ABSTRACT
Three critical issues surrounding the validation of predictive biomarkers in oncology are discussed in this chapter, specifically, the choice of endpoints, types of clinical trial designs (selected, unselected, adaptive), and issues of added complexity (logistics, local versus central testing, and multivariate assays). While overall survival is the ultimate clinical outcome, and therefore the ideal outcome for a maker validation study, we discuss two other endpoints of progression-free survival and toxicity that can be considered for a marker validation study. Designs for marker validation are broadly classified as retrospective versus prospective, where the latter is categorized into enrichment (or targeted), unselected (or all-comers), or adaptive analysis designs. In this chapter, we review and explore the strengths and pitfalls of each of these designs using clinically relevant examples. Finally, we briefly discuss issues surrounding biomarker assays using pertinent clinical examples such as marker assessment methods, feasibility of obtaining the specimens, the reliability and reproducibility of the assay, and additional cost involved with assessing the marker status on every patient. While biomarkers provide an integrated approach to prediction for treatment selection and patient management, careful consideration of the issues outlined in this chapter are needed to determine its clinical utility.
