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Biomarker method validation in anticancer drug development.

Journal Article


Abstract


  • Over recent years the role of biomarkers in anticancer drug development has expanded across a spectrum of applications ranging from research tool during early discovery to surrogate endpoint in the clinic. However, in Europe when biomarker measurements are performed on samples collected from subjects entered into clinical trials of new investigational agents, laboratories conducting these analyses become subject to the Clinical Trials Regulations. While these regulations are not specific in their requirements of research laboratories, quality assurance and in particular assay validation are essential. This review, therefore, focuses on a discussion of current thinking in biomarker assay validation. Five categories define the majority of biomarker assays from 'absolute quantitation' to 'categorical'. Validation must therefore take account of both the position of the biomarker in the spectrum towards clinical end point and the level of quantitation inherent in the methodology. Biomarker assay validation should be performed ideally in stages on 'a fit for purpose' basis avoiding unnecessarily dogmatic adherence to rigid guidelines but with careful monitoring of progress at the end of each stage. These principles are illustrated with two specific examples: (a) absolute quantitation of protein biomarkers by mass spectrometry and (b) the M30 and M65 ELISA assays as surrogate end points of cell death.

UOW Authors


  •   Ranson, Marie (external author)

Publication Date


  • 2008

Citation


  • Cummings, J., Ward, T. H., Greystoke, A., Ranson, M., & Dive, C. (2008). Biomarker method validation in anticancer drug development.. British journal of pharmacology, 153(4), 646-656. doi:10.1038/sj.bjp.0707441

Web Of Science Accession Number


Start Page


  • 646

End Page


  • 656

Volume


  • 153

Issue


  • 4

Abstract


  • Over recent years the role of biomarkers in anticancer drug development has expanded across a spectrum of applications ranging from research tool during early discovery to surrogate endpoint in the clinic. However, in Europe when biomarker measurements are performed on samples collected from subjects entered into clinical trials of new investigational agents, laboratories conducting these analyses become subject to the Clinical Trials Regulations. While these regulations are not specific in their requirements of research laboratories, quality assurance and in particular assay validation are essential. This review, therefore, focuses on a discussion of current thinking in biomarker assay validation. Five categories define the majority of biomarker assays from 'absolute quantitation' to 'categorical'. Validation must therefore take account of both the position of the biomarker in the spectrum towards clinical end point and the level of quantitation inherent in the methodology. Biomarker assay validation should be performed ideally in stages on 'a fit for purpose' basis avoiding unnecessarily dogmatic adherence to rigid guidelines but with careful monitoring of progress at the end of each stage. These principles are illustrated with two specific examples: (a) absolute quantitation of protein biomarkers by mass spectrometry and (b) the M30 and M65 ELISA assays as surrogate end points of cell death.

UOW Authors


  •   Ranson, Marie (external author)

Publication Date


  • 2008

Citation


  • Cummings, J., Ward, T. H., Greystoke, A., Ranson, M., & Dive, C. (2008). Biomarker method validation in anticancer drug development.. British journal of pharmacology, 153(4), 646-656. doi:10.1038/sj.bjp.0707441

Web Of Science Accession Number


Start Page


  • 646

End Page


  • 656

Volume


  • 153

Issue


  • 4