Decentralized Clinical Trials: Bust or Breakthrough?

Applied Clinical Trials

Decentralized clinical trials (DCTs) are shapeshifting.

Originally piloted 15 years ago and more recently catalyzed by the COVID-19 pandemic, DCTs took center stage in 2020 and 2021—mostly out of necessity, but with great promise for their potential to dramatically improve patient access, enrollment, trial speed, data quality, and population representation. Now, in the third quarter of 2024, the market landscape looks less rosy than the earliest depictions.

While the value of the global DCT market is projected to increase over the next six years from $8.5 billion in 2023 to $13.3 billion by 2030 (growing at a compound annual growth rate of 6.6% in the forecast period), these projections are lower than they were in 2022. Other financial indicators suggest that the market remains volatile. According to LinkedIn employee data, the number of employees in companies most aligned with providing DCT software has declined over 20% from their highs.1 In DT Consulting’s new report, “State of Digital in Clinical Operations 2023,” two-thirds (69%) of respondents said they expect their digital budgets to stay flat or decrease.2

Even so, in the uber conservative clinical research industry where people’s lives are at stake, the fact that DCT excitement has tempered from a rolling boil to a gentle simmer is hardly surprising. Even in less risk-averse industries, adoption of disruptive technologies tends to follow a natural slackening, as noted by Gartner’s Hype Cycle.3 Have we hit the “peak of inflated expectations” with DCTs or the feared “trough of disillusionment”?

One of the issues is that sites and sponsors are facing challenges with adoption of decentralized elements. An Association of Clinical Research Professionals survey reveals that sites lack the training and budget to implement DCTs.4 Additionally, the top-cited reason sites declined participation in decentralized trials in another survey was hesitancy to adopt these methods without a sufficient budget to cover additional training or the integration of new technologies.5

Decentralized methodologies remain a stable feature of trial activity, albeit at a lower level after the COVID peak in 2020, and the negative news does not diminish the positives of DCTs. The question remains: Is this study model a bust or a breakthrough? Time will tell, but certainly DCTs are changing shape.

Ahead, five industry leaders, each with deep-domain experience designing, implementing, and measuring DCTs, provide their perspectives on how these types of studies are evolving and their impact on an ever-changing research industry.

1. Ken Getz, MBA, Tufts CSDD Executive Director

The Tufts Center for the Study of Drug Development (CSDD) in collaboration with the Partnership for Advancing Clinical Trials (PACT) consortium recently revealed compelling results from a new study on 60 clinical trials that deployed decentralized solutions.6 Funded in its first year by the Reagan-Udall Foundation and Medable, the consortium is committed to collecting and analyzing evidence on DCT experience and its impact on trial performance.

PACT member companies indicated that they anticipate one-third of all protocol procedures, and half of all study visits, could be performed remotely. And companies use, on average, four distinct DCT solutions per clinical trial, most often in support of study visit activity.

In this initial dataset, wide variation was observed in the ways that companies deployed DCT solutions. Select outcome measures—such as screen failure rates, participant completion, and dropout rates—were similar to industry benchmarks, although many of the clinical trials using decentralized elements had not yet completed enrollment. On the other hand, actual timelines for clinical trials supported by decentralized solutions were more likely to beat planned timelines from first site activated to first patient enrolled, and from first patient to last patient enrolled. The results also showed that clinical trials using certain DCT solutions were associated with more diverse patient demographic representation.

Next, Tufts CSDD and the PACT membership will work to increase the size of the analysis dataset and generate more granular insights in year two to inform DCT adoption and optimize use by disease condition, patient preference, and other factors.

2. Pamela Tenaerts, MD, Medable Chief Scientific Officer

Trials using technology or local facilities have been around in one way or another for decades.The use of technology matured in the mid-2010s when the nomenclature coalesced around mobile, digital, and virtual clinical trials and exploded during the pandemic as DCTs. We had hoped that the pandemic would have allowed DCTs to fly over the trough of disillusionment but, as the Gartner Hype Cycle predicts, we find ourselves following the curve.

The nomenclature used for decentralized trials is still evolving, and we will likely abandon the DCT reference altogether someday. Instead, we will simply deploy various decentralized elements in trials in a fit-for-purpose way based on where they are best suited based on evidence (i.e., such as the PACT Consortium’s recent report around DCT impact on diversity). In the same way we no longer specify whether we have a “paper” boarding pass or a “digital” boarding pass—just a boarding pass—we will just say we are running a clinical trial.

Adoption of novel clinical trial methodologies is tricky. A 2023 Tufts CSDD Impact Report indicated that it typically takes six years for a company to adopt an innovation and 20 years for widespread adoption.⁷ Yet, digital endpoint use has doubled every three years since 2015, so there are signs of growth. With harmonized regulatory guidance, adapted workflows for sponsors and sites, an optimized site experience, better platform technology, and evidence of value, the industry will rapidly embrace decentralized trials again. Sponsors will surgically apply the right elements to accelerate reliable evidence generation while keeping participants safe.

3. Daniel Eisenman, PhD, Advarra Executive Director of Biosafety Services

As DCTs started gaining momentum during the pandemic, researchers were quick to put guardrails around their use, saying that highly complex or logistically unique therapies would not be candidates for full decentralization.⁸ Oncology, for example, was too risky for a fully digital-based trial. However, that belief has changed with the availability of new treatments such as targeted medications, drugs that can be administered orally or subcutaneously, and the ability to provide home infusions. And, with the emergence of hybrid trials that blend digital tools with some in-person visits, there is now even more flexibility with this model. In fact, today, oncology ranks in the top five therapeutic areas leveraging the decentralized model for trials.⁹

The same benefits that DCTs bring to other therapeutic areas apply to cell and gene therapies (CGTs), especially those intended to treat rare disease patients. It is difficult to recruit patients with a specific rare disease in numbers large enough to produce meaningful results in a clinical trial—especially if scattered over a wide geographical area. DCTs allow for remote tasks and data collection, which reduces the responsibilities and limitations of local sites, allowing for a larger trial network, which can serve a greater number of participants. Yet, the same lingering doubts around the viability of a DCT in oncology a few years ago have blossomed forCGT trials.

Traditionally, CGTs come with complicated logistical requirements—temperature-controlled shipping, safe storage, unique administration of the drug—that were not conducive to a DCT. However, CGTs are evolving just as DCTs. For instance, some investigational CGTs fit the criteria for DCTs while others do not.

One example of a CGT that has less rigid handling requirements and would be a good candidate for a hybrid DCT is freeze-dried bacteria (a live culture genetically engineered) that comes in a packet that patients simply mix with water. Other examples are CGTs that come in the form of topical ointments or nebulizers to be inhaled.

The bottom line is that we cannot rule out DCTs for the rapidly advancing area of CGTs. DCTs could prove to be the key to furthering the development of this incredible science and finding treatments for diseases that have been untreatable. We cannot dismiss DCTs outright—rather, adopt modern trial designs carefully and fit-for-purpose.

As an industry, let’s start each trial asking if it is well-suited to be a hybrid DCT based on all underlying factors, from patient safety to costs and everything in between. For CGT decentralized trials, especially, we need to identify the “Goldilocks zone”—not too much, not too little—just right for the science.

4. Troy Astorino, PicnicHealth Co-founder and Chief Technology Officer

The premise behind DCTs is sound: reduce dependency on overburdened sites and improve patient participation and diversity. However, COVID drove wide-scale DCT adoption before the technology was ready, resulting in broad industry disillusionment. Researchers using DCTs faced major challenges due to technology immaturity, lack of hybrid-native solutions, and narrow data capture capabilities.

Early DCT systems struggled to power smooth, integrated end-to-end trials. This led to friction for all stakeholders and made implementations feel “heavy” because extensive workarounds were needed. Many trials require a mix of site-based and remote components, especially for complex treatments, and initial approaches didn’t effectively accommodate this reality.

Replicating the breadth of traditional site-based data capture, particularly for endpoints sourced from electronic health record (EHR) data, proved challenging for DCT designs.

In response, many DCT providers have pivoted to offering point solutions, such as eCOA or eConsent, which can be more easily integrated into trial designs. While practical, this approach doesn’t fully realize the transformative potential of DCTs. It is important to first identify where virtual and hybrid approaches can truly excel. Observational research has proven to be a successful starting point.

Traditionally, observational studies have been awkwardly forced into site-centric models designed for interventional trials, leading to inefficiencies, high dropout rates, and potential data loss. Two capabilities are crucial to unlock decentralization in observational research. First, comprehensive EHR collection that integrates patient records across all providers to capture a more complete picture of patient health. Second, remote patient engagement to facilitate various forms of active data collection from patients where they are comfortable to improve participation and data quality.

Combining these capabilities creates a solid foundation for virtual and hybrid observational studies. They address the data capture challenges of earlier DCT models while maintaining the benefits of reduced clinical site burden and improved patient accessibility.

Additionally, a unified trial platform simplifies deployment of advanced technologies, including artificial intelligence (AI), across all components of a trial. AI is advancing rapidly to streamline processes, enhance data quality, and generate deeper insights. Limiting technology innovation to DCT components fails to leverage the full potential that modern technology platforms can deliver.

While the early hype for DCTs has subsided, the fundamental opportunity remains. As the industry refines its approach, we can expect to see more efficient, effective, and patient-centric clinical trials, particularly by focusing on strategic applications such as observational research first. This evolution will likely accelerate therapeutic development and, ultimately, improve patient outcomes.

5. Joel Morse, Curavit Clinical Research Co-founder/CEO

The promise of DCT 1.0 has not materialized for three reasons. First, clinical research is a risk-averse industry that typically applies changes thoughtfully, but the pandemic necessitated hasty adoption of DCT technologies.

Rushed implementations sometimes resulted in missteps, so the full potential of DCTs didn’t emerge as fast as expected, causing the industry to rethink their strategies, slow down, and become skeptical.

Second, inflated expectations of DCTs spread like wildfire. These unrealistic expectations became the new measuring stick for DCT success or failure, but it was a manufactured target, and sponsors grew wearier as the goalposts changed. Companies singing the praises of DCT software platforms were now changing their tune. Again, this fueled (undue) skepticism.

Third, the industry focused too much on the software and less on a comprehensive set of data and the overall clinical trial execution requirements. We oversimplified what it would mean to run a decentralized trial by thinking that great software would drive widespread adoption, but technology cannot single-handedly transform a model that has largely been handled the same way for decades.

We now have a deeper understanding and are learning from early mistakes. To fully realize the potential of DCTs, we must realign processes to digital workflows. This includes supporting the collection of comprehensive data sets, optimizing recruitment of the target patient populations, and leveraging both virtual and physical sites.

This holistic approach to trial design will drive the next evolution of clinical trials. DCT 3.0, focused on digital-first principles, is poised to meet the original expectations. DCT 3.0 will be grounded in purpose-built virtual sites, which will serve as the central hub for trial activities and clinical data, coordinating the entire trial.

The most important perspective: The patient

Rita Naman, co-founder of the Mighty Milo Foundation,10 is hopeful that digital technologies and decentralized methodologies will continue to mature and expand. Naman is the mother to 5-year-old Milo, who has SPAX5, an ultra-rare, serious, and inherited neurodegenerative disease that affects children early in life and is characterized by problems with balance, motor coordination, spasticity, peripheral neuropathy, and more. Milo is one of 12 documented cases. There is no cure, so access to investigational therapies is Milo’s best chance for help.

“The value of DCTs, especially for rare disease research participation, cannot be understated,” says Naman. “My son has significant caregiving needs that make it difficult, if not impossible, for him to participate in far-away trials. I pray that this industry will continue to be our beacon of hope and that no one gives up on modern alternatives for research such as DCTs just because technology investment has slowed. Digital tools can open new doors to patients like my son, who face endless, heartbreaking challenges.”