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

Chapter 58

Phase III Trials

Craig Mallinckrodt

58.1 Introduction

The basis for rational drug development is to ask and answer important questions with appropriate studies in a sequence such that the results of early studies influence decisions regarding later studies. The sequence of studies in drug development is typically described as having four temporal phases (Phase I-IV).

The objective of Phase III clinical trials¹ is to confirm the preliminary but inconclusive evidence obtained from Phase II studies that a drug is safe and effective for the intended indication in the relevant patient population. Phase III studies provide the primary basis upon which drugs are approved for use by the various regulatory agencies. This article focuses on the key aspects of the design, conduct and analysis of Phase III trials necessary to yield such confirmatory evidence. Many of the concepts discussed in this paper are also covered in guideline documents produced by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) [1]. The ICH guidelines describe general considerations used by regulatory agencies around the world when evaluating potential new drugs. These guidance documents therefore also provide the primary criteria used by drug developers when designing research programs.

Drugs may be indicated for use in the treatment of a disease (e.g., antibiotics; statins for hypercholesterolemia), the management of symptoms ...