A simple definition for an LDT is that the test reagents are developed by a single lab and all of the testing is performed by that lab. IVDMIAs/LDTs can be used for various purposes including the detection of the presence of a neoplasm in a diagnostic workup using serum. A second purpose has been to analyze the antigens present on a patient's tumor cells to determine the optimal drug therapy for that patient. A LDT in this latter category that was developed by Duke and used for lung cancer was the subject of a recent, highly critical article on the front page of the New York Times. Below is an excerpt from the article: (see: How Bright Promise in Cancer Testing Fell Apart )
When Juliet Jacobs found out she had lung cancer, she was terrified, but realized that her hope lay in getting the best treatment medicine could offer....In February of 2010, she ended up at Duke University, where she entered a research study whose promise seemed stunning. Doctors would assess her tumor cells, looking for gene patterns that would determine which drugs would best attack her particular cancer....The Duke program — considered a breakthrough at the time — was the first fruit of the new genomics, a way of letting a cancer cell’s own genes reveal the cancer’s weaknesses. But the research at Duke turned out to be wrong. Its gene-based tests proved worthless, and the research behind them was discredited....The episode is a stark illustration of serious problems in a field in which the medical community has placed great hope: using patterns from large groups of genes or other molecules to improve the detection and treatment of cancer....While researchers agree there is great promise in this science, it has yet to yield many reliable methods for diagnosing cancer or identifying the best treatment. Instead, as patients and their doctors try to make critical decisions about serious illnesses, they may be getting worthless information that is based on bad science. The scientific world is concerned enough that two prominent groups, the National Cancer Institute and the Institute of Medicine, have begun examining the Duke case; they hope to find new ways to evaluate claims based on emerging and complex analyses of patterns of genes and other molecules. So far, the Food and Drug Administration “has generally not enforced” its regulation of tests created by individual labs because, until recently, such tests were relatively simple and relied heavily on the expertise of a particular doctor....Doctors say the heart of the problem is the intricacy of the analyses in this emerging field and the difficulty in finding errors. The Duke case came right after two other claims that gave medical researchers pause. Like the Duke case, they used complex analyses to detect patterns of genes or cell proteins. But these were tests that were supposed to find ovarian cancer in patients’ blood. One, OvaSure (see: Questions About the OvaSure Test for Ovarian Cancer ; LabCorp Stops Selling OvaSure Test as a Result of FDA Pressure ), was developed by a Yale scientist, Dr. Gil G. Mor, licensed by the university and sold to patients before it was found to be useless. The other, OvaCheck, was developed by a company, Correlogic....
There is no question that, ultimately, tests utilizing multiple biomarkers plus an interpretive computer algorithm will be a key component in the practice of diagnostic medicine. However, what we can now observe are medical scientists in prestigious medical schools like Yale and Duke rushing to market with LDTs that have been inadequately tested and validated. Clinicians and their patients have then jumped on this bandwagon, seeking "scientific" guidance and reassurances in the treatment of cancer. My understanding is that some of these LDT validation protocols have been based on biobanked serum specimens obtained for other clinical trials of cancer patients. Such an approach may have introduced unknown and unforeseen biases into the biomarker validation studies.
As the result of adverse news coverage such as the article referenced above, the FDA will undoubtedly come under pressure to enforce preexisting regulations relating to LDTs. To restate the obvious, there is no substitute for slow, methodical, and knowledge-based medical research. The methodology for validating new and relatively simple diagnostic tests is well known. However and as stated above, "the heart of the problem [in validating multiplexed biomarker tests] is the intricacy of the analyses in this emerging field and the difficulty in finding errors."