Sponsors meet scientists to speed pediatric medicines development.

The Point-Person Project, a child-health research initiative, enables rapid response to opportunities for participation in multicenter pediatric clinical trials.

The clinical translation gap in child health exercise research: a call for disruptive innovation.

In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health.

Inhaled fluticasone propionate by diskus in the treatment of asthma: a comparison of the efficacy of the same nominal dose given either once or twice a day.

STUDY OBJECTIVE: In September 2000, the US Food and Drug Administration (FDA) approved the use of Flovent Diskus (FD) [fluticasone propionate; GlaxoSmithKline; Research Triangle Park, NC], which is an orally inhaled, dry-powder corticosteroid, for the maintenance treatment of asthma at dosages of 50 to 1,000 microg administered twice-daily. Once-daily dosage regimens did not receive approval. This article will detail six clinical trials, five of which incorporated comparative once-daily and twice-daily treatment arms of the same nominal dose of FD. DESIGN: Six 12-week, randomized, double-blind, placebo-controlled studies in patients with mild-to-moderate asthma, including two pediatric asthma trials (patient age, 4 to 11 years) of total daily doses of fluticasone propionate (FP) of 100 or 200 microg, and four adult and adolescent studies of total daily doses of FP of 100, 200, or 500 microg. RESULTS: Twice-daily dosing was numerically superior to once-daily dosing at the same nominal dose in all comparative studies for the primary end point, change in predose FEV(1). In five trials, the results of the once-daily dosage of FP were statistically indistinguishable from those with placebo. One trial demonstrated the superiority of FP, 500 microg once-daily, over placebo; however, the effect size was half that observed with twice-daily dosing. Once-daily FP dosing showed no advantage in safety or in patient adherence to medication. CONCLUSIONS: In the FDA review of once-daily dosing of the FD regimen, 100 or 200 microg once-daily dosing was not shown to be significantly better than placebo. FP 500 microg once-daily was found to be superior to placebo, but at about one half the effect size as the same nominal dose given bid. No advantage in patient safety or adherence was demonstrated for once-daily administration over twice-daily administration, and once-daily administration is not currently recommended.

Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries. Report of an NCI Workshop, December 3-4, 2003.

To develop approaches to prophylaxis/protection, mitigation and treatment of radiation injuries, appropriate models are needed that integrate the complex events that occur in the radiation-exposed organism. While the spectrum of agents in clinical use or preclinical development is limited, new research findings promise improvements in survival after whole-body irradiation and reductions in the risk of adverse effects of radiotherapy. Approaches include agents that act on the initial radiochemical events, agents that prevent or reduce progression of radiation damage, and agents that facilitate recovery from radiation injuries. While the mechanisms of action for most of the agents with known efficacy are yet to be fully determined, many seem to be operating at the tissue, organ or whole animal level as well as the cellular level. Thus research on prophylaxis/protection, mitigation and treatment of radiation injuries will require studies in whole animal models. Discovery, development and delivery of effective radiation modulators will also require collaboration among researchers in diverse fields such as radiation biology, inflammation, physiology, toxicology, immunology, tissue injury, drug development and radiation oncology. Additional investment in training more scientists in radiation biology and in the research portfolio addressing radiological and nuclear terrorism would benefit the general population in case of a radiological terrorism event or a large-scale accidental event as well as benefit patients treated with radiation.

The CTSA mentored career development program: supporting the careers of child health investigators.

UNLABELLED: Training translational scientists is a priority of the Clinical and Translational Science Award (CTSA) consortium. OBJECTIVES: 1) Describe the landscape of CTSA Mentored Research Career Development Awards (CDA) and 2) evaluate participation and outcomes of child health investigators in these programs. DESIGN: Survey of the CTSA Child Health Oversight Committee (CC-CHOC) and review of nonresponders' CTSA Websites. RESULTS: Thirty-two of 53 CC-CHOC members (60%) responded and all nonresponder Websites were reviewed. Institutions supported 1,166 CDA positions from 2006 to 2011, with 134 awarded to child health investigators (11.5%). Respondents reported a mean of 29.8 KL2 positions (95% CI 17.5-42.2) during their award period, with a mean of 2.8 (95% CI 1.8-3.8) awarded to child health investigators. The proportion of child health awardees varied from 0% to 50% across institutions. We identified 45 subsequent National Institutes of Health (NIH) awards to the 134 child health investigators (34%). CONCLUSIONS: The CTSA program contributes substantially to training the next generation of translational investigators. One-third of child health investigators obtained subsequent NIH awards in the short follow-up period demonstrating success of the CTSA CDA programs. Child health investigators are represented variably across the consortium. Pediatric institutions can partner with the CTSA program to further support training child health investigators.

Meeting the demand for pediatric clinical trials.

High-quality, cost-effective pediatric clinical trials require a robust research and regulatory infrastructure and a properly trained workforce.