Background

The FDA’s draft guidance offers recommendations to sponsors, investigators, and stakeholders on implementing Decentralised Clinical Trials (DCTs) for drugs, biological products, and devices. DCTs involve trial-related activities occurring outside conventional clinical trial sites. They encompass fully decentralised trials where all activities happen away from traditional sites, including participants’ homes or local healthcare facilities. Hybrid DCTs involve a mix of in-person visits to traditional sites and other activities conducted at alternative locations, like participants’ homes. Numerous clinical studies already integrate decentralised components and the adoption of Decentralised Clinical Trials (DCTs) has the potential to expand access to diverse patient populations and improve trial efficiency.

Moreover, advancements in clinical care have embraced electronic communication and information technology to engage with study participants across different locations, such as telehealth services. This has resulted in a reduction of in-person site visits. Additionally, the utilization of Digital Health Technologies (DHTs) has widened the scope of trial-associated data that can now be collected remotely from trial participants.

FDA Guidance

The FDA issued a draft Guidance to DCT in May 2023 for consultation.  The draft guidance covers different topics, for example:

• Investigational Product (IP): Decentralized clinical trials might be suitable for IPs that are easy to use or administer, possess well-understood safety profiles (refer to FDA Draft Guidance section III.F), and do not necessitate complicated medical evaluations. However, for situations where the IPs administration or intricate medical appraisal needs to occur at a clinical trial site and some subsequent evaluations can be conducted off-site via methods such as telehealth, domiciliary visits, or local health care providers, the use of hybrid decentralized trials may pose a more fitting option (refer to FDA Draft Guidance section III.B).
• Potential challenges with DCTs might encompass coordinating trial activities among multiple non-traditional trial sites, individuals, and facilities. DCTs must have specific strategies to aid in the decentralization process. Where applicable, such strategies should incorporate the use of local healthcare facilities, local Healthcare Professionals (HCPs), local clinical laboratories, home visits to trial participants, and direct IP distribution to participants at their locations.
• Discussion of any concerns related to the feasibility, design, implementation, or analysis of a DCT must be done at early stages with the appropriate FDA review groups. Furthermore, proper training, supervision, risk evaluation and management are crucial elements for the successful execution of a DCT.

Other aspects of DCT were explained in the draft guidance in sections III (A-I).

Additional Considerations

In my personal professional opinion, I feel the draft guidance would benefit from the inclusion of the following:

FDA Section III-H: Safety Monitoring Plan and Site Safety Alerts

In certain research models, adverse events (AEs) are recorded using technological solutions, which can also alert the study team to severe AEs in some instances.

In my opinion, for patient safety, continuous direct interaction between patients and medical staff is key. The technological aids used for the research may not have the proper cellular/Wi-Fi connectivity required for instant site notification and timely response. Relying merely on technology for alerting HCPs to serious AEs could result in delayed intervention and potentially place patients at risk.

Therefore, it is not advisable to depend solely on technology tools for alerting/reporting of serious AEs requiring intervention unless those tools are purposely designed and verified for use as monitored emergency notification systems.

FDA’s Section III-I Software Implementation during DCTs

Examples of measures to be implemented by both site personnel and sponsor to ensure that the recorded/reported study data is adhering to Attributable, Legible, Contemporaneous, Original, Accurate, Complete (ALCOAC) principles:

Site personnel:

In order to guarantee that subject-reported patient outcomes are accurately documented, it is imperative for site personnel to institute a consistent review of the electronic Patient Reported Outcome (ePRO) devices.

Study sponsor:

Ensure maintenance of data integrity, i.e., reviewing the software audit trail on regular basis

Summary

DCTs improve convenience for those participating in the trial and minimize the strain on caregivers by incorporating remote participation. They also aid research efforts on rare diseases or conditions affecting population groups with restricted mobility or limited access to conventional trial locations. This approach can potentially enhance participant engagement, recruitment, enrolment, and retention, leading to a wider and more diverse clinical population representation.
Recent advancements in technology have greatly increased the accessibility of clinical studies to larger and varied demographic groups. Nonetheless, technology itself is not a guarantee for the successful completion of these studies. In clinical trials, which require Direct Data Capture (DDC) or electronic Clinical Outcome Assessment (eCOA) completion by the site staff and patients, technology tools are frequently employed. These tools are generally dependable and constantly improving. However, they need human supervision, to ensure compliance with guidelines and regulations, and to reduce risks to study data and subjects’ safety.

List of References

For a copy of the FDA draft guidance document please click here FDA Draft Guidance-Decentralized Clinical Trials for Drugs, biological products and devices

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