Weighing Risks in a Pediatric Anthrax Vaccine Clinical Trial

by Brendan Abel, JD

Countless regulations have been enacted over the past 35 years to protect children from unnecessary clinical testing. Federal regulations, the Belmont Report, and professional guidelines all state that children should be enrolled in clinical trials only when the research is a high imperative. Federal research regulations insist that absent a potential for direct benefit to the participating child, research should take place only if there is “minimal risk” or “minor increase over minimal risk.”

Thus, it was surprising that one year ago, the National Biodefense Science Board (NBSB), an advisory panel to the Secretary of Health and Human Services, recommended that HHS develop and implement a study of pre-exposure anthrax vaccine in pediatric populations. Such a vaccine would subject children to risks with little potential for therapeutic benefit. The matter is now in front of the President’s Commission for the Study of Bioethical Issues, at the request of Secretary Kathleen Sebelius, who in May visited the Commission to ask for advice regarding the ethical issues raised by this potential study. The  Commission’s recommendation is expected early next year.

Much of the controversy surrounding anthrax-vaccine testing in the pediatric population relates to the issue of timing. Since the vaccine can be used either prophylactically or as a post-exposure treatment, the government is considering whether children should be tested now to determine safety, efficacy, and dosing levels in a structured, controlled environment, or whether it is best to avoid subjecting children to the risks of the testing and to face an (unlikely) anthrax attack without the knowledge that would be gained from such a study.

Many issues confronting the President’s Commission in this inquiry will be familiar to its member ethicists. In what exceptional cases can research in children be justified with little or no therapeutic benefit? If informed consent is obtained from a parent, what if the child does not provide assent? And how would such a study recruit participants? Panel and audience members during the public hearings suggested that children of military personnel or first responders, or even children whose families were affected by the attacks on September 11th may be willing to participate. Surely, these connections point to emotional vulnerabilities or pressures that would make true, objective informed consent far more difficult to achieve.

Yet the proposed study also raises issues that are not often addressed by traditional research ethics. A significant factor considered by research ethicists is the likelihood of an outbreak of disease, or in the case of anthrax exposure, a terrorist attack.  In the case of a vaccine against an infectious disease, epidemiologic modeling can often predict the likelihood and scope of an outbreak. Such evidence-based predictions are not perfect, but they can generally be debated and evaluated dispassionately to inform a risk-benefit assessment.

The likelihood of a bioterrorism attack, on the other hand, is difficult to predict with any kind of certainty. Certain types of modeling, such as the Dark Zephyr Exercise referenced in the NBSB report, consider defense mechanisms to prevent an attack, medical countermeasures, preparedness of government agencies, etc., but predicting the likelihood of exposure is uniquely difficult in this case because it relies so heavily on the volitional act of others.

Many argue that the past decade has been chock-full of examples of decisions to take risks or inhibit individual rights in the name of security from terrorism. They have led to questions, in retrospect, about whether undue emphasis has been placed on the threat of terrorist attack because of an irrational, overinflated fear of not taking a precaution as it relates to a future terrorist attack.

Could these psychological biases influence the ultimate recommendation of the President’s Commission?  How should the seemingly small likelihood of a devastating attack be factored into a decision to allow children to participate in a non-beneficial clinical trial?

There are many fascinating areas of complexity in this issue. Some helpful resources include the NBSB recommendation and the blog of President’s Commission, which includes posts about many of the public hearings.

[Brendan Abel, JD is Senior Perspective Researcher for the New England Journal of Medicine, and a Medical Ethics Fellow at the Division of Medical Ethics, Harvard Medical School.]

The Petrie-Flom Center Staff

The Petrie-Flom Center staff often posts updates, announcements, and guests posts on behalf of others.

One thought to “Weighing Risks in a Pediatric Anthrax Vaccine Clinical Trial”

  1. I wonder if you would comment on the work of Dr. Meryl Nass. Her website indicates that Biothrax is only approved for cutaneous anthrax but not weaponized anthrax. In addition, she states that the heads of Emergent Solutions, the company that produces Biothrax, may have conflicts of interest.

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