We propose to establish a Pediatric Center of Excellence in Pediatric Nephrology at the Children’s Hospital of Philadelphia (CHOP) whose theme is to address barriers to clinical trials implementation in children with kidney disease. Very few high–quality clinical trials have been performed in children with kidney disease. The virtual absence of well-designed trials has resulted in a poor evidence base for clinical practice guidelines and few new treatments for kidney diseases in children.
A number of barriers exist in producing high quality clinical evidence and mounting clinical trials in children with nephrologic diagnoses. As kidney disease in children is uncommon, identification of adequate numbers of children with specific disorders and recruitment for trials is difficult. Additionally, methods to clinically phenotype children with kidney disease in terms of growth, development, nutritional issues, cardiovascular disease risk factors, bone and mineral disorders often vary from study to study, and quality control is variable. Also, rigorous assessment of outcomes important to patients and families is sorely lacking. Expertise in study design and analysis is needed to achieve appropriate inferences from observational data, and to design clinical trials, however, frequently pediatric centers in nephrology lack this expertise.
We propose a pediatric nephrology center of excellence that will address these challenges through a regional and national collaboration of clinical and translational researchers at CHOP, Johns Hopkins, and children’s hospitals participating in PEDSnet. PEDSnet is a consortium of eight academic pediatric health centers that collectively provide care for >4.5 million children. PEDSnet has established a common institutional review board and has harmonized the diverse electronic health record (HER) systems of its participating centers to create a standardized multi-institutional data network in order to facilitate the efficient conduct of observational research, quality improvement and clinical trials. Our specific aims are:
- To expand the evidence base of observational data for clinical trials design through access to expertise in study design and analysis, and clinical phenotyping in childhood kidney disease.
- To leverage the use of electronic health records across the PEDSnet Learning Health System to facilitate identification of patients with specific kidney disease diagnoses for observational research and potential clinical trial enrollment.
- To improve the efficiency of initiating multicenter clinical trials through design and analysis expertise, and expediting enrollment in trials leveraging the master reliance agreements within PEDSNET.
- To foster collaboration in kidney disease research across levels of training, and across centers by supporting enrichment programs in clinical research methods, a pilot and feasibility program, specific research projects in childhood kidney disease and mentoring across the research base.
Progress in achieving these aims will be continuously assessed through annual evaluation and refinement. The CHOP-PCEN will have three biomedical research cores in addition to the Administrative core; a Design and Analysis core, a Clinical phenotyping core focused on Nutrition/CVD risk factors and Bone health, and a Learning Health System Core, as well as a pilot and feasibility program and an enrichment core. We include 2 research project proposals utilizing the cores: “Bone Quality and Vascular Health in Adolescents with Urinary Stone Disease”, “Derivation and Validation of Imaging Biomarkers for CKD Progression” and a third, integrated into the LHS core, “Skeletal Outcomes in Children and Young Adults with Glomerular Disease”.
We illustrate the breadth of funded and proposed research projects and pilot projects by the research base which will also utilize these core resources to develop clinical trials in pediatric nephrology. The PCEN will build upon the strong foundation of pediatric nephrology research at CHOP and Hopkins, as well as the University of Penn Adult Nephrology and Center for Clinical Epidemiology and Biostatistics. We will accomplish our goals by building on a research base of 39 investigators, with 150 funded projects totaling over $35 million in annual direct costs. Over $12 million of this funding is led by likely users of core services and directly relevant to pediatric nephrology. Through peer-review of proposals in Year 1 by experts internal and external to CHOP, we will select five pilot projects for funding in Years 2-5, 4 supported by the P50, and a fifth pilot funded by our institution. Our goal is to amplify interactions across institutions, and reach out to junior investigators both locally and nationally to use the research core facilities in this PCEN, in order to accelerate translation of discoveries to therapies for the millions of children with kidney disease in the U.S. and many more worldwide.