Safeguarding Children : Pediatric Medical Countermeasure Research

In response to the January 6, 2012 request by Health and Human Services Secretary Kathleen Sebelius, the Presidential Commission for the Study of Bioethical Issues conducted a thorough review of the ethical considerations of conducting clinical trials of medical countermeasures (MCMs) with children, including the ethical considerations involved in conducting a pre- and post-event study of anthrax vaccine adsorbed (AVA) for post-exposure prophylaxis with children. The Bioethics Commission held four public meetings on this topic and heard from many speakers addressing a wide range of issues related to this report. At Secretary Sebelius’s request, the Bioethics Commission sought the advice of bioethics and public health ethics scholars, members of stakeholder communities, pediatric research scientists, and officers of local government and federal regulatory agencies. In addition, the Bioethics Commission solicited public comment and received many informative responses. Safeguarding children is one of our nation’s foremost obligations, and the ethical conduct of pediatric MCM research is one of the ways in which our society fulfills its duty to protect children both as individual research participants and as members of society to the greatest extent ethically and practically possible in the event of an attack. Because children substantially lack the developed capacities necessary for adequately informed and voluntary decision making, they cannot consent to participate in research in the relevant ethical and legal sense. Extra protections are therefore necessary to ensure that children are not placed at excessive risk for the benefit of others. The Bioethics Commission offered six recommendations to guide the ethical conduct of pediatric MCM research. The Bioethics Commission concluded that in the case of pre-event pediatric MCM research, absent exceptional circumstances, all research must be designed to pose only minimal risk to child participants. When pre-event pediatric MCM research cannot be conducted as a minimal risk study, only research that poses no more than a minor increase over minimal risk — a level that is still very limited and poses no substantial risk to health or well-being — should proceed to national-level ethical review under current regulations (45 C.F.R. § 46.407/21 C.F.R. § 50.54). The Bioethics Commission proposed an ethical framework to ensure the thoroughness and ethical rigor of such national-level review. Regardless of whether pre-event research is conducted, post-event pediatric MCM research should be planned in advance and conducted when MCMs are administered to children in an emergency. When untested MCMs are made available to children in an emergency, research protections should be in place. In addition to generally reviewing the ethical considerations of MCM research, Secretary Sebelius requested that the Bioethics Commission specifically address the ethical considerations of pediatric testing of AVA. (The Bioethics Commission has not been provided a protocol to review, nor is it within the purview of the Bioethics Commission to sit as an institutional review board or a national-level review panel under 45 C.F.R. § 46.407/21 C.F.R. § 50.54.) The Bioethics Commission concluded that before ethical pre-event pediatric AVA trials can be considered, further steps must be taken, including additional minimal risk research with adult participants, in order to determine whether the research risks to children — who do not stand to benefit directly from it — can be reduced to a level that poses no substantial risk to their health or well-being