Introduction

The US Food & Drug Administration (FDA) recently published a final guidance document for conducting clinical trials using decentralized elements, in light of the growing use of telehealth, digital health technologies (DHTs), and other components that facilitate remote participation.

This blog covers some of the recommendations unique to DCTs covered in the FDA’s new guidance.

Decentralized Clinical Trials (DCTs)

Decentralized clinical trials (DCTs) are clinical trials that allow individuals to participate in research in a fully remote setting. By eliminating logistical barriers such as long study visits and travel to a physical site, they tend to offer greater convenience for participants and their loved ones. Furthermore, DCTs promote greater engagement and enable the recruitment of more diverse study populations, thereby strengthening the reliability and applicability of research outcomes.

The FDA’s Recommendations for DCTs

The FDA addresses various topics as they relate to decentralized elements in clinical trials. 

Designing a DCT Study

Trial Setting

Study designs for DCTs must be able to accommodate the variability in settings they may take place—at home, a local care clinic, or mobile research unit—so that they can produce consistent data no matter the location or who is carrying out trial activities. This is especially critical in trials where participants are expected to use the investigational product (IP) and perform study activities independently, where instances of human error can potentially compromise data validity.

Statistical Analysis

The FDA also notes that approaches to statistical analysis in DCTs may need modification if certain design elements (i.e. size of control and treatment groups, etc.) were implemented based on data from site-based clinical trials. The agency recommends liaising with the proper FDA review division for these matters.

Conducting Remote Study Visits and Activities

Telehealth

If the data being collected from study visits doesn’t warrant in-person interactions, sponsors should consider utilizing telehealth to reduce participant burden. However, factors such as disease severity and the nature of the IP may affect whether or not telehealth visits are appropriate, and the protocol should clearly outline circumstances for when visits should be conducted via telehealth or in-person.

In-Person Visits

Trial personnel or local healthcare providers (HCPs) may conduct trial visits in DCTs at participants’ homes or local facilities. The FDA stresses that local HCPs that are not familiar with the study protocol should only perform activities that they are qualified to perform in normal clinical practice, and that activities that require specific knowledge of the trial protocol and IP should be carried out by trial personnel who have been properly trained.

Leveraging Digital Health Technologies

The FDA's guidance for using digital health technologies (DHTs) in clinical trials offers recommendations on selecting and evaluating DHTs, ensuring their verification, validation, and ease of use, and incorporating them into clinical trial endpoints.

Some of these considerations include:

• Selection of DHTs: Utilize technologies that are relevant to evaluating the indication being studied, are suitable for the study population, and whose technical performance has been properly evaluated.
• Ease of Use: Make sure DHTs used in clinical trials are fit-for-purpose and are evaluated for usability.
• Personal Devices: Allow participants to use their own DHTs and relevant technologies as appropriate.

To promote clinical trial accessibility and the enrollment of representative study populations, sponsors should offer the option to provide DHTs to trial participants, even if they are able to and opt to use their own personal devices.

Ensuring Ethics Compliance

Informed Consent

Informed consent in a DCT must be obtained in compliance with institutional review board (IRB) standards. This includes ensuring consent is obtained by trial personnel (i.e. investigators or clinical research nurses and coordinators) who have been sufficiently trained on the study protocol and can provide proper credentials to address any questions or concerns participants and/or their loved ones may have.

IRB Oversight

When suitable, the FDA advises using a central IRB for decentralized clinical trials to streamline the review process for the protocol, informed consent documents, and other critical trial information.

Administering Investigational Products

Drugs and Biologics

It’s crucial to evaluate the suitability of administering IPs outside traditional sites based on their safety profile and stage of development. For example, IPs that have high-risk or unknown safety profiles may necessitate in-person oversight at a clinical trial site with study staff. IPs that are well-characterized with low-risk profiles may be administered by local HCPs, remote study personnel, or participants themselves. 

Sponsors should also assess the complexity of care and urgency for treatment in the event of an adverse reaction for IPs based on their safety profiles and type of trial, such as dose escalation studies. This evaluation should consider the specific risks of the IP and the health conditions of the study population. Investigators must ensure that trial participants have access to necessary local healthcare services to manage these risks adequately.

Medical Devices

An investigational device’s safety, intended use, and usability should all be taken into consideration when determining if a DCT setting is appropriate to implement. Devices intended for home use may not require direct investigator oversight unless needed to mitigate serious risks. However, devices intended for use in clinical settings should be administered by qualified personnel under investigator supervision. Follow-up assessments or post-implantation procedures can be conducted by trained local healthcare professionals (HCPs) or trial personnel, potentially via telehealth, provided there are robust plans for managing any adverse events.

Monitoring for Participant Safety

Safety monitoring plans in DCTs must account for handling and documenting adverse events and other related issues with IPs. These should ideally be brought to the attention of study personnel, however there may be some situations where local HCPs identify adverse clinical events or concerning symptoms. It’s vital that participants receive clear guidance on how to report these events and contact trial personnel for any questions or concerns that arise, including opportunities to meet outside of scheduled study visits.

Additional safety-related considerations for DCTs include:

• DHT Use: The type of data DHTs will collect, how that data will be used, and instructions for how participants and trial personnel should respond to abnormal findings should be documented in safety monitoring plans.
• IP Safety: Significant safety risks with IPs, such as those attributed to remote administration, should be reported to the FDA, IRB, investigator(s) and other relevant stakeholders. 
• Laboratory testing and imaging: Some protocols may allow routine monitoring to take place at local facilities.

Conclusion

The FDA's finalized guidelines for conducting clinical trials with decentralized components marks a shift towards executing more flexible and patient-centric research, leveraging technology and other strategies to facilitate trial participation regardless of location. By addressing the nuances of trial design, ethical considerations, and other aspects of study DCT execution, these guidelines aim to set sponsors up for success as they go on to develop their treatments and devices in remote settings.