Why FDA Should Oversee Laboratory Developed Tests

By: Peter Lurie, M.D., M.P.H.

Today FDA is issuing a report that illustrates the real and potential harms to patients and to public health from certain laboratory developed tests (LDTs) – tests that are designed, manufactured and used in a single laboratory.

Dr. Peter LurieWhen FDA first began regulating medical devices under the Medical Device Amendments in the 1970s, we chose not to enforce applicable regulatory requirements for LDTs because they were relatively simple tests generally confined to local labs, and often used for rare conditions.

But times have changed. LDTs have increased in complexity and availability and are now frequently used to diagnose common, serious medical conditions, including cancer and heart disease, with potentially greater impact on patients. And yet, LDTs are still under a general policy of enforcement discretion. That means they have rarely undergone FDA review to determine whether they are accurate, reliable, and provide clinically meaningful results. It also means that FDA’s own adverse event reporting databases rarely capture problems associated with a faulty LDT. Nevertheless, the Agency was able to pull together 20 case studies based on information available in the public domain that show how lack of LDT oversight may be causing or is causing significant harm to patients.

Some LDTs provide positive results even though the patient doesn’t have the disease. For example, a patient can receive a false positive result from a test that is supposed to determine whether someone has been infected with the bacteria that cause Lyme Disease. Patients may then undergo unnecessary treatments and potentially delay diagnosis of their true condition. Such false positives can be even more detrimental when the test is for ovarian cancer, which could prompt women to remove their ovaries.

The report cites other tests that may produce the opposite problem: false negatives. These tests may suggest that a patient doesn’t have a disease or condition, when in fact they do. That’s the case for a test for the gene mutation that makes an excess of human epidermal growth factor receptor 2 (HER2), which promotes the growth of breast cancer cells. Patients who express HER2 typically take drugs that target HER2, in addition to standard chemotherapy. The majority of tests used to detect HER2 protein or gene amplification are LDTs, but, at least in the past, approximately 20 percent of tests may have been inaccurate. That means that some breast cancer patients may not receive the best treatment when the test fails to detect high HER2 levels.

Noninvasive Prenatal Testing to detect a range of fetal chromosomal abnormalities is an example of testing that may result in either false negatives or false positives. Women with false-positive results may abort a normal pregnancy; women with false-negative results may deliver a child with an unanticipated genetic syndrome. The report also lists tests that have no clear relevance to the disease being tested and others that are based on disproven scientific concepts.

And the costs of this lack of oversight are staggering. We were able to derive an estimate of the public health cost for five of the 20 cited tests. For the CARE Clinical Autism Biomarkers Test alone (one of those cited in the report), FDA economists estimated a total public health cost of $66.1 million.

FDA has proposed to step up our oversight of LDTs. We issued a draft guidance last year which we’re currently working to finalize, that proposes to phase in enforcement of premarket review requirements for LDTs. FDA oversight would help ensure that tests are supported by rigorous evidence, that patients and health care providers can have confidence in the test results, and that LDTs have more scientifically accurate product labeling.

As this report demonstrates, strengthening FDA’s oversight over LDTs is critical to protect both patients and the public health.

Peter Lurie, M.D., M.P.H., is FDA’s Associate Commissioner for Public Health Strategy and Analysis

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