This study utilizes both public and private data sources to estimate clinical phase transition and clinical approval probabilities for drugs in the development pipelines of the 50 largest pharmaceutical firms (by sales). The study examined the development histories of these investigational compounds from the time point at which they first entered clinical testing (1993-2004) through June 2009. The clinical approval success rate in the United States was 16% for self-originated drugs (originating from the pharmaceutical company itself) during both the 1993-1998 and the 1999-2004 subperiods. For all compounds (including licensed-in and licensed-out drugs in addition to self-originated drugs), the clinical approval success rate for the entire study period was 19%. The estimated clinical approval success rates and phase transition probabilities differed significantly by therapeutic class. The estimated clinical approval success rate for self-originated compounds over the entire study period was 32% for large molecules and 13% for small molecules. The estimated transition probabilities were also higher for all clinical phases with respect to large molecules.