ABSTRACT
A good understanding and characterization of the dose-response relationship is a fundamental step in the investigation of any medicinal drug. The basic difficulty in getting the right dose is the trade-off between wanted and unwanted effects. For example, if the dose is set too high, safety and tolerability problems are likely to arise, while selecting too low a dose makes it difficult to establish adequate efficacy. However, even if it is generally agreed that understanding the dose-response relationship is important, dose-finding trials commonly address a variety of different objectives that range from exploratory modeling to confirmatory hypothesis testing. This chapter contains a brief overview of dose-finding problems encountered at different stages of drug development, explains the common objectives of clinical dose-response trials, and describes key statistical methodologies which can be applied to such trials. We review multiple comparison procedures applied to dose-response testing and pairwise comparisons with a control. Moving beyond purely confirmatory analyses, we also discuss recently introduced hybrid dose-finding methods that combine principles of multiple comparisons with modeling techniques. We also present a case study to illustrate how the approaches can be used in clinical practice.
