Biomarker-based clinical trials

Increasing scientific knowledge is generating promising marker candidates for diagnosis, prognosis assessment, and therapeutic targeting. To apply these results to maximize patient benefit, a disciplined application of well-designed clinical trials for assessing the utility of markers should be employed. We review issues to consider when designing a clinical trial assessing the usefulness of a predictive marker, that is, a marker intended to be used to select a specific therapy for a patient based on the biomarker’s status. First the use of biomarkers in the early stage trial setting (phase I and II) will be reviewed. The discussion will then turn to the multiple possible options for validating a predictive biomarker in the phase III setting. The pros and cons of retrospective vs prospective validation will be reviewed. Finally the multiple approaches to prospective validation will be compared. Multiple examples from oncology will be used to illustrate the principles.