NEW YORK – While much of the action around reforming laboratory-developed test regulation has involved a greater role for the US Food and Drug Administration, several lab organizations and federal legislators have proposed that the Centers for Medicare & Medicaid Services (CMS) handle LDT oversight through CLIA.
With the VALID Act — which would formally give the FDA authority over LDTs — facing an uncertain future, there is perhaps an opening for alternative approaches to LDT regulation. However, Reynolds Salerno, director of the division of laboratory systems at the US Centers for Disease Control and Prevention and designated federal official of the US Clinical Laboratory Improvement Advisory Committee (CLIAC), indicated that CMS has little interest in regulating LDTs under CLIA and believes these tests should fall under the FDA's authority.
CLIA, short for the Clinical Laboratory Improvement Amendments, is a set of standards instituted by Congress in 1988 to govern the practice of clinical laboratories and ensure the quality of testing done at these facilities. CLIAC is run by the CDC and provides the US Department of Health and Human Services advice and guidance on clinical laboratory standards and practices.
CLIA's framework for regulating testing within clinical labs differs significantly from the FDA's approach to regulating in vitro diagnostics, and this divide has become a point of controversy and concern as in recent decades the complexity and prominence of LDTs have grown.
Advocates of increased FDA oversight of LDTs note, for instance, that CLIA does not have a mechanism for tracking all the LDTs currently available or monitoring them for adverse effects. Additionally, they argue that CLIA doesn't ensure the clinical validity of LDTs or that equivalent tests deliver equivalent results across laboratories.
Opponents of a greater role for the FDA in LDT regulation have argued in response that LDTs are not medical devices and should not be regulated as such. Rather, they suggest that these tests and other lab activities are analogous to medical procedures and are therefore a better fit for regulation through CLIA than the FDA.
"What we do in the lab … is we are taking our scientific knowledge, our medical knowledge, our understanding of the technology, and we are creating a procedure, a recipe we follow that had a protocol, and then we are going through that procedure, producing a result, and then interpreting it," said Eric Konnick, assistant professor of laboratory medicine at the University of Washington and chair of the Association for Molecular Pathology's professional relations committee.
AMP has called for modernization of CLIA to better regulate LDTs and address some of the concerns raised by proponents of increased FDA authority. In 2015, the organization put out a plan detailing changes to CLIA that would improve oversight of LDTs, or LDPs — laboratory developed procedures — as AMP calls them in order to make clear its position that they are more akin to medical procedures than devices.
The AMP plan proposed a risk-based system with labs having to submit moderate- and high-risk LDPs to CMS or a designated third-party reviewer before putting it into practice. The plan would also expand CLIA's existing proficiency testing program to require that all LDPs undergo such testing. Additionally, the proposal would establish a database containing analytical and clinical validation information on all moderate- and high-risk LDPs. It would also establish new tools and requirements for reporting potential LDP errors. To pay for these functions, CMS would be allowed to charge labs additional user fees.
"Our proposal is to overhaul the [CLIA] system and bring it up to date," Konnick said. "The idea is basically [to] preserve innovation, patient access, medical practice and add some transparency into what the performance [of a given LDP] is and that sort of thing."
While the AMP proposal is perhaps the most fully fleshed out plan for updating CLIA to better handle LDT oversight, the general idea has been put forth by a number of lab and provider groups. In 2021, more than a dozen organizations including AMP, the American Association for Clinical Chemistry, the American Hospital Association, and the American Medical Association, wrote to Salerno asking that CLIAC "conduct a public meeting to discuss the modernization of the CLIA regulations for laboratory-developed tests" and to gather "information on how CLIA oversight can be updated to ensure that physicians, other healthcare professionals, and patients continue to have access to high quality, accurate LDTs."
The idea has also received some attention from legislators, albeit significantly less than the VALID Act. In 2020 and 2021, US Sen. Rand Paul, R-Ky., introduced the Verified Innovative Testing in American Laboratories, or VITAL, Act, which would deny the FDA authority over LDTs and require CMS to hold a public meeting and issue reports to the relevant congressional committees on updating CLIA regulations. AMP has issued statements supporting VITAL's passage.
In the House, US Rep. Michael Burgess, R-Texas, introduced over a decade ago legislation that would have updated CLIA to allow for more extensive oversight of LDTs under CMS in order to forestall their regulation by the FDA.
Neither the Burgess nor the Paul bill has received meaningful support in Congress, however.
Konnick said that CMS's position on the idea of modernizing CLIA to enable LDT oversight has been unclear.
"I actually don't know what CMS's position is," he said, adding that he has not seen CMS engage with the idea publicly and has "no idea what is going on behind the scenes."
"That's been one of the kind of mysteries of this," said an industry observer. "Where is the CLIA program on this?"
In an email to 360Dx this week, CLIAC's Salerno provided some clarity, saying that "CLIA modernization would not provide the necessary oversight of LDTs," adding that "CLIA regulates laboratories, not tests," and that "oversight of LDTs is much different than regulating laboratory practice."
Salerno also said that HHS, where CMS and CLIAC are housed, "supports a legislative framework for FDA oversight of in vitro clinical test (IVCT) analytical and clinical validity."
"Regulating diagnostic tests is within FDA's purview," he said. "FDA has the experience and expertise to ensure that tests are safe and effective with appropriate analytical and clinical validity."
Salerno also indicated that both LDTs and IVDs should be under a single regulatory regime, echoing an argument commonly made by VALID's proponents.
"It would provide critical consistency and be beneficial for patients and providers for all tests to be under the same oversight framework, regardless of who makes the test," he said.