Anthrax Vaccine Testing in Children: Strict New Guidelines

Miriam E. Tucker

March 19, 2013

New guidelines issued today impose stringent rules guiding the ethical conduct of anthrax vaccine trials in children.

A 13-member independent advisory body called the Presidential Commission for the Study of Bioethical Issues has issued a set of 6 recommendations that address anthrax vaccine testing in both pre- and postattack situations.

"This was one of the most difficult ethical reviews that any bioethics commission has ever conducted…Our nation ethically must protect children enrolled in research studies, and we must also do our best to develop the knowledge needed to save children's lives during a possible emergency," said Dr. Gutmann, president and Christopher H. Browne Distinguished Professor of Political Science at the University of Pennsylvania, Philadelphia, during a press briefing.

Preevent research poses particular ethical challenges with regard to children, who can't legally give consent and wouldn't stand to benefit directly from the study, Commission Chair Amy Gutmann, PhD, said.

In the event of an anthrax attack, federal guidelines call for the use of both antibiotics and anthrax vaccine to protect against persistent spores in the environment. The vaccine in question, anthrax vaccine adsorbed (Biothrax, Emergent BioSolutions Inc), is licensed for preexposure use in adults and has been administered to over 1 million adults in the military. However, it is not licensed for postexposure use in anyone and is not licensed for children at all.

The panel began its deliberations upon request from US Health and Human Services secretary Kathleen Sebelius on the basis of a recommendation from another advisory committee that anthrax vaccine research in children be conducted, pending ethical review. The need was highlighted following a 2011 federal government exercise in San Francisco, California, which revealed that a large-scale anthrax release would expose about 7.6 million individuals, including 1.7 million children.

In advance of any known anthrax attack, the panel advised that in general, such studies proceed only if they involve "no more than minimal risk" to the children under study. "Minimal risk" is defined as the degree of risk encountered in daily life in a normal environment or during a routine physician visit.

Before any such research is conducted in children, studies need to be done in animals and in the youngest adults in order to assess the risks to the greatest degree possible. In minimal-risk situations, studies should start with the oldest children (ie, 16- and 17-year-olds) and progress downward only after evaluation at each step, a process known as age deescalation.

If it's not possible to conduct a pre-event study that involves no more than minimal risk, then the study must pose "no more than a minor increase over minimal risk," meaning that it still poses no significant health risks. And in that case, any proposed study must undergo a "national-level review." In such situations, the report details the ethical framework for proceeding.

Such "minor" increased risk might be akin to that incurred with skin biopsy or chest radiography, Dr. Gutmann noted.

Two of the recommendations address a post-anthrax attack situation, in which the ethical calculation is less problematic because there would be some potential direct benefit to the child. Protocols for such studies should be planned in advance to collect data in the event that the vaccine must be administered on an emergency basis after an attack, the panel said.

Dr. Gutmann said that these recommendations also provide a bioethical framework for other pediatric studies of "medical countermeasures (MCMs)," the collective term referring to the use of federally regulated drugs and products in response to attacks with potential chemical, biological, or radiological agents.

"Pediatric MCM research warrants an ongoing national conversation to ensure an unwavering commitment by our society to safeguard all children both from unacceptable risks in research and through ethically sound research that promotes their health and well-being," she said.

All Bioethics Commission members file conflict of interest statements with the Department of Health and Human Services. No member needed a waiver to serve on the Commission or to participate in the writing of this report.