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

Chapter 59

Phase IV Trials

Simon Day

59.1 Introduction

To understand the place of phase IV trials, it is necessary to contrast them with phase III trials and the purpose of phase III. Strictly speaking, phase IV is the phase coming after phase III, but many phase IV studies have all the same look and feel (and in many cases, very similar purposes) as phase III studies. The definitions of different phases make most sense in the context of development of new medicines (typically, although not exclusively, by the pharmaceutical industry), where the end of phase III is generally the point at which an application to health authorities is made for a marketing authorization. However, many clinical trials (typically those using licensed drugs) are sponsored by governments, academia, or charities. Although these inevitably come after the point of initial authorization/marketing (i.e., postmarketing), they often have objectives that are similar to a phase III study, and their design and execution are very similar to classic phase III studies.

59.2 Definitions and Context

Before defining what a phase IV trial is, we have to be clear about what a trial is and what it is not. Clinical trials are typically thought of as randomized interventional experiments, where very specific types of patients are enrolled, treatments (or controls or placebos) are blinded, follow-up measures are carefully standardized, a primary endpoint is clearly defined, and so on. However, many of these features are not ...