Category: U.K

The US Food and Drug Administration (FDA) has reportedly released a draft guidance detailing its recommendations on performing decentralised clinical trials (DCTs) for drugs, biological products and medical devices.

With the draft, FDA is committed to providing trial sponsors, researchers, and other stakeholders with guidance on how to accelerate DCT adoption to facilitate drug development, reported European Pharmaceutical Review.

FDA’s New Draft Guidance

The newly issued draft guidance is developed on the recommendations the agency detailed in 2020. With the earlier guidance, FDA aimed to help study teams facilitate trial decentralisation in response to the disruptions (e.g. travel restrictions, site closure, quarantines) and public health emergencies caused by the COVID-19 pandemic. 

“The FDA has long considered the benefits of decentralised clinical trials. Advancements in digital health technologies and the COVID-19 pandemic – when in-person visits were limited or unavailable for many trial participants – have accelerated the broader adoption of these activities,” explained FDA Commissioner Dr. Robert Califf.

This new draft offers recommendations related to the FDA’s conditions for investigations of medicinal products when applied to decentralised studies and meets the requirement outlined in section 3606(a)(1), FDA Omnibus Reform Act (FDORA).

FDA released the guidance a few months after the EU regulators demonstrated their recommendations on DCT to help protect the rights and well-being of the trial participants.

In the draft guidance, FDA provides stakeholders with recommendations on DCT design, conducting remote clinical trial visits and clinical trial-related activities, the adoption of digital health technologies (DHT) as enablers of clinical research, the responsibilities of the involved stakeholders, and how investigational medicine should be administered.

Breaking Down the Recommendations

Providing a framework for DCT design, FDA stresses the importance of having a physical location while conducting DCTs to ensure easy access to participant records and investigators’ care.

The trial protocol should clearly define when a tele-health checkup is required and when a patient needs an in-person visit.

FDA urges investigators to confirm participant identity during each remote visit.

According to the agency, the protocols for using DHTs in a virtual trial to gather data for trial endpoints should be compatible with the draft guidance “Digital Health Technologies for Remote Data Acquisition in Clinical Investigation”.

Additionally, in the newly released draft guidance, the FDA has urged sponsors to strive for enhancing participant diversity and inclusiveness in clinical trials. 

FDA stresses the importance of engaging local healthcare providers (HCPs” in trial activities to build trust with at-risk participants, thus improving the inclusion of diverse populations. 

While DCTs and hybrid models can encourage a much higher enrollment rate, FDA suggests investigators recruit only as many participants as they can efficiently manage to provide enough supervision of trial-related activities. 

According to the agency, while taking remote consent from the trial participants, they should be informed about whom to contact in case they face any health issues during the trial period and who can access their personal health information (PHI) acquired during the DCT.

FDA underscores leveraging central IRB in decentralised trials as a key to facilitating the review of the protocol, the informed consent documents, and other pertinent trial data.

In addition, investigational products (IP) should be administered to the participants only under the in-person supervision of the investigator or the supervision of a sub-investigator answerable to the investigator.

It’s recommended for sponsors to take into account the type of an investigational device, its prospective application, and the associated risks to determine its use cases efficiently.

IPs can be directly delivered to the participants’ location and the trial protocol should clearly define the methods of preserving the integrity and stability of the IP.

FDA recommends the use of a centralised distribution system to facilitate the delivery of IP to trial participants.

The sponsor is responsible for thoroughly monitoring the DCT processes while ensuring the trial is being conducted per the general investigational protocols and considerations included in the IND or IDE applications. 

The implemented safety monitoring plan in a trial should be devised considering the decentralised nature of the investigation. It should ensure any adverse events are detected early, correctly captured, and efficiently addressed.

FDA suggests sponsors implement high-end DCT software that can help manage electronic case report forms (eCRFs) and electronic informed consent (eConsent), schedule trial activities, sync data input in DHTs, and more. 

High-end DCT platforms such as ObvioHealth can efficiently address the issues of data inaccuracy and the interoperability essential to produce robust trial outcomes and endpoints.

Wrapping Up

Decentralised and hybrid study models are considered the way forward to decrease the patient burden. Offering participants the support and flexibility they need, DCTs also help improve data quality. 

The result: augmented trial result and accelerated drug development

“As we seek to improve our evidence generation system, decentralised clinical trials may 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,” commented FDA Commissioner.