Clinical Trial Designs for Predictive Marker Validation in Cancer Treatment Trials

摘要: Current staging and risk-stratification methods in oncology, while helpful, fail to adequately predict malignancy aggressiveness and/or response specific treatment. Increased knowledge of cancer biology is generating promising marker candidates for more accurate diagnosis, prognosis assessment, therapeutic targeting. To apply these exciting results maximize patient benefit, a disciplined application well-designed clinical trials assessing the utility markers should be used. In this article, we first review major issues consider when designing trial usefulness predictive marker. We then present two classes designs: Marker by Treatment Interaction Design Marker-Based Strategy Design. design, assume that splits population into groups which efficacy particular treatment will differ. This design can viewed as classical randomized with upfront stratification second after status known, each randomly assigned either have therapy determined their or receive independent status. The value assessed comparing outcome all patients marker-based arm non-marker-based arm. detailed sample size calculations scenario. discuss advantages disadvantages designs appropriateness situations assist investigators seeking rigorous, trials.