Phase I trials originated with evaluation of new cytotoxic agents, "chemotherapy," for cancer. Once an maximum tolerated dose has been determined in phase I, conventionally, treatment Efficacy is evaluated in phase II. Most phase II designs are based on a binary indicator of Efficacy, with secondary aims to estimate a variety of other outcomes, such as pharmacokinetic or pharmacodynamic variables. In oncology, most phase II trials of a new experimental treatment are single-arm, without randomization against a standard treatment. Phase II–III designs are a separate topic, but they are quite important and thus worth mentioning. These designs hybridize phase II screening and confirmatory phase III into a single trial. The continual reassessment method is a model-based sequentially adaptive phase I dose-finding design. The idea of adding so-called "expansion cohorts" to phase I trials began innocently enough, since it is based on what seems to be common sense.