FDA and CMS Address LDT Regulation Before Energy and Commerce Committee

Last week, the U.S. House of Representatives Energy and Commerce Committee heard testimony about oversight of laboratory developed tests (LDTs) from representatives of the U.S. Food and Drug Administration (FDA) and Centers for Medicare and Medicaid Services (CMS). The opportunity to speak at the hearing, titled "Examining the Regulation of Diagnostic Tests and Laboratory Operations," was invitation only. The agencies presented a united front in supporting FDA oversight of LDTs.

Jeffrey Shuren, director of the Center for Devices and Radiological Health at the FDA, spoke about the agency's regulation of medical devices and in vitro diagnostic devices (IVD) and explained the history leading up to the framework released last year. He also noted current proposals from the lab community that "acknowledge that LDTs must demonstrate that they are analytically valid and clinically valid." He cited problematic LDTs like those referenced in the FDA's report released last week (see Box, p. 4), to demonstrate the need for oversight. For example, his written comments highlighted one test discussed in the report that is used to determine a patient's response to statin therapy. The FDA found there wasn't an adequate link between the genetic variant and statin response. But 150,000 patients received the test, and the FDA asserts the problematic results cost $2.4 billion due to under or overtreatment with statins.

Identifying LDTs as a type of IVD, Shuren explained "[m]odern LDTs are often complex, have a nationwide reach, and have high-risk uses, and without oversight could present risks for patients and health care providers who rely on the results of LDTs to make medical decisions." "In many cases, the only difference between many modern LDTs and other IVDs is where they are manufactured, and the accuracy and reliability are every bit as important for modern LDTs as for any other IVD." Citing examples of the complexities involved, the written testimony discusses high risk tests such as companion diagnostics and moderate risk tests such as a blood test to detect heart attack, suggesting they require FDA oversight because inaccurate test results could delay treatment. "In both cases, the Agency's premarket review and post-market controls are essential to ensuring patients don't experience grave consequences from inaccurate results."

Discussing test modifications, the FDA's written submission contrasted simple changes that likely don't require review: "such as modifying the salt used in a buffer solution, or making an increase in the number of samples that a laboratory analyzer can process at one time." On the other hand, review would be required for "highly complex modifications that affect a test's performance—such as changing the measuring range of a marker to detect lower levels or adding a new marker to a panel of markers—or a test's intended use, such as changing the intended use of a Hemoglobin A1c test from monitoring glucose control in someone who already has diabetes to using that test to diagnose diabetes." When such a change can increase the risks posed by the testing or affect test performance or intended use, the FDA argues it should be exercising oversight concerning such modifications.

FDA's Next Steps
Shuren's written statement reported that the FDA "has completed its review of the public comments on the draft guidance documents that it received through an open public docket and a two-day public meeting, as well as feedback received from several webinars FDA held with stakeholders to discuss concerns and address questions." He outlined the following steps that the FDA is now taking:

• Coordinating with CMS on laboratory oversight and FDA plans to develop draft guidance regarding quality system requirements for LDTs, "to provide clarity for laboratories on how they can leverage compliance with CLIA requirements to satisfy those applicable FDA guidelines";
• Working with CMS and accrediting bodies and CLIA-exempt state laboratory programs, "to identify any potential overlaps between CMS and FDA activities" and look for ways to increase efficiency; and
• "Ongoing meetings with stakeholders, including laboratories, patients, traditional IVD manufacturers, and medical practitioners."

In response to questioning from the committee, Shuren indicated that the FDA intends to finalize its regulatory framework in 2016.

CMS Backs Up FDA
Patrick Conway, CMS' deputy administrator for innovation and quality and chief medical officer, also provided testimony, explaining the roles of CMS, the FDA and the Centers for Disease Control and Prevention under CLIA. His written statement to the committee clarified that CLIA "merely regulates how and by whom the test is conducted and reported out, rather than the scientific principles behind or the clinical validity of the test system itself." He added that CMS defers to FDA to determine clinical validity of a test.

Conway explained that "CLIA does not regulate the scientific principles behind or the clinical validity of any test— that is, the ability of the test to identify, measure, or predict the presence or absence of a clinically relevant condition or predisposition in a patient."

Further he added: "CMS does not have a scientific staff capable of determining whether a test is difficult to successfully carry out or likely to prove detrimental to a patient if carried out improperly. This expertise resides within the FDA, which assesses clinical validity in the context of premarket reviews and other activities aligned with their regulatory efforts under the Food, Drug, and Cosmetic Act."

Takeaway: The FDA and CMS are presenting a united front concerning the need for FDA oversight of LDTs and 2016 promises to bring changes for laboratories offering LDTs.