Washington—Last fall's anthrax attacks provided the first test of the US medical system's preparations for bioterrorism. As physicians and scientists from a host of government and academic organizations felt their way through the crisis, eventually limiting the medical damage to five deaths in 22 cases, they bungled research opportunities, said Greg Koski, MD, PhD, director of the Office for Human Research Protections, at a recent meeting.
"We in a sense squandered an opportunity to get meaningful data," Koski told a Department of Health and Human Services (DHHS) advisory committee that helps guide research policy. "That's very alarming."
In particular, Koski lamented the scant data collected on the safety and efficacy of anthrax vaccine after just 2% of postal and other government workers eligible for the injections opted for them. The result, in his view, of a tangled net of arcane regulations and official hesitations, participation in research "became a negative instead of a positive," said Koski. "Postal workers saw themselves as guinea pigs. We shot ourselves in the foot."
Koski's pointed comments came as the National Human Research Protections Advisory Committee sifted through research rubble left in the wake of last fall's terrorist attacks. The discussion focused on the limitations of the current system of research oversight. Committee members were concerned that the reams of DHHS and US Food and Drug Administration (FDA) rules designed to vet prospective research in calm times will prove a roadblock to quick action during possible future emergencies.
RESEARCH VS PRACTICE
Much of the problem stems from confusion over what qualifies as "research" as opposed to "practice" in unprecedented situations, said John Livengood, MD, who oversees research protection issues at the Centers for Disease Control and Prevention (CDC). Activities considered normal medical practice are generally exempt from federal rules meant to protect research subjects. But in the confusion of a crisis the line quickly blurs. Livengood provided a clear example: While postexposure treatment of workers at the Hart Senate Office Building was not considered research, similar measures for postal workers were. That meant postal workers had to confront complex consent forms that emphasized possible, though largely unknown, risks.
In addition, dispensing drugs for research requires approval by an institutional review board (IRB) at every site. The challenge in overcoming the sheer inertia of this task becomes clear when considering, say, a crop duster attack that sprays billions of anthrax spores over a large city. If 30 hospitals responded, would all need IRB approval before offering antibiotics or vaccines?
Things can be just as complicated in nonresearch situations, said Livengood. The CDC violated the law, he said, when it shipped antibiotics cross-country. The FDA prohibits interstate trafficking in drugs for off-label use. In this case, some of the drugs were meant for postexposure prophylaxis of children, an indication never considered, said Livengood.
EMERGENCY PLAN ENVISIONED
Exceptions to regulatory hindrances in both examples could be made, but such bureaucratic navigation in the midst of an emergency wastes precious time, said Koski. With the threat of bioterrorism now realized, he urged President Bush to implement a national research plan that could be invoked during a crisis. "The system built to deal with [human research] does not fit with . . . an emergency, when we find ourselves trapped by regulations that will impair our ability to do the right thing," said Koski. "It's time for the president to take the initiative."
However, Livengood and others said that, with some prodding, the current system could be more responsive. Committee member Alan Fleischman, MD, senior vice president of the New York Academy of Sciences, said that his academy's IRB began considering research initiatives by the early afternoon of September 11. With that experience in mind, the IRB has now approved two research protocols for the next disaster. "We know we want to intervene in the first few hours," said Fleischman, urging other committee members to consider the approach. "There's nothing that mandates inefficiency; it doesn't have to be inherent."
The CDC's review board also acted quickly, said Livengood, although he acknowledged the system's limitation. "It would be very difficult to ask local sites not to wait for IRB approval" before proceeding with emergency responses classified as research, he said.
Monica Schoch-Spana, PhD, a senior fellow at the Johns Hopkins Center for Civilian Biodefense Strategies who is studying medical responses to the anthrax attacks, distilled her impressions for the committee. "We have a moment to be proactive. We can envision the ideal process and then build it instead of reacting."
