Telehealth Framework Sets Stage for Decentralized Clinical Trials in Oncology

The use of digital technologies and the emergence of telemedicine capabilities during the COVID-19 pandemic have allowed decentralized clinical trials (DCTs) to gain momentum in the clinical landscape.^1,2 DCTs are characterized by having some or all of its activities take place at locations other than a traditional clinical trial site. These alternate locations can include the patient’s home, a local health care facility, or a nearby laboratory.

DCTs offer the advantage of faster data collection, improved data quality, and analysis. Patient access and engagement are also enhanced with DCTs. They also offer further clinical research opportunities for clinicians who might not have access to traditional trial locations.³

Decentralized supply chains and existing facilities such as laboratories, imaging centers, urgent care centers, or emergency departments, can be leveraged with patient screening, enrollment, and trial logistics being managed by a remote team.⁴

“The challenge that decentralization of a clinical trial can help address is access,” Shaalan Beg, MD, said in an interview with Targeted Therapies in Oncology. “There are many barriers to clinical trial enrollment, which is why less than 5% of people with cancer end up enrolling in clinical trials,”⁵ Beg, an adjunct associate professor of internal medicine at The University of Texas Southwestern Medical Center in Dallas, said.

“A lot has to do with the way trials are designed and includes the inclusion or exclusion criteria and the intervention itself. But the biggest structural barrier is that most clinical trials are not available at the locations where people with cancer are seen…in the community setting,” Beg said.

Clinical trials traditionally use large, urban academic centers to recruit, enroll, educate, treat, and follow-up with patients. Alternatively, DCTs tend to rely on technology, such as mobile phone technologies, to engage with patients, but they also leverage local clinics or home health providers to decentralize some or most of the data collected.

Are DCTs a Good Fit for Oncology?

For many years, oncology wasn’t considered a good fit for DCTs because it was felt that the patients were too sick or the therapy was too toxic. However, that belief has changed with the availability of new treatments such as targeted medications, medications that can be administered orally or subcutaneously, and the ability to provide home infusions (TABLE³). Beg mentioned 2 programs: the Penn Home Infusion Therapy program based at the University of Pennsylvania and the Huntsman at Home initiative out of the Huntsman Cancer Institute at the University of Utah.

The Penn Home Infusion Therapy program consists of a multidisciplinary team of clinical pharmacists trained in home infusion who are available 24 hours a day. The nurses on the care team undergo extensive training and customized orientation with every member of the care team, learning to assess, educate, and care for patients undergoing infusion.⁶

The Huntsman at Home initiative has demonstrated overall reductions in health care costs and utilization, according to a study by O’Neil et al.^7,8 In a retrospective case-control study, a total of 169 patients admitted to Huntsman at Home were compared with 198 usual-care patients.

A total of 5 dichotomous groups were evaluated, including sex (female vs male), age (≤ 65 vs < 65 years old), income (≥ $78,735 vs < $78,735), Charlson Comorbidity Index (≤ 2 vs < 2), and current systemic anticancer therapy vs no current systemic anticancer therapy.⁷

Among patients admitted to the Huntsman at Home program, investigators observed an overall reduction across all 4 health care costs and utilization outcomes compared with patients who received usual-care treatment. In at least 2 of the 4 outcomes for each subgroup, outcomes favored patients who were enrolled in the Huntsman at Home program. Findings were statistically significant (P < .05).⁷ Kathi Mooney and colleagues wrote in their paper that “oncology hospital at home program shows initial promise as a model for oncology care that may lower unplanned health care utilization and health care costs (FIGURE).”⁸

“Being able to administer cancer treatments is increasingly becoming feasible outside of the traditional clinic, and even at home,” Beg said. “I’m not saying that all cancer treatments can be given at home, but there is a significantly large segment of treatments that are conducive for at-home delivery.

Overcoming challenges to deliver care is important. Another obstacle associated with traditional clinical trials stems from difficulty in reaching enrollment numbers.

"Many oncology trials are behind on enrollment,” Beg said. Traditional clinical trial enrollment may take years to complete; further, the time it takes to review and approve new medications is also considerable. “By improving clinical trial access, you’re able to bring those patients into clinical trials and complete the study in a timely manner,” he said. “You are also able to enroll patients who otherwise would not be seen at traditional trial centers.”

One advantage that is associated with the use of DCT methods, Beg noted, is that oncology is one of the few specialties where clinical trials are considered part of standard patient care. “That’s very different from other specialties or conditions,” Beg said. “In other conditions, a patient may be seeing their regular doctor but may also be seeing a different clinical trial doctor,” Beg continued.

In oncology, the physician and their team know that a particular procedure is part of the clinical trial and another procedure is part of the standard of care. DCT methods can allow the trial participant to maintain their relationship with their primary oncologist as usual, as the research team provides infrastructure for any research-related procedures. This limits the burden on the primary oncologist and doesn’t affect their workflow, according to Beg.

Alternatively, in a traditional trial arrangement, community oncologists would need to refer patients to a clinical trial site, which can disrupt their relationship with the patient. There could be financial implications around this as patients are referred and treated at trial sites, Beg explained, and sometimes patients are unable to travel long distances to large cancer centers.

Benefit to the Patient and Oncologist

For the patient, the benefit of participating in DCTs manifests in their quality of life. Beg said that when a patient is seen in their oncologist’s office over a period of time, they get used to interacting with the staff every week or every month, and this can go on for years, so those relationships are established and built up. It can be very disruptive if a patient has to enroll in a clinical trial that’s farther from home and routines have to be adjusted, whether it be work routines or caregivers’ routines. “Patients don’t always want to do that because it can affect family members,” he said.

Beg pointed out that there might be resistance from the patient, from a cultural perspective, of having a health care professional in their home, delivering cancer treatments in front of grandchildren and other family members, especially when not everyone in the household may be fully informed. “But most of the time, the benefit outweighs the risk,” he said. “Easing the burden so family members don’t have to take time off from work, patients don't have to worry about transportation to the clinical trial center, or scheduling conflicts, are important factors.

Adopting DCT methods also benefits the oncologist by allowing the community oncologist to be part of the drug development process and opening up other resources and the potential for building additional expertise. “Most community oncologists would agree that the best care a patient can receive is within a clinical trial,” Beg said.

For the community oncologist, explaining to the patient about the potential of traditionally formatted clinical trials, only to be informed that too many logistical or geographic challenges exist, is tragic. “We need to figure out what the best structure is for community oncologists to support trials incorporating decentralized methods,” Beg said. “At the same time, we have to understand how to best incentivize oncology practices to support these activities.

Living in a Post–COVID-19 World

As patients and physicians emerged from the COVID-19 pandemic, investigators realized that many components available to DCTs had been available before the pandemic. Beyond its effect on administering treatment, decentralizing trials identified more participants to enroll, reduced the burden for patients who were enrolled by limiting the number of unnecessary visits to the trial site, and improved the efficiency of the administrative staff by bringing in only patients who were eligible for the clinical trial. “The technology was in alignment. COVID-19 has shown us that we can deliver cancer treatments and that remote tools will not compromise the clinical care we deliver,” Beg said.

In particular, care that’s delivered in the patient’s home can lead to a level of personalization that was not seen previously. “We’re seeing research staff and nurses who are able to go to the patient’s home and assess how they are living.” Beg said. “They can identify any structural barriers that may prevent a patient from following clinical trial protocols, and they can develop a relationship with the patient, their family members, and even their pets.” Regardless, if a trial follows a traditional methodology or incorporates decentralized methods, the principal investigator needs to ensure that any research activity that is taking place is reaching a level of compliance. This includes appropriate documentation, a delegation of responsibility log, and other regulatory documents that are required and maintained.

Beg said that if procedures are carried out in the patient’s home or at another facility, there may be steps that the sponsors and investigators of the trial have to complete; these all must be in place to allow for adequate oversight. “If not performed appropriately, we may be placing an undue burden on the community oncologist,” Beg said.

Huntsman at Home Program Data

Improving Costs and Efficiencies

A recent study demonstrated that implementing decentralized approaches can significantly improve trial efficiency and lower costs by reducing screen failure rates and making consent and enrollment more convenient. This eases the burden of time and travel by providing interventions remotely, facilitating remote measurement of outcomes, and increasing trial speed by minimizing protocol amendments.⁹ Use of DCT methods may provide operational efficiencies by automating certain manual data collection tasks while allowing for more frequent communication with participants and more productive site personnel.⁹

In the study, research sponsors quantified the net financial impact of deploying remote and virtual approaches to support clinical trial execution. This was carried out by the Tufts Center for the Study of Drug Development, which is an independent academic group within the Tufts University School of Medicine, in collaboration with Medable Inc, a technology provider of DCT software as a service.⁹

Investigators developed an expected net present value (eNPV) model to demonstrate the cash flows for new drug development and commercialization to assess the f inancial impact of DCTs. The measure of DCT value is the increment in eNPV that occurs, on average, when DCT methods are employed vs when they are not. They noted a substantial value when DCT methods were used in phase 2 and 3 trials. If used, sponsors would see an increase in value of $20 million per drug that enter phase 2 trials, which translates to a 7-fold increase in return on investment.⁹

FDA Guidance

As interest in DCTs gains momentum, the FDA has weighed in with draft guidance. The guidance¹⁰ provides recommendations for trial sponsors, investigators, and other stakeholders for implementing DCTs. The guidance applies to DCTs where some or all of the trial-related activities occur at locations other than the traditional clinical trial sites.

The document invites comments from the public on DCT design, remote clinical trial visits and clinical trial-related activities, digital health technologies (referring to any transmission of data remotely from trial participants wherever they are located), roles and responsibilities, informed consent, and other topics.¹⁰

“We expect the final guidance will be available soon,” Beg said. “The guidance will address those areas that are somewhat unclear [regarding] roles and responsibilities in research and how it should be interpreted.”

“Decentralization in clinical trials is happening. It’s not something in the future. The real question is: How can we increase its presence to solve the problem of clinical trial access?” Beg asked. He suggests that the first step is to make it part of the regular care continuum.

“Demystifying the processes so it be- comes part of the standard clinical research activity will promote the further adoption of decentralized methods. Institutional review boards, the FDA, sponsors, and investigators are increasingly becoming familiar with these processes.

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