The U.S. Food and Drug Administration has reviewed 20 laboratory developed tests (LDTs) used to diagnose serious medical conditions, including cancer and heart disease, and found the products may be causing or are causing significant harm to patients.

The FDA has not actively regulated LDTs in the past, but the agency hinted that its stance may be changing.

FDA intervention could have an impact on information technology used within the labs for analyzing and distributing results from these increasingly complex tests, and enabling the speed with which the information is delivered. But, these systems are only as good as the laboratory developed tests on which they rely, the accuracy of which is now being questioned by the FDA.

An LDT is an in vitro diagnostic test device intended for clinical use and designed, manufactured, and used within a single laboratory. Despite the increasingly important role of LDTs in healthcare, the FDA has generally exercised enforcement discretion towards these tests which have rarely undergone review by the regulatory agency to determine whether they are accurate, reliable, and provide clinically meaningful results.  

That changed this week with the publication of a report in which the FDA examined “events” involving 20 LDTs illustrating the real and potential harms to patients.

“In some cases, due to false-positive tests, patients were told they have conditions they do not really have, causing unnecessary distress and resulting in unneeded treatment,” states the report. “In other cases, the LDTs were prone to false-negative results, in which patients’ life-threatening diseases went undetected. As a result, patients failed to receive effective treatments. Other LDTs provided information with no proven relevance to the disease or condition for which they are intended for use, while still others are linked to treatments based on disproven scientific concepts.”

Also See: Lab IT Put to the Test

While the FDA has historically not actively regulated LDTs, the regulatory agency has now come to the conclusion that oversight of these tests is needed to address several serious concerns.

“As a matter of policy, we decided not to actively enforce existing requirements on LDTs because at the time they were generally simple, low-risk tests used on uncommon conditions and often in a local setting,” Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health, testified on Tuesday before the House Energy and Commerce Subcommittee on Health. “But, over time they have become increasingly more complex, higher-risk, are used on common conditions like heart disease, and they may be offered on a national basis. In addition, we’ve been coming across increasing examples of problematic LDTs.” 

In particular, Shuren said that ovarian cancer tests have been developed by labs without proper validation to show that the variant they detect is clinically meaningful, and some have been used in clinical practice in the United States.

According to Shuren, some of these tests provide very high numbers of false-positive results and some continue to make inflated claims concerning clinical benefit, even after comprehensive evaluations of women with ovarian cancer have failed to find any link between the disease and the genetic variant identified by the LDT. Consequently, he said women who received false-positive results from these tests may have had unnecessary, major surgery to remove their ovaries.

To address these and other concerns, the FDA last year issued draft guidance that proposes to phase in enforcement of premarket review requirements for higher-risk LDTs such as those used to guide treatment decisions, including the many LDTs with the same intended use as cleared or approved companion diagnostics. The FDA is currently finalizing guidance to ensure that tests are supported by rigorous evidence and that LDTs have more scientifically accurate product labeling.

“Doctors and patients don’t care about who makes their test. They do care that their tests are accurate, reliable, and clinically valid,” concluded Shuren.

In a written statement, the American College of Medical Genetics and Genomics notes that while the FDA is currently working on a final regulatory framework for LDTs and policymakers are considering how best to clarify the rules for LDTs “both the FDA and Congress must recognize that LDTs are used in a wide variety of settings, and that LDTs used for genetic testing and counseling need to be differently treated than other more routine diagnostic tests due to the rarity and genetic variability of genetic diseases,” states the organization. “The ACMG believes that any oversight framework must ensure high quality genetic testing remains available to physicians and patients and that it keeps pace with the rapid innovation that currently characterizes this field.”    

Register or login for access to this item and much more

All Health Data Management content is archived after seven days.

Community members receive:
  • All recent and archived articles
  • Conference offers and updates
  • A full menu of enewsletter options
  • Web seminars, white papers, ebooks

Don't have an account? Register for Free Unlimited Access