Although the concept of decentralized clinical trials was first introduced in the early 2000s, real interest in this approach to clinical research did not occur until the COVID-19 pandemic. During that time, many clinical trials had to pivot to a decentralized approach to continue operating. The success of these studies provided clear evidence of the feasibility and benefits of the decentralized format. While most trials containing decentralized aspects today are hybrid studies incorporating both in-person and virtual elements, the majority of studies do include at least one digital component, with greater adoption of the decentralized approach anticipated across all applicable studies going forward.
Why Decentralized Trials?
In conventional clinical trials, all activities take place at central sites — typically hospitals, clinics, or universities located in major urban centers. Patients must travel to the site for all doctor visits, assessments, and treatments. As such, participation is often limited to those people living nearby to these sites or those who have the time and means to afford any necessary travel. Not surprisingly, even in 2021, only 5% of Americans participated in clinical trials despite the potential they represent for improved outcomes,1 and approximately 70% of people live more than a two-hour drive from clinical trial sites.2
In decentralized trials, more of the activities involved in clinical trials take place within patients’ homes or nearby satellite sites (e.g., local doctors’ offices, clinics). Many different digital tools are leveraged, from electronic consent (eConsent) forms and processes to telehealth, in-home nursing and blood collection, electronic monitoring devices, web-based portals for electronic patient-reported outcomes (ePROs), and automated reminders.3 There is greater flexibility in scheduling and patients and the overall patient burden is reduced. Education of patients in the home environment also tends to result in greater medication adherence.4 With this approach, patients located in remote locations can participate in clinical trials. So can patients with diverse cultural and ethnic backgrounds, leading to greater diversity,5 which is recognized as a crucial issue that must be addressed.
The end result is often more rapid enrollment (up to 50% faster) and greater retention of trial participants, both of which help reduce trial costs and delays.6 Cost reductions can be as much as 10–25% according to some estimates.7 The dropout rate for conventional trials is, in fact, often about 30%. In many cases, the workloads on trial sites are reduced because much of the activities are performed remotely by others, including the participants. Furthermore, automated data capture reduces data transcription errors, and collection of data in real time facilitates faster analysis, trending, and identification of potential issues.
While there have been few fully decentralized or virtual trials to date, most of which have been small, early-phase studies, as the benefits of this approach are repeatedly demonstrated and digital tools and technologies continue to advance, there is growing recognition of their value for larger, later-phase trials.2 Currently hybrid trials in which a limited number of site visits are necessary and much of the activities are performed remotely are increasingly common.
2000s: Initial Explorations
The first attempts at conducting decentralized trials took place in the early 2000s. In 2003, McAllindon conducted a feasibility study for Internet-based trials.8,9 In 2004, Boston University ran an Internet-based randomized clinical study investigating the use of glucosamine as a treatment for osteoarthritis. In that same year, Eli Lilly conducted a hybrid trial to investigate the erectile dysfunction drug tadalafil using eConsent, remote monitoring, shipment of the study drug to patients’ homes, and ePROs. Additional Internet-based trials were conducted in 2005–2007 by Boston University and the University of California at San Diego. The concept of the first fully virtual trial was also first raised within Pfizer in 2007.
Regulatory guidelines used to support these earliest decentralized trials could be found in FDA guidance on requirements for electronic records in clinical trials initially issued in 1997 and updated in 2003. The agency issued separate guidance on PROs that included discussion of ePRO requirements.9
2010s: First Fully Decentralized Trial
Pfizer’s fully decentralized REMOTE Participatory Patient-Centered (PPC) clinical trial for Detrol LA involving 600 patients from 10 states with overactive bladder took place in 2011.8 Additional decentralized trials were conducted in this decade by companies such as Novartis, GSK, Sanofi, Johnson & Johnson, and McKesson, among others.8,10 Vendors supplying new software and digital tools also began to appear during this period, such as Science37, and larger CROs like IQVIA began offering virtual trial solutions.8
During this decade, the Trial Innovation Network was also founded (2016) by the National Center for Advancing Clinical and Translational Science to support advances and innovations designed to facilitate clinical research.11 By 2023, the organization has consulted in more than 400 clinical study proposals that have included recommendations for eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and other features.
2020s: Rapid Acceleration of DCT Adoption
Adoption of decentralized trials accelerated dramatically during the COVID-19 pandemic. Lockdowns prevented patients from visiting trial sites, and for many clinical studies the only way to continue operating was to pivot to a virtual format. One survey found that 85% of respondents transitioned to remote or virtual trials during the pandemic.7 By the end of 2021, more than 1000 decentralized trials were underway — one and a half times the number in 2020.10 The rapid switch to decentralized trials that took place in 2020 and 2021 provided clear evidence that this approach was an effective and valid means of collecting clinical data with many benefits.
Indeed, the number of decentralized trials continues to increase. The number of clinical trials with a virtual and/or decentralized component started in 2022 was nearly a third larger than that in 2021.7 In addition, in Europe, it is predicted that within the next few years on average two-thirds of studies will include at least one decentralized technology.7 Meanwhile, in the United States, while just 3.3% of trials incorporated decentralized elements from 2010 to 2016, that number has risen to over 12% of studies from 2019 to the present.9
The need to move to decentralized trials during the COVID-19 pandemic prompted the FDA to issue temporary guidelines.9 The European Medicines Agency (EMA) also published recommendations on decentralized trials.7 The first formal guidance from FDA was released in May 2023, with the final version issued in September 2024.12 Guidelines from EMA were also published in June 2023 and by the Canadian Institute of Health Research in late 2024.7
Decentralized trials today leverage eConsent processes, telemedicine, ePRO tools for real-time data collection, wearable devices and sensors for continuous monitoring, mobile nursing networks and clinics, direct-to-patient drug delivery, artificial intelligence–based recruitment strategies, integrated engagement approaches that include social media, patient advocacy groups, and others, and very often are hybrid designs incorporating both virtual and in-person components.6
Going Forward: Overcoming Hurdles
The final FDA guidance outlines a number of activities involved in decentralized trials, emphasizes the importance of effective digital health technologies, and outlines several regulatory challenges given that regulatory requirements for decentralized trials are the same as those for conventional clinical studies.12 Sponsors remain ultimately responsible for compliance of decentralized trials, even though they may transfer certain specific responsibilities to contract research organizations (CROs). It is suggested that a central institutional review board (IRB) be used to review and approved clinical studies rather than multiple local IRBs. Investigators continue to be responsible for ensuring the safety and welfare of participants, even when they are seeing local healthcare practitioners.
Challenges remain when it comes to running fully decentralized trials. Ensuring patient compliance, data accuracy, and data security; managing logistics of in-home care, telemedicine, and local/mobile physician/clinic visits; and ensuring ongoing compliance with regulatory requirements can be daunting. Providers of digital technologies and software supporting decentralized trials continue to introduce novel solutions, however, that are designed to overcome these issues while also increasing the accessibility and ease of participation by patients that previously would not be willing to take part in clinical trials.8
It is also important to keep in mind that decentralized trial solutions are not appropriate for all studies.1 There are cases in which advanced assessments and tests are required that can only be conducted at an investigator site. Similarly certain treatments known to have risks of severe side effects can only be safely administered in a hospital or clinic setting.
For all other cases, the growing awareness and desire of people to manage their own health, increased familiarity and comfort across all age groups with digital technologies, improved digital tools, and expanding number of CROs with experience operating decentralized trials will lead to further adoption of hybrid and ultimately fully virtual clinical trials.2
One notable indication of where decentralized trials may be heading can be found in strategic partnership between Walgreens and the Biomedical Advanced Research and Development Authority (BARDA) announced in August 2024.13 The collaboration is focused on increasing innovation in decentralized trials as part of the Decentralized Clinical Operations for Healthcare and Research (D-COHRe) program, which was formed to strengthen decentralized clinical trial capabilities in support of drug development, particularly to support investigation of drug candidates in real-world environments that could be needed during future public health emergencies. Walgreens will use its decentralized clinical trial platform, which engages patients and potential patients as they follow their routine healthcare journeys.
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References
1. Leclerc, Diane. “The Changing Landscape of Decentralized Clinical Trials.” The Medicine Maker. 6 Sep. 2024.
2. Agrawal, Gaurav, Rachel Moss, Ralf Raschke, Stephan Wurzer, and John Xue. “No place like home? Stepping up the decentralization of clinical trials.” McKinsey. 10 Jun. 2021.
3. Sacks, Leonard. “The Evolving Role of Decentralized Clinical Trials and Digital Health Technologies.” CDER Conversations. 2 May 2023.
4. Halle, Casey and Esther Chipps. “The Industry Shift Toward Decentralized Clinical Trials: Impacts on Quality Management, Participant Outcomes, and Data Management.” Clinical Researcher. 15 Aug. 2024.
5. New Data Reveals Decentralized Clinical Trials Linked to Improved Diverse Participation Across Many Underrepresented Demographics. Medable. 28 Jan. 2025.
6. Butani, Anand. “The Rise of Decentralized Clinical Trials: Transforming Medical Research in the Digital Age.” LinkedIn Pulse. 16 Feb. 2025.
7. “Decentralized clinical trials – Key trends and statistics.” Medidata. Accessed 11 Mar. 2025.
8. “Everything You Wanted To Know About Decentralized Clinical Trials.” TrialX. 22 Jun, 2022.
9. “The Evolution of Decentralized Clinical Trials.” Sterling IRB. Accessed 11 Mar. 2025.
10. “Everything You Need to Know About the Advent of Decentralized Trials.” 5 Aug. 2024.
11. Hanley, Daniel F Jr, et al. “Decentralized clinical trials in the trial innovation network: Value, strategies, and lessons learned.” J. Clin. Transl. Sci. 7:e170 (2023).
12. “Recent FDA Guidance Signals Future Growth for Decentralized Clinical Trials.” McQuire Woods. 24 Oct. 2024.
13. Walgreens and BARDA Form Strategic Partnership to Strengthen Decentralized Clinical Trials Model and Reporting. Walgreens Boots Alliance. 19 Aug. 2024.