Guidance Breakdown: Our Top 10 Takeaways from the FDA's Guidance on Conducting Decentralized Trials
The FDA’s final guidance on DCTs adds clarity on HCP task log, inspection requirements, and data variability. We break it down.
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In Septemeber, the FDA issued final guidance on decentralized clinical trials (DCTs), addressing some key issues from the draft guidance raised by clinical experts and industry groups, including providing more information on requirements to keep a task log of HCPs, physical inspection requirements, and clarifying challenges around data variability in DCTs.
The agency defines DCTs as occurring at non-traditional clinical trial locations, such as a participant’s home or in a local healthcare facility. These local providers and clinical laboratory facilities may be used in a trial with decentralized elements to manage trial participants, and use digital health technologies and telehealth to obtain data. The FDA noted that trials with decentralized are subject to the same regulatory requirements as those with non-decentralized elements.
The final guidance provides recommendations for using decentralized components in clinical trials such as:
Use of decentralized health technologies and software
Roles and responsibilities for sponsors and investigators
Using local HCPs as well as remote clinical trial visits
Trial design, conduct, and oversight
The final guidance also outlines informed consent and institutional review board oversight, what investigational products can use a DCT, how to package and ship investigational products, and patient safety processes and procedures.
At the Drug Information Association Global Annual Meeting in 2023, clinical trial experts were supportive of the draft guidance overall, but raised issues with the reporting requirements outlined in the guidance. They noted a lack of clarity in the reporting requirements could create uncertainty, and cited Form FDA 1572 as a potential problem for decentralized trials when determining what research locations would need to be stated on the form.
In comments responding to the draft guidance, industry groups were also largely positive, but stakeholders asked for a broader definition of DCTs, wanted more clarification on how DCTs appeared to be held to a higher standard in the draft guidance than for centralized trials and made requests to FDA for more virtual inspections in DCTs.
Changes from the draft guidance
The final FDA guidance incorporates significant changes from the draft version. Extensive rewriting and editorial revisions have been made to enhance clarity throughout the document. Notably, the FDA has removed all mentions of a requirement to create and maintain a local task log of HCPs contracted for routine clinical services.
The guidance now provides more specific examples addressing data variability challenges in DCTs. It emphasizes the need to limit variability in activities performed by HCPs, trial personnel, and participants. For instance, the FDA recommends considering training and video supervision for participant-performed activities like home spirometry tests.
The guidance also advises specifying which activities can be conducted remotely, at trial sites, or based on participant preference.
Regarding sponsor responsibilities, the FDA has clarified the use of local HCP networks for contracted services. Sponsors are now explicitly required to ensure these networks are qualified to perform contracted activities and to maintain records of all contracted service providers, including their roles and assigned tasks.
The final guidance also provides more detail on FDA inspections for DCTs. It specifies the need for a physical location where FDA inspectors can access trial records, either in paper form or electronically, for participants under the clinical investigator's care. This location is typically the address listed on Form FDA 1572 for investigational new drugs or in the investigational device exemption application, though alternative locations can be designated.
The guidance also emphasizes the need to facilitate remote or in-person interviews with trial personnel during inspections.
Here are our top 10 takeaways from the final guidance more broadly.
1. Decentralized elements must be carefully coordinated by sponsors
Sponsors must track and record the roles of all involved entities and ensure the integrity of decentralized elements.
The FDA clearly expects sponsors to be responsible for managing all decentralized aspects of the trial, including activities such as shipping investigational products (IPs) and coordinating local HCPs.
Sponsors must ensure that local HCPs are qualified to perform delegated tasks and that data collection from decentralized sites adheres to the protocol.
Specific coordination efforts should include networks of HCPs, laboratory facilities, and mobile research units to support decentralized operations.
2. Protocols must address variability in data collection
Clear guidelines and training must be established to ensure consistent data quality across remote and traditional settings.
The design and conduct of decentralized trials need to minimize variability in data collection. For example, if participants conduct tests like spirometry at home, the results may vary compared to those obtained at traditional clinical trial sites.
To reduce variability, protocols should include specific instructions for participants and trial personnel on how to perform decentralized assessments and provide training or video supervision when needed.
3. Sponsors must manage investigational product distribution and HCP networks
The guidance specifies that investigational product distribution must be tracked, and records of the receipt and disposal of products must be maintained.
Sponsors must supervise the shipping, handling, and accountability of investigational products (IPs). This includes direct shipments to trial participants or local HCPs. Sponsors must ensure IP integrity during shipping, especially for products that require temperature control or other special handling conditions. Additionally, sponsors must work with networks of local HCPs who are qualified to perform tasks like administering IPs or conducting assessments.
4. Data management plans must be comprehensive
The guidance stresses the importance of detailing the entire data flow, from collection to final storage, and ensuring data security.
Sponsors are required to implement a comprehensive data management plan. This plan must document the origin, flow, and handling of data collected from all sources in a decentralized trial. The plan should include how data is transmitted from local HCPs, clinical laboratory facilities, and trial personnel to the sponsor. A key element is creating secure and validated methods for data acquisition and storage.
5. Informed consent can be obtained remotely,but must meet all regulatory standards
Remote informed consent must provide participants with clear information on trial activities, HCP involvement, and how their data will be used.
The guidance allows informed consent to be obtained remotely, either electronically or via paper. The process must meet FDA’s regulatory requirements, ensuring participants understand the trial and its risks.
In decentralized settings, the person obtaining consent must have detailed knowledge of the protocol and be capable of answering participant questions. To ensure consistent review of protocols and consent documents, a central Institutional Review Board (IRB) for decentralized trials is recommended.
6. Decentralized trials require tailored safety monitoring plans
The plan must account for the decentralized elements, detailing how safety data will be collected, reviewed, and acted upon.
Safety monitoring plans must be adapted to the decentralized nature of the trial.
The plan should describe how adverse events and medication errors will be reported, whether they are identified remotely or during in-person visits.
Remote safety monitoring may include digital health technologies, and the protocol must specify how data from these technologies will be monitored and addressed.
The guidance stresses that trial participants must know how to report adverse events and where to seek care in case of emergencies.
7. Investigators remain responsible for participant safety and oversight
Delegation of tasks does not relieve the investigator of their responsibilities; regular data review and participant follow-up are required.
Even in decentralized trials where certain activities are delegated to local HCPs or remote personnel, investigators are still responsible for protecting participant safety and ensuring trial activities are conducted per the protocol.
This includes reviewing data from HCPs and remote personnel to identify any discrepancies or missing information. The investigator must confirm that participants have received the investigational product (IP) and that assessments are being performed correctly.
8. Packaging and shipping of investigational products must maintain integrity
Detailed documentation of IP handling, shipping, and receipt is critical for maintaining trial integrity.
The guidance specifies that investigational products must be shipped with packaging that ensures their integrity. This is especially important for products requiring specific storage conditions, such as temperature-controlled environments.
Sponsors must ensure that shipping containers include clear instructions for participants or local HCPs on handling, storing, and returning unused IPs. Investigators must authorize shipments and track receipt and usage of the IPs.
9. Digital health technologies must Be accessible and secure
The guidance emphasizes providing DHTs to participants who lack access and ensuring data is securely collected and transmitted.
Digital health technologies are often used to collect data remotely in decentralized trials.
Sponsors must ensure that these technologies are validated for their intended use and accessible to all participants, regardless of socioeconomic status. For participants without access to the required technology, sponsors should provide the necessary devices and telecommunication services. Additionally, DHTs must be secure and comply with FDA regulations on data privacy.
10. FDA oversight includes remote regulatory assessments and inspections
The guidance makes clear that all records related to decentralized activities must be accessible for FDA inspection, whether remotely or on-site.
The FDA may conduct remote regulatory assessments and inspections for decentralized trials.
Sponsors and investigators must ensure that trial records are accessible and that trial personnel are available for interviews, either in person or remotely. For decentralized trials, the physical location for inspections may include the investigator’s home office, a local clinic, or other relevant sites.
Our recommendations
Develop a comprehensive data flow diagram. Create a data flow diagram and include it in the data management plan or other trial-related documents. It should visually depict the flow of data from all sources (e.g., participants, local HCPs, DHTs) to the sponsor. This should include methods and technologies used for remote data acquisition.
Implement a "visit type" tracking system. Make sure your study records capture the visit type (telehealth or in-person), location, date, and data originator for all trial-related interactions. Update your electronic case report forms (eCRFs) or other data collection tools to include fields for recording this information.