The Association for the Accreditation of Human Research Protection Programs, Inc., (AAHRPP) included an article in their quarterly newsletter, Advance, about UNMC's activation of its Rapid Response IRB for pandemic clinical trials. This article is being reprinted with their permission from the Spring 2020 issue of Advance.
Six years ago, the University of Nebraska Medical Center (UNMC) activated its Rapid Response Institutional Review Board (IRB) to review the protocol for an investigational drug to treat a patient critically ill with Ebola. Today, UNMC is once again on the front line of the fight against a deadly pathogen: the coronavirus that causes COVID-19.
This time, UNMC’s Rapid Response IRB is serving in an expanded role as the central IRB for the Special Pathogens Research Network and its 10 Regional Ebola and Special Pathogens Treatment Centers (RESPTCs).
The RESPTCs enrolled nearly 300 of the 1,063 COVID-19 patients worldwide for a clinical trial of remdesivir, an experimental antiviral drug. That trial has completed; the next phase of the investigation compares remdesivir to remdesivir plus baracitinib. The National Institutes of Allergy and Infectious Diseases (NIAID) is the regulatory sponsor.
The remdesivir trial began in late February when UNMC enrolled the first patient. To facilitate the experimental treatment, in less than 48 hours the Rapid Response IRB reviewed and approved the protocol, including reliance agreements with other trial sites and procedures for obtaining informed consent.
It was the first test of the effectiveness of the central IRB process, "and it worked beautifully," says Bruce Gordon, MD, Assistant Vice Chancellor for Regulatory Affairs and Executive Chairman, Institutional Review Boards at UNMC.
A collaborative process
Dr. Gordon credits the quick turnaround, in part, to a process created during the Ebola outbreak and to recent tabletop training exercises involving the RESPTC IRB partners. To save time during the review of the investigational Ebola treatment, the Rapid Response IRB worked with the investigator to complete the IRB application.
"We changed the review paradigm and made it a collaborative process," Dr. Gordon says. "We had the investigator present at the IRB deliberations, so we could negotiate changes in the application and in the conduct of the research related to protecting subjects, and then make those changes on the spot." After Ebola, and until COVID-19, the process remained "tucked away," Dr. Gordon says, "used primarily during drills to keep us on our toes."
Those drills made a difference, especially since the most recent ones focused on adapting UNMC’s rapid response process for central IRB review. The changes reflect updated Common Rule requirements for single IRB (sIRB) review of federally funded multisite studies. As an NIAID study, the remdesivir trials are subject to this requirement.
"We were still testing the rapid responses IRB model," Dr. Gordon says, "when the pandemic struck," and 13 Americans arrived at UNMC after being exposed to the novel coronavirus. All were passengers on a cruise ship where nearly 700 guests and crew members tested positive for COVID-19. One passenger became the first participant in the remdesivir clinical trial.
A leading biocontainment and quarantine center
UNMC was the logical place to isolate, monitor, and treat the American passengers. The university is known worldwide for its infectious disease expertise. UNMC also is home to the nation’s largest biocontainment unit and the only federal quarantine facility. In addition, UNMC was one of the first facilities authorized by the Centers for Disease Control and Prevention to conduct COVID-19 tests.
When the first coronavirus study request came in, for a biospecimen collection protocol, the Rapid Response IRB lived up to its name, seizing every opportunity to streamline the review while ensuring adequate protections for research participants.
Dr. Gordon and the investigators drafted the application and consent documents together. Reliance agreements, consent forms, and other necessary documents also were easy to pull together because they had been assembled as part of the multi-institutional tabletop exercises.
The goal of the exercises that had been conducted was to streamline a process that typically took weeks and cut review time down to 48 hours or less. That’s exactly what happened.
"Before the pandemic, we conducted tabletop exercises to work out the processes and procedures, and we felt that we were 90% there," Dr. Gordon says. "All that was left was to conduct one more full-scale exercise, which we did—in real life."
UNMC’s efforts are receiving national attention and drawing praise from the research community, including AAHRPP. Elyse I. Summers, JD, AAHRPP President and CEO, cites the "can-do spirit" and efficiency of UNMC’s Rapid Response IRB.
"This is an inspiring example of the innovations that AAHRPP-accredited organizations are capable of, even in the midst of a global pandemic," she says. "It’s also a powerful reminder of how AAHRPP-accredited organizations are equipped to respond to the challenges of an ever-more complex research environment."