Fit-for-purpose biomarker method validation for application in clinical trials of anticancer drugs

Abstract

Clinical development of new anticancer drugs can be compromised by a lack of qualified biomarkers. An indispensable component to successful biomarker qualification is assay validation, which is also a regulatory requirement. In order to foster flexible yet rigorous biomarker method validation, the fit-for-purpose approach has recently been developed. This minireview focuses on many of the basic issues surrounding validation of biomarker assays utilised in clinical trials. It also provides an overview on strategies to validate each of the five categories that define the majority of biomarker assays.

Figure 1

Overview of fit-for-purpose biomarker method validation. The fit-for-purpose approach to biomarker method validation tailors the burden of proof required to validate an assay to take account of both the nature of technology utilised and position of the biomarker in the spectrum between research tool and clinical end point. Ultimately, fit-for-purpose requires an assessment of the technical ability of the assay to deliver against the predefined purpose. Abbreviations: IHC=immunohistochemistry; LBA=ligand binding assay; MS=mass spectrometry; PD=pharmacodynamic; POM=proof of mechanism; POC=proof of concept.