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

Chapter 8

Benefit/Risk Assessment in Prevention Trials

Joseph P. Costantino

8.1 Introduction

Benefit/risk assessment (B/RA) is a mathematical procedure to estimate the probability of detrimental outcomes, beneficial outcomes and the net-effect anticipated from exposure to a given agent. B/RAs of health-related outcomes are used for public health planning, decision-making regarding health care financing and therapeutic decision-making in clinical practice [12,24]. Information obtained from B/RAs based on findings from controlled clinical trials, particularly those with double-masking of treatment, are most informative for health care planning and decision-making because such information is less likely to be biased than is information obtained from observational studies [20,23,26]. Thus, B/RAs in prevention trials are an excellent source of information to use as the basis for the types of health care planning and decision-making mentioned above. However, in a prevention trial a B/RA is primarily performed as a supplement for planning, monitoring and analyzing the trial. It is designed to provide a global assessment of all potential beneficial and harmful effects that may occur as a result of a treatment that is being evaluated as a means to reduce the incidence of some particular disease or condition. The Women’s Health Initiative (WHI), the Breast Cancer Prevention Trial (BCPT) and the Study of Tamoxifen and Raloxifene (STAR) are examples of large-scale, multicenter prevention trials ...