Laboratory Developed Tests (LDTs) have become a source of convenience and hope for patients, but they have also triggered controversy about the safety of their impact on consumer expectations, and about the accuracy of the clinical results they provide. In 2014, the Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid Services (CMS) had proposed a baroque regulatory regime to govern the labs and the tests providing LDT services. Three years later FDA and CMS backed off the complex approach in favor of a more streamlined, less bureaucratic way to gain both safety and quick benefits for consumers.
A LDT can be as simple as your local clinic’s procedure to estimate the level of sodium in blood, or it can be as sophisticated as a search for specific protein sequences in your DNA. LDTs can be “chemistry tests, such as glucose or protein, performed on body fluids other than blood,” e.g., from lungs or joints, or from the lower respiratory tract for an influenza test.
Sophisticated genetic testing is used in identifying rare diseases such as Huntington’s. If a test for Huntington’s had to be subjected to the usual FDA verifications and audits needed to obtain FDA approval for a commercial version, the cost per patient would be prohibitive and the lab could not afford to offer the test.
Recently, the FDA approved a home test kit from 23andMe that can detect three genetic mutations found in about 2% of people with Ashkenazi, or Eastern European Jewish descent. Those mutations are associated with the development of cancers. There are many types of cancer that are not caused by those mutations, so additional tests will be welcomed, provided they offer high accuracy. When a test can give false positive or false negative indications, it can cause consumers to make radical alterations to their future plans, or it could encourage a patient to skip treatment that is actually needed.
Under development in a US lab and also in an Australian lab is a blood test that can spot Alzheimer’s disease up to 20 years before the symptoms are obvious. The developers claim 90% accuracy. Given the large proportion of our population who will suffer from Alzheimer’s in their later years, such a test is eagerly awaited.
Unfortunately, a lab developed test for Alzheimer’s may need years of additional development. Part of the developers’ difficulty comes from knowing the correct status of an individual that their test says has Alzheimer’s disease. The gold standard indication of Alzheimer’s is the presence of “tangles and plaques” in the brain, but that is usually confirmed by a brain autopsy. Reliance on a brain autopsy slows progress since the researchers must await natural and accidental deaths of their test subjects. There are other tests that can suggest probable Alzheimer’s, but they have an accuracy of just 35%.
The FDA in 2014 proposed to “oversee the quality of these laboratory tests, alongside the CMS which regulates the laboratories themselves.” While many commenters agreed that oversight may be needed for some tests, a dual regulatory approach from FDA and CMS was thought to be overkill and likely to suppress innovation by the labs that have been producing much needed tests.
By 2017, the FDA backed down to a more tailored approach in which it felt the need for premarket review for certain tests with a focus on analytical and clinical validity as the basis for test approval. It also wants adverse event reporting and public availability of test performance information.
There remains some opposition to this proposal of lighter regulation, so to avoid future conflicts, the FDA now wants a bill from Congress that will codify its authority to oversee LDTs. It is reassuring to see agencies seeking Congress’s approval rather than presuming that they have the authority to do whatever they want to do.