A year ago, clinical trials across the globe were put on hold as COVID-19 began its devastating impact on our world. Patients were unable to receive their treatment, biopharma lost money and time, and the healthcare industry raced to find solutions to meet the need for continued research, ensure the safety of those enrolled in clinical trials, and develop a vaccine.

One positive born out of this pandemic has been the accelerated adoption of clinical trial models that lessen the burden of participation on the patient and family care circle. Decentralized clinical trials are the model everyone is talking about—but what are they? It’s imperative to establish standard terminology as this model continues to advance our industry and confusion from interchangeable terminology use abounds.

Understanding the Terminology

The Food and Drug Administration (FDA) and European Medicines Agency (EMA) have adopted the term “decentralized clinical trial” (DCT) for any trial that does not follow a traditional, site-centered clinical trial model and instead utilizes mobile technology, local healthcare providers, telemedicine, or any measure that modifies the traditional role a site plays in a clinical trial.^1,2,3

This term is most appropriate for this kind of model because there is no central element to the study. The site, personnel, investigator, and vendor may be in different locations, leveraging technology and remote solutions to fulfill the protocol. While elements of DCTs have been around for years—including use of satellite sites and home healthcare—the strategic concept of building a trial around decentralization is still fairly new.

There are many ways to implement DCTs—they can be fully decentralized or hybrid decentralized clinical trials. This decentralization of the traditional model shifts the patient to the center, providing access to participation in the patient’s ecosystem (rather than the traditional site’s ecosystem), and lessening their burden to participate.

You may have heard of this model referred to as a “virtual trial,” “remote trial,” or “site-less trial.” “Remote trial” is not completely accurate because many DCTs are not entirely remote. “Site-less trial” is not appropriate either, as it implies there is no site participation. This is not the case—sites and site teams are an essential part to any clinical trial, traditional or decentralized.

“Virtual trials” is a common misnomer for DCTs because data can be collected through remote visits and assessments. This term creates confusion and shouldn’t be used to refer to a DCT because “virtual trials” is already used to refer to trials that happen during the preclinical phase. Virtual trials use computer or in silico simulation to assess safety and efficacy of promising compounds in imaginary patients. At no point are humans participating in these trials, so they are very different from the human-centric DCTs.

DCTs in Pediatric Clinical Trials

The standardization of accepted terminology is important when we consider pediatric clinical trials. As pediatric patients are a vulnerable population, virtual modeling and simulation studies are often used in pediatric development programs to leverage available data and design the most efficient trials to assess the drug in the pediatric population. Confusing this type of “virtual trial” with a decentralized trial will lead to confusion in discussion amongst development stakeholders and regulatory agencies.

The FDA and EMA are both encouraging standard use of DCTs to prevent confusion and to increase efficiencies. Some regulatory agencies have expressed concerns about delays or even rejection of submissions if incorrect terminology is used when referring to DCTs, as there could be confusion around the true design of the study. Pediatric clinical studies already face significant hurdles to development and approval—further delay over terminology confusion needs to be avoided.

DCTs have much to offer pediatric development programs. The burden to participate in any trial is large—a child who is in school and requires the support of family members to participate can create a significant barrier to enrollment and participation. Leveraging measures that decrease on-site visits can have huge potential for the success and retention of pediatric patients in clinical trials.

The beauty of a DCT is there is no one way to do it—the very nature of them is to design a trial that fits the unique aspects of the patient needs and the specific therapeutic area needs.

Designing a study around the patient and their family, instead of the site, opens the door for many improvements to a study—from increased enrollment and retention, to improved data quality, to increased diversity of enrolled patients. As the adoption of DCTs continues to accelerate and become the norm, let’s agree to say what we mean and mean what we say—let’s decentralize the traditional clinical trial and put our patients and their families at the center.

References:

1. Food and Drug Administration, Center for Drug Evaluation and Research. CDER 2021 Guidance Agenda: New & Revised Draft Guidance Documents Planned for Publication in Calendar Year 2021. https://www.fda.gov/media/134778/download
2. European Medicines Agency. EMA Regulatory Science to 2025: Strategic reflection. Published 2020. https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/ema-regulatory-science-2025-strategic-reflection_en.pdf
3. Clinical Trials Transformation Initiative. Decentralized Clinical Trials. Published September 2018. https://www.ctti-clinicaltrials.org/projects/decentralized-clinical-trials.