On May 2, FDA published a draft guidance on decentralized clinical trials (DCTs) to provide recommendations for sponsors, investigators and others on implementation of DCTs, as required by the Food and Drug Omnibus Reform Act (FDORA).

Background

DCTs include both fully decentralized trials – where all trial activities take place at locations other than trial sites – and hybrid trials – where some trial activities take place outside the traditional site. These alternative sites can include a primary care provider’s office, a local laboratory, or a participant’s home.

DCTs hold promise to increase enrollment in trials, particularly by people in demographics not commonly enrolled in trials. FDA recognized that DCTs have “the potential to expand access to more diverse patient populations,” such as people who don’t live near an academic medical center, or have limited mobility. It continues, “By enabling remote participation, DCTs may enhance convenience for trial participants, reduce the burden on caregivers, and facilitate research on rare diseases and diseases affecting populations with limited mobility or access to traditional trial sites. This may help improve trial participant engagement, recruitment, enrollment, and retention of a meaningfully diverse clinical population.”

Key Positions

Comparison with current regulations: FDA made clear, in the guidance, that the same regulations that govern traditional clinical trials (for drugs and devices) also govern DCTs. This includes a physical location for all records, adverse event reporting, IDE application (as necessary), relevant licensing laws, IRB oversight and more.

Reducing variability: The guidance recommends the use of a designated clinical laboratory to reduce variability in results such as blood levels and radiological scans.

Data management plan: The FDA encouraged the establishment of a data management plan (DMP). A DMP, in this context, is a way for the sponsor to account for multiple sources of data collection. DMPs should include information about the “methods used for remote data acquisition” and transmission of data. Data provenance is also mentioned. Later, the guidance recommends quality control measures to reduce variability of data.[1]

Routine care and trial participation: A remaining concern regarding the difference between local health care providers involvement in DCTs and routine care is partially addressed in this guidance. The FDA states that providers who are doing routine care do not need to be listed on the FDA forms as part of the trial;[2] however, this does not address any billing questions regarding these services.

Informed consent and IRBs: Like centralized clinical trials, informed consent and IRB oversight is a requirement of DCTs.  The guidance recognizes that informed consent may be obtained remotely. DCT informed consent should include, in addition to the elements required for traditional clinical trials, information about who will have access to personal health information. FDA recommends the use of a central IRB.

Safety and other considerations: FDA also considers what types of products are well-suited for DCTs, particularly where the investigational product is being remotely administered. The guidance recommends that when the safety profile of the investigational product is well-established and there is little risk of immediate adverse events, remote administration of the product may be acceptable. Some products will be well-suited for self-administration, particularly those who not only meet the above characteristics but also are shelf-stable under normal storage conditions. Packaging and distribution of these products is addressed in the guidance.

Safety monitoring: As with all trials, a safety monitoring plan is required. DCTs have an additional layer of complexity around monitoring safety, which must be addressed in the plan.

Software and DCT: Software and digital health tools used in DCTs are addressed in this guidance. The guidance recommends that sponsors consider a number of factors when selecting these tools, including ensuring that the technologies are suitable for use by all trial participants, that the tools are valid, and meet the recommendations in previous guidances. FDA considers the use of electronic records in DCTs, but allows for remote providers to upload forms or documents securely, rather than directly entering data into the case report forms.

Telehealth: FDA notes that live video or audio interactions are not part of the electronic record and not subject to FDA regulations around electronic records for trials. Privacy and security of these interactions must be protected, and local telehealth laws apply. If these interactions are captured for the record, they must comply with Part 11 requirements.

Takeaways

While this is non-binding guidance, entities involved in DCTs or support of DCTs should review this guidance as it provides direction by the FDA in addressing issues raised by DCT.  Among the more interesting issues is the position regarding data management plans and consideration for products that may be conducive to DCTs. 

FDA is accepting comments on this draft guidance for 90 days after publication in the federal register on May 3.

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[1] The type and scope of quality control measures should be tailored to the criticality of the data and the complexity of procedures done by the local HCPs.

[2] Local HCPs contracted to provide trial-related services that are part of routine clinical practice (e.g., performing physical examinations, reading radiographs, obtaining vital signs) and where a detailed knowledge of the protocol, IP, and the investigator’s brochure is not necessary should not be listed on Form FDA 1572 as subinvestigators. However, local HCPs should be included in a task log (as described below in this section).

[*] IP, and the investigator’s brochure is not necessary should not be listed on Form FDA 1572 as subinvestigators. However, local HCPs should be included in a task log (as described below in this section).