The Early Detection Research Network's Specimen Reference Sets: Paving the Way for Rapid Evaluation of Potential Biomarkers
ABSTRACT BACKGROUND: The mission of the National Cancer Institute's Early Detection Research Network (EDRN) is to identify and validate cancer biomarkers for clinical use. Since its inception, EDRN investigators have learned a great deal about the process of validating biomarkers for clinical use. Translational research requires a broad spectrum of research expertise, and coordinating collaborative activities can be challenging. The EDRN has developed a robust triage and validation system that serves the roles of both "facilitator" and "brake."Content:The system consists of (a) establishing a reference set of specimens collected under PRoBE (Prospective Specimen Collection Retrospective Blinded Evaluation) design criteria; (b) using the reference set to prevalidate candidate biomarkers before committing to full-scale validation; (c) performing full-scale validation for those markers that pass prevalidation testing; and (d) ensuring that the reference set is sufficiently large in numbers and volumes of sample that it can also be used to study future candidate biomarkers. This system provides rigorous and efficient evaluation of candidate biomarkers and biomarker panels. Reference sets should also be constructed to enable high-quality biomarker-discovery research.Summary:We describe the process of establishing our system in the hope that it will serve as an example of how to validate biomarkers for clinical application. We also hope that this description of the biospecimen reference sets available from the EDRN will encourage the biomarker research community-from academia or industry-to use this resource to advance biomarkers into clinical use.
- [Show abstract] [Hide abstract]
ABSTRACT: Biomarkers, quantitatively measurable indicators of biological or pathogenic processes, once validated play a critical role in disease diagnostics, the prediction of disease progression, and/or monitoring of the response to treatment. They may also represent drug targets. A number of different methods can be used for biomarker discovery and validation, including proteomics methods, metabolomics, imaging, and genome wide association studies (GWASs) and can be analysed using receiver operating characteristic (ROC) plots. The relative utility of single biomarkers with biomarker panels is discussed, along with paradigms for biomarker development, the latter in the context of three large-scale biomarker consortia, the Critical Path Predictive Safety Testing Consortium (PSTC), the NCI Early Detection Research Network (EDRN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). The importance of systematic optimization of many parameters in biomarker analysis, including validation, reproducibility, study design, statistical analysis and avoidance of bias are critical features used by these consortia. Problems including introduction of bias into study designs, data reporting or data analysis are also reviewed.Biochemical pharmacology 08/2013; 87(1). DOI:10.1016/j.bcp.2013.08.026 · 4.65 Impact Factor
- Clinical Chemistry 12/2013; 60(2). DOI:10.1373/clinchem.2013.216382 · 7.77 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: This article describes the principles of marker research with prospective studies along with examples for diagnostic tumor markers. A plethora of biomarkers have been claimed as useful for the early detection of cancer. However, disappointingly few biomarkers were approved for the detection of unrecognized disease, and even approved markers may lack a sound validation phase. Prospective studies aimed at the early detection of cancer are costly and long-lasting and therefore the bottleneck in marker research. They enroll a large number of clinically asymptomatic subjects and follow-up on incident cases. As invasive procedures cannot be applied to collect tissue samples from the target organ, biomarkers can only be determined in easily accessible body fluids. Marker levels increase during cancer development, with samples collected closer to the occurrence of symptoms or a clinical diagnosis being more informative than earlier samples. Only prospective designs allow the serial collection of pre-diagnostic samples. Their storage in a biobank Upgrades cohort studies to serve for both, marker discovery and validation. Population-based cohort studies, which may collect a wealth of data, are commonly conducted with just one baseline investigation lacking serial samples. However, they can provide valuable information about factors that influence the marker level. Screening programs can be employed to archive serial samples but require significant efforts to collect samples and auxiliary data for marker research. Randomized controlled trials have the highest level of evidence in assessing a biomarker's benefit against usual care and present the most stringent design for the validation of promising markers as well as for the discovery of new markers. In summary, all kinds of prospective studies can benefit from a biobank as they can serve as a platform for biomarker research. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.Biochimica et Biophysica Acta 12/2013; 1844(5). DOI:10.1016/j.bbapap.2013.12.007 · 4.66 Impact Factor