ABSTRACT
Developing biomarkers for use in the clinical setting is a long and strenuous process. Several preclinical and clinical studies are needed to prove the value of a predictive marker for clinical decision-making. Overall, the evaluation must prove the utility and the reliability of the candidate biomarker. This chapter will describe the theory behind development of predictive biomarkers and in addition give an example on predictive biomarker development based on our experience with Tissue Inhibitor of Metalloproteinases. The chapter will cover 10 of the most important issues to be considered when developing and validating predictive biomarkers in cancer (1) describe the clinical need; (2) specify a research hypothesis to guide the research; (3) test the hypothesis in preclinical models; (4) select or develop an analytical platform; (5) identify available clinical samples and perform a retrospective study of the potential biomarker; (6) refine the assay and perform an additional retrospective study if necessary; (6a) if necessary modify the analytical platform, study the preanalytical variables; (6b) perform an additional retrospective study employing the improved assay; (7) develop the assay to standards compatible with daily clinical routine; (8) perform a prospective study with the biomarker as a secondary aim; (9) design a clinical trial including the biomarker; (10) implement the biomarker in daily routine diagnostics.
