The need for systematic validation of proteomics biomarkers and lack of standardization of validation methods among researchers [71, 96, 97] has led to the establishment of the Early Detection Research Network (EDRN) and the Prospective Specimen Collection, Retrospective Blinded Evaluation (PRoBE) collaboration with the National Cancer Institute (NCI) [25, 98]. One important identified cause of unsuccessful biomarker validation is the lack of concordant experimental outcome from independent research groups . Prensner et al therefore suggested a three-phased biomarker validation pipeline, starting with a discovery phase, followed by validation in a retrospective cohort, and then final validation in a prospective cohort . Mandrekar et al emphasized that critical planning is essential in biomarker validation design and that the use of prospective randomized controlled trials as a gold standard enables a distinction between prognostic and predictive biomarkers . Analytic validation, clinical qualification/validity and clinical utilization has been recommended as vital steps in the rigorous evaluation of biomarkers and surrogate endpoints in chronic diseases [72, 99].