Dose finding - A challenge in statistics

A good understanding and characterization of the dose response relationship of any new compound is an important and ubiquitous problem in many areas of scientific investigation. This is especially true in the context of pharmaceutical drug development, where it is mandatory to launch safe drugs which demonstrate a clinically relevant effect. Selecting a dose too high may result in unacceptable safety problems, while selecting a dose too low may lead to ineffective drugs. Dose finding studies thus play a key role in any drug development program and are often the gate-keeper for large confirmatory studies. In this overview paper we focus on definitive and confirmatory dose finding studies in Phase II or III, reviewing relevant statistical design and analysis methods. In particular. we describe multiple comparison procedures, modeling approaches, and hybrid methods combining the advantages of both. An outlook to adaptive dose finding methods is also given. We use a real data example to illustrate the methods, together with a brief overview of relevant software.