Vol. 25 No. 11 Page 14
There has been a great deal of debate in the last few years around which agency should regulate clinical laboratories, what kind of review process is necessary for the tests they develop, and even whether these tests are only tests or are actually laboratory procedures. Amid all the discussion about laboratory-developed tests (LDTs), one point tends to get lost: whatever we call them and however they’re regulated, these tests are a crucial element of modern patient care.
LDTs exist to serve unmet medical needs, whether that’s diagnosis of rare diseases for which no commercial test is available or testing of emerging diseases for which no commercial test has had time to get through regulatory review. For many of the diseases and conditions that LDTs cover, there may never be a commercially available, FDA-cleared assay. As the clinical community proceeds with LDT discussions and regulations, it’s imperative that we retain mechanisms enabling clinical laboratories to continue to serve all the needs of their physician and patient communities.
LDTs in Practice
There is no single registry of tests developed by clinical laboratories, but a widely used estimate tells us there are roughly 100,000 such tests in the U.S. today. Those have all been developed by clinical laboratories, which are currently regulated and overseen through CLIA. In recent years, many of these tests have increased in complexity—largely due to the rise of sequencing-based tests and the need for more sophisticated interpretation. In light of this, the FDA, which has previously chosen not to enforce its ability to regulate these tests, is now reconsidering its stance. The agency has announced plans to regulate LDTs the same way it does any commercially available diagnostic test, though this has not yet become official. Some stakeholders argue that CLIA oversight alone is sufficient even for more complex tests being developed today. I am not writing this in support of one opinion over another; there are good reasons for either CLIA or FDA to oversee LDTs. The point I would like to convey here is that it is important to consider the extraordinary value that LDTs can offer, regardless of where regulation comes from.
LDTs have become a useful alternative to commercially available tests for a number of situations. Clinical labs that operate certain tests at small volume can significantly lower their costs and reduce turnaround time by performing in-house LDTs rather than sending those few samples out to reference labs. They can also provide much-needed diagnostic information for patients with rare diseases for which there simply are no commercially available tests because the market isn’t large enough to justify the assay development and clinical trial costs a company would have to pay for an FDA-cleared test. And in the case of emerging disease outbreaks, LDTs have become a tremendously useful public health tool during the months or years it may take for companies to develop and achieve regulatory approval for new tests. For all of these situations, physicians around the country rely on LDTs to provide useful information to help guide treatment for their patients.
Even when LDTs serve low-volume needs, that doesn’t make them any less important in healthcare. These tests provide answers for patients on diagnostic odysseys and they help healthcare providers track and stop epidemics. We hear a lot about the dearth of therapeutic treatments for rare diseases because there aren’t enough patients to interest big pharma; LDTs are the testing analogy, meeting the needs of patients who cannot possibly hope to get the attention of commercial test developers. If well-funded companies can’t afford assay development and full FDA review for these indications, it’s hard to imagine how budget-crunched clinical labs could do so.
I have spent quite a bit of time in the clinical laboratory realm, and as I look at the various sides of the debate about LDT regulation, one thing is clear. The passion we see throughout these discussions says a lot about the clinical community: everyone in these discussions, from regulators to lab managers, just wants to ensure high-quality testing for physicians and patients. There are many different opinions on how to accomplish that, but when you boil it down to the basics, we are all pulling for the same ultimate outcome.
What I’d like to hear more about in these discussions, though, is that the real outcome isn’t just a great test; it’s getting important answers to a physician for a patient. There is still a great deal of unmet need among commercially available diagnostics, and when properly regulated, LDTs may satisfy that need. For patients who need a test to rule in or out whatever disease or condition they might be facing, they are less concerned about which agency regulates the test or who developed it than they are about knowing that the results it provides are accurate and reliable. The physicians treating them simply want the right diagnosis, quickly, from a lab they can trust. We as a medical community owe it to both of these groups to ensure there will always be a way to provide those answers.