Clinical trials, a crucial phase of drug development, continue to evolve as new technologies allow researchers to manage them without participants coming to a physical location. Historically, they had to go somewhere to get medications and report results. Now reporting is done online and drugs are delivered by mail, in what are called decentralized trials (DCTs). The trend began before the Covid-19 pandemic, but it has significantly increased drug companies’ need to use this approach.
The very first DCT was done by Pfizer in 2011. It was known as the REMOTE (Research on Electronic Monitoring of Overactive Bladder Treatment Experience) trial, part of a so-called Investigational New Drug Application with the FDA.
“The scientists managing the study recruited participants on the Internet, relied on online questionnaires and electronic diaries, and delivered the drug under investigation directly to participants’ homes,” says Rob Goodwin, vice president and head of operations for global product development at Pfizer. Recruiting participants was a challenge. “It wasn’t easy to bring patients in through the Web,” continues Goodwin. “Not having a central study site presented a logistical challenge. But we learned a lot. It was a springboard for several other trials, and it set us up well for the pandemic.”
A few years later the FDA officially called for “new strategies to modernize clinical trials to advance precision medicine, patient protections, and more efficient product development.” In a 2019 statement, then-FDA chairman Scott Gottlieb said that critical medical innovations could be delayed or completely lost because the cost of testing had gotten so high. He said the U.S. needed “a more agile clinical research enterprise capable of testing more therapies or combinations of therapies against an expanding array of targets more efficiently and at a lower total cost..”
Traditionally, drug trials have been performed by clinicians or researchers affiliated with an academic medical center or hospital. Participants come to the facility, where drugs are dispensed, vital signs measured, and tests carried out. Such trials remain the gold standard, says Yosef Khan, principal for clinical trials and real-world evidence at Premier, a healthcare improvement company, and remain necessary for products such as surgical and medical devices. But in many cases they drain sponsor resources and impose a burden on participants, many of whom might not live nearby and/or face transportation and time challenges.
Three factors, says Khan, have led DCTs to evolve during the past 20 years. The first is frustration on the part of clinical researchers about the length of trials and the resulting attrition among participants. Then there is the rapid growth of technologies that allow researchers to conduct remote trials or access clinical registries, which are vast databases containing real-world data about medical conditions and how doctors are treating them. Finally, the government has given a push. The federal 21st Century Cures Act was passed in 2016 to accelerate the “discovery, development and delivery” of medical therapies. It encouraged biomedical research investment and facilitated more rapid innovation in review and approval processes, among other things. Khan says additional regulation remains necessary to ensure that the data collected in DCTs going forward is accurate and reliable.
Decentralized trials offer a range of benefits, including reducing the needed size of research teams and lowering costs for drug companies. More participants may be attracted to trials that eliminate worries about travel and time demands. And perhaps most importantly, because physical boundaries disappear online, researchers can broaden their participant pool to more accurately include people of diverse ethnicities, genders, and ages.
This addresses real problems with how medical science has proceeded until now. “Studies show persistent minority underrepresentation in clinical trials, even for conditions that affect them disproportionately,” reports the Journal of the American Medical Association. “Black people accounted for only four percent of 300,000 participants in trials of cardiovascular and diabetes medications approved by the FDA from 2008 to 2017, and Hispanic individuals accounted for 11 percent.” (Black Americans represent about 12.8% of the population, and Latinos 18%.) Recruiting minority participants for Covid-19 vaccine efforts in the past two years has been a challenge, according to some researchers. Improving the diversity of trials is critical, says Khan: “If I have only white men in the trial, can I really say the drug will work for all demographics?”
“There is great hope that DCTs will increase diversity, bring in unmet populations, and increase retention,” says Pfizer’s Goodwin. “I would say it’s too early to determine whether these efforts are panning out…You’re trying to create the best experience for the patient, but some populations have concerns and simply won’t join a trial. The challenges aren’t simply related to technology. We must continually focus on making patients comfortable.”
Despite the clear benefits DCTs offer—including, says Khan, the ability for small biotech startups to more easily carry out clinical trials—they come with challenges. Sending drugs to individuals by mail can be complex and even pose a risk if shipments are lost or compromised. Wearable biometric devices, often required for modern trials, are still relatively finicky, and troubleshooting them remotely can be difficult. There are also privacy concerns about online reporting, though blockchain technology offers some ways to protect personal healthcare data.
“When the pandemic hit, we weren’t new to DCTs, which gave us the ability to move quickly,” says Goodwin. “To develop the coronavirus vaccine, we were able to take advantage of existing technology such as telemedicine, and work with local labs, so patients didn’t have to travel. We used e-diaries and a range of apps that people could download to their mobile devices, though some people chose to use physical diaries to record signs and symptoms. We taught people to swab themselves, and had the swabs picked up at their homes.”
Pfizer doesn’t rely on in-house technology for its DCTs—it partners with third-party companies that handle many aspects of remote trials. Medable, umotif, and snapIoT are among the companies operating in this industry.
Ultimately, says Goodwin, “a hybrid approach is the way of the future.” In such cases, participants might show up in person at the beginning of the study for necessary lab tests and paperwork, and return only if the study required it or if they experience an adverse event.
Despite hurdles, remote trials are likely to become standard practice. “Change is difficult,” says Khan. “But we have to continue accelerating the use of DCTs.”