This week CMS has published a short but instructive informational piece described as ”Lab and CLIA FAQs”. The core question posed and answered is “What is CMS’s authority regarding Laboratory Developed Tests (LDTs) and how does it differ from FDA authority?” This clarification is welcome because there has been considerable confusion and controversy over the roles of the two agencies. Misinformation has been rampant, suggesting significant redundancy between the two programs, implying that CLIA offers an alternative mechanism for approving a new test and/or hinting that somewhere secretly housed within the CLIA program is regulatory authority to assure the clinical validity of tests.
CMS first cites the FDA definition of an LDT “an in vitro diagnostic test that is manufactured by and used within a single laboratory (i.e. a laboratory with a single CLIA certificate.)” CMS reiterates what FDA has been saying all along: LDTs meet the statutory definition of a device, are subject to FDA regulatory oversight, but have been generally afforded enforcement discretion.
The FAQ then addresses each of the misunderstood and sometimes misrepresented issues described above. The document begins by succinctly describing the very different objectives of the two programs. CLIA “regulates laboratories that perform testing on patient specimens in order to ensure accurate and reliable test results.” FDA “regulates manufacturers and devices … to ensure that devices are reasonably safe and effective.” To cut to the quick CMS clearly asserts and explains the regulatory schemes for the two agencies are different in focus, scope and purpose and are intended to be complementary not duplicative.
In support of this point, CMS notes the very different endpoints and processes of CMS versus FDA oversight. CMS points out that “when a laboratory uses a test system that has not received FDA clearance or approval, such as a LDT, the laboratory may not release any test results prior to establishing certain performance characteristics relating to analytical validity”. But this requirement is not equivalent to or a substitute for the FDA premarket review process. A CLIA assessment of the analytical validation of a new test occurs during the routine biennial survey of the laboratory, an event that can occur months or years after new testing has been initiated. This is distinctly different from the FDA review of analytical validity which is done prior to test marketing. It is also noted by CMS that the FDA analytical review is more in-depth and more comprehensive focused on the safety and effectiveness of the unique test system not the operating characteristics of the lab itself.
Finally the guidance dispels the belief (wishful thinking) that the CLIA certification of the laboratory somehow or other confers clinical validity on each of the tests within the lab’s testing menu. The FAQ’s judgment is short and sweet. “CMS’ CLIA program does not address the clinical validity of any test.” (Emphases theirs)
In short order this FAQ provides clear facts on the differences between CLIA and FDA regulatory oversight. It is not a particularly closely held secret that the LDT route is currently the overwhelming path of first choice to market. While the FDA path may currently be a lonely journey, in making this choice perhaps Frost was right:
Two roads diverged in a wood, and I—
I took the one less traveled by,
And that has made all the difference.