Pharmacometrics: Impacting Drug Development and Pharmacotherapy

Drug development continues to be expensive, time consuming, and ineffi cient, while pharmacotherapy is often practiced at suboptimal levels of performance (1–3). This trend has not waned despite the fact that massive amounts of drug data are obtained each year. Within these massive amounts of data, knowledge that would improve drug development and pharmacotherapy lays hidden and undiscovered. The application of pharmacometric (PM) principles and models to drug development and pharmacotherapy will signifi cantly improve both (4, 5). Furthermore, with drug utilization review, generic competition, managed care organization bidding, and therapeutic substitution, there is increasing pressure for the drug development industry to deliver high-value therapeutic agents. The Food and Drug Administration (FDA) has expressed its concern about the rising cost and stagnation of drug development in the white paper Challenge and Opportunity on the Critical Path to New Products published in March of 2004 (3). In this document the FDA states: “Not enough applied scientifi c work has been done to create new tools to get fundamentally better answers about how the safety and effectiveness of new products can be demonstrated in faster time frames, with more certainty, and at lower costs. . . . A new product development toolkit—containing powerful new scientifi c and technical methods such as animal or computer-based predictive models, biomarkers for safety and effectiveness, and new clinical evaluation techniques—is urgently needed to improve predictability and effi ciency along the critical path from laboratory concept to commercial product. We need superior product development science to address these challenges.” In the critical path document, the FDA states that the three main areas of the path that need to be addressed are tools for assessing safety, tools for demonstrating medical utility, and lastly tools for characterization and manufacturing. Pharmacometrics can be applied to and can impact the fi rst two areas, thus positively impacting the critical path.