Expanded FDA Oversight of Laboratory-Developed Tests

The Food and Drug Administration (FDA) defines “laboratory-developed tests” as in vitro diagnostic products “that are intended for clinical use and designed, manufactured, and used within a single clinical laboratory” whose general operation is certified by federal regulations dating back to 1988.[1],[2],[3] The tests may have many uses within medicine, such as to identify specific infections, cancers or genetic conditions, and anticipated responses to certain treatments.

In May 2024 the FDA finalized a new regulation to increase its authority over laboratory-developed tests to improve the safety and effectiveness of these widely used diagnostics. The new rule, which has already been challenged by some test developers in federal court,[4],[5] will be phased in starting in May 2025 and will take at least four years to fully implement. Until the rule is fully implemented, many laboratory-developed tests will continue to be available despite limited evidence supporting their use.[6] Moreover, even after full implementation, exemptions will allow the continued use of many existing laboratory-developed tests, including tests that are not modified following the expanded FDA oversight.

Prior to implementation of the new rules, the FDA’s oversight of laboratory-developed tests has been through general regulatory oversight of the clinical laboratory, not though review of individual tests. Thus, such tests were sold and used based on laboratory certification alone, with no requirement that the FDA confirm them to be safe and effective for a specific purpose.[7] In the early 2010s problems began to surface as some laboratory-developed tests were widely used beyond the direct supervision of the clinical laboratory where they were developed.[8] In 2015 the FDA issued a report about this problem, which further described 20 examples of laboratory-developed tests (see Table, below) that illustrated the need for regulatory oversight of individual tests.[9],[10]

Table: Examples of Problematic Laboratory-Developed Tests Identified by the FDA[11]

In 2022 the New York Times examined laboratory-developed tests used to screen maternal blood for a variety of rare (1 in 5,000-20,000 births), serious genetic abnormalities in fetuses.[12] All of the tests had false positive results at least 80% of the time the screen gave a positive result. In response to those incorrect test results, some people reportedly considered or even had abortions. Although such prenatal conditions are rare, they are frequently screened for. In 2020, one of the test developers was said to have performed more than 400,000 screenings (about 10% of all pregnancies in the United States) for just a single genetic abnormality.

According to a recent estimate, 70% of clinical decisions in the United States rely on one or more laboratory-developed tests and there are approximately 80,000 different laboratory-developed tests in use.[13] Some tests will remain exempt from the expanded FDA oversight, including public health surveillance tests, some blood tests to guide organ transplantation, some tests used by blood banks, some Department of Defense and Department of Veterans Affairs tests, and tests developed and used by integrated health care systems.[14] The effects of the new regulations will thus be limited to a subset of new or updated diagnostic tests.

The uncertain future of expanded FDA oversight

It is uncertain whether the FDA under the second Trump administration will continue to support expanded oversight of laboratory-developed tests and defend against legal challenges to the new regulations. Before the election, the American Clinical Laboratory Association, the Association for Molecular Pathology and others challenged the new rule in court, arguing that it represents overreach by the FDA that will hamper consumer access to needed clinical tests.[15],[16] In November 2024 — on behalf of itself, the American Cancer Society Cancer Action Network and four other cancer-related groups — Public Citizen filed an amicus brief supporting the new rule in federal district court in Texas. The brief argues that the rule is supported by federal law and justified by the increasing use and complexity of laboratory-developed tests.

What You Can Do

Before you rely on any medical test, including laboratory-developed tests, to make important medical decisions, ask your clinician to help you understand the test results, their accuracy and their limitations. In situations where test results are frequently inaccurate or a medical decision is very important, such as whether to have surgery or another procedure, discuss with your clinician the need for a confirmatory test.
 

References

[1] Aaron DG, Adashi EY, Cohen IG. The US FDA's new rule for regulating laboratory-developed tests. JAMA Health Forum. 2024;5(10):e242917.

[2] Food and Drug Administration. The public health evidence for FDA Oversight of laboratory developed tests: 20 case studies. November 16, 2015. https://www.nila-usa.org/images/nila/The%20Public%20Health%20Case%20for%20FDA%20Oversight%20of%20LDTs%20110915(2)_508ed%20(1).pdf. Accessed November 4, 2024.

[3] Food and Drug Administration. Definitions and general oversight: laboratory developed tests FAQs. November 3, 2024. https://www.fda.gov/medical-devices/laboratory-developed-tests-faqs/definitions-and-general-oversight-laboratory-developed-tests-faqs. Accessed November 12, 2024.

[4] Public Citizen. ACLA v. FDA. November 4, 2024. https://www.citizen.org/litigation/american-clinical-laboratory-assn-v-fda/. Accessed November 13, 2023.

[5] Liebman S. DiSanbatino D, Mercer A. LDT final rule series: part 2 – response to the rule. June 6, 2024. https://www.fdalawblog.com/2024/06/articles/fda/ldt-final-rule-series-part-2-response-to-the-rule/. Accessed November 13, 2024.

[6] Food and Drug Administration. Laboratory developed tests. https://www.fda.gov/medical-devices/in-vitro-diagnostics/laboratory-developed-tests. Accessed November 4, 2024.

[7] Food and Drug Administration. Webinar transcripts. Final rule: Medical devices; laboratory developed tests. May 14, 2024. https://www.fda.gov/media/178736/download?attachment. Accessed November 4, 2024.

[8] Aaron DG, Adashi EY, Cohen IG. The US FDA's new rule for regulating laboratory-developed tests. JAMA Health Forum. 2024;5(10):e242917.

[9] Food and Drug Administration. The public health evidence for FDA Oversight of laboratory developed tests: 20 case studies. November 16, 2015. https://www.nila-usa.org/images/nila/The%20Public%20Health%20Case%20for%20FDA%20Oversight%20of%20LDTs%20110915(2)_508ed%20(1).pdf. Accessed November 4, 2024.

[10] Ibid.

[11] Ibid.

[12] Kliff S, Bhatia A. When they warn of rare disorders, these prenatal tests are usually wrong. New York Times. January 1, 2022. https://www.nytimes.com/2022/01/01/upshot/pregnancy-birth-genetic-testing.html. Accessed November 4, 2024.

[13] Aaron DG, Adashi EY, Cohen IG. The US FDA's new rule for regulating laboratory-developed tests. JAMA Health Forum. 2024;5(10):e242917.

[14] Food and Drug Administration. Laboratory developed tests. https://www.fda.gov/medical-devices/in-vitro-diagnostics/laboratory-developed-tests. Accessed November 4, 2024.

[15] Public Citizen. ACLA v. FDA. November 4, 2024. https://www.citizen.org/litigation/american-clinical-laboratory-assn-v-fda/. Accessed November 13, 2023.

[16] Liebman S. DiSanbatino D, Mercer A. LDT final rule series: part 2 – response to the rule. June 6, 2024. https://www.fdalawblog.com/2024/06/articles/fda/ldt-final-rule-series-part-2-response-to-the-rule/. Accessed November 13, 2024.