ABSTRACT

Phase I clinical trials play an important role as a translational bridge between preclinical trials and subsequent phase II and III trials in the development of therapeutics. For serious or life-threatening diseases such as cancer or AIDS, the early-phase clinical trials in these areas may involve ˆrst-in-man trials like for other diseases, but with patients who have

CONTENTS

4.1 Introduction ..................................................................................................53 4.2 What Is the Optimum Dose? ......................................................................55 4.3 Dose-Finding Designs Based on Toxicity Alone ..................................... 57

4.3.1 Rule-Based Designs ......................................................................... 57 4.3.1.1 3 + 3 Design ......................................................................... 57 4.3.1.2 Accelerated Titration Design ...........................................58