By Deborah Borfitz 

March 5, 2024 | Decentralized clinical trials (DCTs) today are both more fit-for-purpose and business-as-usual than uncertain and unavoidable, as was the case during the height of the COVID-19 pandemic, according to Darlene Ellenor, director of project operations for eClinical development and delivery at ICON. Among the key challenges with DCTs are keeping sites and patients engaged, dealing with the near-constant inflow of data from digital platforms and wearable devices, and quantifying the value of various decentralized study components.  

Ellenor was speaking to a packed house about the “next phase” for DCTs at the recent Summit for Clinical Ops Executives (SCOPE) in Orlando. At ICON, one of the biggest contract research organizations in the industry, she leads teams working on fully decentralized trials as well as those assisting project managers in deploying hybrid studies. 

ICON has been doing DCTs for more than six years, well before the pandemic broadly popularized the model, she says. Here as elsewhere, requests for proposals (RFPs) for DCTs have more recently been on the decline with sponsors opting to employ them more sensibly and selectively.  

In terms of the sponsors that ICON works with, the appetite for DCTs between 2022 and 2023 remained largely stable in the biotech space, increased slightly (13%) among pharma clients, and grew significantly (92%) in the government sector due primarily to ongoing COVID studies, says Ellenor. Based on a 2023 poll of account directors, vice presidents, and general partners at ICON who have established key relationships with top pharma and biotech companies, roughly one quarter of sponsors have corporate goals around DCTs, and half are considering adopting such goals. 

RFPs for DCTs represent all study phases but most commonly phase 2 to 4 studies with a slight uptick in requests specific to phase 3 and 4 trials, she reports. From an indication perspective, an increase was seen between 2022 and 2023 for DCT studies in neurology, oncology, and immunology. Industrywide, she adds, oncology studies have been gaining momentum in the DCT space. 

Over the same period, shifts have also been seen in the DCT components making up those proposals, continues Ellenor. ICON’s expansion of its own digital platform resulted in huge growth on that front (up 239%), although the company continues to support third-party digital platform vendors with whom sponsors have partnered. But overall, ICON’s reliance on outside platforms decreased by 62%.  

A solid increase (up 88%) has been seen in DCT proposals using concierge services, she notes. These include tech support, compliance checks with electronic patient-reported outcome (ePRO) questionnaires and help with direct-to-patient shipment of materials that both support patients on their DCT journey and reduce some of the burden on sites. 

The number of DCT proposals using wearable health technologies remained roughly the same for the two years, Ellenor says, but the number of proposals using in-home services was down (by 36%). Direct-to-patient shipments also fell (by 43%), reflecting adoption of the fit-for-purpose strategy with DCTs. 

Patients Want Options

A survey of close to 4,000 patients across North America, Europe, and Japan that was conducted by ICON a few years ago found that 26% of respondents preferred to do study procedures on-site, says Ellenor. The majority preferred a hybrid approach combining remote and on-site visits or had no preference, which means they want options. 

As to how far they are willing to travel for procedures that need to be done on-site, the vast majority (90%) indicated less than an hour, she says, with nearly 60% of patients saying they’d be more willing to make the trips if they were to receive logistical support for those visits. When it comes to diaries and PROs, the method preferred by most patients (72%) is digital rather than paper. 

Patients’ desire for options was a repeating theme throughout the conference as well as a key finding of a 2022 survey conducted by two nonprofit organizations (TransCelerate BioPharma and the Center for Information and Study on Clinical Research Participation), adds Ellenor. 

In another recent poll aimed at investigators, Ellenor says, the top identified concerns with DCTs were increased risk to patients participating remotely (29%) and the potential to dilute patient care (28%). The therapeutic areas where DCTs can most benefit patients, they said, are cardiology, infectious disease, and neurology studies—a perspective having considerable overlap with the therapeutic areas they find most beneficial to their own site staff. 

Less than 10% of countries have issued DCT regulations and guidelines—the Food and Drug Administration (FDA) and European Medicines Agency (EMA) being the two big exceptions as of last year. Among the many topics covered by both FDA and EMA guidelines is the need to expand DCTs and use risk assessment, she says. 

The EMA guidelines recommend involving patient organizations as well as investigators in the process of protocol design, whereas the FDA talks about documenting a strong DCT strategy in plans and indicating in the protocol when remote and on-site visits are to occur. “These two strategies are what we encourage our sponsors to adopt,” says Ellenor. 

Filling the Gaps

ICON typically conducts at least 40 global clinical studies at any one time with varying degrees of DCT components, Ellenor shares. Questions asked by regulatory authorities are most typically related to eConsent or eSignature, concierge services, direct-to-patient shipments, and in-home services. 

Gaps in DCTs still exist in terms of change management, patient-centricity, data integrity, and diversity, she continues. Among the barriers to implementing or expanding DCTs are not having a process or a roadmap and, perhaps more importantly, the associated costs and lack of employees with the knowledge and experience to implement them. Other potential obstacles include finding the right vendors and integration of new and existing technologies. 

Adopting or expanding DCTs, “is not just a matter of flipping a switch,” Ellenor says. “You have to spend time... doing things like DCT vendor qualification and validation, which can take three to six months and has a significant cost impact.” A DCT operational model will also need to be created and SOPs modified.  

DCTs are intended to be patient-centric and are moving closer toward that goal, which means accommodating their desire for options, says Ellenor. Since not all patients want procedures done in their home, perhaps some of them can be conducted in the community where they live such as at a local lab or imaging center. Likewise, telehealth and on-site visits might be offered during off-peak hours to help lower the barrier to participation, especially for single mothers working a full-time job. 

Relative to traditional studies, DCTs collect more data directly from patients, Ellenor says, which presents data integrity challenges. Data needs to be ingested in a near-real-time way for purposes of assessing the “health” of the data, doing risk management and producing reports in a timely manner. “Especially in a DCT, we need to be able to visualize that data to look at those trends... [to] ensure those endpoints are being met.” To that end, she adds, ICON is implementing a new role for a “digital risk evaluator” for its DCT studies. 

DCTs are starting to make trials more diverse, says Ellenor, “but there is still more room for improvement.” The FDA recently published guidelines pointing to the importance of creating an inclusion development plan and documenting how underrepresented populations will be encouraged to enroll in trials and engaged once they’ve enrolled. This might mean providing 24/7 interpreter or language support, she offers as an example. 

Benefits and Challenges

ICON has conducted 120 DCT studies and seen positive outcomes in individual case studies, Ellenor reports. These have included a consistent 10% improvement in patient recruitment compared to enrollment rates seen in similar traditional studies. Patient retention has also increased, most significantly in studies supported by concierge or in-home services. 

Diversity has also improved in some DCT trials—up to 400% with an operational strategy in place—and compliance as well, particularly those using ePRO, she says. Enrollment can also be quite fast (28 to less than seven days). 

But doing DCTs, particularly the fully decentralized variety, is not easier than traditional studies, she stresses. It is challenging, at least at first, due to issues around digital recruitment, third-party digital platforms, patient retention, and syncing of incoming data.  

Recruiting patients into DCTs requires a multi-faceted approach, just like with traditional studies, and not the use of social media exclusively, says Ellenor. ICON invested in its own digital platform that has capabilities missing from third-party offerings and spends time training sites to counter resistance in adopting some new technologies. 

When visits are being done remotely, ICON uses concierge services or at a minimum encourages sites to keep in touch with patients, she says. On studies that use wearables and present the risk of a higher data bill for patients, ICON recommends the provisioning of devices. 

The Value Prop

Showing the value of DCTs from the patient perspective can be a matter of doing a survey at the conclusion of such studies that asks participants about their level of satisfaction with the different DCT components that were used and if they would be willing to participate in DCTs in the future, Ellenor says. Learning if they live in a rural or urban area can additionally help determine if geographic barriers are coming down. 

ICON has started to conduct a similar poll with sites at the conclusion of DCTs to assess their level of satisfaction with the decentralized study components and get their ideas for improving future studies, says Ellenor. Sponsors, meanwhile, are encouraged to embed a DCT strategy early enough in the pipeline so there is time to implement it—meaning, not after a protocol has already been written. 

This would allow sponsors to maximize the benefits that DCT studies can bring by, for example, “choosing a single digital platform that can be used across their entire portfolio,” Ellenor says. Under the best of circumstances, she adds, DCTs tend to be a cost-neutral proposition with the shifting of low-value activities from sites to concierge services. 

Two additional benefits of DCTs—the environmental and social impacts—are real but harder to quantify. Some sponsors believe DCTs can help them accomplish their environmental stewardship goals. DCTs can also be “quite attractive to patients who are very environmentally and socially conscious, and that in turn can increase enrollment in those populations.” 

So, what does the future hold for DCTs? ICON believes they are here to stay but evolving and impacting all sponsors and indications, Ellenor says. DCTs have disrupted the way clinical trials get conducted and artificial intelligence will be complementary, adding “an extra layer of much-needed change and efficiency.”