The FDA warns patients about some prenatal genetic tests

The Food and Drug Administration on Tuesday warned expectant parents about the risk of false positive results from a thriving array of prenatal blood tests that screen fetuses for rare genetic conditions.

The announcement followed a New York Times study in January that reported the occurrence of false-positive results in some of these tests, known as non-invasive prenatal screening tests or NIPTs. This article cited women who received false positive screening results for extremely rare conditions; featured examples of misleading marketing from companies selling the tests; and described some reports of pregnancies that were terminated on the basis of a screening without a confirmatory test.

The agency warned physicians not to diagnose genetic disorders based on these results alone and stressed the need to follow positive screenings with more reliable “diagnostic” tests. It said it was “knowledgeable about reports” that some women “have terminated pregnancies based solely on the results” of these genetic screening tests.

“While genetic non-invasive prenatal screening tests are widespread today, these tests have not been reviewed by the FDA and can make claims about their performance and use that are not based on solid science,” Dr. Jeff Shuren, Director of the Agency’s Director. Center for Devices and Radiological Health, said in a statement.

The tests are taken by over a third of pregnant women in the United States. However, they fall into a category called laboratory-developed tests, which are not regulated or approved by the FDA. In its safety release, the agency said it was working with Congress “on legislation to establish a modern regulatory framework for all tests,” including category covering those views.

The agency’s warning comes after several reports dating back years, about misinterpretations of the views as being definitive. But criticism has intensified in recent months, with 97 Republican lawmakers sending a letter to the FDA in January, prompted by the Times article.

“This is an area that has been of concern to the agency for a long time,” said Alberto Gutierrez, the former director of the FDA office that oversees many medical tests.

The lack of regulation of laboratory-developed tests “has led to many cases where laboratories have claimed more than they should based on the data available,” he added.

The warning comes with no consequence for manufacturers of prenatal tests. But it encouraged them to submit their products for voluntary approval. A spokeswoman for the agency declined to say whether it was currently working with any manufacturers on this front.

In just over a decade, the tests have gone from laboratory experiments to a large industry, where companies such as Labcorp and Quest Diagnostics have entered the business together with many start-ups.

A major test manufacturer, Natera, said that in 2020 it performed more than 400,000 screenings for one type of condition, called microdeletions – equivalent to testing about 10 percent of pregnant women in America. In a conference call with investors in 2021, it revealed that 75 percent to 80 percent of its core business in prenatal testing included micro-erasure screenings.

Immediately after the FDA warning was issued on Tuesday, Natera’s share fell more than 7 percent, but it had regained much of its value by mid-morning on Wednesday.

“Natera fully supports the FDA’s communication regarding NIPT and has long believed that it is crucial for patient care to educate patients and nurses about the strengths and limitations,” the company said in a statement.

Myriad, another test manufacturer, said it would support an FDA role in regulating laboratory-developed tests. Labcorp said it appreciated the FDA’s guidance on this topic and that “screening tests should be followed with diagnostic testing where appropriate.”

Other major test manufacturers, including Quest and BioReference Laboratories, did not immediately return requests for comment.

The Times survey included a review of 17 brochures from companies selling prenatal screenings. At that time, 10 of the brochures did not mention that a false positive could happen. Mr. Gutierrez reviewed some of the materials, describing them as “problematic” and “misleading.”

“Many laboratories that offer these tests claim that the tests are ‘reliable’ and ‘very accurate’, and offer ‘peace of mind’ to patients,” the agency wrote, citing examples published by The Times in January. “The FDA is concerned that these claims may not be supported by solid scientific evidence.”

After reviewing the scientific literature, the agency said that although prenatal screening tests “generally work well to rule out disorders”, they are less reliable when delivering positive results. The most reliable positive results are for Down syndrome. For more rare genetic disorders, caused by small missing sections of chromosomes known as microdeletions, the agency found that a positive screening result can be a false positive between 70 percent to 98 percent of the time.

Their results are consistent with the Times article, which identified five microdeletion screenings, where about 85 percent of the positive results are false positives.

“This is a strong response,” said Liz Richardson, who leads The Pew Charitable Trusts’ health products project and has authored reports calling for the regulation of prenatal testing. “It still places a great deal of the burden, in my opinion, on consumers and healthcare providers to know how to interpret these tests when really the burden should lie on the company to communicate in a truthful and non-misleading way,” she added.

“While this is a useful first step, I believe that what is needed is a more comprehensive reform of the FDA’s oversight of these tests, as well as other laboratory-developed tests.”

A bill seeking to provide further oversight is currently in Congress. The valid law is a bill in both chambers that will authorize the FDA to regulate laboratory-developed tests in the same way that it regulates diagnostic tests. The bill is due in committee this spring.

In a statement, Representative Chip Roy of Texas, one of the authors of the congressional letter and opposed to abortion, welcomed the FDA’s announcement as “another step toward protecting lives.”

“Parents deserve complete information when making complicated medical decisions for their children – especially when these tests can be a matter of life or death,” he said.

Susan C. Beachy contributed research.

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