The Impact of Early-Phase Trial Design in the Drug Development Process.


Division of Translational Research and Applied Statistics, Department of Public Health Sciences, University of Virginia Health System, Charlottesville, Virginia. [Email]


Many of the therapeutic agents that are being used currently were developed using the 3+3 decision rule for dose finding. Over the past 30 years, several dose-finding designs have been proposed and evaluated, including the "continual reassessment method" (CRM) and the "Bayesian optimal interval design" (BOIN). This research investigates the role of the choice of an early-phase design on the likelihood that drugs entering the drug development pipeline will have 2 successful phase III trials.Experimental Design: Using simulation, each agent in a population of hypothetical agents was tracked through the drug development process, from initial dose finding to 2 confirmatory phase III trials. Varying the designs of the phase I, II, and III trials allows for an assessment of the effect of the choice of designs on the proportion of agents with successful phase III trials.