ABSTRACT
Most clinical trials are longitudinal in nature. In practice, it is almost impossible to enroll and randomize all required subjects at the same time. Clinical data are accumulated sequentially over time. As a result, it is of interest to monitor the information for management of the study. In addition, it is of particular interest to obtain early evidence regarding efficacy, safety, and benefit/risk of the test drug under investigation for a possible early termination. Thus, it is not uncommon to employ a group sequential design with a number of planned interim analyses in a clinical trial. The rationale for interim analyses of accumulating data in clinical trials with group sequential designs have been well documented in the Greenberg Report (Heart Special Project Committee, 1988) more than three decades ago. Since then, the development of statistical methodology and decision processes for implementation of data monitoring and interim analyses for early termination has attracted a lot of attention from academia, the pharmaceutical industry, and health authorities (see, e.g., Jennison and Turnbull, 2000).
