In his State of the Union address last week, Obama gave a big nod to genetic testing. He announced a “Precision Medicine Initiative” that will “bring us closer to curing diseases like cancer and diabetes and to give all of us access to the personalized information we need to keep ourselves and our families healthier.” “Precision medicine” is the latest term for medical treatments that are customized with the help of genetics, and, according to some people, Obama’s FDA is about to kill precision medicine while it is still in its cradle.
Could the FDA really do such a thing? The answer is buried right at the heart of a perennial dilemma in medicine: Should we balance the risks of nascent medical innovations against the need to protect patients from harm and fraud?
The major innovations in genetic testing come from small clinical labs associated with medical schools and other academic research institutions, and these labs don’t have the resources to meet the new regulatory burden.
The supposed threat to the future of genetic medicine comes from the FDA’s plan to close a decades-old regulatory loophole, which exempts certain kinds of diagnostic laboratory tests from the agency’s standard regulatory requirements. Most manufacturers of medical diagnostic tests have to prove to the FDA that their tests work before they can be sold, and, after approval, companies have to track and report any adverse events linked with the tests.
But the FDA has allowed an exception to these requirements: home-brew lab tests that are developed and used in-house by hospitals and other medical institutions. These "laboratory developed tests," or LDTs as they’re called in regulatory jargon, are exempt from the FDA's approval and tracking requirements, as long as they are designed, manufactured, and used only within a single lab. While it may seem odd to exempt any diagnostic test from the requirement that it be safe and effective, the LDT loophole is actually tremendously useful. It makes it possible for small hospital labs to customize their tests so that they better meet the needs of their patients and physicians. Instead of being limited only to commercially marketed, pre-established tests, pathologists and other specialists in a clinical lab can use their professional expertise to roll out their own custom tests, assembled from off-the-shelf, FDA-approved parts and reagents. This is particularly important when there is no commercially marketed alternative available, such as a diagnostic test for a rare disease.
When the FDA created the LDT exemption, the idea was that these tests would remain both simple and local. That is, an LDT wasn't supposed to rely on too many complicated components that could fail, such as complex hardware or fancy software that automatically interprets the results, and it was supposed to be limited to in-house use. Much has changed since the exemption was created in the 1970s, and there are now thousands of LDTs that are neither simple nor limited to local patients. And so the FDA, after considering action for more than a decade, has proposed a new regulatory framework, which would require many (but not all) LDTs to conform to the standard regulatory requirements.
Unfortunately, the poster child for the complex, widely distributed LDTs targeted by the FDA is what many expect to be the biggest medical innovation of the 21st century: genetic tests. Genetic tests have many features that the FDA says should not be part of an LDT. They depend on complex, high-tech devices and software, and they are often sold on a national scale, not just to in-house patients. A faulty genetic test can be risky: Because these tests are often used to help physicians decide which drug to give a patient, or to diagnose a risk for serious disease in an otherwise healthy person, a bad test can lead to the wrong treatment, with serious consequences.
So given the risks, shouldn't labs that offer them be required to prove that they work? The answer seems like an obvious yes. Writing this month in the Journal of the American Medical Association, Dr. Joshua Sharfstein, a former deputy commissioner of the FDA and now at Maryland's Department of Health, argues that the new FDA regulations will both protect the public and advance the science behind genetic tests. Citing the case of a faulty genetic test marketed by the company Celera and performed for more than 150,000 patients, Sharfstein argues that LDTs need to be regulated so that the FDA can detect problems and take defective products off the market. The new regulations will actually promote innovation, Sharfstein says, because it will then be clear which LDTs really work and which are merely the high-tech equivalent of patent medicine.
But many in the biomedical research community argue that the FDA should not regulate genetic LDTs. In a counterpoint to Sharfstein's article, medical geneticists James Evans and Michael Watson write that the agency's proposed regulations "may have the unintended effect of derailing the long-awaited emergence of genomic medicine.” Evans and Watson's main argument is that the major innovations in genetic testing come from small clinical labs associated with medical schools and other academic research institutions, and these labs don’t have the resources to meet the new regulatory burden. By imposing regulations, the FDA will put these small, innovative players out of business and leave the field to "large commercial entities" with near-monopoly power and few incentives to keep up with the latest science.
This is a common view among researchers in medical genetics, who are eager to see cutting-edge science developed into products that will actually help people. Much of the development for genetic testing truly does occur in small labs associated with academic institutions, or in start-up companies spun off from those institutions. These labs have to be nimble and flexible—frontier science being what it is, the field of genetic medicine is evolving rapidly.
And that is where the problem lies. The technology we use to perform genetic tests has outstripped our knowledge of how genes contribute to disease. The result is that it’s relatively easy to create and physically perform a genetic test, but much more difficult to design one that tells you something meaningful. Therefore, one of the biggest challenges for the field is to establish that these tests actually provide clinically useful information. As one review put it, we need to "build the evidentiary framework needed to support the clinical utility and validity of genomic tests."
The fact is that we're beta testers in the emerging era of genetic medicine. For the most part, we don't know how genetic testing will change the medical practice. As bad as that may sound, medical progress often happens this way. Even after clinical trials, we don't really know how a new innovation will work out in practice until it's tested in the population at large. The challenge for the FDA is to figure out how to balance our safety with the needs of a fragile, overhyped, but still promising area of medicine.