ABSTRACT
This chapter provides an overview of state-of-the-art seamless phase I/II dose escalation oncology designs that utilize both efficacy and toxicity outcomes in dose assignment decisions. It presents statistical background, defines experimental objectives of a phase I/II trial, and discusses adaptive designs to achieve these objectives in practice. The chapter also discusses several important types of phase I/II designs for trials where efficacy and toxicity are correlated binary random variables. It describes phase I/II designs for more complex settings, namely when the toxicity is binary and efficacy is continuous, when efficacy outcomes are delayed, and when study patients have heterogeneous prognostic profiles. In some settings, such as oncohematology trials, efficacy without toxicity is viewed as too stringent an outcome. A Bayesian decision-theoretic framework for phase I dose-finding designs were developed by Whitehead and Brunier and Whitehead and Williamson in the context of toxicity outcomes.
