Pandemic paralysis: H1N1 influenza underscores barriers to timely research
"[With] a virus that's moving quickly, this is an unfortunate circumstance."
As the world faces its first flu pandemic in more than 40 years, researchers say slow, complicated ethics review processes hinder their ability to respond effectively to emerging infectious diseases.
H1N1 influenza A first surfaced in Mexico in April, but has spread quickly around the world. The World Health Organization officially declared it the first pandemic since 1968 on June 11th. So far, health authorities have considered this influenza virus to be of only moderate severity but are concerned that it could mutate into a more virulent strain in the fall.
Researchers are racing against the clock, attempting to learn about the virus in time to inform the public health efforts to fight it. That effort could be stymied if IRBs can't move quickly to approve protocols, says Jeremy J. Farrar, FRCP, director of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam. Farrar, an infectious disease specialist, has been on the frontlines of the H5N1 avian flu outbreak in Asia and traveled to Mexico earlier this year to assist researchers with the H1N1 virus.
He says research has lagged behind other sectors of the response to the new flu virus.
"The WHO has done a good job; the epidemiologists have done a good job. There's been a lot of information about the virus," Farrar says. "But we have almost no information on the clinical side. There's been no attempt to randomize a single patient yet to treatment. We don't yet know what the viral clearance dynamics within individual patients are, although it does look as if patients don't clear the virus for a very long time. "
Although the first signs of resistance to antivirals are being reported, systematic clinical research is required to reveal the extent of the problem.
"We have made the initiation of clinical trials so complicated and we're now suffering because of that," Farrar says.
Frederick G. Hayden, MD, FACP, influenza research coordinator for the Wellcome Trust in London, says he knows of no prospective multicenter studies under way in the United States regarding the H1N1 virus.
"I think a contributory factor is that ethics approval, developing protocols, getting it through regulatory approval and IRB ethics approval takes a lot of time — months," he says. "We are not in fact nimble in our responses in terms of mounting those kinds of studies. And when you have a virus that's moving as quickly as H1N1, this is really an unfortunate circumstance."
Case in point: SARS
Hayden and others point to the 2003 outbreak of severe acute respiratory syndrome (SARS) as an example of how delays in approvals by ethics boards and IRBs hindered important clinical studies.
Raphael Saginur, MD, FRCPC, chief of the infectious disease division and chairman of the research ethics board (REB) at Ottawa Hospital in Ontario, says REBs and investigators were frustrated by the lack of coordination of institutions during the SARS outbreak. As a result, he and representatives from other Canadian REBs have been working with the Public Health Agency of Canada to figure out a streamlined approval process for pandemic research.
But speed is not the only issue, Farrar says. He says IRBs have become so risk averse and worried about litigation that they put unreasonable and impracticable restrictions on researchers.
As an example, he points to a trip he took to Mexico earlier this year, to an intensive care unit caring for H1N1 victims. Among them were an infant, a 12-year-old child who weighed more than 200 pounds and a pregnant woman.
"Those are three of the major risk [groups] for this H1N1 pandemic in terms of severity of disease," Farrar says. "And not a single one of those individuals, in another setting, would have been enrolled into a clinical trial. You wouldn't enroll a pregnant woman into a clinical trial – no ethical committee would allow you to do that. The infant wouldn't have been enrolled into a clinical trial anywhere because of being an infant. And the 12-year-old wouldn't have been included because they weren't so-called 'normal.'"
As a result, he says, no one knows how to treat these types of individuals when they're infected.
Social science research
The problem doesn't just affect biomedical studies. Gigi Kwik Gronvall, PhD, a senior associate at the Center for Biosecurity at the University of Pittsburgh Medical Center, says important social science research into emergency response often gets bogged down in IRB review, to the point that the situation passes before a study can be mounted.
"Researchers need to be able to conduct interviews of patients and caregivers to evaluate the response, to be able to ask people about control strategies that have worked for them," Gronvall says. "So you can actually engage in research, bring your expertise to bear and maybe show that research to people who can make decisions based on it so that it has a chance of being relevant."
Farrar says he's hopeful that the problem has become more of a priority for the world health community. A June conference at the WHO in Geneva brought together experts to discuss research ethics in international epidemic response, he notes. Some IRBs are beginning to rethink their approach to focus more on facilitating research. Ultimately, Farrar says, a structural solution is needed.
"I think organizations like the WHO, like the NIH, the (Medical Research Council in the United Kingdom) really do need to look at this from a perspective of definitely protecting people — that has to be the number one," he says. "But you've got to temper that with the fact that there are nasty things out there that we need to learn how to manage, how to treat and how to prevent."
As the world faces its first flu pandemic in more than 40 years, researchers say slow, complicated ethics review processes hinder their ability to respond effectively to emerging infectious diseases.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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