Sponsors are reacting rapidly to the coronavirus outbreak and trials are being delayed, especially those that take place in hospital or emergency care settings, while a significant number are shifting toward the use of remote patient interactions over traditional visits.
“Virtually every study is going to see some level of change, whether that’s a simple operational change … or minimizing the number of enrollment days or sites,” says Greg Dombal, president and COO of Halloran Consulting Group, which advises trials on quality and regulatory concerns. “We’re going to see most studies be amended to include some greater level of flexibility for patient follow-up and much greater control within the study to manage patient safety and caregiver safety” whether that’s collecting a little bit of additional data about travel or exposure to COVID-19.
Many trials are seeking to implement measures that will allow their trials to continue, said David Borasky, vice president of WCG Clinical’s IRB compliance. Most of the trial protocol modifications being considered are ones that incorporate remote methods of gathering data and distributing trial drugs, he said.
Sponsors are looking more and more into options like telemedicine, home healthcare and creative measures that don’t significantly impact the trial yet allow patients to avoid public areas and human contact, Borasky said. For example, a sponsor might consider measuring certain physical attributes over the phone, mailing a participant their trial drugs or sending out a healthcare individual to participants’ homes to collect samples for continued safety testing. They might also consider dropping procedures if they’re useful but not essential to the study or making changes if a participant is infected and isolated or in quarantine.
These changes “make sense” and should generally not be contested in getting approval from IRBs, as they’re unlikely to find them problematic and “should be able to approve those changes rapidly so there’s no disruption,” Borasky said, noting that he hasn’t encountered any firsthand examples of ones that have gotten pushback yet.
“There should be solutions that sponsors have at hand that they can implement with their protocols that allow them to continue … as close to protocol as possible, get all the detail they intend to in a timely manner, and do so in a way that minimizes the exposure … of everyone involved in the study,” Borasky said.
“Certainly, we wouldn’t want a research site insisting that somebody who is sick come in just for the sake of coming in for a visit that the protocol requires,” he added.
“What we have sponsors doing is looking and saying … how many of [these procedures] do we really need them to come in person to do, and how many of those could we shift to something that’s done remotely. They’re looking at it critically and saying, if we had to do a shift, what are the things we must have, what are the things we can get rid of, what are the things we can get but we have to do it differently?” Borasky said.
The FDA said that it understands protocols may need modifications to keep trials running, and it encourages sponsors to “document all deviations from the protocol and the reasons for these deviations and work with IRBs and FDA review divisions.”
The agency acknowledges that allowing some aspects of a trial to be conducted remotely may be necessary to continue studies. “FDA recognizes that the use of alternative technologies may enable investigators to continue to provide the appropriate monitoring,” the agency said, adding that modifying protocols could also affect the informed consent process.
The FDA cautioned that trial participants could be exposed to COVID-19 during trials but said it “is committed to working with sponsors and exercising appropriate flexibility under these extenuating circumstances.”
COVID-19 is “fairly uncharted waters” for most IRBs and likely unfamiliar territory for sponsors as well due to the fact that there’s been no true global pandemic in recent history, Borasky said. The SARS outbreak of the early 2000s, for example, did have an impact on clinical trials but was never considered as threatening as the coronavirus and didn’t come close to its number of global cases.
On the trial delay front, one sponsor that imports all of their clinical trial material through South Korea has been affected by an embargo to the airline they use, calling into question if they can maintain an adequate clinical supply of their trial drug. While the issue doesn’t appear to cause an immediate trial delay, it’s very likely they will see some of their next trials delayed due to the disrupted supply chain, Dombal said.
In another instance, a company kicking off an international trial with several European site startups is facing an unknown level of delay if they don’t initiate by April, he said, due to the summer holiday season that would push back first enrollments to fall.
“What we’ll see is a compounding effect on delays,” Dombal said. “If some of those sites are not initiated in the spring, and they’re initiated in June, they won’t see their first enrollments until the fall. It will be tacked onto the end of that trial.”
He also expressed fears that there could be staff shortages through the course of the summer if COVID-19 becomes a severe burden to the U.S. medical system like it has in Italy.
“We could very, very easily see lack of resources at hospitals and doctors’ sites for enrollment through the summer and the fall, and we may see slow enrollment that will translate to a delay in a clinical trial that lasts into next year,” he said.
“They’re working with their teams, their sites, their CROs, to put in risk mitigation plans and to alleviate site concerns for patients so that they can keep existing programs running and be prepared to react,” Dombal said. “Most clinical groups and most sponsors are just trying to be prepared to adjust effectively … and there’s this continuity planning with patients in mind, and that’s really complicated, really hard work, because it’s so unknown.
Lindsay McNair, WCG’s chief medical officer, said she believes that the protocol changes being considered and made by sponsors may cultivate greater interest in virtual trials even after the coronavirus outbreak is under control.
“If it’s safe to do here, why isn’t safe to do in other studies as well? This may help to move the needle toward reducing patient burden in other trials,” she said. “If people take measures in these studies that are going on to reduce the burden on patients and not make them come to the hospital, they may be feasible in other studies.”