Fit-for-Purpose Biomarker Assay Validation - From Research Tool to Diagnostic Test
About the Speaker
Dr Jeff Cummings PhD is a Staff Scientist working within the Clinical and Experimental Pharmacology Group of the Cancer Research UK Manchester Institute as its quality assurance (QA) manager. Jeff has been at the forefront of academic QA over the past 10 years. He co-founded the NTRAC QA group in 2004 and since then has chaired and steered the group through it various manifestations to its present form as the ECMC QA and Translational Science (QATS) group. Jeff has 34 years’ experience in cancer pharmacology and his present research interests are focused on biomarker method validation and qualification and quality control procedures. He has published over 170 papers, including the first reports on the validation and characterisation of circulating tumour cells (CTC) utilising advanced statistical analysis as 2 separate Technical Advances in BMC Cancer as well as guest editing a special issue of the Journal of Chromatography on Quantitative Analysis of Biomarkers by LC/MS. He recently led the QATS group accreditation initiative to CLIA, ISO17025 and ISO15189 standards, steered the Manchester Institute through an MHRA GCP Clinical Laboratory Regulatory Inspection and was elected to the Council of the British Testing and Measurement Association (BMTA).Abstract
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.
