The Public Health Evidence for FDA Oversight of Laboratory Developed Tests: 20 Case Studies

Executive Summary

Laboratory developed tests (LDTs) serve an increasingly important role in health care today. They also have become significantly more complex and higher risk, with several notable examples of inaccurate tests placing patients at otherwise avoidable risk.

While laboratories that offer LDTs are subject to the Federal Food, Drug, and Cosmetic Act (FD&C Act), in addition to the Clinical Laboratory Improvement Amendments (CLIA), FDA has generally exercised enforcement discretion towards these tests (i.e., generally not enforced applicable provisions under the FD&C Act and FDA regulations).

Therefore, most laboratories that offer LDTs follow only the regulatory requirements of CLIA, which are intended to regulate the operations of laboratories, but are not specifically intended to regulate in vitro diagnostic devices. Despite the contention from some that “CLIA is enough,” all of the tests described as problematic in this report were offered from laboratories following the minimum requirements of CLIA.

We examined events involving 20 LDTs that illustrate, in the absence of compliance with FDA requirements, that these products may have caused or have caused actual harm 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. 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. In addition to patient harm, inaccurate or unreliable tests can be costly to society. We estimated these costs, if sufficient data were available.

Inclusion of a test in this report does not necessarily mean that it continues to be offered.