Clinical trials have existed for centuries, shaped by brilliant minds, historical events, and medical crises. When COVID emerged, many research sites closed or patients stayed away as non-COVID trials paused. Decentralized clinical studies experienced a metamorphosis, putting into action what had previously been primarily ideas.
What is a decentralized clinical trial?
Decentralized clinical trials (DCTs) allow study participation to take place away from large research sites and academic centers, where patients traditionally must go for every visit. Study participants can avoid or reduce commutes to study locations through the use of:
- eConsent
- Telemedicine
- Wearable sensor devices
- Electronic clinical outcome assessments
- Electronic health records
Drugs and devices are sometimes shipped directly to patients’ homes. When needed, home health nurses perform blood pressure, ECG, phlebotomy, and other necessary services at the patient’s home.
DCTs have the potential to revolutionize our industry.
Many patients travel an average distance of about 25 miles to a research site. Some fly hundreds of miles. For eligible participants who live in rural areas, or who do not have transportation, or are unable to travel due to disabilities, financial limitations, child care, or work responsibilities, those miles might as well be infinite.
“Decentralized clinical trials are a key patient-centric development that is a direct response to participants telling the industry how to make participation more appealing,” said Dan McDonald, Imperial vice president of business development. “And they open up trial participation to a much broader and more diverse population.”
A search at clinicaltrials.gov finds 80 clinical studies with “decentralized” in the protocol title or study description.
The pandemic sparks decentralized clinical studies
The idea to make trials more patient-centric originated long before COVID but progressed at a gradual pace. When the urgency of the pandemic threatened the clinical trials industry, DCTs quickly evolved; however, the supporting technology and clinical team capabilities lagged.
“The pandemic forced a pilot study on a grand scale,” said Kenneth Getz, executive director and research professor at the Tufts Center for the Study of Drug Development. Getz is an internationally recognized expert on clinical trial management practices and trends. “More companies and their collaborators are using virtual and remote technologies but struggling behind the scenes to integrate and manage them routinely.”
COVID “forced clinicians to adopt and scale up approaches previously resisted,” Getz said. “When you are forced to do a pilot versus doing it at your own pace, it catches a lot of people flat-footed. ‘Let’s deploy DCTs, then think through how we can make it work.’”
Benefits of decentralized clinical trials
Convenience
The most obvious benefit is the convenience of taking part in a clinical trial from home or with minimal travel. Fewer site visits or visits closer to the patient’s home allow those with disabilities or other constraints to participate. This could lead to greater clinical trial enrollment for patients in minority populations or living in geographic locations not normally represented in trials.
My colleague Imogene Cheese interviewed four oncology study participants, and they told her that travel to the site for scans and blood tests was a burden. Lucy’s trial was in London, and each visit to the site was one hour each way by train. “You would go in on Wednesday, and go and have your bloods done, and go and see the doctor,” she said. “Then you would have to go back on Thursday for the treatment. The idea of it was it would all be much speedier because you’d done a load of stuff on Day 1. But it just never worked out quite like that. I’m lucky because it was only one hour away. But when I was very ill, it wasn’t brilliant having to do this over two days.”
An option for testing closer to home would have made Lucy’s participation easier and saved her precious time.
When patients can ask questions any time from home and focus on their everyday lives rather than pay for a hotel room and child care while missing work for another visit at an out-of-town medical facility, they are more likely to complete the trial.
Enrollment and retention
Faster enrollments and increased patient engagement can quicken a trial pace and reduce its cost. According to the National Center for Biotechnology Information (NCBI), trial retention rates for decentralized trials are 89 percent versus 60 percent for traditional trials.
DCTs have the potential to target more diverse participants, leading to trials that are more equitable and representative. For example, twice as many Black Americans as White Americans die from multiple myeloma, yet only 5 percent of clinical trial participants are Black.
Technological devices can track and record real-time measurements, providing investigators with accurate data and saving staff hundreds of hours previously spent recording patient diaries. It can show unreported drug effects or interactions not noticed by the patient. This data gives doctors real-time visibility of symptoms and allows for more time with patients.
Challenges
While technology can be a blessing, it can also be an unintended curse. Traditional trials rely on paper and pens, a nurse coordinator, and designated equipment at an investigative site.
However, every participant in a DCT may have his own personal handheld device or mobile technology. This requires technicians to train study staff members and patients on how to use the equipment and software and to problem-solve technology issues. All this adds time and expenses to the trial.
Getz said sponsors often prefer to issue their own private equipment. Patients might have older smartphones or are using outdated or no longer supported operating systems preventing them from downloading applications. Sometimes, study devices are not returned or, if used for multi-years long clinical trials, become obsolete. “There any many details we don’t typically think about,” he said. “There is a lot that has to be worked out and addressed.”
Engaging additional technology requires capturing more third-party data sources, such as home devices, electronic data systems, and wearable devices. This is in addition to drawing data from multiple separate patient health records that are not integrated. “The average patient has 5-6 health records that are not integrated,” Getz said. “These are on different and often incompatible systems. We have to figure out how to coordinate and collect data.”
Trying to organize all this data makes executing protocols in a timely manner more difficult. Organizations are trying to create a unified platform, but limited progress has been made so far. “It’s the Wild West with many different formats unique to each technology,” Getz said. “How to carefully coordinate and integrate a diverse and disparate collection of technologies is a challenge.”
Decentralized clinical studies can extend the trial timeline
A DCT can actually take longer than a traditional trial to close a database. Volume is one part. “There is a large percentage of data collected that is not even required,” Getz said. “It’s nice to have but not needed.”
A key problem yet to be resolved is how to combine all the data, run analyses, and create a central data repository that can easily integrate data coming in from so many different sources. “This is a very complex challenge that adds difficulty to trials,” Getz said. “The DCT movement is far ahead of the single unified platform movement. The tech exists; creating the infrastructure to coordinate all these technologies is still far behind. It will take years to work out.”
Where decentralized clinical studies work well
Chronic conditions, endocrine disorders, and other illnesses in which the patient is not immunocompromised can lend themselves well to decentralized clinical trials. Dermatology patients can take a photo of a lesion, and then a physician or artificial intelligence can determine how the treatment is working. Researchers can communicate through telemedicine, text messaging, wearable devices, and other home equipment to verify patients are taking their medications properly or otherwise check in on them.
Alzheimer’s disease patients need raters who meet standardization with training that is very specific. However, new apps are being developed that can, for example, capture motion disturbance, but humans still need to perform the ratings.
The hybrid trial
The majority of decentralized trials are hybrid, which use technology to treat study participants remotely or with minimal in-person visits at local medical centers, doctors’ offices, and even pharmacies. The particular trial determines what technology is required.
Most complex trials and conditions in which patient safety is at risk, such as cancer-related and immune-compromised diseases, must remain traditional. X-rays, magnetic resonance imaging, endoscopies, and other such tests can only be performed in medical facilities. At least 40 percent of trials have not been able to adapt to a decentralized format. Might there be fully decentralized trials in the future? It’s possible, but that’s a long way off.
Only about 20 percent of conditions lend themselves to 100 percent decentralization. But, said Getz, the primary issue is patient preference. “The vast majority of patients want options favoring hybrid approaches. They want a connection to site personnel and high touch components along with the convenience and benefits of impersonal approaches.”
That means a hybrid trial—a combination of traditional and decentralized—is a more patient-centric solution.
Facing decisions
When designing a trial, researchers need to decide:
- Whether to use a DCT, hybrid or traditional study design
- Which solutions to deploy
- Which vendors to contract with
- How to find sites capable of implementing these solutions
- What additional investment will be required
- Whether timelines need to be adjusted
- How to adapt a traditional study design to a partially or fully remote design
“There are many questions and curveballs that need to be addressed,” Getz said.
For example, if temperature-sensitive drugs are sent to a local health center or directly to the patient’s home, provisions must be made to ensure they are stored properly. Other considerations include data security, patient privacy and confidentiality, local staff availability, and technical support.
The current state of decentralized clinical studies
Now that COVID has eased, researchers are slowing the pace of DCT adoptions and examining protocol designs and clinical trial execution plans more deliberately. The clinical studies themselves will be trial and error, Getz said, as companies figure out how to best manage trials.
They must determine whether they have the appropriate collaborative teams and coordinated and integrated systems in place to support the demands of DCT deployments.
What challenges or successes have you experienced deploying DCT/virtual components? Scroll down and share your information.
