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The U.S. Department of Health and Human Services (HHS) announced last week that the FDA can no longer require some lab tests, including tests for COVID-19, to undergo FDA review prior to going on the market, a move that surprised many. The announcement covers only laboratory-developed tests (LDTs), that is, tests assembled and used within a single lab. This can include tests developed by academic and medical center labs as well as testing behemoths like Quest, Genova, and LabCorp. HHS did not exempt tests made by one company and sold to other labs or commercial firms.

HHS also rescinded all previously-issued FDA guidance documents and informal statements of policy concerning LDTs, taking the position that any FDA regulation can be legally accomplished only through the process of notice and rulemaking or new legislation passed by Congress, both of which can take years.

It is important to note that HHS’s decision covers all LDTs, not just those for COVID-19. As we’ll see later in this post, this not only has disturbing implications for testing during the pandemic, it is also a boon to quacks and fringe medical practitioners who were already exploiting the lax regulation of LDTs to fabricate dubious diagnoses and sell bogus treatments to patients.

Before HHS rescinded the FDA’s authority altogether, the agency’s regulation of LDTs came in fits and starts. By way of background, the FDA regulates in vitro diagnostic devices (IVDs), which analyze human samples (such as blood, saliva, tissue, and urine) as medical devices. However, in the past, it did not use this authority to regulate a particular type of IVD, the laboratory-developed test.

Instead, it focused on commercial test kits, which are broadly marketed to laboratories or directly to the public. These tests have to undergo the same pre-market approval process as other medical devices regulated by the FDA. In some cases, this means clinical studies demonstrating that the device is safe and effective for its intended use. An LDT could avoid this review, even when it’s used for the same purpose as an FDA-approved test. For example, there are both LDTs and FDA-approved tests for vitamin D. This has led to complaints of a double standard from labs facing the much stricter standard.

There is some oversight of labs that offer LDTs. A federal law, The Clinical Laboratories Improvement Act (CLIA), requires assessment of whether a lab is able to test according to instructions and detect what is intended to be detected, that is, the test’s analytical validity. However, a key element is missing in that evaluation: clinical validity. Does the test accurately diagnose or predict the risk of a particular clinical outcome?

For example, Great Plains Laboratory sells the “IgG Food MAP with XMAP® Technology”, an LDT, to health care practitioners. Because Great Plains is CLIA certified, this test, presumably, accurately “detects all food antibodies” as advertised and is therefore analytically valid. But do the test’s results give a clinician information to accurately diagnose or to predict risk? Not if the clinician is practicing science-based medicine.

Historically, LDTs were developed by hospitals, researchers, and academic medical centers for their own use. That is no longer true. In the past 15 years or so, there has been an explosion in the use of LDTs by commercial labs and biotechnology companies. A few years ago, the FDA estimated that there were about 11,000 LDTs offered by 2,000 laboratories, giving impetus to stricter oversight of the burgeoning LDT market.

In 2014, the FDA announced it would henceforth use its medical device regulatory authority to oversee LDTs. Then, in late 2016, the agency reversed course and announced it would not finalize its draft guidance on LDTs, although it maintained the agency retained the authority to regulate them (and took action against LDTs based on that authority just last year). There were efforts in Congress to come up with a regulatory solution via a new law, but those efforts have yet to bear fruit.

Prior to HHS’s pulling the FDA’s jurisdiction, labs wanting to market COVID-19 LDTs were required to get emergency use authorizations (EUAs) from the FDA. Under this procedure, labs could begin using self-validated LDTs as long as they submitted an EUA to the FDA within 15 days.

An FDA spokeswoman said in May that there were problems with some COVID-19 tests whose developers had applied for an EUA, indicating that the requirement was effective in weeding out bad tests. According to a New York Times report

“Some of the laboratories didn’t do their validation properly, making it impossible to tell if they had a good test or not” [the agency spokeswoman] said. “Others included data that suggested the test did not perform well, likely missing far more positive cases than authorized tests.”

Other laboratories, she added, had manufacturing problems such as contamination. And several made unsupported claims in their labels for home testing.

At the time HHS took action, over 170 labs had notified the FDA that they had validated their own LDTs and were awaiting FDA authorization. HHS’s decision mooted that necessity.

(Labs can still voluntarily seek an EUA, which will allow them to avail themselves of the liability protection afforded by the PREP Act. Labs bypassing FDA pre-market approval will forego this protection.)

Pros and cons

According to the Washington Post, the move

came as a surprise to many at the FDA and was a point of intense disagreement between HHS Secretary Alex Azar and FDA Commissioner Stephen Hahn . . . [who] vociferously opposed the change, arguing that the agency has the authority to regulate [LDTs] during a public health emergency like the current pandemic.

Public health experts told the Post that

the shift could result in unreliable coronavirus tests on the market, potentially worsening the testing crisis that has dogged the United States if more people get erroneous results. They argued the change is unlikely to solve current testing problems, which at this point are largely due to shortages of supplies such as swabs and chemical reagents.

Former FDA Commissioner Scott Gottlieb, who served in the Trump Administration, was critical as well, telling Axios:

We’ll see a plethora of DTC [direct-to-consumer] Covid tests enter the market, where tests ship directly to consumers and are processed in a central lab operating outside FDA oversight.

Dr. Michael Carome, director of Public Citizen’s Health Research Group told the New York Times:

Suppose you get a Covid test and you actually have the infection and it comes back negative, . . . You may believe you’re OK and that may leave you in your home, exposing family and friends to the virus when you should quarantine.

Critics include former FDA officials Peter Lurie and Alberto Gutierrez, the latter calling HHS’s action “Letting the Wild West be the Wild West”.

Others, however, supported the move as helping “new and more innovative tests to market more quickly”, charging that the FDA’s review “sharply slowed testing” at the beginning of the pandemic, according to the Washington Post.

“This is what we needed and asked for five months ago,” said Melissa Miller, director of the University of North Carolina Medical Center’s Clinical Molecular Microbiology Laboratory.

And:

The emergency use authorization “requirement meant well. But in my opinion was a disaster,” Michael Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health, wrote on Twitter.

FDA regulatory practitioners who had represented clients trying to obtain COVID-19 test EUAs were critical of the FDA as well, charging that

the lack of adequate testing at the outset of the pandemic can be directly linked to FDA’s controversial laboratory-developed test (LDT) policy . . .

Signaling the implications of the administration’s decision beyond the pandemic, Jeff Allen, president and chief executive of Friends of Cancer Research, told the Times

“I think it’s quite alarming” . . . He noted that a growing number of tests are in development to help determine whether cancer patients are responsive to certain drugs. “It’s really important for the performance of those tests to be assured.”

Mr. Allen and other critics also note that the new plan appears to leave the F.D.A. with no knowledge of what lab-developed tests are being devised, much less how they are performing.

It is unclear whether the FDA will now have the authority to remove an LDT lacking clinical validity from the market. According to the Washington Post,

Administration officials who defended the change said that the tests still will be subject to CMS regulation [that is, CLIA] and that the FDA will have the authority to take a bad test off the market.

But it is not clear to me whether they are referring only to the agency’s authority to take action under CLIA, which applies only to analytical validity. Or, are they saying the agency can still remove a test from the market for lack of clinical validity or other failings not covered by CLIA? Since HHS’s position is that the FDA lacks authority to regulate LDTs at all, and it quashed all existing FDA policy on the subject in the process, I don’t see how the FDA would have jurisdiction to take action. In this opinion, I am joined by patient safety activist Madres Tomes, CEO of Device Events and a former FDA manager, who said HHS’s action

removes the post-market oversight that is required for devices cleared or approved by the FDA. That oversight is critical in these times to ensure that providers are using the best tests available.

Dr. Gottlieb also noted that the FDA might not be able to “take needed enforcement actions against bad tests” because of HHS’s decision.

A boon for quacks?

However COVID testing might be affected, I worry that HHS’s taking the FDA out of the picture will embolden labs inventing dubious tests and marketing them to fringe practitioners and scientifically naïve consumers, a subject we have addressed regularly here on SBM. As a journal article criticizing dubious lab tests (covered in this SBM post) noted, there are now whole laboratories devoted to CAM testing. CAM practitioners, such as naturopaths, “promote and sell a wide range of tests, many of which are of dubious clinical significance”. Some “have little or no clinical utility and are widely discredited”. Results “are often accompanied by extensive clinical interpretations which may recommend, or be used to justify, unnecessary or harmful treatments”.

(As a warning to consumers, both Quackwatch and Naturopathic Diaries offer lists of these dubious tests. It is important to note that while all non-standard tests are LDTs, some are legitimate FDA-approved tests used for illegitimate purposes.)

Among these are direct-to-consumer “personalized” dietary recommendations based on DNA testing, which David Gorski aptly characterized as “modern astrology”. As well, autism charlatan Amy Yasko uses a “DNA Nutrigenomic Test” to make dietary supplement recommendations (conveniently available for purchase from her husband’s online store) to parents of autistic children. Although it had, regrettably, not taken action against either of these tests, the FDA has now lost all authority to do so. Labs know this and, I predict, will exploit this regulatory void.

In a 2015 post, pediatrician John Snyder wrote poignantly about how dubious tests exploit patients and complicate his medical practice:

What I find to be a common theme with these patients is that they and their parents are summarily taken advantage of by their alternative care providers when they are given a fictitious diagnosis and treated with a variety of useless potions, elixirs, and false hopes. Often, parents bring their children to these providers because they are frustrated by their child’s chronic complaints of fatigue, pain, or other somatic issues that have eluded a satisfactory diagnosis or treatment. Invariably, the diagnosis that has remained so elusive to me is quickly found and treated by these much more “holistic” and open-minded providers. In fact, I have never seen a consultation note from one of these providers indicating any uncertainty as to diagnosis or treatment regimen. Typically a large battery of expensive, inappropriate, and sometimes outright fraudulent lab tests is ordered, often from equally questionable laboratories. Again, there are invariably interesting findings prompting tailored and bizarre treatments. In typical red-flag sCAM fashion, some of these providers have their own supplement store, available online only to their patients, prominently displayed on their website. These providers are perceived as being more holistically informed about health and wellness then “conventional” doctors like myself, as if there are two distinct ways of treating illness and maintaining health…as if there is truly such a thing as alternative medicine.

It can be very difficult to manage patients who are being simultaneously “treated” by such providers. . .

[Emphasis added; links in original.]

As a possible solution, one lab trade group has called for a single regulatory standard covering all diagnostic testing, LDTs and otherwise. That sounds like a sensible solution, as long as it doesn’t include a get-out-of-jail-free card for quack tests. It may take this pandemic to finally spur Congressional action.

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Posted by Jann Bellamy

Jann J. Bellamy is a Florida attorney and lives in Tallahassee. She is one of the founders and Board members of the Society for Science-Based Medicine (SfSBM) dedicated to providing accurate information about CAM and advocating for state and federal laws that incorporate a science-based standard for all health care practitioners. She tracks state and federal bills that would allow pseudoscience in health care for the SfSBM website.  Her posts are archived here.