Decentralized Clinical Trials — A Round-Up of Public Comments on FDA Draft Guidance

Ever since the FDA issued draft guidance in May regarding decentralized clinical trials (DCT), the public has been submitting their comments and feedback, as well as requesting clarity on certain points. Commenters range from individuals to sponsors, research institutions, and professional organizations, to patient advocacy groups. Commenters include Mayo Clinic, Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard, ACRP, and the Society for Clinical Research Sites.

The concerns and requests for clarity are diverse. Some commenters questioned the binary distinction between fully conventional and fully decentralized clinical trials. They suggested that decentralizing tools can be implemented even in conventional clinical trials, thus creating a type of hybrid trial design.

Several institutions and professional organizations challenged the FDA’s assertion that “the variability and precision of the data obtained in a DCT may differ from the data in a traditional, site-based clinical trial.” They asserted that there is no empirical data or evidence that supports such a statement.

Here are a few other highlights.

Maintenance and storage of documents

The draft guidance states, “For inspectional purposes, there should be a physical location where all clinical trial-related records for participants under the investigator’s care are accessible and where trial personnel can be interviewed.”

Several commenters requested that the FDA acknowledge cloud-based solutions where clinical trial documentation can be stored. Reflecting on the digital nature of decentralized trials, one group suggested that inspectors should be able to access such records remotely, thus removing the need for a personal visit to any physical location.

They also suggested the use of videoconferencing technologies that inspectors could use to interview remote clinical trial staff.

That said, another commenter expressed concerns about the challenge for investigators to navigate multiple software platforms to manage e-consents, case reports, IRB approvals and other documentation.

The Use of Patients’ Own Digital Health Devices (BYOD)

Decentralized clinical trials often rely on digital health devices, such as fitness trackers or monitors. In some cases, patients may want to use their own devices, a scenario called BYOD — Bring Your Own Device. In large trials, the use of BYOD may be necessary. The ease of participants utilizing their own devices maybe needed for long-term collection and engagement.

The draft guidance did not address BYOD specifically and some commenters have requested they do so.

Considerations include the criteria for using BYOD, the comparability of data between BYOD and devices that are provided by the sponsor, as well as the need for investigators and research staff to be trained to use a variety of devices.

Roles and Responsibilities

Clinical trials require the filing of FDA’s Form 1572 Statement of Investigator, which requests the names and qualifications of the principal investigator (PI) and sub-investigators. Several commenters requested clarity regarding who should be listed and how PIs should oversee remote health care providers.

SCRS referred to a 2022 Site Landscape Survey, in which overwhelmingly the site’s answer to the question “what have you experienced to be the biggest challenges for your site in participating in decentralized trials” was “oversight of remote vendors that would interact with the patient, record source data”. ASCO fears that “much of the language in the guidance could add burdens to local facilities and health care providers (HCPs), overstate the risks of data collected through decentralized means, and, in fact, discourage involvement in decentralized research studies.”

In a decentralized clinical trial, community health care providers may be reporting adverse events or collecting and documenting data, but they may or may not be considered sub-investigators.

The draft guidance states, “The decision to include individuals as sub-investigators in a DCT should be based on their assigned responsibilities.” This includes local health care providers (HCPs) that are contracted to provide trial-related services that may be part of routine clinical practice (e.g., performing physical examinations, reading radiographs, or obtaining vital signs).

Some institutions have requested clarified thresholds for staff that may need to be included in Form 1572. One commenter suggested a clearer distinction between trial personnel and “Local HCPs” performing non-interventional activities.

The Patient’s Voice

Several commenters suggested that the draft guidance lacked adequate recognition of need of sponsors to design DCT protocols and recruitment plans with the patient perspective in mind.

Overall, commenters welcomed the FDA’s attention to DCTs and recognized the opportunity to expand access to clinical trials by patients who live in underserved areas. They generally applauded the FDA for supporting the use of DCTs to reflect the needs of patients enrolled in trials and for leveraging lessons learned during the COVID-19 pandemic.

Comments are now closed, and the FDA will consider them before issuing final guidance.