Board seeks anthrax vaccine trial ethics review

Opponents say risks of attack so small that children wouldn't benefit

An advisory board to the U.S. Department of Health and Human Services has recommended that a proposal to hold pediatric trials of the anthrax vaccine be reviewed by an ethics board before proceeding.

The National Biodefense Science Board (NBSB) was formed by HHS in 2006 to consider ways to prevent and respond to potential public health emergencies that might arise from biological, chemical or nuclear incidents.

The board was asked to consider whether trials of the vaccine, which has been used with adults for years, should be conducted with children. The concern of trial proponents is that in the event of a domestic anthrax attack, doctors would have little guidance as to the appropriate doses for children exposed to the pathogen.

A decade ago, five Americans died and 17 others were sickened by anthrax spores deliberately sent through the mail. In 2010, the FBI concluded that a single person, Dr. Bruce Ivins, planned and executed the attacks.

Although there have been no other domestic anthrax attacks since the 2001 letters, some remain convinced that another such attack could occur and that children could be affected.

"Our job as public health emergency experts and people who deal with preparedness response — disasters, bioterrorism, you name it — is to anticipate the unexpected," says Daniel Fagbuyi, MD, FAAP, medical director of disaster preparedness and emergency management at Children's National Medical Center in Washington, DC, who serves on the NBSB.

"While people may be complacent and say that everything is fine, when something happens, the people who criticized planning ahead will be the same ones saying, 'Isn't this your job? You should be anticipating all these kind of things.'"

Opponents of the anthrax trials proposal argue that the likelihood of a domestic anthrax attack that affects children is so small that a child participating in a trial has almost no possibility of benefitting from it.

"I don't think you can do a trial on children from which they can't possibly derive benefit," says Paul Offit, MD, chief of the infectious diseases division and director of the Vaccine Education Center at The Children's Hospital of Philadelphia. Offit testified before the NBSB on the issue last summer.

Smallpox comparison

Offit, who says he generally argues in favor of pediatric vaccine programs, opposed a plan in 2002 to test smallpox vaccines in children, when he was a member of the Centers for Disease Control and Prevention's Advisory Committee for Immunization Practices

"I felt the same thing there — that the chances that a child would be exposed to smallpox were essentially zero, and therefore, it didn't make sense to do that trial."

The smallpox trials proposal drew criticism, and eventually was scrapped.

Offit notes that the anthrax vaccine is actually much safer than the smallpox vaccine.

"The way this (anthrax) vaccine is made is much more similar to the diphtheria and tetanus vaccines," he says. "You take protein that is made by the bacteria, and inactivate it. It's going to be a very safe vaccine. So I don't think the children are at any risk, I just don't think those children are likely to have any benefit."

Proponents argue that the only alternative to trials is to wait for an attack to occur and then give any children exposed a combination of antibiotics and vaccine. Vaccine dosages would have to be guessed at.

"We can say to parents, well, we have used it in adults and that's as much as we have information on, and it's an emergency now," Fagbuyi says. "You can either take it or not take it, understanding the risks of mortality with an infection, especially a pulmonary, inhalational kind of infection."

At the NBSB meeting on Oct. 28, the recommendation to seek an ethics review before proceeding with a trial was suggested by Ruth Berkelman, MD, director of the Center for Public Health Preparedness and Research at Emory University in Atlanta.

Berkelman says that proponents made their case that vaccine trials would be useful.

"We were asked, 'Is there a need for this, did people think it would be helpful to have this information in case there was a wide-scale anthrax event?' And the answer was yes, it would be helpful to have a pre-event trial.

"At the same time, the ethical considerations in children on this particular issue are quite large," she says. "We don't have ethicists on our board. And I thought this had such a large ethical component to it that it was important that ethicists review this issue."

Assembling a review board

The NBSB did not specify what board should carry out the review, or if one should be assembled specifically to answer this question. Fagbuyi says a board comprised of ethicists, public health experts and others representing the interests of children could be gathered to handle the issue.

The offices of HHS's Assistant Secretary for Preparedness and Emergency Response and of the NBSB itself didn't respond to interview requests from IRB Advisor regarding the next steps for the board's recommendation.

Fagbuyi says the ethics review also should consider the IRB process for any potential pediatric anthrax vaccine trials.

"Who's going to be the IRB of record, who's going to be responsible?" he says. "There needs to be good dialogue about who's going to take that on. Is it going to be local IRBs, or a national IRB? That's one of the things they're going to have to deal with."

Mark Schreiner, MD, chairman of the Committee for the Protection of Human Subjects at The Children's Hospital of Philadelphia, says he sees no current medical need for a pediatric anthrax trial.

"There is no current threat — it's very much a hypothetical threat," he says. "In order to approve research in children, it has to either be minimal risk or there has to be only a minor increase above minimal risk, or there has to be the prospect of direct benefit.

"Risks to children are getting killed in cars, and other trauma and things like that," he says. "To go to all this effort when we could save many more lives by providing kids around the world with clean water and vaccinations against known risks. There are so many things whose risks are orders of magnitude greater than this."

In addition to suggesting the ethics review, Berkelman also suggested a feasibility study to determine whether any parents would be willing to volunteer their children for anthrax vaccine trials.

Fagbuyi says he believes that some populations who may consider themselves uniquely vulnerable in the event of an attack — military personnel, EMS workers, firefighters, etc. — may be more willing to enroll their children in trials.

"It is common knowledge that some military personnel have wondered whether they are in harm's way, with the thought that they don't want to expose their family if they're going to be on the front lines," he says. "There are other populations — those who work in biosafety labs, those who do studies with anthrax, those who work with wool and animal hides. Those are the ones who may be interested in those types of studies."

Reference

Minutes of the Oct. 28 NBSB meeting are available at http://www.phe.gov/Preparedness/legal/boards/nbsb/meetings/Documents/102811mtgsum.pdf