Cross-posted with Biopolitical Times on December 9th, 2015.
Generally the stock of research hospitals, laboratory developed tests (LDTs) were traditionally considered relatively benign and straightforward, tending not to require premarket review in the U.S. by the F.D.A. However, with the advent of genetic testing and private biotech company research, LDTs are now being used to diagnose common and serious diseases such as heart disease and cancer—highlighting the need for regulatory oversight to manage the diagnostic consequences of unvalidated testing. Over the last year, the F.D.A has been working towards new guidance of LDTs while seeking comments from the public. On November 16, the administration released a report of 20 case studies depicting the negative public health impact caused by LDTs that don’t perform as promised.
Robert Pear covered the issue for The New York Times, remarking that “Inaccurate and unreliable medical tests are prompting abortions, promoting unnecessary surgeries, putting tens of thousands of people on unneeded drugs and raising medical costs.” These are non-trivial findings. Beyond the personal harm caused by these mistakes, the costs are impressive. For example, an inaccurate genetic biomarker test for autism that was given to 2,027 children had an estimated social cost of $66.1 million, far outweighing the profits provided to the company.
In addition to these immediate individual and social harms, there is also a looming existential threat to the healthcare and research communities. These tests are in the limelight largely because they form the backbone of “precision medicine,” an effort to which the current Administration is now committed. The promise of precision medicine rests in knowledge: if we can test and sequence and analyze, then we will know; and if we know, then we may be able to conquer. But if we can’t trust the data, the logic falls apart. Without reliable signals, all we have is noise, and there is nothing precise about that.
Among the cases described in the report are an ovarian cancer test marketing an accuracy rate of 94% that was in fact just .8%, a cancer biomarker test offering suggested treatments that have never been validated as a result of a test that has never been validated, and an RNA-based test for breast cancer patients that failed in a recent trial to positively diagnose a single individual correctly. The errors in these tests can lead to unnecessary treatment as well as the withholding of potentially life-saving treatment.
The test that perhaps fared the worst was noninvasive prenatal cell-free DNA testing (NIPT). This is a blood test given to a pregnant woman to provide genetic information about her fetus. These tests were described as yielding “both many false-positive and false-negative results.” The report mentions one woman who got an abortion after screening positive for Patau syndrome who then found out from post-abortion testing that she had actually been carrying a healthy pregnancy all along.
Although these findings are striking, it is worth remembering that all medical tests have an error rate. Particularly when a disease is rare, a positive result is often no reason for concern. However, these findings make it clear that the current regulatory framework is insufficient. Every one of the tests described in the report was carried out at a CLIA-certified lab (Clinical Laboratory Improvement Amendments). CLIA certification on its own says nothing about the safety, effectiveness, labeling, or marketing of the tests themselves. CLIA also does not require adverse event reporting, allow removal of unsafe devices from the market, or require informed consent for patients participating in clinical studies of their tests. The F.D.A. is right to target false labeling and flawed trial designs, and to call for greater accuracy and accountability. In light of outlandish claims, high costs, and evidence of harm, failing to provide oversight of the tests themselves by way of the “LDT” designation is merely outdated and irresponsible.
The F.D.A. seeks to play the challenging dual role of enabling innovation while protecting American consumers and patients. But importantly, the administration recognizes that providing more oversight of LDTs at this stage is crucial to the advancement of both ends. The success of “precision medicine” may well depend on it.