ABSTRACT
This chapter focuses on introducing the adaptive threshold design for integrating biomarker threshold selection in Phase 2 or 3 studies. The Food and Drug Administration (FDA) is increasingly interested in lending its support for properly designed clinical trials, which used adaptive mechanisms to bring the right therapy to patients. The current FDA guidance states: an adaptive design is defined as a clinical trial design that allows for prospectively planned modifications to one or more aspects of the design based on accumulating data from subjects in the trial. Statistical innovations have paved the way to addressing statistical challenges in integrating biomarker cutoff finding and testing multiple biomarker subgroups within the hypotheses testing framework for treatment effect in clinical trials. The procedure enables exploring several cutpoints in the range of biomarker expression values. This is ideal in the Phase 2 setting of clinical drug development program.
