is returned to the sponsor for disposal.

Safety monitoring

The guidance offers direction on developing safety monitoring plans that are designed for a DCT, including providing information on communicating adverse events, seeking medical assistance, the role of health care providers (HCPs) in performing trial-related activities, and the data collected and the manner of collection. Additionally, the guidance indicates that when unreasonable or significant safety risks emerge due to remote administration of the investigational product, the sponsor must discontinue the elements of the trial presenting the risk and notify all regulatory, oversight bodies, and investigators. 

Electronic systems

The guidance highlights the importance of electronic systems in managing DCT operations, emphasizing the need for appropriate systems training, the ability of HCPs to submit trial-data, requirements for HCPs to be listed as authorized data originators, and requirements and exemptions from 21 CFR part 11.

Addressing stakeholder concerns

The new guidance also addresses key concerns that stakeholders raised about the prior FDA draft guidance on DCTs from May 2023.

• Data variability: To ensure consistency and completeness of the data, DCTs should include specific instructions in the protocol for performing data collection activities, and investigators should review data provided by local HCPs. Also, DCT participants performing tests independently at home (e.g., spirometry) should undergo training or video supervision (e.g., telehealth visit) to reduce potential data variability. 
• Local healthcare providers qualification: If a DCT uses contracted services, sponsors should ensure that networks of local HCPs are qualified to perform their duties and should keep a record of their roles and assigned activities.
• Physical location for inspections: FDA suggests establishing a "physical location where a responsible person is available to facilitate the FDA inspectors' access to trial-related records (either paper or electronic access) for participants under the clinical investigator's care and to facilitate interviews with trial personnel (either in person or remotely)."