BPCA INNOVATIVE TRIAL DESIGNS FOR DOSING, SAFETY, AND EFFICACY IN PEDIATRIC THERAPEUTICS

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BACKGROUND AND INTRODUCTION For the last 25 years the scientific community, including academia, the National Institutes of Health (NIH), the Food and Drug Administration (FDA) and the pharmaceutical industry have worked to improve the knowledge of medications used in children. Congress has passed legislations to provide incentives for drug development plans in pediatrics. The responsibility for the implementation and oversight for improving drug development has been delegated primarily to the FDA (for on-patent drugs) and to the NIH (for off-patent drugs). Even though the legislations have improved the number of clinical studies conducted in children, gaps remain in areas such as developmental pharmacology, ontogeny of drug metabolism and effects, and the validation of outcome measures and endpoints in pediatric research. In addition, gaps in knowledge for failed efficacy trials remain as well as what prevent FDA labeling of drugs in pediatrics. The National Institute of Child Health and Human Development (NICHD) and others in the scientific community are concluding that the harmonization of basic, translational, and clinical research with relevant outcomes such as endpoints, biomarkers, and epidemiology data are vital to the future direction of effectively treating pediatric patients in a personalized way. For that reason, the NICHD encourage the Best Pharmaceuticals for Children Act (BPCA) Clinical Program, specifically the Pediatric Trials Network (PTN), to begin to incorporate and adopt a new paradigm of promoting clinical research in personalized pediatric therapeutics that will provide a greater understanding of the interrelationship among disease processes, and therapies across the developmental spectrum. This requires novel therapeutic approaches and hence the need for this Innovative Trial Design project to be issued under the BPCA PTN. This Task Order is for the PTN to provide innovative trial designs important for the advancement of pediatric therapeutics that can lead to advances in scientific knowledge and improvements in pediatric drug labeling in this current PTN cycle. These trial designs include but are not limited to the following: • Platform Trials • Randomized Pragmatic Trials • Therapeutic related Registries The data collated from the clinical trials (including trial designs, outcome measures, biomarkers, and endpoints) can ultimately be incorporated and utilized for many therapeutic areas in pediatric medicine based on the scientific needs determined by the BPCA prioritization process as well as the priorities of the NICHD. Therefore, it is evident that although all individual trials (studies) can provide useful information, the integration of this acquired knowledge from the different studies in this task order will provide a more comprehensive data analysis that will lead to a better scientific assessment to determine the best treatment approaches in adolescent and pediatric populations. More specifically, while each of these trials are important, receipt of the final report that includes the integrated data from all clinical trials performed under this task, is necessary to retain the comprehensive nature of the research conducted. The integration of the results of these innovative trial designs, which will be presented in a final report, will provide data to advance the science and knowledge gaps in the dosing, effectiveness and safety of therapeutics used in the pediatric populations. The integration of the data will also inform and provide a scientific platform for the development of a personalized therapeutics hub within the NICHD. SCOPE To perform innovative trial designs, with clinically relevant outcomes such as endpoints, biomarkers, and epidemiology data included as part of every protocol, to obtain comprehensive and comparative analysis of the data for the advance of the science and knowledge gaps in the dosing, effectiveness and safety of therapeutics used in the pediatric populations. In an effort to better understanding the ontogeny (developmental effect) of drugs in pediatrics, that there may be the need for data to be collected from adult patients in this population in order to improve the knowledge gaps in pediatrics.