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

Chapter 65

Prevention Trials

Ross L. Prentice

65.1 Introduction

There is a considerable history of the use of randomized clinical trials to assess strategies for the primary prevention of disease. For example, in the US, major coronary heart disease prevention trials date from the 1960s [7,9,10] to the present, while a number of trials have been initiated over the past one to two decades that focus on the prevention of major cancers and other important diseases. Primary prevention trials generally focus on reducing the occurrence rate of one or more diseases, in contrast to screening trials, which aim to reduce mortality rates through early detection and effective treatment of disease.

However, the history of primary prevention trials is quite modest compared with that of therapeutic trials that assess strategies for the treatment of established disease. In fact, the role and place of primary prevention trials in relation to other research strategies remains controversial, and is an important topic for further methodologic research. It is useful to review some basic features of prevention trials to explain the reasons for controversy, and to highlight research needs.

First, consider the nature of the interventions or the treatments to be assessed or compared. In therapeutic research, these arise typically from basic biological research in conjunction with drug screening studies. While such sources may also generate primary disease prevention hypotheses, particularly for chemoprevention ...