By Deborah Borfitz

January 4, 2022 | Decentralized clinical trials (DCTs) are a valued option for many would-be study participants as well as a chance to customize the research experience and cater to their needs, according to Ken Getz, founder and chair of the Center for Information & Study on Clinical Research Participation (CISCRP). Findings of CISCRP’s 2021 Perceptions and Insights study indicate interest in DCT approaches is quite high provided they don’t interfere with the quality of patients’ personal relationship with study staff. 

“The site is still considered a sacred and integral part of the relationship with the patient, so the options that are offered have to include the opportunity for in-person contact,” says Getz. Patients also want to feel that convenience is being considered to help reduce and manage the burden of participation, as they have consistently expressed since CISCRP began administering the biannual survey in 2013.

Acknowledging the burden makes study participants feel like “part of the team,” says Jim Murphy, CEO of Greenphire, the leading clinical trial payment automation provider. Oftentimes, feeling connected is a tougher proposition in DCTs than traditional clinical trials where patients have a personal relationship with someone they trust.

It can be more difficult in a remote environment to troubleshoot issues that may arise, potentially amplifying frustrations, adds Murphy, who empathizes with their plight. Only a few months ago, Greenphire hosted its inaugural Patient Convenience Summit where Getz revealed results of the Perceptions and Insights survey, completed by 11,793 people (including 5,505 trial participants) around the world, including higher-than-customary responses from folks abroad.

Back in March, Greenphire also joined the newly launched Decentralized Trials & Research Alliance working to accelerate the adoption of patient-focused approaches to DCTs. Those methods include timely payments to sites and patients, says Murphy.

Greenphire supports sites by taking over labor-intensive admin tasks so they can concentrate on providing care, recruiting participants, and completing studies, he continues, most notably via investigator payment solution eClinicalGPS. The companion solution for participants is ClinCard, streamlining their reimbursement for out-of-pocket costs (e.g., travel to a local lab) and micro-payments for rewarding protocol-compliant behavior (e.g., filling out an ePRO diary for the week) and recognizing the time and effort involved.

For both traditional and hybrid trials with decentralized components, Greenphire provides a “bridge to the patient,” says Murphy. When studies are fully virtual, the company can literally function as the “connective tissue” helping to sustain the site-patient relationship.

As Murphy and Getz are both aware, DCTs are still in the early stage of development with sites and patients encountering some of the inevitable hiccups. And those are precisely the places that now have their attention. 

Not ‘Either-Or’

The latest CISCRP survey gathered more granular insights about the adoption of virtual and remote support that accelerated during the pandemic, says Getz, including differences in experiences and perceptions by population subgroup such as race and ethnicity. “We also wanted to see if attitudes about clinical research safety and willingness to participate would change now we’re into this pandemic-facilitated operating environment.”

While awareness about the importance of clinical research rose, continues Getz, general attitudes toward such studies changed surprisingly little. But self-reported understanding of trials decreased since the 2019 survey—particularly among diverse communities and those who have never participated in clinical research.

Some people expressed concern about the safety of trials but the willingness to participate remains relatively strong—a finding consistent with previous surveys. Participants who identify as Black or African American tend to have more concerns about the safety of trials, Getz says, while those in the Hispanic and Latinx community were less willing to use remote or virtual approaches. “But the differences were really pretty small overall” and in keeping with prior survey findings.

The hybrid model of DCTs can accommodate their voiced desire to maintain quality interactions with study staff, Murphy adds. Technology has played a critical “bridging role” in allowing some study visits to be conducted remotely as a matter of convenience, if not patient retention, but virtual-only trials are a rarity because they’re applicable to a relatively narrow subgroup of study types and indications. The necessity of collecting data from multiple sources also makes them difficult to execute.

“People who join clinical trials have altruistic intent… and trust is huge,” says Murphy. “It is hard to build trust with someone you don’t meet face to face but at the end of a digital connection.”

Getz agrees, saying it speaks to the need for sponsors and contract research organizations to think about DCTs as a balance between convenience of the virtual elements and the personal touch of in-person interactions. It’s not an “either-or” proposition.

The amount of patient support Greenphire handles around the world is a good proxy for the level of clinical trial activity that is happening, Murphy notes. By that yardstick, the pandemic has “materially suppressed” the rate of enrollment into non-COVID studies even well into fall of 2021.

Given the availability of technology, he says, that begs the question: Do people still feel unsafe going to the doctor, delaying their diagnosis, or are they feeling disconnected and unmotivated to seek out trials? “I don’t know that [DCT technology] is the problem but I don’t know that it’s the solution yet either.”

Gaining Experience

About one-quarter of patients state that they prefer trials be completely remote, while most of the rest have voted for a mix of virtual and in-person components, says Getz. But how sites can accommodate the various preferences of individual patients in a clinical trial is “very nuanced.”

Mature, high-volume sites and site networks that are more comfortable working with DCT technologies—telemedicine, wearable devices, smartphone applications, in-home health assessment tools and specimen collection, use of patient health information and electronic medical records, home clinical trial supplies, and ePRO questionnaires—"like the idea of offering options to different groups of patients.”

Those sites tend to work in the major chronic disease areas or on vaccine trials, continues Getz. Sites focused in areas such as rare diseases and oncology, where patient subpopulations are narrowly defined and hard to find, often lack experience with some DCT technologies. They may in fact be conducting their first-ever trial.

Based on anecdotal reports, inexperienced sites had a particularly difficult time in the early days after the pandemic-related lockdown managing their relationship with DCT vendors, says Getz. But the process quickly streamlined thanks to exceptional efforts by those companies to be responsive and accommodating.

Moving forward, study sponsors must consider the nature and scope of a trial, and the type of sites they want to engage, with their planned DCT approach, says Getz. But the pandemic has forever changed the equation by effectively forcing site staff to gain experience with technology in a matter of weeks.

When asked if they would be willing to use DCT-enabling technology, most patients say yes, he adds. Their response is much more mixed when asked if they’re open to having telemedicine replace an in-person visit.

‘Neutralizing’ Burdens

“One of the primary reasons for people to drop out of a clinical study is they feel like the burden is greater than they expected,” says Murphy, adding that Greenphire endeavors to “neutralize” the unsettling cost and inconvenience.  “We want to make sure patients feel like their time is valued and their expenses are being reimbursed in a way that shows the sponsor and the site care—and that applies whether it is a decentralized trial, a traditional trial, or somewhere in between.”

With DCTs, more trial activity is happening outside of sites’ physical supervision, making compliance with study protocols more complicated, Murphy says. The burden of trial-related activities falls more heavily on participants and is “probably [mentally] straining in some new ways.”

Greenphire’s role, he adds, is to create ways to reinforce desired behaviors and facilitate compliance. The means can be as simple as paying participants $5 as a thank you for their 20 minutes of time and engagement in filling out an ePRO diary for the week.

It is comparatively easy to “meet every patient where they are” in the clinic setting because the site team serves as the intermediary between participants and the sponsor technology deployed for a trial—including systems for randomization, electronic data capture, and electronic clinical outcome assessment, says Murphy. With DCTs, the process can be more “bespoke” if sites use their own homegrown telemedicine system or a provided solution and there is potentially multiple mechanisms for collecting clinical data.  

Without question COVID-19 has fostered an accelerated rate of evolution in the use of technology that is likely to persist over the long term along with a “better blend” of home and in-clinic visits, says Murphy. That transition will be “absolutely fundamental,” given the ever-increasing complexity of study protocols that Getz has been reporting on for nearly 25 years now.

Movement in this direction had already begun prior to 2020, says Getz, highlighted by the introduction of solutions designed to address the growing level of customization in clinical trials, fragmented nature of executing protocols, and increased interest in patient engagement. “The pandemic brought this all into very clear focus and facilitated more piloting, more experimentation, and more innovation.”