EUA or eIND? Testing drugs in an emergency
Concerns about H1N1 emergency use authorizations
With the end of the 2009-2010 flu season, it's easy to get complacent about the threat of pandemic flu. After all, the much-feared H1N1 virus appears to be on the wane in the United States, and total deaths here didn't reach some dire predictions made last summer.
But the World Health Organization has warned that the H1N1 virus could continue to mutate and may not be fully conquered until 2011.
And some argue that the health research community so far hasn't taken sufficient advantage of this flu strain to study the effectiveness of drugs used to treat it.
"I feel like there's a real ethical imperative for us, when we do see these outbreaks, to collect data as best we can," says Andrea Meyerhoff, MD, MSC, DTMH, an adjunct associate professor and infectious disease specialist at Johns Hopkins School of Medicine in Baltimore, MD. "The public expects us as a medical and public health community to hold to certain scientific standards."
Meyerhoff is concerned that with the advent of the Food and Drug Administration's Emergency Use Authorization (EUA) process, drugs that might have been given to research participants as part of a clinical trial are instead being distributed under EUAs with less oversight and insufficient data collection afterward.
The EUA was introduced in 2004 as a way to allow the use of unapproved drugs or devices without IRB approval in emergency infection situations when there are no adequate approved and available alternatives. The FDA may issue an EUA when it concludes, based on existing evidence, that it is reasonable to believe that an intervention may be effective at diagnosing, treating or controlling a serious or life-threatening disease or condition.
No IRB, informed consent
But Meyerhoff says the use of EUAs which lack not just IRB approval but detailed informed consent and may not require extensive data collection bleeds away potential patients from clinical trials that could give officials better information about the drugs.
During the H1N1 emergency, the FDA has issued three EUAs for antiviral drugs. In a recent letter to the Journal of the American Medical Association, Meyerhoff looks at one of them, peramivir.1 Meyerhoff says the October 2009 EUA issued for peramivir marked the first time that an EUA had been issued for an unapproved drug.
She notes that the FDA fact sheet for peramivir cites results from four clinical trials. Only one was a multi-dose study and that one did not include the dosage that FDA eventually authorized in its EUA. At the time the EUA was issued, only 33 patients had ever received this authorized dose. And Meyerhoff says that because reporting requirements for EUAs are limited, important questions about the drug's safety and effectiveness may not be answered.
She says clinical trials planned by peramivir's manufacturer hoped to enroll 300-400 patients by spring 2011.
"What we saw was that as soon as the EUA was issued, about 500 patients lined up to get the drug, with relatively little oversight," Meyerhoff says. "I see a sort of race between actually enrolling patients in clinical trials vs. doling out the drug without a whole lot of mechanisms in place to see how well it works or what kind of safety profile eventually evolves."
Using an eIND
Meyerhoff says she would prefer to see such drugs distributed in these types of situations through another FDA mechanism, the emergency Investigational New Drug (eIND) regulation. That mechanism also allows for quick turnaround in urgent situations, but still requires IRB oversight.
"(Under the eIND provision,) an individual patient can get access to an investigational drug just as an individual not enrolled in a clinical trial," she says. "The physician who wants to use the drug can access the drug and the IRB oversight requirement can actually kick in once they're using the drug. So there's still IRB oversight, but there's still a little bit of adjustment so that the drug can get to the patient as quickly as possible."
Meyerhoff says that when she was a medical officer at the FDA, she handled many emergency use INDs for individual patients, and could usually turn them around in a day.
She says IRBs could help encourage the use of this mechanism by having a procedure in place to act quickly as well.
"IRBs may have a provision for some kind of fairly quick convening," she says. "Sometimes the institution has a standing IRB that has some kind of emergency provisions available. Certainly if we're envisioning an outbreak of influenza where there were new agents needed, an institution would want to look at how quickly they can get their IRB together."
Meyerhoff says IRBs should let researchers know that this method of approving drugs for emergency use is available.
"Clinicians don't always understand that they can get an individual patient use IND," she says. "That's something I think would be very important to make sure is known up front."
- Meyerhoff A, Lietman P. Losing the Opportunity to Study Influenza Drugs. Letter. JAMA 2010 Mar 3;303(9):878-9.