Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs

Chapter 57

Phase II Trials

Oliver N. Keene

57.1 Introduction

Phase II trials typically represent the first time a new molecule or intervention is investigated in patients with the disease of interest. Before this, the compound will usually have been studied in healthy volunteers (phase I trials), and there may be some proof of pharmacological effect, but it is not until phase II that efficacy in the disease can be explored. The role of phase II trials is to provide initial proof of efficacy, reassurance on safety, and guidance on appropriate doses and dosing regimens before more comprehensive testing of the intervention in phase III trials. Trials in this phase are considered exploratory or for learning, in contrast to phase III trials which are confirmatory.

Studies that specifically address the issue of initial evidence of efficacy and safety in the disease in question are often referred to as proof of concept or phase IIa trials; those that investigate different doses or dosing regimens are correspondingly called dose-ranging or phase IIb trials (although these definitions are not universal). Both aims can sometimes be addressed within a single study. These issues are, however, separated for simplicity in this discussion.

Design of phase II studies represents a challenge. These trials should not be viewed as “mini Phase III trials” and the design needs to reflect the exploratory nature of this phase. For proof of concept, sufficient data are needed to allow further progression ...