Are we over-regulating diagnostic tests?

Diagnostic tests, such as blood tests and scans, are valuable tools for clinicians to treat medical problems. Does this mean that the more tools we have, the better? In a recent op-ed in STATRina Wolf, vice president at XIFIN health IT company, argues that current US Food and Drug Administration (FDA) policies are hindering access to new diagnostic tests, to the detriment of our health. She asks:

“Should we be making it easier for companies to bring new tests to market, rather than having a process that is so complicated and expensive that they give up? Have we set up a system so complex that we’re inadvertently stifling diagnostic innovations and possibly endangering the health of our nation?”

Wolf paints a picture of dozens of life-saving tests held back from doctors by a tangle of red tape. But is that really what diagnostics regulation at the FDA is like? We’ve written extensively about the FDA’s lax regulations of medical devices. What you may not know is that the protocol for approving diagnostic tests is just as minimal. 

No real test for diagnostic tests 

Here’s a brief summary of how it works. Tests that analyze human samples (blood, tissue, etc) that are created for commercial sale are called “In Vitro Diagnostics” and are regulated by the FDA using the same process as medical devices. IVDs that are Class I (lowest risk) do not need premarket review. IVDs that are Class II or III and are shown to be “substantially equivalent” to an existing test can be approved through the 510(k) pathway. Tests that are approved this way do not need to have been tested in humans through a clinical trial to prove effectiveness and safety, which has caused significant patient safety issues around the world

Diagnostic tests that aren’t equivalent to a predicate have to go through “premarket approval,” where the FDA evaluates whether “scientific evidence shows that the possible benefits to health from the intended use of a device outweigh the possible risks.” However, there are some exceptions to premarket approval, including “De Novo” classification, which are device types that have not been marketed in the US but have been used in other countries and are “reasonably well understood.” Devices can also be exempt if they are for diagnosing “orphan” diseases, diseases that affect fewer than 4,000 patients a year.

An explosion of genetic tests

If a diagnostic test was developed, manufactured, and used only within a single laboratory, it is redefined as a “Laboratory Developed Test” and is not subject to FDA approval. According to a report from the Congressional Research Service, when the LDT designation was created in 1976, it mainly covered genetic tests developed by academic or research laboratories to diagnose rare diseases. But over the past few decades, the use of the LDT designation has dramatically increased as development of genetic tests has become more popular. Now, there are more than 10,000 LDTs now on the market, none of which are evaluated for clinical validity before being used. 

This is no small danger. The FDA knows that faulty LDTs may have caused “patients being over- or undertreated for heart disease; cancer patients being exposed to inappropriate therapies or not getting effective therapies; incorrect diagnosis of autism; unnecessary antibiotic treatments; and exposure to unnecessary, harmful treatments for certain diseases such as Lyme disease.” 

The FDA has attempted to regulate LDTs over the past few years, but has faced significant pushback from companies that sell genetic tests. The most the FDA has been able to do is issue a non-enforceable “discussion paper” on how they would like LDTs to be regulated. Legislators on both sides of the aisle are working to try and pass legislation that would allow the FDA to regulate LDTs (while further streamlining approvals for low-risk diagnostic tests), but it is unclear when this bill will be passed.

Do we need fewer “roadblocks”?

Wolf’s argument that the FDA’s red tape is preventing important diagnostic tests from getting to market contains several holes. She wants some diagnostic tests to be approved based on “Right to Try” or “coverage with evidence,” policies that would allow unapproved tests to be marketed and used, for the purpose of getting more evidence on whether the test works. These would expose many patients to harms of inaccurate tests and dangerous overtreatment, a outcome nearly guaranteed by the fact that this is happening with unregulated LDTs. Wolf also does not specify how “Right to Try” for diagnostics would work, given that this designation is typically reserved for drugs for terminal illnesses.

On social media, doctors and policy experts countered Wolf’s argument. Former FDA commissioner Robert Califf tweeted, “While i’m in favor of reducing unhelpful bureaucracy, this is way off base. We need is better evidence so we can have confidence that new tests actually provide value.” 

The FDA’s protocol for approving diagnostic tests is no more stringent than their approval process for devices; in many ways, it is dangerously lenient. As Califf wrote, we need evidence of value before approving diagnostic tests, not less.