Regulation of Clinical Tests: In Vitro Diagnostic (IVD) Devices, Laboratory Developed Tests (LDTs), and Genetic Tests

In vitro diagnostic (IVD) devices are used in the analysis of human samples, such as blood or tissue, to provide information in making health care decisions. Examples of IVDs include (1) pregnancy test kits or blood glucose tests for home use; (2) laboratory tests for infectious disease, such as HIV or hepatitis and routine office blood tests such as for cholesterol and anemia; and (3) tests for various genetic diseases or conditions. More recently, a specific diagnostic test—called a companion diagnostic—may be used to select the best therapy, at the right dose, at the correct time for a particular patient; this is often referred to as personalized medicine.

Federal agencies involved in the regulation of IVDs include the Food and Drug Administration (FDA) and the Centers for Medicare & Medicaid Services (CMS). FDA derives its authority to regulate the sale and distribution of medical devices, such as IVDs, from the Federal Food, Drug, and Cosmetics Act and the Public Health Service Act. CMS’s authority to regulate IVDs is through the Clinical Laboratory Improvement Amendments of 1988. FDA regulates the safety and effectiveness of the diagnostic test as well as the quality of the design and manufacture of the diagnostic test, and CMS regulates the quality of clinical laboratories and the clinical testing process.

Traditionally, most genetic tests have not been subject to premarket review by the FDA. This is because in the past, genetic tests were developed by laboratories primarily for their in-house use—referred to as laboratory-developed tests (LDTs)—to diagnose rare diseases and were highly dependent on expert interpretation. However, more recently LDTs have been developed to assess relatively common diseases and conditions, thus affecting more people, and direct-to-consumer (DTC) genetic testing has become widely available over the Internet. In June 2010 FDA announced its decision to exercise its authority over all LDTs. FDA has provided a number of reasons for the decision to assert its enforcement authority over LDTs, including that the public needs assurances that LDTs are sound and reliable. FDA has not yet finalized guidance with respect to all LDTs. A provision in the Food and Drug Administration Safety and Innovation Act stipulates that the agency “may not issue any draft or final guidance on the regulation” of LDTs without “at least 60 days prior to such issuance,” first notifying Congress “of the anticipated details of such action.”

Concerning DTC genetic tests, which are mostly LDTs, the Government Accountability Office (GAO) testified in 2010 before the Subcommittee on Oversight and Investigations of the House Committee on Energy and Commerce that the results of DTC genetic tests for disease risk were “misleading and of little or no practical use to consumers.” The GAO investigation focused on four genetic testing companies that were “frequently cited as being credible by the media and in scientific publications.” The cost of these genetic tests ranged from $299 to $999. The tests provided risk predictions for diseases such as diabetes, hypertension, multiple sclerosis, leukemia, breast cancer, and prostate cancer.

The extent to which LDTs should be regulated by the FDA, in conjunction with CMS, has been a subject of debate. Some clinical laboratories and manufacturers of LDTs have maintained that LDTs should be outside of the FDA’s regulatory purview. Legislation was introduced in the 110th and 112th Congresses with the aim to clarify regulatory oversight as well as support innovation. Approaches have included, among others, streamlining regulation by concentrating it in a single federal agency or requiring the FDA to assert its enforcement authority over LDTs.