Conducting ethical pre-event medical countermeasure trials with children

The Presidential Commission for the Study of Bioethical Issues was asked to enumerate the ethical considerations of conducting pediatric clinical trials of medical countermeasures (MCM), which are interventions to protect children in case of a terror attack. The ethical dilemma of conducting trials before an event occurs (pre-event) stems from our dual obligation to protect children in an emergency and to protect individual children, who are not ethically or legally capable to consent to accept risks on behalf of others during research. MCM research adds ethical challenges as it involves research on a hypothetical condition with an undefined, and perhaps unknowable, likelihood of occurring. Barring exceptional circumstances, ethical analysis indicates that in pre-event MCM research when there is no prospect for direct benefit, children cannot be exposed to research risks that are greater than those they would encounter in everyday life or routine medical examinations. Careful and thoughtful research design that includes informed characterization of research risks, minimization of unavoidable risk, and age de-escalation might allow for the development of minimal risk trials across the phases of childhood. The Commission further specified considerations to augment current regulatory guidance for the exceptional circumstances contemplated under section 407 in Subpart D (special protections for children) of the human research protections regulations. Concepts further specified included “reasonable opportunity” to address a “serious problem,” “sound ethical principles,” and adequate provisions for parental permission and child assent.