FDA Oversight of Laboratory Developed Tests Essential for Patient Health and Safety

Evidence-Based Oncology, September 2014, Volume 20, Issue SP14

On July 31, 2014, the FDA announced a draft guidance for regulating laboratory-developed tests (LDTs), which include many genetic tests, based on the level of risk they carry to a patient. I was pleased to hear of this decision and had, in fact, called on the Obama Administration to do exactly that. These tests play a pivotal role in patient care, and it is critical that they be safe and effective.

Protecting Americans’ health and genetic information has been a central mission of mine during my career in Congress. As a microbiologist, I was well aware of the enormous medical potential of the Human Genome Project when it began in 1990. As a member of Congress with years of experience working in health policy, I also understood the potential for abuse this advancement could present. When the era of personalized medicine was just around the corner, I wanted to make sure everyone would have the same opportunity to benefit from this incredible tool without fear of losing their jobs or their healthcare.

In 1995, I introduced the Genetic Information and Nondiscrimination Act (GINA) to protect all Americans from any employment or health insurance discrimination based on their genes. I hoped that for the first time, science and policy would go hand-in-hand and the law’s protections would be in place by the time the human genome was sequenced. The latter happened in the year 2000, but GINA was not signed into law by President Bush until 2008, after almost 14 years of advocacy and education among my colleagues.

The dream of personalized medicine is now becoming a reality. Doctors can order genetic tests to determine disease risk or treatment options with a turnaround time unheard of when GINA became law. Doctors can now prescribe specifically tailored therapies based on the genetic status of a cancerous tumor. For example, 80% of patients with non-small cell lung cancer with a mutation in their EGRF gene can benefit from a drug that targets this specific mutation. However, only one-fifth of patients with this type of cancer have the EGFR mutation, so it is imperative that doctors use genetic testing to identify those patients who will respond to the drug and not waste time—and the $12,000 that each treatment costs—giving it to those who cannot benefit from therapy. With the genetic test, doctors can target an incredibly effective drug to those patients from whom they expect the best response.

The drug in this example was found to be safe and effective in an extensive review process required for FDA approval. However, some genetic tests, like this one to assess the EGFR mutation, are considered LDTs and have not been subject to FDA review. Without the FDA’s review process, how can we be sure of the reliability of these genetic test results?

Originally, LDTs were used to measure routine physical data such as cholesterol levels or white blood cell counts, and they were often designed, manufactured, and used in a single laboratory, such as a particular hospital. As such, while the FDA maintained the statutory authority to regulate these tests, it chose not to, due to the tests’ simple nature and limited use. Since the completion of the Human Genome Project, however, LDTs have become much more sophisticated, and the repercussions of a false result can now be dangerous. The regulatory framework, however, has remained the same, with no assurance that the tests are reliable, safe, and effective.

The Clinical Laboratory Improvement Amendments (CLIAs) directs CMS to oversee laboratory safety and ensure that LDTs are conducted in laboratories that meet clinical quality standards for personnel and laboratory practices. CLIA does not, and is not, authorized to ensure that laboratories performing LDTs produce evidence of effectiveness, nor does it require the reporting of post market adverse events. This means that under the current regulatory framework, patients and their doctors have no guarantee that the tests upon which they base important medical decisions are valid, reliable, safe, or effective. The FDA’s recent action would change all of this, providing clarity and security for patients.

This situation is not hypothetical. In June 2008, one of the largest clinical laboratory companies, LabCorp, began marketing OvaSure, an LDT designed to detect early-stage ovarian cancer by measuring the levels of 6 proteins in a blood sample. This kind of test is extremely valuable to patients with a risk of ovarian cancer. Removing the ovaries from an early-stage ovarian cancer patient, before the cancer has had the opportunity to spread, could save her life. Ninety percent of patients who catch the disease in the early stage are still alive 5 years later, but only 30% are likely to survive for 5 years if the cancer is caught late. Unfortunately, the vast majority of ovarian cancer cases are caught late.

While the need for an early diagnostic test is critical, an unreliable test could be extremely dangerous: a false positive may lead a woman to have her ovaries removed unnecessarily, and a false negative could be fatal. With only CLIA oversight, LabCorp was not required to prove that the 6 proteins the test detected could accurately predict disease. OvaSure was rushed to market before this crucial validation step and was later found to have an unfortunately high false positive rate. Many healthy women had unnecessary surgery to remove their ovaries, thinking they had ovarian cancer, only to discover after their surgery that they did not. In October 2008, just 4 months after its introduction, the FDA stopped the sale of OvaSure in the interest of public safety— they used a technicality to pull the product, given the lack of a published framework for oversight of LDTs. Because the research underpinning OvaSure had been performed at Yale University, and not at LabCorp, OvaSure qualified as a medical device rather than an LDT. Had the DA been able to review this product through its currently proposed regulatory framework for LDTs, the test would never have made it to market in the first place.

LabCorp’s OvaSure is not the only complex screening test the FDA has stepped in to regulate, which demonstrates the need for a new metric to guide oversight. FDA’s recent proposal allows for proactive identification of riskier tests, eliminating the risk to patients of LDTs that are only regulated after they hit the market. This risk-based approach also puts all diagnostic test makers on equal footing, with each company required to prove its tests’ effectiveness, regardless of how the test was produced.

When laboratories provide doctors with data that directly impact patient diagnosis and treatment, doctors should have confidence that these tests are valid and the results reliable.

The FDA’s newly announced framework for oversight provides for greater patient protection. Regulation by the FDA will ensure that LDTs are safe and effective, adverse events are properly reported, unsafe devices can be removed from the market, and patients are protected by informed consent procedures prior to their use of any investigational devices.


Now that genetic information is used regularly to guide treatment decisions, from cancers to cardiovascular disease, FDA is correct to take these steps to ensure that doctors are receiving test results that are accurate, safe, and effective. GINA empowered Americans to look into our own genes without fear of losing our healthcare or getting fired. This decision by the FDA will further empower patients to trust the results they receive, so that they and their doctors can make important, and lifesaving, healthcare decisions. Rep Louise M. Slaughter (D-NY) has been a member of the House of Representatives since 1986. As chair of the House Rules Committee from 2007 to 2010, she helped guide the Affordable Care Act to passage.