FDA Regulation of LDTs: A Report Justifies the Need for It

It is time to regulate laboratory-developed tests that cost Medicare $9.7 billion in the year 2012 alone.

Medicare covers them, private payers cover them, and providers and patients make clinical decisions on the results they generate—isn’t it time to regulate laboratory-developed tests (LDTs), which cost Medicare $9.7 billion in 2012 alone? The FDA believes so, and in preparation has issued a report that details the potential harm to patients resulting from false-negative or false-positive test results. This follows a draft guidance issued about a year back that included a risk-based framework to define regulatory oversight of LDTs for clinical laboratories that develop them.

By definition, an LDT is an in vitro diagnostic that is designed, manufactured, and used within a single laboratory. A test that is even partially designed outside the laboratory that offers or uses it, no longer falls within the class.

And this definition is site-restricted. For example, if several clinical laboratories form a network within an entity, an LDT developed by one of these laboratories cannot be used by another laboratory within that network. If a component used within the test is manufactured for the laboratory by a third party, the FDA will cease to consider the device an LDT.

Lakshman Ramamurthy, PhD, vice president at Avalere Health wrote in a blog that LDTs, also known as “home-brewed” tests, are created in response to unmet clinical needs. However, the tests have come a long way. “LDTs have expanded in their reach and are purchased by and shipped to nationwide laboratories and utilized across the country,” he writes.

The new FDA report provides case studies that underscore the importance of regulating the tests beyond the current requirements of the CMS-developed Clinical Laboratory Improvement Amendments (CLIA) and the Federal Food, Drug, and Cosmetic Act. The report claims that events associated with 20 case studies presented in the report resulted from adherence of the test developers to the minimum requirements of CLIA. The following Table includes a few examples from the report.

Table. Examples of Problematic Laboratory-Developed Tests (LDTs) Included in the FDA Report

LDT Name



Clinical Consequence

Cost Impact of Inaccuracy


Screen and detect ovarian cancer.

Lack of validation that test detects ovarian cancer.

Inflated accuracy claims.

False-positive results could result in unnecessary removal of ovaries.

Not yet known.

Whooping Cough (Pertussis) PCR Test

Rapid and improved diagnosis of whooping cough.

False-positive results.

Incorrect diagnosis resulting in incorrect treatment.

Not estimated.

Oncotype DX HER2 RT-PCR

Use HER2 receptor expression level to guide treatment.

Poor sensitivity.

False-negative results because of low sensitivity can result in disease progression due to lack of treatment.

$775,278 estimated per false-negative case.

KIF6 “Statincheck” Genotyping Assay

Predict risk of heart disease and response to statin therapy.

Biomarker not validated to predict coronary heart disease or statin response.

Incorrect validation.

Unproven product claims.

Over- or under-treatment with statins.

Not estimated.

“As this report demonstrates, strengthening FDA’s oversight over LDTs is critical to protect both patients and the public health,” wrote Peter Lurie, MD, MPH, FDA’s Associate Commissioner for Public Health Strategy and Analysis, in his blog post published yesterday.

In April this year, the FDA and CMS announced the formation of a task force to avoid duplication of efforts by the agencies. While CMS, through CLIA, ensures quality of the laboratory processes used to develop the tests, the FDA plans to enforce the premarket review requirements to confirm analytical as well as clinical validity of the tests.

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