By Kurt R. Karst –
Earlier this week, the Presidential Commission for the Study of Bioethical Issues (“Commission”) announced in a Federal Register notice that it is seeking comment on several ethical issues associated with the development of medical countermeasures for children. The announcement follows an October 2011 report from the National Biodefense Science Board, titled “Challenges in the Use of Anthrax Vaccine Adsorbed (AVA) in the Pediatric Population as a Component of Post-Exposure Prophylaxis,” in which the Board recommended that the Department of Health and Human Services (“HHS”) move forward with testing AVA before a public health emergency, but only after certain ethical considerations are adequately addressed and reviewed. Earlier this year, HHS Secretary Kathleen Sebelius asked the Commission to “conduct a thorough review of the ethical considerations of conducting clinical trials of medical countermeasures in children,” including with AVA.
The Commission is interested in public comment on myriad issues, but specifically:
- How to conceptualize and consider risk and societal value when reviewing pediatric clinical research in general and for medical countermeasures in particular;
- The types of information, data, or facts needed to ensure evidence-based decision-making for conducting pediatric medical countermeasure research;
- Possible criteria, if any, that might classify proposed studies testing medical countermeasures for pediatric use as minimal risk;
- Ethical issues related to access to and allocation of medical countermeasures previously studied within pediatric populations in a public health emergency;
- Scientific and public health strategies that could minimize the risk or ethical concerns associated with pediatric medical countermeasure research;
- Strategies for communicating risk to prospective participants and their families; and
- The role communities play in the design and support of pediatric research and pediatric medical countermeasure research.
Over the past decade – since the anthrax attacks in late 2001 – FDA has played a key role in facilitating the development of medical countermeasures. In addition to establishing the current Office of Counterterrorism and Emerging Threats, which, among other things, coordinates FDA’s Medical Countermeasures Initiative, FDA finalized regulations in May 2002 know as the “Animal Efficacy Rule.”
The Animal Efficacy Rule provides that under certain circumstances, and where where human efficacy trials are not feasible or ethical, animal studies can be relied on to provide substantial evidence of effectiveness of a drug or biological product (21 C.F.R. Part 314, Subpart I and 21 C.F.R. Part 601, Subpart H). Evaluation of the product for safety in humans is still required, and cannot be addressed by animal studies alone. In addition, approval under the Animal Efficacy Rule is subject to certain postapproval commitments.
Only a few products have been approved under the Animal Efficacy Rule, beginning with the February 2003 approval of NDA No. 020414 for pyridostigmine bromide to increase survival after exposure to Soman "nerve gas" poisoning. More recently, in April 2012, FDA approved NDA supplements for LEVAQUIN (levofloxacin) Injection, Tablets, and Oral Solution for the treatment and prophylaxis of plague due to Yersinia pestis in adults and pediatric patients 6 months of age and older.
The lack of use of the Animal Efficacy Rule may be due to certain challenges, including the unavailability of qualified animal models that can predict efficacy of new drugs or biologics. In 2011, the National Research Council prepared a consensus report, titled “Animal Models for Assessing Countermeasures to Bioterrorism Agents,” which addresses the challenges stemming from developing and testing medical countermeasures against biothreat agents in animal models, and that makes several recommendations.