Integrated Planning of Phase II/III Drug Development Programs

Abstract

The aim of phase II is to provide a solid basis for a reliable decision whether to stop or continue drug development. If the results of phase II are promising enough for a go-decision, they provide the basis for planning the proceeding phase III trial. Obviously, there is a strong link between phase II and III and, hence, an integrated planning is advantageous. This chapter presents methods to determine the sample size allocation between phase II and III as well as the go/no-go decisions in an optimal way. For this purpose, a utility function is set up that includes (fixed and variable per-patient) costs of the phase II/III program on the one side and expected revenues after successful launch of the drug on the market on the other. Determining the parameters such that they maximize the expected utility thus leads to the largest overall value. The principle of optimal planning of phase II/III programs in terms of sample size and go/no-go decision rule is described by means of two-group trials with one normally distributed outcome.