FDA Report Asserts Case Studies Support Need for More Oversight of LDTs

The U.S. Food and Drug Administration (FDA) released a 30-plus page report detailing case studies it says demonstrate the need for the FDA to abandon its policy of enforcement discretion and exercise more robust oversight of laboratory developed tests (LDTs). Washington D.C. lawyer, Jeffrey N. Gibbs, of Hyman, Phelps & McNamara P.C., who works with medical device and in vitro diagnostic companies, explains the report is likely a response to a Congressional request last year that the FDA provide evidence of the harms associated with LDTs and "was obviously timed to coincide with [the] House hearing on LDTs."

An FDA Voice blog article announcing the release of the report describes the report as an illustration of "the real and potential harms to patients and to the public health from certain laboratory developed test (LDTs)." The report covers 20 case studies that the FDA asserts demonstrate the risks of false positives and false negatives from certain LDTs. FDA Voice blog author, Peter Lurie M.D., M.P.H., FDA's Associate Commissioner for Public Health Strategy and Analysis claims the lack of FDA oversight of LDTs has led to "staggering" costs and indicates the report estimates the "public health cost for five of the 20 cited tests."

The FDA report, titled The Public Health Evidence for FDA Oversight of Laboratory Developed Tests: 20 Case Studies is available on the FDA website. It categorizes the case studies according to the problems raised: false positives, false negatives, lack of relevance to the tested disease, tests linked to disproved scientific concepts, tests undermining drug approval or treatment selection, and unvalidated tests. The cases were gathered, according to the FDA, from "publicly available information in medical journals, media reports and FDA Warning letters."

The report detailed 20 different LDTs that while compliant with CLIA regulations, did not require approval of the FDA. A couple of the tests have been withdrawn or not brought to market, but most are currently available commercially. According to the FDA report, they "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."

Among the tests disputed by the FDA include assays to determine the risk for ovarian cancer; a test for whooping cough; tests to help guide treatment of patients with breast cancer, prostate cancer and melanoma; non-invasive prenatal testing; and vitamin D deficiency testing, among others. Gibbs notes that some of the tests mentioned in the report have been discontinued.

He also predicts the report is unlikely to "shift opinions substantially." While the report provides "ammunition for those pressing for FDA oversight," opponents of LDT regulation may assert the case studies "present a skewed view of the performance of LDTs, and disregard the benefit side of the ledger" and test companies will likely characterize the "FDA's very brief description and conclusions as incomplete and misleading," Gibbs explains. Indeed, the American Clinical Laboratory Association was immediately dismissive of the report. "These so-called case studies are not representative of the thousands of LDTs utilized on a daily basis by providers to positively impact patient care," the ACLA said in a statement.

Takeaway: The FDA backs up its claims that LDTs need more oversight with case studies addressing specific tests it asserts are problematic.