Laboratory-developed medical tests (LDTs)—now a 20-billion-dollar industry—have long escaped FDA oversight despite their potential risks. Though these tests promise to detect diseases, the lack of regulation has led to unreliable results and patient harm. CSPI has led the fight for regulation despite decades of industry resistance; finally, the FDA is moving to vet these tests. Until these changes take effect, problematic and unregulated LDTs are worth knowing more about.

What are laboratory-developed tests?

Laboratory-developed tests are a subset of in vitro diagnostic tests (IVDs) that claim to detect diseases and conditions from blood, saliva, or tissue samples. Although the FDA has the authority to regulate medical devices, including IVDs, under the 1976 Medical Device Amendments to the Federal Food, Drug, and Cosmetic (FD&C) Act, LDTs went unregulated due to their limited use at the time.  

But LDTs have now grown into a $20 billion unregulated industry, producing unreliable and potentially harmful tests. In fact, as far back as 2015, the FDA identified 20 problematic LDTs that caused—or likely caused—significant harm to patients.  

Learn more: Lab-developed tests: Everything you need to know

FDA regulation of LDTs is coming

In May 2024, the FDA finally released a final rule to better regulate LDTs. The rule clarifies that the FDA has the right to oversee LDTs as medical devices. This means they should be subject to the same regulatory requirements as IVDs, including mandatory adverse event reporting, premarket review, and labeling requirements. The rule establishes a four-year phase-in plan, but does have some major exceptions, including exempting from review tests that were already being used before the rule change.  

For now, patients and healthcare providers should remain vigilant. The graphic below may help better understand the process. The tests in yellow are LDTs and under “enforcement discretion,” meaning the FDA has been choosing not to regulate them. Understanding the risks of available LDTs is critical to making informed healthcare decisions.

Grail’s Galleri multicancer early detection (MCED) test

The Galleri multicancer early detection (MCED) test is currently available in the U.S. with a prescription and claims to detect signals for 50 types of cancer. However, it has not yet received FDA approval, and under the FDA Final Rule, such approval will likely be required before broader adoption. Clinical trials are ongoing in the UK, where the test is not yet commercially available, but are controversial. Additional trials are set to begin in the U.S. to determine if it improves cancer outcomes or saves lives.

Galleri reports a high specificity of 99.5 percent, meaning it has a low false positive rate of only 0.5 percent. On the other hand, the test's overall sensitivity is 51.5 percent, meaning it missed about half of actual positive cancer cases across all cancer types and stages. This data highlights the test's limitations, as false negatives—cases where cancer is present but not detected—remain a serious concern.

Quest’s AD-Detect Test

Not FDA-approved, the AD-Detect test by Quest measures two beta-amyloid proteins in the blood, a hallmark of Alzheimer’s disease. Available to any adult reporting memory or cognitive difficulties, the test requires a $13 Quest physician service fee for ordering. But it’s not clear whether it would help since 30 to 40 percent of older adults with elevated beta-amyloid levels never develop Alzheimer’s. Plus, receiving an abnormal result could lead to challenges in obtaining health insurance coverage.

The AD-Detect test’s reliability is also unclear since it has not yet been validated against PET scans, the gold standard for Alzheimer’s diagnosis. Based on only 209 individuals, Quest’s data summary indicates a high rate of false positives, suggesting that many test results may inaccurately signal Alzheimer’s risk. While more advanced blood tests like PrecivityAD2 offer alternatives by testing for p-tau and ApoE proteins, these, too, lack insurance coverage and do not surpass the diagnostic insights provided by a neurologist’s comprehensive evaluation.  

Check out the latest: How to keep your memory sharp

Theranos

Major news outlets have extensively covered Elizabeth Holmes and the Theranos scandal, in which Holmes claimed (falsely and fraudulently) that the company's LDTs could run more than a thousand tests from a single finger prick to diagnose diabetes, cancer, and other diseases.

In this case, the FDA played a role in shutting down the fraudulent Theranos. Though Theranos sought FDA approval, the FDA cleared only one test early on based on data submitted, and the agency did not approve any additional Theranos devices. Within two months of the initial clearance, the FDA halted distribution after inspections of Theranos’ facilities revealed severe issues with the company’s other tests and an unapproved blood collection device, both of which posed risks to patient safety. As a result, the FDA notified the Centers for Medicare and Medicaid Services (CMS), who noted additional potential violations under the program that ensures quality laboratory testing (CLIA). Now, the FDA’s 2024 final rule can work to better protect the public from unreliable diagnostic tools by ensuring no tests are offered when the FDA identifies test concerns.  

Natera’s Panorama Test

Natera’s Panorama Test, a type of noninvasive prenatal testing (NIPT), has revolutionized prenatal screening for Down syndrome, significantly reducing the need for invasive diagnostic procedures, and is highly reliable compared to older, riskier Down Syndrome detection methods. However, accuracy and reliability decline sharply when NIPT technology is used to detect less common genetic conditions. That’s because some of these rarer conditions (which may cause heart defects, intellectual disabilities, and a high infant mortality rate) are often the result of microdeletions (small missing chromosome segments) or extra or missing chromosomes, which can be more difficult to detect. Though microdeletion testing is typically offered as an optional add-on, and it is unclear how frequently doctors recommend it, Natera performed over 400,000 screenings for a single microdeletion, representing about 10 percent of pregnant people in the US in 2020 alone.  

The accuracy of these tests for rare conditions is concerning—positive results are incorrect about 85 percent of the time. As prenatal tests expand to include rarer genetic conditions, the proportion of incorrect positive results grows, raising serious questions about the reliability and clinical utility of these screenings. Thus, the American College of Obstetricians and Gynecologists recommends offering this type of screening test for more common genetic conditions like Down Syndrome, but advises against using them for other conditions.

CSPI’s work on LDT regulation and continuing challenges

For years, CSPI has been working to protect the public and hold companies accountable. In 2023, CSPI filed a complaint against EpicGenetics for false claims that its fibromyalgia test is “99 percent accurate,” even though the company’s own study indicates it generates false negative test results 7 percent of the time and false positives nearly one-third of the time. The company also markets its 100Sure Test as 100 percent accurate in diagnosing “Immune Deficiency Disease,” or IDD, even though IDD is not a medically recognized disease but instead, a term created by EpicGenetics to fit the results its tests generate.  

CSPI has also called on Congress and the FDA to strengthen the regulation of LDTs. In 2014, the FDA released draft guidance requiring premarket reviews by the FDA before the highest-risk LDTs could be released to the market. However, in 2017, the FDA withdrew this attempt in response to pushback from trade associations, academic medical centers, and Congress.

Since then, several attempts have been made to create legislation to address this issue, including the Verifying Accurate Leading-Edge IVCT Development (VALID) Act. Introduced repeatedly in the last three years, this act proposes a uniform regulatory framework for all IVDs, including LDTs. Despite CSPI’s calls for action, this bill failed to pass in Congress, so CSPI led a coalition to pressure the White House to advance the FDA’s own proposal to regulate LDTs. And the Biden administration finally came through.  

While the FDA's final rule marks a critical step forward, opposition remains. Industry groups like the American Clinical Laboratory Association have already challenged the rule in court, and legislative threats could further hinder its implementation. Despite these hurdles, CSPI continues to support the FDA in protecting patients; in November 2024, our Litigation Department filed an amicus brief supporting the FDA's May 2024-issued final rule ensuring LDTs meet rigorous safety and efficacy standards.

Although the road ahead may be uncertain, the FDA’s actions signal a long-overdue commitment to reducing harm while enhancing the benefits of these essential diagnostic tools.