Validation of New Cancer Biomarkers: A Position Statement from the European Group on Tumor Markers

Abstract

BACKGROUND:Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT:In this review, we discuss the key steps in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before initiation of the study.

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

“…Validation of a (bio)marker assay for clinical use requires evaluation of its analytical validity, clinical validity, and clinical utility [18,50,51,52]. Every laboratory test must show acceptable level of analytical validity to have any clinical utility [50,53].…”

“…Every laboratory test must show acceptable level of analytical validity to have any clinical utility [50,53]. Many parameters are used for analytical validation of biomarker assays, including accuracy, trueness, precision, reproducibility, repeatability, linearity, and robustness [52,54]. Analytical validation of IHC tests has gained attention recently [55].…”

Future microfluidic and nanofluidic modular platforms for nucleic acid liquid biopsy in precision medicine

“…[8][9][10][11][12][13][14][15][16][17][50][51][52][53][54][55] Reliable quantification of mRNA and microRNA levels for diagnostic and prognostic purposes requires optimal RNA quality and quantity. However, the different instances along the RNA and miRNA analysis workflow can lead to length, sequence, and structure-specific biases in the final expression analysis of a given set of small RNAs.…”

“…Equipment and analysis costs, throughput, and normalization 6,7 still represent obstacles for large-scale nucleic acid biomarker validation [8][9][10][11][12][13][14] and adoption in the clinics [15][16][17] Differences in the nucleic acid purification method, detection technology, and laboratory protocol often lead to different profiling results. Consequently, interpretation of differential expression data and comparisons across different studies has to be done with a note of caution, as standard deviations can span several orders of magnitude.…”

Establishing the Evidence Bar for Molecular Diagnostics in Personalised Cancer Care

“…There have been thousands of studies published in the scientific literature claiming cancer biomarkers are clinically useful, but these biomarkers hardly ever reach clinical application for a wide variety of reasons [9]. Most of the issues relate to analytical and clinical validation, demonstration of clinical utility, regulatory approval, health technology assessment, reimbursement and adoption in clinical practice [10]. …”