Last week, the Association for Molecular Pathology announced the formation of a working group to produce a white paper about regulatory oversight of laboratory-developed tests (LDTs), a topic that has gained much attention following recent deliberations in the FDA regarding potential policy changes to current regulation.
The FDA sessions have sparked a flood of commentary and position statements from regulatory pundits, trade organizations, patient advocacy societies and other groups concerning appropriate regulation of LDTs. As the discourse on this subject continues to unfold, all stakeholders should have a clear understanding of the unique needs that LDTs address in healthcare and the various measures employed by current regulation to evaluate the quality of such tests.
LDTs are tests that are developed by a single clinical laboratory for use only in that laboratory. These tests are usually provided to satisfy a testing niche that is not addressed by other commercially available tests. One example would be genetic tests that focus on a specific subset of the general population, such as Everist Genomics’ OncoDefender-CRC, which examines gene expression levels in tumors of early stage colorectal cancer patients to identify those who are likely to benefit from adjuvant chemotherapy.
Due to the fact that genetic tests are often more labor intensive than other types of tests and require highly-specialized equipment, these tests are usually performed in large laboratories as a service to healthcare providers and other laboratories. While LDTs are not required to go through the FDA’s premarket approval process, these tests must go through rigorous validation procedures and must meet several criteria before results can be used regarding patient care.
The Clinical Laboratory Improvement Amendments (CLIA), established by Congress in 1988, provides quality standards to ensure the accuracy, reliability and timeliness of patient results regardless of where the test is performed. Administered by the Centers for Medicare & Medicaid Services (CMS), the Food and Drug Administration (FDA), and the Centers for Disease Control (CDC), CLIA classifies diagnostic tests into three categories: waived tests, tests of moderate complexity and tests of high complexity. The classification of the test determines the complexity of the requirements that are applied.
These requirements include proficiency testing programs to evaluate the accuracy of test results as well as rigorous personnel standards to ensure that lab staff members have appropriate credentials and experience. Importantly, laboratories are also required to have proper systems and processes for monitoring testing equipment and must have an overall plan to monitor the quality of all areas of the laboratories ongoing operations. Simply stated, these regulatory standards place a high level of accountability on laboratories to ensure the quality of the tests they perform.