www.econstor.eu Optimal designs for dose finding studies

Identifying the “right” dose is one of the most critical and difficult steps in the clinical development process of any medicinal drug. Its importance cannot be understated: selecting too high a dose can result in unacceptable toxicity and associated safety problems, while choosing too low a dose leads to smaller chances of showing sufficient efficacy in confirmatory trials, thus reducing the chance of approval for the drug. In this paper we investigate the problem of deriving efficient designs for the estimation of the minimum effective dose (MED) by determining the appropriate number and actual levels of the doses to be administered to patients, as well as their relative sample size allocations. More specifically, we derive local optimal designs that minimize the asymptotic variance of the MED estimate under a particular dose response model. The small sample properties of these designs are investigated via simulation, together with their sensitivity to misspecification of the true parameter values and of the underlying dose response model. Finally, robust optimal designs are constructed, which take into account a set of potential dose response profiles within classes of models commonly used in practice.