Introduction
Background
Pharmacotherapy requires safe and effective management of drug administration. It implies an understanding of drug pharmacokinetics (PK) and pharmacodynamics (PD) so that individual dosing guidance, when necessary, can be provided to optimize patient response within their individual therapeutic window. Pediatric pharmacotherapy can be challenging due to (1) developmental changes that may alter drug kinetics; (2) pathophysiologic differences between children and adults that may alter pharmacodynamics and disease etiologies; and (3) other factors that may result in varied safety and efficacy outcomes. The situation becomes more convoluted when one considers the complications associated with treating critically ill children and the paucity of well-controlled pediatric clinical trials.
Despite the efforts of the Food and Drug Administration and the U.S. Congress, this situation is not likely to substantially improve due to the lack of economic incentives for pharmaceutical companies in the pediatric market. Children make up a relatively small segment of the market, at about 20 to 25 percent of the total adult market. Owing to the high cost of developing drugs (estimated at over $800 million from discovery to commercialization), pharmaceutical manufacturers are compelled to address larger markets first. This often means postponing or omitting drug testing in children. Other testing-related issues have reinforced this trend. These issues include the difficulty of recruiting children for clinical testing and the higher rates of noncompliance in such tests. Patent extensions for pediatric testing offered by the Food and Drug Administration have mitigated this trend to an extent; however, many pharmaceutical manufacturers remain reluctant to invest in pediatric clinical trials.
Pediatric Knowledgebase
The Pediatric Knowledgebase is an initiative of the Division of Clinical Pharmacology and Therapeutics at The Children's Hospital of Philadelphia that aims to improve pharmacotherapeutic outcomes in pediatrics, using data from the electronic data warehouse, Lexi-comp and other in-house data sources. It provides a comprehensive drug therapy-focused view of patient data with potential scenario-based forecasting results. The primary goal of the Pediatric Knowledgebase is to bring pharmacotherapeutic analyses into the clinic by creating a user-friendly graphical user interface for patient-optimized care. The anticipated outcome of the Pediatric Knowledgebase project is to establish a methodology by which drug dosing guidance can be incorporated into hospital decision-support-algorithms and made accessible with point-of-care solutions.