FDA Issues Draft Guidance on Decentralized Clinical Trials
This week the U.S. Food and Drug Administration released a new draft guidance that provides recommendations for sponsors, investigators and other stakeholders regarding decentralized clinical trials (DCTs) to advance medical research.
FDA Commissioner Robert M. Califf, M.D., acknowledged that the benefits of decentralized clinical trials, which were accelerated with advancements in digital health technologies and the COVID-19 pandemic-when in-person visits were limited or unavailable for many trial participants.
Decentralized clinical trials can enhance convenience for trial participants, reduce the burden on caregivers, expand access to more diverse populations, improve trial efficiencies, and facilitate research on rare diseases and diseases affecting populations with limited mobility, Dr. Califf adds.
The new draft guidance, which builds on guidance from 2020, covers recommendations on:
- design considerations for a DCT;
- conduct of remote clinical trial visits and clinical trial-related activities in a DCT;
- use of digital health technologies to remotely acquire data in a DCT;
- roles and responsibilities of the sponsor and investigators in a DCT;
- obtaining informed consent (IC) and institutional review board oversight of the IC process in a DCT;
- determination of the appropriateness of investigational products for use in a DCT;
- packaging and shipping of investigational products in a DCT;
- safety monitoring of trial participants in a DCT; and
- software used to support DCTs.
Here are a few of our key takeaways.
Record-keeping and documentation should still be centralized
In a DCT, some or all trial-related activities will occur at locations other than traditional clinical trial sites. This can include a participant’s home or a nursing home. However, all clinical trial documentation and records should be kept in a physical location for inspection purposes.
Protocols Should Specify Remote and In-Person Activities
Remote clinical trial visits and clinical trial-related activities are important strategies to make trials more convenient and more accessible to trial participants. Investigators can leverage telehealth technologies to reduce in-person visits when appropriate. Sponsors and investigators must ensure adherence with telehealth laws when protocols include telehealth visits.
Alternatively, clinical research staff, or health care providers (HCPs) who are not part of the research team, but are located to close to participants’ homes can perform certain trial-related activities at their local offices or HCPs can be deployed to participants’ homes. In general, local HCPs should perform trial-related activities that are similar to the services they are qualified to perform in their clinical practice. Trained and qualified research staff should conduct activities that require detailed knowledge of the protocol. If local HCPs are used, it is important to include their trial-related activities and service fees in the clinical trial budget.
The protocol should specify how adverse events will be evaluated and managed in the DCT model
Variability and precision of data
A critical consideration in a DCT, when delegating trial-related activities to local HCPs, is the potential for variability in the data collected as compared to a site-based clinical trial. Data variability can affect the validity of findings of non-inferiority trials. FDA should be contacted when considering a decentralized model of non-inferiority trials. In addition to training, quality control measures should be in place to help reduce variability.
Roles and Responsibilities of Sponsors and Investigators Remain Largely the Same, with Some Important Differences
Investigators are responsible for the conduct of the DCT and the oversight of individuals delegated to perform trial-related activities, including ensuring that these delegated activities and/or tasks are conducted according to the investigational plan, applicable regulations, and relevant laws.
A key difference between DCTs and traditional site-based clinical trials is the extent to which the investigator uses telehealth, trial personnel working remotely, local health care providers, and/or digital health technologies in the conduct of the trial. Whether the trial can be conducted entirely using remote visits or a hybrid trial design is appropriate depends on the types of assessments and procedures needed to collect endpoints and monitor safety.
Consider Additional Training for Research and Non-Research Staff
The decentralized features of the trial may necessitate additional training, coordination, and standard operating procedures to ensure consistent implementation.
A critical consideration in a DCT when delegating trial-related activities to local HCPs is the potential for variability in the approach across different practices (e.g., documenting vital signs, physical examinations, and evaluation of adverse events). In addition to training, quality control measures should be in place to help reduce variability.
Additional Documentation May be Necessary
As part of preparing and maintaining adequate case histories, investigators must maintain a task log of local HCPs who perform trial-related activities. The task log should include:
- Names and affiliations of the local HCPs,
- Description of their roles and assigned tasks,
- The dates these local HCPs are added to the log, and
- The locations where these activities are conducted.
The task log should be dated and signed by the investigator when initially created and updated when new local HCPs are added. The task log should be available to FDA during inspections.
IRB and Informed Consent
Institutional review board (IRB) oversight is required to ensure the process of obtaining a remote informed consent is adequate and appropriate.
With a DCT, the informed consent process must include notifying participants of whom to contact for answers to pertinent questions about the research and research participants’ rights and whom to contact in the event of a research-related injury to the participant.
The informed consent should describe who will have access to the trial participant’s personal health information obtained during the DCT, including any health care providers or laboratories not directly part of the research team or site.
The FDA recommends the use of a central IRB in DCTs to facilitate efficient review of the protocol, the informed consent documents, and other relevant trial-related information.
FDA’s regulatory requirements for investigations of medical products are the same for DCTs and traditional site-based clinical trials. The latest draft guidance provides recommendations to clarify and advance the use of decentralized clinical studies. DCTs may add a level convenience to trial participation that opens clinical trials to more diverse clinical populations and leads to improved enrollment, engagement and retention of participants. Essential to the success of DCTs is the decentralization plan which will include, as appropriate, the use HCPs, and local laboratories, home visits, and distribution of the investigation product. FDA should be contacted to review specific issues pertaining to the implementation of decentralized clinical trials.
