ABSTRACT
In clinical research, the response in a dose response study could be a biological response for safety or efficacy. For example, in a dose-toxicity study, the goal is to determine the maximum tolerable dose (MTD). On the other hand, in a dose-efficacy response study, the primary objective is usually to address one or more of the following questions: (i) Is there any evidence of the drug effect? (ii) What is the nature of the dose response? and (iii) What is the optimal dose? In practice, it is always a concern as to how to evaluate the dose-response relationship with limited resources within a relatively tight time frame. This concern led to a proposed design that allows less patients to be exposed to the toxicity and more patients to be treated at potentially efficacious dose levels. Such a design also allows pharmaceutical companies to fully utilize their resources for development of more new drug products (see, e.g., Arbuck, 1996; Babb, Rogatko, and Zacks, 1998; Babb and Rogatko, 2001; Berry et al., 2002; Bretz and Hothorn, 2002).
