The Food and Drug Administration’s (FDA) guidance on conducting clinical trials during the pandemic provides reassurance that IRBs and research organizations can employ flexibility as they make changes to accommodate a world in which many patient visits are conducted remotely. (The guidance is available at: https://www.fda.gov/media/136238/download.)
The guidance does not change or modify existing regulations, but synthesizes existing regulations and emphasizes the built-in flexibility, said Lindsay McNair, MD, MPH, MSB, chief medical officer of WIRB-Copernicus Group (WCG) of Princeton, NJ.
“Considering how quickly the FDA must have gotten this out, it was nicely done and covers a lot of different things that sponsors and researchers are thinking about,” McNair said.
Take Advantage of Changes
The important message from the FDA guidance was for research organizations to take advantage of changes prior to IRB approval, said Michael Linke, PhD, chair of the University of Cincinnati IRB and adjunct professor of medicine at the University of Cincinnati College of Medicine.
For example, the guidance, issued in March 2020 and updated in April, offers a discussion on how sponsors, clinical investigators, and IRBs may determine that research participants’ safety is best served by continuing a trial per the protocol or discontinuing the use of the investigational product or participation in the trial. They can make a decision based on particular circumstances.
Another potential change is how trials conduct study visits with participants. These can be changed to remote visits for safety.
“There has always been an allowance that changes made to protocols that stop immediate harm to subjects can be done without IRB approval, but it’s a situation that rarely came up,” McNair said. “In circumstances like this, saying to research participants, ‘We don’t want you to come into the hospital right now; we want you to be monitored remotely’ is a change that could prevent an immediate harm to subjects. Therefore, you don’t need preapproval from the IRB, but should notify the IRB that you’ve made this change.”
Early on, IRBs became more flexible. “We’re not expecting or requiring research sites to get IRB approval of [COVID-19 change] notices they send to participants,” said James Riddle, MCSE, CIP, CPIA, CRQM, vice president of institutional services and strategic consulting with Advarra in Columbia, MD. “Advarra will ask that if you are going to make a permanent change to your research to continue remote visits after the crisis is passed, that the change in research would be submitted to the IRB. You can imagine that during the course of this crisis that research sites might get more comfortable with using remote visits and telemedicine and want to continue those visits after the crisis is over. If they want to continue remote visits, they will need to submit a modification to the IRB.”
Guidance Helps Research Sites Cope
The FDA’s guidance was timely, helping research sites cope with the crisis even as their institutions were shutting down. For instance, research organizations suddenly were faced with closing clinical trials or quickly changing them as their sites were not open for study participant visits. Many were unsure of how to proceed and whether they needed to obtain IRB approval for changes.
Traditionally, researchers need IRB approval for protocol changes before implementing them. This can take days or weeks. But there has been an exception for changes when there is an immediate or apparent hazard, said David Borasky, MPH, CIP, vice president of IRB compliance with WCG.
“Historically, we would see these exceptions when there was an unexpected reaction to study medicine. The investigator would stop dosing immediately, and then tell the IRB about it,” Borasky said.
At the start of the pandemic, many researchers were uncertain of how to proceed. When U.S. colleges began to shut down because of COVID-19, WCG received multiple inquiries from research sites, sponsors, and others, and then the FDA guidance was published, he added.
“The timing was great,” Borasky noted. “The biggest takeaway message is the FDA is reiterating the fact that there’s a lot of flexibility in the regulations for research sites, research sponsors, and IRBs,” Borasky said. “I see that as encouragement that all of us who are players in this should be utilizing that flexibility.”
The guidance leaves out details about remote monitoring, but it emphasizes the need for documenting everything correctly. “If it means changing the endpoints of the study, then communicate with the reviewing division of FDA,” McNair said. “Basically, the guidance emphasizes that any changes that occur due to COVID-19 or if individual participants in the study are diagnosed with infection, then make sure all is documented and submitted with the clinical study report at the end of the study, so it can be considered when assessing the impact on the study and data.”
WCG and other IRBs are promoting flexibility in regulatory compliance, Borasky said. “We’re saying to our study partners, ‘We recognize that you have to quickly make changes to minimize potential exposure to the virus in the best interest of research participants and study teams,’” he explained. “Implement that immediately and then notify the IRB.”
The guidance provides reassurance. “If the FDA is OK with eliminating a number of data points, without making the study invalid, then the IRB is OK with it — if the sponsor reaches out to the IRB to do that,” Borasky said.