Regulators Speak About Decentralized Clinical Trials

Applied Clinical Trials

The concept of decentralized clinical trials (DCT) is still in its infancy in the industry, although the pandemic has facilitated its adoption.

FDA has issued a guidance document for operating under the pandemic, as did EMA which outline several characteristics of DCTs, including remote study visits, clinical outcomes assessments (COAs), monitoring and inspections, to name a few. Although FDA has encouraged the use of DCTs andEMA conducted workshops on the topic, formal guidance has yet to be issued regarding the concept. At the second annual meeting of the Decentralized Trials and Research Alliance (DTRA), regulators discussed their perspectives and experiences on DCTs. This article will summarize key points made by Leonard Sacks (Office of Medical Policy, CDER at FDA), Ditte Zerlang Christensen (EU Project Manager at DKMA Danish Medicines Agency), and Catherine Ela, Head of Clinical Trials Department at the Medical Technology Health Information Innovation & Research Directorate of the Israeli Ministry of Health.

Some support for DCT technologies

Much discussion surrounded digital tools, such as eConsenting, to promote DCTs. While FDA has been encouraging the use of eConsenting for some time, Sacks observed the rapid adoption of eConsent during the pandemic, which helped the agency evaluate its adoption on a large scale. eConsenting allowed patients to maintain social distance and encouraged remote visits. Ela indicated, however, that regulators at the Ministry had differing perspectives on eConsenting and that the adoption of eConsenting by sponsors in Israel was limited. All regulators agreed that DCT is an ecosystem and that sponsor engagement with regulators is essential.

Fragmentation and inconsistency risks

During the pandemic, regulators learned that DCTs can introduce data fragmentation and inconsistency (due to many technology systems and vendors being used), which could increase study risks. For instance, when patients conduct procedures away from the investigator (e.g., entirely electronic procedures or remote procedures performed by vendors), the investigator’s ability to evaluate the patient holistically may be compromised. Sacks suggested a supervisory structure, such as a traveling nurse, to ensure data consistency and quality; without proper supervisory infrastructures, data inconsistencies and missing data increase study risks. Another factor to consider is the preparation and organization of data sources during regulatory inspections; for example, Sacks observed that travel nurses report medications differently than hospital or pharmacy records. If there are disparities in interpreting patient discharge or adverse event reports, regulators are highly concerned. Consequently, integrating data from multiple data sources into a single location and aggregating them to ensure consistency during inspections is beneficial.

Regulators concurred that infrastructures for patient supervision must be designed so that investigators and site personnel can oversee patient safety in a DCT environment. Roles must be clearly defined and documented. In addition, regulators suggested implementing integrated technological infrastructures and data centralization to enable staff to supervise patients and regulators to draw a comprehensive picture or storyboard of staff activities and roles.

Oversight Is crucial

The regulators emphasized the importance of study oversight. Christensen indicated that a stakeholder meeting hosted by EMA discussed the significance of sponsor oversight in DCTs, explicitly ensuring the centralization and consistency of data across multiple DCT platforms. Other factors include implementing risk-based approaches to patient and study monitoring and establishing communications plans and systems to maintain contact with patients, sites, and study personnel.

Harmonization on DCTs

Before releasing guidance documents, all regulators were in accordance with harmonizing the DCT concept. In particular, regulators want sponsor organizations to test more DCT concepts, collaborate with regulators, and share their experiences, which will aid them in drafting guidance documents. FDA should soon release a DCT guidance document; however, for the time being, FDA recommends adhering to its guidance document on the use of digital health technologies in clinical trials.

While the DCT concept is still in its infancy, the fact that regulators encourage DCT practices indicates it is here to stay. Much work between the industry and regulators will need to occur before DCTs can become a harmonized approach and guidance; while EMA expects to issue guidance on DCTs soon, FDA has yet to commit to a defined date for releasing its guidance, and other agencies, such as Israel, want to wait and see how other agencies roll out their DCT guidances.