The Early Detection Research Network: A National Infrastructure to Support the Discovery, Development, and Validation of Cancer Biomarkers

Abstract

In 2000, the NCI (Rockville, MD) established the Early Detection Research Network (EDRN) to identify, develop, and validate biomarkers to improve the detection of early-stage cancers and risk assessment. This consortium of more than 300 investigators at academic institutions and in the private sector is working collaboratively to bring biomarkers and imaging methods to clinical fruition. Although significant roadblocks have hindered the field of biomarker discovery and validation, the EDRN has helped overcome many of them by setting well-defined strategies and milestones focused on solving defined unmet clinical needs. The EDRN has implemented measures to improve biomarker discovery and validation, such as data sharing, use of common data elements, generating multidisciplinary and multi-institutional collaborations within a cohesive and productive team environment, and putting emphasis on quality control and data replication for all candidate biomarkers for reaching a "go" or "no go" decision. A measure of the success of the EDRN is the number of biomarkers tests or devices approved by the FDA to which EDRN investigators have made significant contributions and the number of biomarkers tests developed by EDRN investigators that are available in Clinical Laboratory Improvement Amendments laboratories.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."

Figure 1:. EDRN Organizational Structure:

The four structural components of the EDRN have distinct but complementary roles. Biomarker Developmental Laboratories discover, develop, and characterize new biomarkers or refine existing biomarkers. Biomarker Reference Laboratories conduct assays for EDRN validation trials. Clinical Validation Centers conduct validation trials on biomarkers developed by both EDRN and non-EDRN investigators. Data Management and Coordinating Center assists with protocol design, works with the Clinical Validation Centers to conduct biomarker validation trials and maintains the data and biospecimen tracking systems. EDRN Steering Committee is composed of all the EDRN Principal Investigators and is responsible for overseeing the activities of EDRN and setting priorities. Network Consulting Team is composed of independent scientists and clinicians. They review and evaluate the research conducted by the EDRN. Modified from Srivastava, S. The Early Detection Research Network: 10-Year Outlook. Clinical Chemistry, 2013;59 (1):60–67.

Figure 2:. Phases of Biomarker Discovery and Validation:

The EDRN has developed a five-phase approach for biomarker development and validation. The 5-step approach to biomarker validation includes Phase 1 – Preclinical Exploratory; Phase 2 – Clinical Grade Assay Development and Verification; Phase 3 – Retrospective Longitudinal Trial, Phase 4 – Prospective Screening Trial, and Phase 5 – Cancer Control. Adapted from Pepe MS, Etzioni R, Feng Z, Potter JD, Thompson ML, Thornquist M, et al. Phases of biomarker development for early detection of cancer. Journal of the National Cancer Institute. 2001;93(14):1054–61.

Figure 3:. EDRN Biomarker Triage System:

EDRN has developed a triage system with a series of “go or no-go” decisions. Only when biomarkers have passed this rigorous process of verification, is a large clinical validation study undertaken.