of a clinical laboratory, which is more stringent and provides a baseline level of quality assurance compared to a research laboratory setting. A report by the Secretary’s Advisory Committee on Genetics, Health, and Society in 2008 delineated concerns with the current CLIA standards and oversight of clinical laboratories and made recommendations for improving the oversight of clinical laboratories (SACGS, 2008). The second standard referenced in this chapter is oversight by FDA. FDA has not enforced its authority for oversight of LDTs, which is one pathway for the translation of an omics discovery into a clinical test, and FDA has not yet defined its regulatory approach to oversight of omics-based tests, especially when developed as an LDT. Implementation of the committee’s recommendation could lead to an increased workload for FDA, with an impact on the finite resources of FDA. This issue is not addressed by this report. FDA’s responsibility for assuring the safety and effectiveness of any medical device, including omics-based tests, does not require demonstration of clinical utility, which is a standard required by payers. However, FDA is the federal regulatory agency with authority for oversight of testing and should be seen as a partner in the test validation phase. Therefore, the committee uses the CLIA and FDA regulatory standards as a minimum for assuring the quality of a test prior to use in a clinical trial to direct patient management.
FIGURE 3-1 Omics-based test development process, highlighting the test validation phase. The first stage of omics-based test development is comprised of two phases: discovery and test validation. In the test validation phase, the omics-based test undergoes analytical and clinical/biological validation. Statistics and bioinformatics validation occurs throughout the discovery and test validation stage as well as the stage for evaluation of clinical utility and use. The bright line signifies the point in test development where a fully defined, validated, and locked-down clinical test method is necessary. Changes to the test after the bright line is crossed require a return to the test validation phase, approval by the Institutional Review Board (IRB), and possibly consultation with the Food and Drug Administration (FDA).