ABSTRACT
This chapter focuses on acute myeloid leukemia. It describes conventional methodology used to evaluate new drugs is incongruent with clinical reality. The chapter explores phase 1 trial whose sole endpoint is toxicity that is quantified using standard criteria and evaluated using a “3+3 design” in order to determine a dose for a subsequent phase 2 trial. It explains a single-arm phase 2 trial formally concerned only with a single measure of efficacy. The chapter describes a large randomized phase 3 trial intended to compare the new drug with standard treatment. Proposals for “quicker” phase 3 trials and adaptive randomization enable study of many more drugs. Even with randomization, however, decisions to move from phase 2 to phase 3 typically are based on early outcomes in phase 2 rather than survival or disease-free survival time. The phase 2 selection design randomizes patients thus flying in the face of the concept of the phase 2 trial as single arm.
