A Lot of Specialized Lab Tests Were Unregulated. FDA Is Trying to Close the Loophole

When a health provider wants to offer a diagnosis or treatment recommendation, they may send samples of your blood, tissue, or saliva to a laboratory that can run specialized diagnostic tests. Those laboratory-developed tests (LDTs) are used to diagnose a wide range of conditions, including cancer, Alzheimer’s disease, COVID-19, and more.

While other types of diagnostic tests must be cleared for use by the Food and Drug Administration (FDA), manufacturers of LDTs have operated in a loophole. To ensure the reliability and safety of LDTs, the agency published a new rule on May 6 to regulate these tests as medical devices.

The new rule covers clinical tests designed, manufactured, and used within a single laboratory, including certain tests developed by academic medical centers and companies like Labcorps and Quest Diagnostics. The agency said greater oversight will reduce the risks of patients getting unnecessary treatment or missing health conditions due to inaccurate results.

“No one truly knows exactly how many of these tests are out there, or who makes which one, let alone which tests have a concerning number of issues, such as inaccurate results,” Jeff Shuren, MD, JD, director of the Center for Devices and Radiological Health at the FDA, said in a media call in April.

According to the rule, manufacturers of LDTs must now follow certain requirements. Those include registering the tests with the FDA, undergoing a review process before the tests are sold, reporting adverse events related to the test, and labeling the test and its results clearly. The changes will be phased in over four years, starting with the tests that pose the greatest risk to the patient.

The FDA says it will “exercise enforcement discretion” for tests that were in use before May 6. These tests are effectively exempt, so long as labs don’t modify them to change their indications for use, the technology they require, or how well and safely they work.

The FDA’s final rule was contentious. Opponents of the rule say that increased FDA oversight will slow the pace of test development, which could hamper hospitals’ ability to respond to emerging public health threats. Some say that small labs and academic medical centers won’t be able to afford to go through the regulatory hoops. They may be less willing to invest in making tests for rare diseases, which commercial labs are less likely to see as profitable.

“We firmly maintain that LDTs are not medical devices and regulating them as such would be harmful to patients and would severely hamper innovation in the next generation of diagnostics,” Susan Van Meter, president of the American Clinical Laboratory Association, said in a statement.

Others applauded the FDA, saying the step toward patient safety is long overdue.

“This is an industry with vast under-appreciated reach into clinical medicine,” Peter Lurie, MD, MPH, president and executive director at the Center for Science in the Public Interest, told Verywell.

“Many of the diagnostic tests that are used are, in fact, laboratory-developed tests. And I think that many consumers would be surprised, and perhaps dismayed, to learn that until now, the FDA has exercised no regulatory authority over them whatsoever,” Lurie added.

Regulating a Multibillion-dollar Industry

For most of the common lab tests, the samples are run on machines within the hospital. This includes standard tests for complete blood count, cholesterol levels, liver enzymes, and sodium and potassium levels.

To test for other health factors, a provider may need to outsource. Innovative lab tests have been developed to detect proteins, genetic mutations, and biological markers for various diseases.

LDTs are not typically used on hospital premises, either because they test for rare conditions or use highly specialized technologies. This category only covers tests that are overseen by a clinician and doesn’t include direct-to-consumer tests like 23andMe genetic tests.

“If you want to know if you have some exotic antibody to babesiosis, then there’s a very high chance that your hospital does not have a test for that in-house, so it will be sent off to one of a few locations in the country that is capable of doing the test. That’s an LDT,” Lurie said.

When LDTs first appeared, they were less common, more specialized, and mostly served local populations. Now, major laboratories are testing samples from across the country using advanced software and technology, and this has ballooned into a multibillion-dollar industry.

LDTs are required to adhere to standards set by the Clinical Laboratory Improvement Amendments (CLIA) program, which ensures that tests are safe and effective. But that review only happens every two years, so a test may be used in patients for months before CLIA reviews it.

FDA review, on the other hand, requires manufacturers to show that a test is clinically valid. That is, whether the test accurately identifies, measures, or predicts the presence or absence of a clinical condition in a broader patient population.

Lurie served as an associate commissioner at the FDA and penned a report in 2015 arguing for regulation of LDTs. He said the point of the regulations is essentially to minimize the risk of false positives or false negatives from the LDTs.

“Clinicians put a lot of stock in the results of these tests. They’re going to use these tests to make decisions upon which somebody’s life or death might actually happen,” Lurie said.

In 2022, the FDA warned about potential false results from prenatal genetic tests and said it was aware of cases in which people chose to end pregnancies based on those results without confirmation from other tests.

Concern About Tests for Rare Diseases and Public Health Labs

Leaders of some academic medical centers expressed concern that the FDA rule would make it more difficult to respond to public health emergencies and address rare diseases.

In a public comment, Marie-Louise Landry, MD, director of the clinical virology laboratory at Yale New Haven Hospital, said that LDTs have been key to serving critically ill hospitalized patients within her health system. She said the lab she leads offered COVID-19 testing for weeks before commercial tests were available, as well as testing for pathogens like norovirus before public health labs were able to do so.

“As an academic hospital laboratory, we do not have the funds to pay for the FDA submission process for our LDTs. Thus, with this rule, our ability to provide this much-needed testing for patient care and to respond to viral disease outbreaks will end. We will lose the expertise and the infrastructure,” Landry wrote.

Academic medical centers argued that if they don’t develop tests for rare diseases, they may not be created because they tend not to be profitable for commercial laboratories.

The FDA said that if there is no agency-approved test for a rare disease, a laboratory can create an LDT without going through the approval process. However, as soon as the FDA clears a test, the LDT will no longer be exempt from regulation.

Lurie said that while rare disease tests are “a valuable public service,” that doesn’t mean they ought to be exempt from FDA review of their efficacy and ensure they’re effective.

“I do understand what the concern is, but I also think that the public has an expectation that the products that it receives are subject to oversight by an independent body,” Lurie said.