A population approach to initial dose selection.

Before a drug can be marketed, an initial dose must be established. Sheiner et al. argue that a population approach leads to the most informed and rational decision making. We discuss the choice of an initial dose from both a predictive and estimative viewpoint. Our criteria are based upon evaluating the probabilities that a patient from the specified population obtains a response that is at least of a specified size. We demonstrate the approach using a simulation study and compare estimation of population parameters and initial dose using Bayesian and likelihood-based methods.