A POPULATION APPROACH TO INITIAL DOSE SELECTION

Before a drug can be marketed, an initial dose must be established. Sh einer et al.(1) argue that a population approach leads to the most inf ormed and rational decision making. We discuss the choice of an initia l dose from both a predictive and estimative viewpoint. Our criteria a re based upon evaluating the probabilities that a patient from the spe cified population obtains a response that is at least of a specified s ize. We demonstrate the approach using a simulation study and compare estimation of population parameters and initial dose using Bayesian an d likelihood-based methods. (C) 1997 by John Wiley & Sons, Ltd.