agents (see Appendix B). These tests were used to select patient therapy in the three clinical trials identified in the IOM committee’s statement of task. In addition, the committee examined six tests that are currently commercially available (Table 6-1): Oncotype DX (Genomic Health), MammaPrint (Agendia), Tissue of Origin (Pathwork Diagnostics), OVA1 (Vermillion), AlloMap (XDx), and Corus CAD (CardioDx), as well as one test that did not advance to clinical use (OvaCheck). These cases reflect a number of diseases and types of omics research. The committee also reviewed the development and use of human epidermal growth factor receptor 2 (HER2) testing, one of the earliest single-biomarker tests to guide the choice of cancer therapy. This last case study illustrates the challenges involved in the development of a single analyte test and suggests how the complexity could be magnified for multianalyte, omics-based tests. Despite many years of research and development, challenges remain in defining the optimal test method and interpretation for HER2 testing.


Examination of what transpired in the development of the omics-based tests at Duke University was based on presentations to the committee, a panel discussion with Duke University researchers and administrators, documents provided by the National Cancer Institute and Duke University, and the peer reviewed literature. The Duke case study is illustrative of the more systemic challenges involved in the development of omics-based tests and the need for rigorous criteria for test development, and is discussed in more detail in Appendix B. For the other case studies, the committee reviewed publicly available materials, including peer reviewed publications and Food and Drug Administration (FDA) 510(k) clearance decision summaries. The committee also invited presentations on the development of Oncotype DX and MammaPrint (Shak, 2011; van ‘t Veer, 2011). Each of the six summaries for the commercially available tests was sent to the respective company for review of factual accuracy and completeness.

Detailed case studies were prepared for Oncotype DX, MammaPrint, Tissue of Origin, and AlloMap. The organization of the detailed case studies reflects the test development process that the committee recommends in Chapters 2-4, including candidate omics-based test discovery and confirmation, development into a defined and validated omics-based test, and evaluation for clinical use. Shorter case studies were assembled for HER2, OVA1, OvaCheck, and Corus CAD, and include details on discovery, development, and clinical use. Case studies appear in Appendix A.

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