Overcoming burdens in the regulation of clinical research in children. Proceedings of a consensus conference, in historical context

Abstract

Background: Many investigators are concerned that the modes of implementation and enforcement of the federal regulations designed to protect children are unduly impeding pediatric clinical research.

Objective: To assess regulatory impediments to clinical research involving children and to develop recommendations to ameliorate them.

Participants: The Pediatric Endocrine Society and The Endocrine Society convened a consensus conference involving experts and stakeholders in patient-oriented research involving children and adolescents in 2008.

Consensus process: Following presentations that reviewed problematic issues around key regulations, participants divided into working groups to develop potential solutions that could be adopted at local and federal levels. Presentations to the full assembly were then debated. A writing committee then drafted a summary of the discussions and main conclusions, placing them in historical context, and submitted it to all participants for comment with the aim of developing consensus.

Conclusions: Recommendations designed to facilitate the ethical conduct of research involving children addressed the interpretation of ambiguous regulatory terms such as "minimal risk" and "condition" and called for the development by professional societies of best practice primers for common research procedures that would be informative to both investigators and institutional review boards. A call was issued for improved guidance from the Office for Human Research Protections and Food and Drug Administration as well as for the development by professional societies of a process to monitor progress in improving human subject research regulation. Finally, a need for systematic research to define the nature and extent of institutional obstacles to pediatric research was recognized.

Figure 1

Process for OHRP-FDA joint review of "407" referral (under 45CFR 46.407/21CFR50.54). A referral involving an FDA-regulated product is submitted to OHRP, which convenes a 407 panel, meanwhile posting the submission for public comment. The Pediatric Ethics Subcommittee of the FDA Pediatric Advisory Committee reviews the submission and, in a public forum, makes a recommendation to the FDA Pediatrics Advisory Committee. The recommendation of the latter is forwarded to the FDA Commissioner and OHRP, which submit their recommendation to the Secretary, HHS for approval (1), who then (2) directs OHRP to provide feedback (3) to the IRB. If OHRP feedback involves stipulations, the IRB responds directly to OHRP.