By Melinda Young
The risk-benefit ratio can be different when studies are proposed in response to a national bioemergency, such as Ebola outbreaks and epidemics.
“You might need to tolerate a greater amount of risk to subjects,” says Bruce Gordon, MD, assistant vice chancellor for regulatory affairs, and executive chairman of the IRB at the University of Nebraska Medical Center. Gordon also is a professor of pediatrics. The medical center includes a 10-bed biocontainment unit, one of the largest in the United States. The center treated several Ebola patients in 2014.
The bioemergency research tradeoff is that there might be a greater amount of benefit to society, he adds. “The principles don’t change,” Gordon notes. “Some things become more important when society is under a threat, and some recede in importance compared with these other principles.”
For example, several cities in the United States experienced widespread alarm when a small number of Ebola cases cropped up in hospitals in 2014-2016. Weak surveillance and public health infrastructure contributed to an Ebola pandemic in Western Africa. The disease resulted in a handful of cases in the U.S., some involving American healthcare professionals who returned sick after working in these regions to help local medical systems that were overwhelmed with dying patients. About 11 people in the U.S. were infected with Ebola, and most were infected while in West Africa. (For more information, visit: http://bit.ly/326Aj4X.)
Some of these American healthcare workers returned to the U.S. and were put in quarantine; few had contracted the virus. Two healthcare workers at a Dallas hospital were diagnosed with Ebola after they had cared for an Ebola patient who traveled from West Africa to the U.S. The patient died, but both healthcare workers recovered.
“There was a lot of angst and concern in 2015 around the patients who came back to the United States, but these were more public health issues than research,” Gordon says. “People weren’t concerned about someone having research done on them; they were concerned about someone coming to my city with Ebola and infecting my family.”
This led to a sense that the medical profession had to find a cure and vaccine for the virus before it escalated outside of West Africa. “What IRBs don’t speak to is the concern of society for whether this patient with Ebola should be in my city,” Gordon says. “We’re addressing the issue of how do we have access to an investigational drug.”
One risk when investigators conduct research during a bioemergency is separating what is research and what are public health interventions, he says. “There are a lot of things to be learned in the research setting,” Gordon explains.
Taking an earthquake as a metaphor, he notes that research takes second to removing people from the rubble and into a clean shelter. “IRBs don’t have to be concerned about it, but the people doing emergency response have to prioritize,” he adds.
Emergency response planners sometimes can be open to bioemergency research. They understand the importance of these studies and include research in their planning, Gordon says.
“They can include the notion of research and construct an appropriate infrastructure to allow that research to happen, but it isn’t their primary concern,” he adds. “If you rate the things that have to be done immediately after an earthquake, in the wake of a bombing, or during an influenza epidemic, research will come in 18th or 19th.”
When IRBs are presented with research studies involving the aftermath of a bioemergency or natural disaster, they should look for new threats to subjects, including ethical and moral threats, Gordon says.
“IRBs are well advised to plan for these before the emergency,” he adds. “If you live in California and you expect an earthquake, it’s not unreasonable to think about how you would handle research during that emergency.”
For instance, University of Nebraska Medical Center created a rapid response IRB that can meet within 24 hours to review a research proposal involving an investigational drug. “We don’t know what the investigational drugs are in advance, but we can be prepared to review the research,” Gordon explains.
The rapid response IRB is composed of eight members and a quorum of five. There are alternates backing up the eight members. The IRB chair is the dean of public health and has experience investigating epidemics for the CDC. The rapid response IRB members have backgrounds in infectious disease, intensive care, and emergency medicine, he says.
“We have processes that allow us to take a different review paradigm than what we usually do,” Gordon says.
Usually, the IRB review process is linear, with each step completed before the next step begins. Under the rapid response IRB, all steps happen concurrently. For instance, the IRB writes the protocol and informed consent with the investigator. The IRB’s questions are asked while the investigator is present at a meeting, and they are answered and changes made at that same time, he explains.
“The creation and completion of the application involves a close working relationship with the investigator at the time the protocol is reviewed,” Gordon says. “They send the investigator out of the room when it’s time for a discussion and vote.”
An example is an Ebola drug study in 2015: “When we reviewed a drug study for an Ebola patient in 2015, we had serious questions of whether this patient could provide consent,” Gordon says. “The investigator was there to tell us that the patient was awake and flying across the Atlantic Ocean.”
Hearing this news, the IRB and investigator decided to have the Ebola patient’s wife fly to Omaha to sign an informed consent form.
“We created the rapid response IRB for mundane reasons,” Gordon notes. “Some researcher didn’t get the protocol in on time and had a multimillion-dollar grant, but the rapid response IRB fit in beautifully when we had an actual emergency.”
During the Ebola bioemergency, the principal investigator worked on getting the biocontainment unit ready for the patient while a colleague helped with the study protocol, he says. “We got the study approved while she was busy bringing up the biocontainment unit,” Gordon adds.
Another aspect of bioemergency research is the challenge of maintaining participants’ privacy. With Ebola, so much media attention focused on the few cases in the United States that patients’ names became known.
“Patients’ names got out, and there was little we could do about it,” Gordon says. “Our usual approach is to keep patient’s privacy and confidentiality, but in the setting of a public health emergency, part of the response is rapid sharing of information,” he adds. “IRBs need to know that the usual patient data protections might not be appropriate or possible in the setting of an epidemic.”