ABSTRACT
In clinical trials, it is not uncommon to modify trial and/or statistical procedures during the conduct of clinical trials based on the review of interim data. The purpose is not only to efficiently identify clinical benefits of the test treatment under investigation, but also to increase the probability of success of clinical development. Trial procedures are referred to as the eligibility criteria, study dose, treatment duration, study endpoints, laboratory testing procedures, diagnostic procedures, criteria for evaluability, and assessment of clinical responses. Statistical methods include randomization, study design, study objectives/hypotheses, sample size, data monitoring and interim analysis, statistical analysis plan, and/or methods for data analysis. In this chapter, we will refer to the adaptations (or modifications) made to the trial and/or statistical procedures as the adaptive design methods. Thus, an adaptive design is defined as a design that allows adaptations to trial and/or statistical procedures of the trial after its initiation without undermining the validity and integrity of the trial (Chow, Chang, and Pong 2005). In their recent publication, with the emphasis of the feature of by design adaptations only (rather than ad hoc adaptations), the Pharmaceutical Research Manufacturer Association (PhRMA) Working Group on Adaptive Design refers to an adaptive design as a clinical trial design that uses accumulating data to decide on how to modify aspects of the study as it continues, without undermining the validity and integrity of the trial (Gallo et al. 2006). In many cases, an adaptive design is also known as a flexible design.
