Understanding the New FDA Guidance on Decentralized Clinical Trials

In 2024, the US Food and Drug Administration (FDA) issued final guidance on the use of decentralized clinical trials (DCTs), Conducting Clinical Trials with Decentralized Elements Guidance for Industry, Investigators, and Other Interested Parties. This new guidance hasn’t introduced radical sweeping changes, but it does acknowledge the DCT practices that have been in place for many years. The guidance isn’t legally enforceable but provides very helpful recommendations for sponsors, investigators, and other stakeholders involved with implementing DCT elements in clinical trials. Medidata and industry associations welcome this FDA guidance as an endorsement of this DCT approach. 

This blog outlines the evolution and some of the key concepts in the DCT guidance.

Evolution of the Recommendations

This DCT guidance comes in response to section 3606(a) of the Consolidated Appropriations Act, 2023 which directed the FDA to issue a final guidance that includes recommendations to clarify and advance the use of DCTs to support the development of drugs and devices. 

A draft for public consultation was released in May 2023, and key changes between the draft and the final guidance are below.

Task Logs

The FDA removed mention of a requirement to create and maintain a local task log of healthcare personnel (HCPs) contracted for trial-related services in routine clinical practice. It was felt that maintaining such a log would be an unnecessary burden.

Data Variability

There had been much debate around the original text on data variability. FDA provided more specific examples surrounding the aspects of this topic. FDA highlighted that the trial design should limit variability from trial-related activities performed by HCPs and trial personnel as well as activities that can be performed by participants at home, such as spirometry tests. Advice in reducing the potential for data variability was given including training and video supervision in the case of participant activities performed independently, and to specify what activities are permitted remotely, at trial sites, and also be based on participants’ preference. 

Sponsor Responsibilities

The agency also updated its responsibilities for sponsors using DCTs that use local HCPs, noting that networks of local HCPs can be used for contracted services which can also allow admission of data collected by non-study personnel into the clinical record.

Inspections

FDA clarified that there needs to be a physical location where FDA inspectors can access records related to the trial—whether paper records or electronic access for “participants under the clinical investigator’s care”—and to coordinate remote or in-person interviews with trial personnel. 

Editorial

Editorial changes were made to improve clarity across the final guidance.

Key Concepts of the Final DCT Guidance

FDA Definition

FDA describes a DCT as a clinical trial that includes decentralized elements, where trial-related activities occur at locations other than traditional clinical trial sites. Trial-related activities may take place at the location of trial participants or in local healthcare facilities that are close to trial participants' locations. DCTs may also include the use of local healthcare providers and local clinical laboratory facilities in the management of trial participants and the use of telehealth and digital health technologies to acquire data remotely.

Hybrid or Fully DCT?

FDA acknowledges that clinical trials can be fully decentralized, or leverage components of decentralization (typically known as hybrid trials). Full DCTs have all their activities in non-traditional trial site locations, while hybrid DCTs could have some in-person visits at traditional sites and other visits at non-traditional trial sites.

Whether a DCT is full or hybrid should be determined on a trial-by-trial basis and is not a one size fits all. Sponsors with simple investigational products may benefit from a fully decentralized trial, while a hybrid solution may be better for an investigational product with a complex medical assessment at a particular study site with remote follow-up visits.

DCT Benefits Recognized by FDA

FDA recognizes the well-known benefits that DCTs bring, including:

• Advances in electronic communications that let patients and clinical site staff interact from different locations, allowing for remote participation and reducing the need for onsite visits. 
• Digital health technologies have expanded the types of data that can be obtained remotely. 
• Obtaining data remotely has multiple benefits such as convenience to the patient, reducing the burden on caregivers and facilitating research on rare diseases and diseases affecting populations with limited mobility or generally limited access to clinical trial sites. With these capabilities, DCTs have the potential to expand access to a more representative patient population. 
• A DCT approach can improve participant engagement, recruitment, enrollment, and retention improving the strength of and broadness of the evidence produced by the trial. 
• In addition, using decentralized elements in a clinical trial can also impact the overall efficiency of a trial and get drugs and devices faster to those that need them. 

FDA also highlights potential challenges—specifically co-ordination of trial activities and facilities in multiple locations. For issues associated with feasibility and design implementation, recommendations included discussions with FDA review divisions early in the process, and the importance of appropriate training, oversight, and continuous risk assessment and management. 

Recommendations for Implementing DCTs

The core recommendations in the main part of the document highlight key sections which discuss: 

• Design and conduct of a DCT.

• Remote clinical trial visits, clinical trial-related activities, and the different combination of DCT elements. 

• The use of digital health technologies, as well as the transmission of data remotely and securely with a focus on telehealth, also referencing Digital Health Technologies for Remote Data Acquisition in Clinical Investigations.

• The roles and responsibilities of the sponsor, investigator, and delegation of trial related activities.

• How FDA plans to conduct oversight and inspections where the investigator should identify a physical location and the responsible person to support FDA inspections.

• Informed consent and institutional review board oversight, and the use of obtaining either electronically or via paper, as well as the associated investigator and delegate responsibilities. 

• Use and administration of investigation products for drug, biological, and medical device products, and associated responsibilities.

• Packaging and shipping of investigational products and how the physical integrity and stability is maintained, as well as ensuring appropriate packaging materials and methods.

• The safety monitoring in DCTs and discussion around the safety monitoring plan and the capturing and reporting of adverse events.

• The use of electronic systems when conducting DCTs.

Additionally in December 2022, the EU published their Recommendations Paper on Decentralized Clinical Trials. Both the EU and FDA papers focus on the use of DCTs based on the main criteria and assessment around patient safety and data integrity, with discussion of the DCT elements, implementation strategies, and emphasis on roles and responsibilities. 

In general, use of DCT elements in clinical trials are not new concepts and have been used for many years. This guidance is an acknowledgement by the FDA and the EU of these practices. COVID-19 was also a catalyst to the provision of these recommendations. 

Medidata has been at the forefront of DCTs for well over a decade, having led industry trade associations on the topic. One such example is the Association of Clinical Research Organizations DCT Working Party for the last 5+ years which developed a DCT Tool Kit to help inform FDA and other authorities on operational and beneficial aspects of this topic.