Most drugs prescribed for children have not undergone age-specific studies of pharmacology, safety or efficacy. To address this problem, the FDA now requires industry to provide data for pediatric age-specific labeling for some marketed drugs and for many new molecular entities. A major barrier to conducting these trials is a lack of institutions and programs capable of performing them. To develop such facilities and conduct high priority trials, NICHD created the PPRU Network. The Children's Hospital of Philadelphia (CHOP) proposes to join this Network and will bring to it a large, diverse population of pediatric patients, a strong record of performance and publishing in clinical trials, the powerful pharmacology and biostatistical resources of the University of Pennsylvania School of Medicine (PENN), and the capabilities of a contract research organization through CHOP's alliance with the Duke Clinical Research Institute.
Aim 1 creates a locus for studies of pharmacology, safety and efficacy of new and available drugs. CHOP's PPRU studies will utilize the General Clinical Research Center. The Pharmacology Core Laboratory is located in close proximity to the Center for Outcomes Research and the Division of Biostatistics. CHOP will use standard operating procedures, systems of internal and external auditing and monitoring and formal training of investigators at all levels to provide quality assurance for protocol performance and data. An Advisory Board will oversee PPRU activities. CHOP proposes to use literature review and metananlyses, and, most importantly, to conduct appropriate clinical trials to gather information about and promote age-specific labeling of drugs ( Aim 2). In addition to studies of conventional drugs, the institution is heavily committed to gene therapy and other molecular approaches to disease and to the development of new delivery systems, formulations, and surrogate markers to promote their use (Aim 3).
Aim 4 addresses the issue of genetic polymorphisms and modeling. The Pharmacology Core Laboratory has expertise in analyzing CYP polymorphisms and has a strategic plan for determining important racial and genetic polymorphisms in children. Training of clinical investigators and pharmacologists will take place in the context of standard operating procedures for each trial ( Aim 5). Continued medical education will be provided by the Center for Epidemiology and Biostatistics (CCEB) and masters and PhD level degrees in Clinical Pharmacology will be encouraged. The institution is providing stipends for medical students to nurture interest in clinical pharmacology. CHOP and PENN have gathered a formidable array of resources to create an imaginative, productive and successful PPRU program.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HD037255-04
Application #
6490452
Study Section
Special Emphasis Panel (ZHD1-DRG-H (02))
Program Officer
Grave, Gilman D
Project Start
1999-01-07
Project End
2003-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
4
Fiscal Year
2002
Total Cost
$185,306
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
McCune, Jeannine S; Bemer, Meagan J; Barrett, Jeffrey S et al. (2014) Busulfan in infant to adult hematopoietic cell transplant recipients: a population pharmacokinetic model for initial and Bayesian dose personalization. Clin Cancer Res 20:754-63
McCune, Jeannine S; Baker, K Scott; Blough, David K et al. (2013) Variation in prescribing patterns and therapeutic drug monitoring of intravenous busulfan in pediatric hematopoietic cell transplant recipients. J Clin Pharmacol 53:264-75
Dombrowsky, Erin; Jayaraman, Bhuvana; Narayan, Mahesh et al. (2011) Evaluating performance of a decision support system to improve methotrexate pharmacotherapy in children and young adults with cancer. Ther Drug Monit 33:99-107
Barrett, Jeffrey S; Narayan, Mahesh; Patel, Dimple et al. (2011) Prescribing habits and caregiver satisfaction with resources for dosing children: rationale for more informative dosing guidance. BMC Pediatr 11:25
Su, Felice; Nicolson, Susan C; Gastonguay, Marc R et al. (2010) Population pharmacokinetics of dexmedetomidine in infants after open heart surgery. Anesth Analg 110:1383-92
Cohen-Wolkowiez, M; Smith, P B; Benjamin Jr, D K et al. (2008) Daptomycin use in infants: report of two cases with peak and trough drug concentrations. J Perinatol 28:233-4
Zuppa, Athena F; Adamson, Peter C; Mondick, John T et al. (2005) Drug utilization in the pediatric intensive care unit: monitoring prescribing trends and establishing prioritization of pharmacotherapeutic evaluation of critically ill children. J Clin Pharmacol 45:1305-12
Zheng, Naiyu; Felix, Carolyn A; Pang, Shaokun et al. (2004) Plasma etoposide catechol increases in pediatric patients undergoing multiple-day chemotherapy with etoposide. Clin Cancer Res 10:2977-85
Zuppa, Athena F; Nadkarni, Vinay; Davis, Lauren et al. (2004) The effect of a thyroid hormone infusion on vasopressor support in critically ill children with cessation of neurologic function. Crit Care Med 32:2318-22
Zhuo, Xiaoliang; Zheng, Naiyu; Felix, Carolyn A et al. (2004) Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos 32:993-1000

Showing the most recent 10 out of 12 publications