Abstract

Fit-for-Purpose Biomarker Assay Validation – From Research Tool to Diagnostic Test

Jeff Cummings, Senior Quality Assurance Scientist, Cancer Research UK Manchester Institute

Biomarkers offer potential to accelerate drug development, present a reliable diagnostic readout of human disease or be predictive of therapeutic outcome during clinical trials. However, they can fail to deliver their promise not because of the underlying science but due to poor choice of assay and lack of validation. The fit-for-purpose (F-P) approach provides a robust solution to biomarker method validation. The approach is conducted in multi-stages but at its core it is based on defining the purpose of the biomarker, choosing an appropriate assay and then demonstrating by experimentation that the assay does indeed achieve its purpose. Comparing technical parameters in isolation of purpose – conventional bioanalytical method validation –does not guarantee that the assays will be successful in the clinical. Technical parameters, although essential, tell you that you are doing the test correctly, but not that you are using the correct test. F-P takes account of the position of the biomarker in the spectrum between research tool and diagnostic test, the nature of the analytical technique from qualitative assay to absolute quantitation and all relevant regulatory requirements. To illustrate these principles, a worked example is presented of circulating tumour cell enumeration as a prognostic/predictive biomarker in cancer research.