ab-developed tests (LDTs) are in the spotlight again. Congress' and the FDA's interests in LDTs means that anyone who develops a “homebrew” must be cognizant of the evolving regulation of this market. The FDA first declined to regulate LDTs back in 1976. Currently, the quality of LDTs is still assured by the CMS through the authority of CLIA. Such tests are not FDA-cleared nor FDA-approved.
In 2006, LDTs were confirmed by the FDA to be historically and explicitly exempted by the Agency from regulation as medical devices. For years, the FDA maintained that LDTs were subject to its jurisdiction but not subject toits regulation. It opted to regulate the active ingredients of LDTs. The Agency argued extending medical-device regulation to LDTs was in direct opposition to the regulatory framework Congress established in CLIA. The FDA also noted that employing LDTs often was the only way physicians and public-health epidemiologists could determine which specific pathogen was causing a patient's symptoms and then select highly specific treatment regimens. The FDA claims LDTs used to assess high-risk (but rather common) diseases and to make critical treatment decisions now are being performed in commercial labs — not in the lab in which the LDT was “brewed.” The existing definition of an LDT has to be honored, or the implementation of LDT regulation must be revisited.
In late 2008, LDTs shared the spotlight with LabCorp's withdrawal of an ovarian-cancer test which did not qualify as an LDT; Yale researchers had developed the test, which did not meet criteria of the type of in-house test the FDA allows to skip pre-market review or 510(k) clearance. Again, the definition of an LDT was questioned. But over the past 35 years, LDTs have morphed into something far removed from the simple, single-indicator tests developed for diagnosing or monitoring rare diseases; they are highly parallel, automated tests which require complex computer software for interpretation. Commercial tests sometimes take years to gain FDA approval for marketing, a costly process, depending on the drug's complexity. LDTs in a diagnostic vendor's hands mean a faster to-market path for new commercial molecular tests, a money-saving proposition and would offer, perhaps, more testing opportunities not now available to patients.
In 2009, the President introduced legislation aimed at regulating LDTs, mainly genetic screening, and those marketed directly to consumers. Today, stakeholders point out that while LDTs present a relatively low risk to patients, inclusive, systematic oversight is needed because of their increased use and complexity. Others argue that labs may be qualified to perform high-complexity testing but do not necessarily have expertise in developing tests. Others wonder about the lack of LDT validation in controlled clinical trials in order to establish expected values and performance characteristics. In 2010, the FDA geared up to regulate LDTs, especially consumer-targeted genetic tests. Clinical labs claimed that more government oversight (e.g., a phase-in period for pre-market review and quality-system requirements for new LDTs) would stifle innovation and slow patient access to critical diagnostics.
Amid ongoing confusion over what makes an LDT an LDT, good news dawned on the disease-detection horizon: Giant African rats detected TB more accurately than commonly used scientific techniques. In December, the American Journal of Tropical Medicine and Hygiene released a new study wherein trained rats analyzed sputum samples of Tanzanian TB patients in a competition with traditional microscopic analysis. Ten of the inquisitive giant pouched Cricetomys gambianus — not monitored by a regulatory agency — revealed 620 new TB-positive patients anyway. They did not even ask for overtime, after having been rewarded with bananas for pausing at samples missed by the scopes that were known to contain TB. The ASTM&H president proffered this as a “realistic, easy-to-implement diagnostic solution for communities that may not have access to other tools.” It certainly does simplify testing and reduce costs. Have we just found a fairly cheap, snout-on solution to this LDT debate?