RESUMEN

Probability of success in phase II dominates the drug development cost calculus, with phase I/II as the critical juncture for proof of concept. Failure to address fundamental pharmacologic questions in early development is alarmingly frequent and a strong predictor of failure. Safety, manufacture, formulation, and commercialization issues are also vital. Systems biology provides a framework to analyze genomic, proteomic, and metabolomic data and construct complex network models of molecular pathophysiology. Biomarkers offer the largest learning opportunity, and combined adaptive protocol designs provide a lean but scientifically robust path to proof of concept. The traditional model of phase I study execution in a clinical pharmacology unit is evolving to a networked model of an integrated early clinical development platform. The power of this platform is enhanced with a proactive multidisciplinary approach to quality and safety, including lean 6 sigma tools and simulations.