In an editorial published on July 7, 2013, the New York Times called for the Food and Drug Administration (FDA) to issue guidelines for the regulation of laboratory-developed tests (LDTs). LDTs are defined by the FDA as tests that are developed by a single laboratory for use only in that laboratory. Although the FDA acknowledges that laboratories that develop LDTs are acting as manufacturers and are subject to FDA jurisdiction, the agency has historically exercised enforcement discretion over LDTs. Essentially, this means that the FDA looks the other way when it comes to LDTs. This was reasonable when most LDTs were single-analyte, easily reproducible assays. In recent years, however, manufacturers have exploited the LDT classification to avoid FDA regulation of sophisticated tests that, in many cases, require complex and proprietary computer algorithms to generate results. Increasingly, these results are being used for clinical decision making and disease management. An example of a complex LDT that is currently widely used is the Oncotype DX breast cancer assay, a multigene expression test designed to provide prognostic information about breast cancer recurrence. Despite the complexity of the Oncotype DX assay and the serious implications of its use (i.e., determining whether or not adjuvant chemotherapy should be used based on the results of the test), this assay has not undergone FDA approval and is marketed as an LDT. The New York Times editorial draws attention to another test, OvaSure, which was designed to detect ovarian cancer at an early stage but was found to be inaccurate after its 2008 release and was pulled from the market 4 months later. The newspaper reports that the FDA, recognizing the need for increased oversight of LDTs, has prepared a draft guidance on how such tests should be regulated but the document has been stalled somewhere within the agency.
In our 2011 white paper titled Regulation of Genetic Testing in the United States (available for download here: www.hayesinc.com/resource-center/white-papers), Hayes expressed the opinion that the current system of oversight is not sufficient to ensure the safe and appropriate use of genetic tests in patient care. We presented several options for oversight, including requiring all LDTs, including genetic tests, to undergo FDA approval; create a two-tier system under which some tests (i.e., those with the highest clinical impact) must undergo FDA approval but allow some tests (i.e., those deemed to have the lowest risk of adverse events) to continue as LDTs under the jurisdiction of the Clinical Laboratory Improvement Amendments (CLIA) and state accreditation agencies; modify CLIA to include genetic test-specific requirements similar to those in New York State or international accreditation systems; or make no changes to regulation of genetic testing. Whichever model it chooses, the FDA must ensure that the regulatory structure is transparent, equal and consistent, robust, flexible and accountable.
It is disconcerting that there is still no guidance from the FDA, 2 years after we first published this white paper. The time has come for the FDA to issue these desperately needed guidelines to ensure the safety and effectiveness of LDTs.