10/11/23

Decentralized clinical trials: Meeting
patients where they’re at
Innovations removing barriers to participation in medicalresearchMove over, COVID. Decentralized clinical trials (DCTs) is now the hot topic in thepharmaceutical industry. In fact, it was the COVID-19 pandemic that pushed DCTs to
the forefront, out of sheer necessity. However, DCTs were around for nearly a decadeprior to the pandemic. In 2011, Pfizer completed its first decentralized clinical trial. An
article in Frontiers in Public Health reports that the earliest studies on the feasibility of“internet trials” date back to 2003 and the first “Trial over the Internet” was patented in
the US in 2007.
“The pandemic didn’t catalyze innovation. These tools existed,” says Craig Lipset, cochair of the Decentralized Trials & Research Alliance (DTRA) and founder of ClinicalInnovation Partners, a consulting agency which provides growth advisory services toorganizations developing and implementing innovative approaches for clinical research
and medicine development.
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Decentralized clinical trials: Meeting patients where they're atLet’s start with a definition of DCTs. The Foodand Drug Administration (FDA) defines
decentralized clinical trials as “those executed
through telemedicine and mobile/local healthcare
providers, using processes and technologies thatdiffer from the traditional clinical trial model.”DCTs should not be confused with virtual clinical
trials, prompted by the pandemic, which have noface-to-face interactions. DCTs permit physicalcontact with the patient. Hybrid trials represent aCraig Lipset

middle ground, in what some consider the best ofboth worlds: a mix of in-person and virtual/remote elements.
In fact, a recent study conducted on behalf of the Trials@Home consortium, part ofEurope’s public-private Innovative Medicines Initiative (IMI), calls for standardized
terminology around DCTs. The study says DCTs should not be referred to as remote or
virtual clinical trials.
Lipset recognizes that the industry is full of jargon, and emphasizes that the publicshould know the research community is working to make trials as accessible as possible,
to give patients the opportunity to participate from anywhere.
Participation in a traditional clinical trial, in person at a clinical trial site, can beburdensome. This requires travel, may require time away from work plus additional
expenses such as childcare. These and other negative impacts could deter potential
participants from joining a research study.
Lipset says innovation such as DCTs must come with guardrails. Study sponsors mustensure participants are safe and protected, while maintaining data integrity. This
includes using consistent forms of measurement, for both traditional trials and DCTs.

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Decentralized clinical trials: Meeting patients where they're at

Despite these caveats, according to a recent Citeline white paper, “Unlocking thePotential of Decentralized Clinical Trials,” the number of trials with decentralized
attributes has gradually increased over time.

As the table above indicates, various tools and techniques are incorporated into DCTs.
The FDA uses an umbrella term, digital health technologies, to refer to many of the tools
used and has issued guidance on remote data acquisition. In January, the FDA’s Center
for Drug Evaluation and Research (CDER) also published its guidance agenda for 2023,
with plans to issue guidelines on DCTs before year’s end.
Likewise, the European Commission (EC), the Heads of Medicines Agencies (HMA) andthe European Medicines Agency (EMA) have published recommendations regarding
DCTs. The paper acknowledges that clinical trials have already adopted many
decentralized elements such as electronic calendars, wearables, phone calls, and online
appointments. How the elements are used depends on several factors, including thetype of study, the trial population, the disease being treated, the condition of the trial
participant, the type of medicinal product, its characteristics, and development stage.

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Decentralized clinical trials: Meeting patients where they're at

The paper advises that these elements “should be considered individually and incombination.”
The Clinical Trials Transformation Initiative (CTTI), another public-private partnershipdesigned to improve the quality and efficiency of clinical trials, has issued
recommendations to guide sponsors in conducting DCTs.

The Study Sponsor’s Perspective
In addition to being more patient-centric than traditional studies, DCTs have thepotential to positively impact a sponsor’s bottom line. According to an impact reportfrom the Boston area’s Tufts Center for the Study of Drug Development, DCT methods
increase value by $20 million per drug, if applied in both Phase II and III trials. In
another study, 75 percent of companies that completed remote and decentralized trials
reported both financial and time savings, and 50 percent reported streamlined patient
recruitment.

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Decentralized clinical trials: Meeting patients where they're at

The Citeline white paper lists the top 10 study sponsors conducting trials with DCT
attributes. Pfizer, which took an early lead as noted above, is in the number one spot.
Joining Pfizer among the top 10 is Sanofi, at number seven.
Kim Hawkins, Global Head of Clinical Project Operations & Dossier Delivery at Sanofi,
shares how her organization has made DCTs a priority since 2015, when it co-developed
the VERKKO trial (in collaboration with Langland and Mendor), Europe’s first fully
remote clinical trial, evaluating a patient-centric online clinical trial platform integrated
with a 3G-enabled wireless blood glucose meter. Hawkins says the trial, which waswidely recognized in the industry as one of the first fully remote clinical trials, marked
Sanofi’s desire to study this different model of running clinical trials.
While Sanofi did not have a drug or a device
under investigation, it supported the study
because it was interested in evaluating
remote trial participation and monitoring.
The study also evaluated the feasibility andefficacy of patient engagement and patientinvestigator interaction through the webbased platform. The VERKKO trial showedthat patient compliance improved 18 percent,Kim Hawkins

the study site spent 66 percent less timeengaged in study coordination activities, andthe online recruitment was completed 56 percent faster compared to the traditionallyconducted “sister protocol” second trial.
In 2017, Sanofi partnered with Science 37 in an effort to use its technical and mobile
capabilities for DCTs. Because Sanofi started building those capabilities into its
portfolio, Hawkins says that, when the coronavirus pandemic hit, “We felt like we werein a good place to continue to support our trials and our participating patients.”
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Decentralized clinical trials: Meeting patients where they're atShe says that, post-pandemic, “We have very strong commitment from our seniormanagement” for DCTs. Sanofi has launched a major initiative, Act for Patients,incorporating digital technology such as DCTs, artificial intelligence (AI), and an
integrated patient platform to modernize clinical trials. Hawkins says this is “anintegrated solution that our patients can use, our sites can use, and our partners can use— all in one platform.”
Sanofi and the University Medical Center Utrecht are leading the IMI €40 million
research project, Trials@Home, to study DCTs, with Hawkins as project co-lead. The
five-year project has workstreams to focus on different areas, including best practices,regulatory, data privacy, and stakeholder communication. The consortium will conduct
a pilot study comparing three different study arms: traditional, hybrid, and DCT, tocompare the pros and cons of each approach (RADIAL study).

The Patient’s Perspective
Ronnie Sharpe knows his way around a clinical trial. He says he has paid his dues,
estimating he has participated in about 15 research studies. Sharpe is COO of Savvy
Cooperative, a patient-owned co-op that connects people with opportunities to share
their health experiences with companies, researchers, and innovators. He co-founded
the co-op with Jen Horonjeff, who grew up with juvenile arthritis.
Sharpe has cystic fibrosis. He lives in Phoenix, and the most recent study heparticipated in was in Tucson, about a two-hour drive away. Initially, he had to makethat trek every two weeks, then every 30 to 45 days. This went on for over four years.
“When COVID hit, I wasn’t thinking about COVID. … What I was thinking was, how isthis going to impact the trial? This drug was definitely saving my life.”
That’s when the clinical trial switched from a traditional to a decentralized model.
Sharpe says a medicine-grade scale was sent to his house. Nurses drew blood samples
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Decentralized clinical trials: Meeting patients where they're atfrom him on his front porch, taking up only
about a half hour of his time. Everything that
had been done at the trial site, except for EKGs,
was now done at his home. The trial
coordinator checked in with him by phone ortext every three to four weeks.
“I absolutely loved the DCT setup,” says
Sharpe. Previously, in addition to traveling twohours each way, he spent four hours on site fora total of eight hours. “I work full time. It

Ronnie Sharpe

wasn’t easy,” he says, explaining that DCTs area more lifestyle-friendly trial design.
Teonna Woolford, who has sickle cell disease, was only 19 when she participated in her
first clinical trial, a traditional design. The trial involved a bone marrow transplant; hermother was the donor. Treatment included chemotherapy and radiation, which Teonna
knew could possibly cause infertility. But her doctor dismissed it and she was willing totake the risk.
As she researched her options for fertility preservation, she found little information andno resources to help pay for the costly procedure. While there were foundations
awarding grant money to people undergoing chemo and radiation due to cancer, there
were none for sickle cell patients. In the end, her body rejected the transplant, she still
has sickle cell disease, and she’s infertile.
That did not discourage Woolford from participating in future clinical trials. LikeSharpe, during the pandemic she participated in a trial that started out as a traditional
design but switched to a DCT. She says it was important the study designers had theflexibility to change up their approach. “That’s why I have a unique perspective,” shesays, “because I’ve done both” traditional and DCT studies. Her initial experience,
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Decentralized clinical trials: Meeting patients where they're atthough, did lead her to co-found, with Drs. Kim Smith-Whitley and Lydia Pecker, theSickle Cell Reproductive Health Education Directive (SCRed), which advocates for highquality sexual reproductive healthcare for individuals living with sickle cell disease.
The goal of the second trial was to assess pain in individuals with sickle cell disease.
Some patients experience daily, chronic pain. The trial involved a drug designed toreduce the stickiness of red blood cells, which can become hard and rigid due to sickle
cell disease.
To track their pain without medication,
participants were required to complete
daily surveys. For Woolford, the constanttext message reminders were very
disruptive to her day. “The questions
every day were the same, so I found it
annoying… I don’t have pain every day.”
There was no option to explain that, soabout a month into the two-month study,
Teonna Woolford

she dropped out of the trial.

“I was just starting a business at the time,” says Woolford, CEO of SCRed, in its second
year of operation. “When you hear DCT, you automatically think it’s going to be moreconvenient.” And, in many ways, it is. “I don’t have to pay for child care, find parking.”
Based on her experience, however, she says, “There shouldn’t be a one-size-fits-all.” Shenotes that some people are too private, others see their home as sacred. “That’s the one
place they can escape” from their disease. Woolford recommends more of a hybrid
approach “to meet the patient where they are.”
Savvy Cooperative’s Sharpe is sold on DCTs. “If we want to talk about patients, DCTs
are where it’s at.”

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Decentralized clinical trials: Meeting patients where they're at

What’s on the Horizon for DCTs?
“We’re already starting to see this future come to light,” says Lipset. More expansive
locations include in-home testing, retail pharmacies, pop-up sites, mobile sites such as
retrofitted ambulances and RVs.
“These are research sites. They just happen to have wheels.”“There is potential to significantly reduce our [drug] cycle time. Every single new
medication that’s on the market goes through a clinical trial, and only about 10 percentof the population participates in a clinical trial,” says Sanofi’s Hawkins. With DCTs, sheadds, “There’s opportunity to have clinical trials be a choice for more people.”
In addition to improved cost savings, increased efficiency, patient access, recruitment,diversity, and retention, Lipset says many sponsors — mostly in Europe — are looking at
DCTs through the lens of corporate responsibility. One focus of the Sustainable
Healthcare Coalition is reducing the carbon footprint of clinical trials. In terms ofsustainability and environmental impact, DCTs outperform their traditionalcounterparts.
However, industry stakeholders agree that patients should be the motivating factor inconducting DCTs. Lipset cautions: “With decentralized clinical trials, patients should
feel more connected to the investigator, not less.”
Savvy Cooperative’s Sharpe sees DCTs as a launchpad for what’s next, what’s truly propatient. He’s optimistic yet skeptical as he asks: “What else is being held back because ofbureaucracy, the healthcare apparatus in the U.S.?”

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About Citeline

Decentralized clinical trials: Meeting patients where they're atCiteline, a Norstella company, powers a full suite of complementary businessintelligence offerings to meet the evolving needs of health science professionals toaccelerate the connection of treatments to patients and patients to treatments. Thesepatient-focused solutions and services deliver and analyze data used to drive clinical,
commercial, and regulatory-related decisions and create real-world opportunities forgrowth.
Our global teams of analysts, journalists, and consultants keep their fingers on the pulseof the pharmaceutical, biomedical, and medtech industries, covering it all with expert
insights: key diseases, clinical trials, drug R&D and approvals, market forecasts, andmore. For more information on one of the world’s most trusted health science partners,
visit Citeline.

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