FDA Analysis of Lab-Developed Tests

Most clinical laboratory testing has very low revenue and margins.  One area that is more profitable is the use of tests that are specifically created by a laboratory and used only in that lab, so of course, we have seen an explosion in the use of such tests.  Now the Food and Drug Administration is raising alarms about the quality of these tests.  (FDA Paper)   The FDA looked at 20 lab-developed tests, finding examples of both false-positive and false-negative tests that had the potential to cause patient harm.  The FDA notes that it initially took the position that it would not extensively regulate lab-developed tests at a point when they were relatively simple, which has led to recent proposals for heightened regulation, which the labs have pushed back against.  Labs are also governed by the Clinical Laboratories Improvement Amendments, but these rules focus on the process of testing, not the actual efficacy or safety of the tests.  Among the concerns the FDA raised to justify more regulation are a lack of clinical evidence indicating the validity of the tests, which typically would require clinical trials, and a failure to adequately disclose the evidence basis for the test; adverse event reporting, labeling adequacy, unsupported manufacturer claims regarding the test and competitive concerns in comparison to multi-lab tests which are already subject to comprehensive regulation.

Among the examples the FDA cited regarding lab-developed tests are several for Lyme’s disease that had high rates of false positives, leading to unnecessary treatment and in some cases patient harm.  Another was an ovarian cancer test that had an incredibly high false positive rate, which obviously would raise patient anxiety as well as lead to over-treatment, including potentially removal of the ovaries.  This manufacturer made inflated claims about the accuracy and utility of the test.  On the other side of the coin are tests with many false negatives, which failed to detect disease when it was there.  These tests include ones used to guide breast cancer therapy and those detecting human papillomavirus.  And then there are the real winners, the tests that have both many false positives and false negatives, which include prenatal genetic tests.  Finally, there are a large number of tests with very limited evidence for clinical utility.  These tests may be accurate in what they report, but the findings don’t have value for physicians or patients in making treatment decisions.  Many genetic tests fall into this category.  These tests are basically a waste of money.  You get the drift and the examples indicate the quality and cost issues associated with bad tests, so the FDA has clearly built a strong case for tougher regulation.  The question is why they ever took it so lightly in the first place.