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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Objective</p> <p>To assess regulatory impediments to clinical research involving children and to develop recommendations to ameliorate them.</p> <p>Participants</p> <p>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.</p> <p>Consensus process</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

Growth Hormone Therapy and Quality of Life in Adults and Children

A fundamental goal of growth hormone (GH) treatment for both adults and children is improvement in quality of life (QOL). Assessments of the therapeutic role of GH depend on its effectiveness in meeting this and other goals (including improved metabolic status in adults and improved growth in children) in relation to economic parameters. However, there are difficulties in interpreting data on GH treatment and QOL. These include controversy about appropriate definitions and measures for assessing QOL, disease adaptation, comorbid conditions, and potential patient selection bias. In GH-deficient adults who have completed linear growth, there is considerable evidence that GH exerts effects on body composition, serum lipids, and bone and mineral density. Several controlled trials have also examined the effect of GH treatment on QOL in GH-deficient adults. They generally indicate improvement in QOL with GH treatment, although there are inconsistencies in the data. Caveats include differing outcome measures and instruments, instruments that are not disease specific, variation in characteristics of patient samples and treatment protocols, evidence of a placebo effect, and some inconsistency among results. Open-label trials in adults also suggest improvement in QOL with GH treatment, although interpretation is limited by potential placebo effects and patient self-selection. Studies in children have generally addressed psychological status, and relatively few specifically focus on QOL. In children with classical GH deficiency, it is intuitive that GH treatment will improve QOL, although hard data are lacking. In children with idiopathic short stature, evidence for improved QOL as a result of GH treatment is not well developed. Translating changes in QOL, together with physiological and metabolic benefits, into economic cost-benefit or cost-effectiveness analyses are needed. In doing so, it will be important to consider subgroups of patients who may derive differential benefit from GH treatment. These analyses are central to the development of a framework for research, decision making, and policy for GH treatment.Cost-effectiveness, Growth-hormones, Quality-of-life, Somatotropin-deficiency

Growth Hormone and Health Policy

GH treatment for short children is representative of many frontline issues in health care policy. In this paper, we highlight key policy issues exemplified by GH, focusing on pharmaceutical innovation, insurance coverage and pricing, and physician decisions, and we discuss their implications for endocrinology and GH use