Published On July 7, 2022
Randomized clinical trials are the mainstay for new medicines. But trial enrollment is often a struggle, with 80% of trials not meeting enrollment deadlines and as many as a third of participants dropping out before the process is over. Part of the problem may be that trial design is trapped in a brick-and-mortar mindset, say critics, where a physical location serves as a single, inconvenient focal point for the delivery of care.
The Covid-19 crisis threw that model for a loop. After trial enrollment dropped 70% in the first months of the pandemic, researchers increasingly turned to remote methods of conducting trials that included telemedicine, wearables, smartphone apps and providers outside the hospital, a paradigm that is collectively called decentralized trial design.
The innovation is likely to be long lasting. The US Food & Drug Administration issued guidance in March 2020 to accommodate DCT designs and, in 2021, updated guidance for sponsors, investigators and institutional review boards. Congress is also deliberating over the 21st Century Cures 2.0 Act, with part of that legislation encouraging the wider adoption of decentralized trials.
“People realized that decentralized trials can make clinical trials more resilient to whatever pops up next—monkeypox, another war,” says Amir Kalali, a physician and co-founder of the Decentralized Trials Research Alliance, a nonprofit collaboration of more than 100 healthcare stakeholders to accelerate the adoption of DCTs. “Most of the methodology has been available, but people needed a gun to their heads to do it.”
About 1,300 decentralized trials using virtual or decentralized components will likely begin in 2022 a 28% increase from 2021 and a dramatic 93% boost from 2020, according to a GlobalData analysis. While that number accounts for less than 0.4% of all clinical trials according to the website clinicaltrials.gov, a recent survey of 127 senior clinical research executives also signals the ongoing shift. Nearly eight out of ten respondents said they plan to run at least one clinical trial using DCT components this year.
In theory, a DCT approach allows investigators to meet participants where they’re at, in their homes or easily accessible community sites, an approach that proponents say will result in faster and more diverse recruitment, improved participant experience and the generation of better data at reduced costs. Asian, Hispanic, Black and Latinos are also consistently and significantly under-represented in traditional clinical trials, an injustice that DCTs hope to right.
But whether DCTs will yield significant improvements over traditional trial processes and practices remains to be seen. “We’re in the early days,” says Sally Okun, executive director of the Clinical Trials Transformation Initiative, a public-private partnership established by the FDA and Duke University. The group is analyzing studies that employed DCT components during the pandemic to understand how these modifications impacted trial conduct. “DCT elements went into play emergently during Covid-19 without sufficient evidence behind them that this is going to make your recruitment more efficient, for example, or this is going to make the consenting process less burdensome,” Okun says.
A white paper on DCTs recently published by the Association of Clinical Research Professionals also raises concerns about data privacy, scalability and participant safety. Successful DCTs will need collaborative teams, including non-traditional partners from the technology world to support the utilization of digital communication and data collection tools safely and securely, says Jeri Burr, a nurse, lead author of the paper and executive director of the University of Utah’s Trial Innovation Center. “We need people who understand the back end of this technology and how these things work to help ensure data integrity,” Burr says.
One significant barrier to DCT adoption remains the digital divide. Around one in 14 Americans lack access to the internet, with rates higher in rural areas and among minority ethnic groups. “Whoever is funding and executing DCTs is going to need to write in support for these target patient populations early on, such as making sure remote monitoring systems are available and easy to use, and that someone is dedicated to tech support,” says Rebekah Angove, executive vice president, research and evaluation at the Patient Advocate Foundation.
Signs are that the clinical trials industry is also not quite ready for a full paradigm shift. Only two out of three clinical trial executives planning to conduct DCTs sites, for example, are prepared to incorporate telemedicine and eConsent software into their operations. That’s in sharp contrast to the proliferation of cloud-based platform solutions and other capabilities offered by technology vendors to enable DCTs, which are being financed at record rates by the venture capital community.
DCTs will only really come into their own once health care stakeholders bridge this gap between the tech industry and the operators of clinical trials—a feat that will take some time to accomplish. “We need to identify incremental milestones for the next few years and build on them and have evidence that we can keep scaling up,” Okun says. “That’s when transformation will begin to happen.”
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