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laboratory-developed-testsHow Do Laboratory Developed Tests Impact Your Business?

The Office of Public Health Strategy and Analysis recently issued a report that reviewed 20 products that relied on Laboratory Developed Tests (LDTs) to determine whether a lack of oversight may have caused actual harm to patients or not. Once, LDTs were relatively simple tests that may not have warranted regulatory compliance. However, these tests are playing an increasingly more important role in healthcare and have become significantly more complex. The concern is that these tests may present with inaccuracies that place patients at what would be considered otherwise avoidable risk.

The report found that these 20 products, in fact, may have caused actual harm to patients. In some cases, patients were told they have conditions they do not really have, due to false-positive tests. This led to unnecessary distress and resulted in unneeded treatment. In other cases, the LTDs produced false-negative results, in which life-threatening diseases went undetected. These misdiagnosed patients failed to receive treatments. Additionally, some LTDs provided information with no relevance to the condition they were intended to be used for, and others were linked to treatments based on disproven scientific concepts. Not only do these situations cause harm to patients, but they are also costly to society.(1)

The report found that FDA oversight of LTDs is needed to address the following:

  • Lack of evidence supporting the clinical validity of tests
  • Deficient adverse event reporting
  • No premarket review of performance data
  • Unsupported manufacturer claims
  • Inadequate product labeling
  • Lack of transparency
  • Uneven playing field
  • Threats to the scientific integrity of clinical trials
  • No comprehensive listing of all LTDs being used

It’s often argued that FDA regulation of LTDs is not necessary because the tests are regulated under the Clinical Laboratory Improvement Amendments (CLIA). CLIA requirements ensure that laboratories and their personnel maintain standards of quality; however, these standards do not ensure that the diagnostic devices themselves are safe and effective.(2) The CLIA survey does not include clinical validation of the LDT, including the accuracy with which the test identifies, measures or predicts a clinical condition or predisposition in a patient. Additionally, the FDA’s review is more in-depth and comprehensive than the CLIA. Because it is focused on the system’s safety and effectiveness, the FDA review may uncover errors in test design or other issues with the test system.(3)

The report found that though the laboratories they reviewed met CLIAs requirements, the tests were still problematic. It was revealed that CLIA does not:

  • Ensure the safety and effectiveness of LDTs prior to marketing
  • Asses the quality of the design and manufacture of devices
  • Ensure test labeling provides adequate directions for use
  • Require truth in marketing materials and other labeling
  • Require adverse event reporting
  • Permit removal of unsafe devices from the market
  • Require informed consent for patients participating in clinical studies of LDTs
  • Establish procedures for the conduct of such studies

These findings support the need for greater FDA oversight of LDTs in a manner that is complementary to the CLIA requirements. The FDA issued a draft guidance that includes a framework for regulatory oversight of LDTs in October of 2014, making it clear that a change is pending. Laboratories would be wise to review the guidance to ensure they are aware of what the future holds for their regulatory requirements.

1 http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm472773.htm
2 Food and Drug Administration. Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs). October 3, 2014. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM416685.pdf.
3 Centers for Medicare and Medicaid Services. Laboratory developed tests (LDTs): Frequently asked questions. October 22, 2013. https://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA/Downloads/LDT-and-CLIA-FAQs.pdf.

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