Analytical Considerations: Discovery or Validation of Biomarkers

A biomarker is an indication of an underlying physiological or pathological process or an intervention. There is growing interest in discovering novel markers which predict response or reflect a change in homeostatic state of an organism. Discovery of novel therapies are hindered by the lack of precise biomarkers to monitor efficacy. Lack of therapy monitoring, or response biomarkers or poor markers being used, have led to several promising therapy candidates failing at various stages of drug discovery. From study design to data analysis, every step of the underlying process is affected by variation of technical nature, and it is imperative to discern those from biological response variation between groups, which indicates its optimal use as a biomarker. Biomarker discovery is very active research area, however, very few markers have proven useful for clinical use. This chapter deals with analytical considerations important for all stages of biomarker discovery, verification and validation. It includes important considerations for study design, biospecimen sample collection, handling, storage and measurement. We further deal with various mode of mass spectrometry data acquisition and robust modalities for data analysis. We have used succinct descriptors with examples to bring out inefficient processes sometimes used at discovery or verification stages and point out literature for remedial strategies.