FDA finalizes decentralized clinical trial guidance

Applied Clinical Trials Online

The FDA’s guidance is part of a broader effort to modernize clinical trials, improve efficiency, reduce participant burden, and expand access, particularly for underrepresented populations and those in geographically or economically constrained areas.

Decentralized clinical trials (DCTs) are clinical trials in which some or all trial-related activities occur at locations other than traditional clinical trial sites, such as via telemedicine or in a clinical trial participant’s home. DCTs differ from traditional site-based clinical trials in the extent in which the investigator uses telehealth, the trial personnel work remotely, the local health care personnel and professionals (HCPs) are engaged to conduct aspects of the clinical trial, and/or the investigator uses digital health technologies in the conduct of the trial.

DCTs have the ability to reach patient populations that are not able to participate in trials at brick-and-mortar sites due to geographical or economic constraints. DCTs have the unique potential to increase enrollment in rare disease clinical trials. This expanded participation also creates an avenue to increase diversity in clinical trials and allow trials to run more efficiently.

Final Guidance

In September 2024, FDA issued its final DCT guidance titled Conducting Clinical Trials with Decentralized Elements. Interestingly, the title changed from the previous draft guidance titled Decentralized Clinical Trials for Drugs, Biological Products, and Devices issued in May 2023.

The title change illustrates that FDA is moving away from separately classifying trials as either DCTs or hybrid DCTs, but rather focusing on the elements of decentralization, such as telehealth visits, visits with local HCPs, or in-home visits with remote trial personnel.

What’s New?

Overall, the final guidance essentially mirrors the draft guidance; however, each section of the guidance has been revised and adjusted to create a slightly more nuanced scope.

Local HCPs

The final guidance removes the discussion on “task logs” and clarifies the scope of various trial personnel roles. The draft guidance initially introduced the consent of “task logs” and provided significant detail on their use.

Local HCPs were to be accounted for in such “task logs,” reflecting a difference between trial personnel and sub-investigators. The final guidance removes the “task log” requirement entirely and instead emphasizes the scope of the roles, stating that local HCPs, when conducting trial activities, are not considered trial personnel and are not considered sub-investigators in a trial if they are operating within their regular scope of practice and conducting activities that do not “require a detailed knowledge of the protocol, investigator’s brochure, or IP [investigational product].”

Instead of requiring a “task log,” the final guidance states that it is the investigator’s responsibility to maintain proper records. Moreover, obtaining informed consent is expressly labeled as a task that a local HCP cannot perform.

The administration of an investigational product to participants must also be performed under the supervision of the investigator or sub-investigator, unless the investigational product has a well-characterized safety profile for which administration is not complex. These products may be administered by local HCPs or remote trial personnel. Whether an investigational product can be dispensed remotely or by a local HCP should be carefully evaluated in accordance with the guidance and the product’s safety profile.

Electronic Systems

The draft guidance initially referred to “software used in conducting DCTs.” The final guidance, however, specifically states that FDA expects electronic systems as outlined under 21 C.F.R. Part 11. FDA is expected to release new final guidance soon.

Fully Decentralized Trials

The final guidance reiterates that fully decentralized trials, in which all activities are decentralized, may be appropriate for investigational products with “well-characterized safety profiles” and those that do not require “complex preparation, administration, or medical assessment.”

DCT Design

The final guidance emphasizes the importance that trial-related activities performed by local HCPs or other trial personnel should “be designed to limit variability in the data collected by including, as applicable, specific instructions in the protocol for performing those activities.” FDA suggested, for example, that training or video supervision could mitigate the risk of data variability compared to self-administered tests.

FDA notes that the protocol should specify which elements are decentralized and that study records should indicate if a visit was conducted via telehealth, including date and name of person conducting the visit. When conducting visits via telehealth, the final guidance notes that sponsors should consider both the investigational product and trial population to determine whether such visits are appropriate.

The sponsor should also consider patient privacy e.g., shared residences that could impact timing of visits. FDA revised the Digital Health Technologies section to address study subjects who may not have access to any protocol-specified digital health technology.

The final guidance states that participants who do not own the protocol-specified digital health technology should not be excluded for that reason and that “sponsor-provided telecommunication services should also be made available.” In addition, the safety monitoring plan should indicate where participants can go for help and receive care and account for the complexities of any decentralized elements.

Sponsor Responsibilities

Sponsor core responsibilities remain the same for DCTs as traditional, brick-and-mortar clinical trials, such as maintaining compliant shipping and administration of investigational products and monitoring the trial, including appropriate safety monitoring. When sponsoring a DCT, however, sponsors are also expected to ensure proper coordination of decentralized activities and account for data from a variety of inputs.

The final guidance also adds new sponsor responsibilities and expressly requires that sponsors maintain records of the networks and other contracted services providers, including their roles and assigned activities.

Investigator Responsibilities

The final guidance requires that study records capture information regarding the visit type (location, date, data originator). FDA clarified that investigators are responsible for reviewing data from local HCPs and other trial personnel to ensure quality and consistency in the data and trial activities.

Investigators must also identify a physical location where a responsible person is available to facility an FDA inspectors’ access to trial-related records.

Laboratory Tests

Some trial protocols will include designated clinical laboratory facilities to perform protocol activities (e.g., phlebotomy or x-rays). Other protocols may permit the use of a variety of clinical laboratory facilities close to the trial participant.

The final guidance notes that use of a local clinical laboratory facility is generally appropriate for routine clinical tests that are well standardized; however, designated clinical laboratory facilities should be used for tests that are specialized or specific to the trial. If appropriate, specimens from participants may be collected by remote trial personnel, local HCPs, local clinical laboratory facilities, or participants using home collection kits and sent to designated clinical laboratory facilities for processing.

Importantly, the final guidance specifies that investigators must maintain a record of all laboratories used or added.

What’s Next?

This final guidance reflects FDA’s effort to modernize clinical trial design and efficiency and to reduce the burden on clinical trial participants. FDA has expressly stated that this final guidance is only a part of a “multifaceted FDA effort.”

Such efforts will likely involve new policies and additional guidance from FDA. In fact, FDA has already simultaneously released new draft guidance, titled Integrating Randomized Controlled Trials for Drug and Biological Products Into Routine Clinical Practice, regarding incorporating trial activities for drugs and biological products into routine clinical practice to expand the role of local HCPs in trial settings, as well as a new revised Part 11 electronic systems Q&A document issued in October 2024.

As before, careful consideration of state telehealth laws and regulations remains critical when conducting DCTs via telehealth. Ensuring uniform application of protocols across state lines to generate consistent data despite variations in telehealth states laws and practice standards is a key component of conducting clinical trials with decentralized elements.

When conducting a DCT, it is imperative that compliance programs include mechanisms for frequent monitoring of updates to both federal and state laws and policies.