By Deborah Borfitz  

January 30, 2025 | Patients with cancer typically have a strong emotional connection with their doctors and nurses that is an important part of their healing process. It follows that those taking an investigational therapy should be offered decentralized clinical trial (DCT) components that serve to enhance that bond rather than do away with it, according to Peter O’Neill, vice president of clinical operations at TuHURA Biosciences, Inc.  

That is far too often not the case, he says. Study sponsors instead try to fit a DCT solution into a trial without ever talking to patients to learn if it would solve any of their problems. “That’s how decentralized trials have gotten some backlash.”  

Finding the “sweet spot” with DCT capabilities in oncology will be the subject of a presentation O’Neill will be making at the upcoming Summit for Clinical Ops Executives (SCOPE) in Orlando. Flexibility is key for anyone with a disease like cancer that has a significant impact on their day-to-day life or is potentially terminal, says O’Neill. 

Electronic patient diaries have been successfully used in cancer trials for decades now, he points out, including a study he worked on 15 years ago involving an elderly patent population. Telehealth can likewise be a valuable option for patients living far from a world-class academic center that treats cancer.   

When COVID hit, and DCTs launched into popularity, industry was quick to implement technology allowing for virtual visits and hire third-party companies to do remote collection of blood samples, says O’Neill. “But it rubbed a lot of sites the wrong way because it made them feel like sponsors were trying to replace them.”  

The move to telehealth visits was useful in keeping patients in trials who had to stay home but missed the importance of face-to-face interactions between patients and sites. “Cancer patients look forward to seeing their doctor and their care teams, and their loved ones want to go with them and learn the status of their disease and what their options are,” O’Neill says. 

Personalizing Options  

Fully virtual trials where patients are having telemedicine visits with one central investigator don’t typically work well in oncology, except perhaps studies focused more on prevention, says O’Neill. A sponsor’s best bet is to give patients choices so they can make a trial work in the context of their unique life circumstances.  

O’Neill’s first experience with offering the virtual visit option was five years ago in a study with patients who had advanced cancer. “We were surprised that there was really no interest... the patients still wanted to see their doctor, even during the pandemic.”  

Patients weren’t the only ones averse to virtual visits, O’Neill says. Sites, too, were crying “too much tech” as each trial invariably came with a different telehealth platform. 

O’Neill says he tried to figure out ways to introduce multiple technologies with a single sign-on, but it’s a complicated proposition given the IT security concerns of academic institutions. Some electronic data capture systems already have this capability to enable sites to access multiple studies with just one set of login credentials, and “industry knows this is where we have to get” with telehealth portals. 

But for oncology trials where the survival benefits for patients may be only a few months—and the ability to offer them an improved quality of life during that time could be pivotal to their recruitment and retention—it’s all about personalized options, he adds. “I think there is a future where every trial should be a hybrid trial, especially larger trials where you are trying to pull patients from a lot of different areas and ages.” 

Tried-and-True DCT Components 

Electronic clinical outcome assessments (eCOA) via widely used patient diaries seems to be an ideal use case for “decentralizing” oncology trials, says O’Neill. The question now is whether to give patients devices or have them use their own. 

Some patients want “separation of church and state, so to speak,” he says. “They don’t want their personal devices they’re using to look at Facebook to also be how they’re participating in a clinical trial.”  

But the sentiments of younger patients may trend a bit more in the other direction. O’Neill reports that early in his career he had success giving patients a Palm Pilot, in the years before the iPhone became the preferred personal digital assistant, to self-report quality-of-life data daily. 

Letting patients get required blood draws at a local lab and then sending the data to the trial site in a compliant manner is often helpful—particularly for patients with a rare cancer who would otherwise have to fly many miles for only that one procedure, he adds. This is yet another option that has been around for a long time and is now considered part of DCTs.  

Role for Digital Twins 

Before getting to the question of which DCT components to include or exclude in an oncology trial, O’Neill says, the first and more important question is this: “How can we develop drugs and show efficacy and safety with less patients in a quicker time to get the effective drugs to patients faster?” 

Not every pivotal trial is going to need hundreds or thousands of participants, he says, turning to the topic of digital twins. But that’s often the enrollment goal simply because nobody is using the data that was already collected in previous like trials enrolling the same patient groups.   

Some sponsors have wisely been looking for ways to use aggregated data from prior datasets to generate an external control arm and thereby power randomized, placebo-controlled oncology studies in a way that reduces the number of patients getting an inactive substance on top of their standard treatment, says O’Neill. Real-world data can similarly be used to create digital twins, but trial data is ideal because it controls for protocol-specified variables and conditions—not to mention the fact that trial participation itself can lead to better outcomes since patients are receiving more focused healthcare and closer monitoring and attention from medical professionals.  

The U.S. Food and Drug Administration has indicated that it may accept external control arms when it's not feasible or ethical to use an internal control. “It would be great to totally replace a placebo group” with a digital twin, O’Neill says, but most industry professionals do not yet see this as a realistic possibility. 

In the near term, the more likely scenario is reuse of data to support a trial, he adds. O’Neill cites as an example a trial for graft-versus-host disease, a complication of cancer treatment, where the control arm are patients taking corticosteroids. Many patients have taken generic corticosteroids so plenty of data is readily available to understand what happens in patients with the disease, in a study setting, when they take such drugs.  

Easing Burdens of Participation 

If there is no other option than to enroll hundreds of patients in a clinical trial, the next question is how to make it as easy as possible to participate, O’Neill says. In oncology, the reality is that the study may be “just a burden” for those in the control group who would be getting the same drug they would be taking anyway. In other cases, the enrollees are patients who have no other treatment options, and the trial therefore offers hope to patients and families.  

Before deciding whether to add decentralization components to a study, he says, the focus should be on collecting “just the data we need,” says O’Neill. “A lot of trials are collecting too much data at too many time points.” 

One common scenario is when study teams try to decentralize a trial after the protocol has been written on the presumption that patients would be going to a single, designated location for study activities, O’Neill continues. It can be impractical to later decide to do blood draws at home when multiple other procedures have already been packed into the visit schedule. Studies must be built “from the ground up” to be as least burdensome as possible. 

To know how to make a trial easier for patients, “it is always great to ask the patients that question,” says O’Neill. Companies have smartly established patient councils for just this reason.  

This includes asking them about having study visits happen virtually. The biggest opportunity here will likely be with patients living far from study sites, he says, not those in a region like Philadelphia who may live five minutes away and would prefer to go see their doctor in person.  

Key Takeaways  

Many of the trial sponsors driving innovation in DCTs are larger companies that can carve out a budget for the added investment, says O’Neill, who is a former senior director of clinical operations at Incyte. The implementation of decentralized options also requires that participants have confidence in DCT research processes (e.g., remote data collection, self-reporting, and virtual interactions) when they aren’t physically present at a research site.  

Trials enrolling hospitalized patients dealing with relapsed or refractory cancers would be inherently difficult to decentralize under any circumstances, he adds. This would include patients being treated with CAR T-cell therapies, a cutting-edge immunotherapy that trains their immune system to target and destroy cancer cells.   

DCTs, when appropriate, “should focus on improving the patient experience,” he emphasizes. “The technology out there should serve the patients and not the other way around.” Technology never seems to fit if those solutions, rather than patients, are the starting point.  

The decentralized trial elements that O’Neill favors incorporating into oncology studies “make patients feel more connected to their teams and research sites feel more connected to their patients... not the ones that are trying to replace the doctor with some centralized site doing a virtual trial.”