The Food and Drug Administration on Tuesday warned expectant parents of the risk of false-positive results from a burgeoning line of prenatal blood tests that screen fetuses for rare genetic conditions.
The advisory followed a New York Times review in January that reported on the incidence of false-positive results in some of these tests, known as non-invasive prenatal screening tests, or NIPT. This article cited women who had received false positive screening results for extremely rare conditions; highlighted examples of misleading marketing by companies selling the tests; and describes some reports of terminated pregnancies based on screening without confirmatory testing.
The agency warned doctors not to diagnose genetic disorders based on these results alone and stressed the need to follow up positive screens with more reliable “diagnostic” tests. He said he was “aware of reports” that some women “have terminated pregnancies based solely on the results” of these genetic screening tests.
“While non-invasive genetic prenatal screening tests are widely used today, these tests have not been reviewed by the FDA and may make claims about their performance and use that are not based on sound scientific evidence. “, said Dr. Jeff Shuren, director of the agency. Center for Devices and Radiological Health, said in a statement.
The tests are taken by more than a third of pregnant women in the United States. But they fall into a category called laboratory-developed tests, which are neither regulated nor approved by the FDA. In its safety notice, the agency said it was working with Congress “on legislation to establish a modern regulatory framework for all testing,” including the category that covers such screenings.
The agency’s warning comes after numerous accounts, dating back years, of misinterpretations of the projections as final. But criticism has intensified in recent months, with 97 Republican lawmakers sending a letter to the FDA in January following the Times article.
“This is an area that the agency has been concerned about for a long time,” said Alberto Gutierrez, the former director of the FDA office that oversees many medical tests.
The lack of regulation of lab-developed tests “has led to many cases where labs have claimed more than they should have based on the available data,” he added.
The warning has no consequences for manufacturers of prenatal tests. But he urged them to subject their products to voluntary approval. A spokeswoman for the agency declined to say whether it is currently working with manufacturers on this front.
In just over a decade, testing has grown from lab experiments to major industry, with companies like Labcorp and Quest Diagnostics entering the business, alongside many start-ups.
A major test maker, Natera, said in 2020 it performed more than 400,000 screenings for a type of condition, called microdeletions – the equivalent of testing around 10% of pregnant women in America. In a conference call with investors in 2021, he disclosed that 75-80% of his core prenatal screening business includes microdeletion screenings.
Immediately after the FDA’s warning was issued on Tuesday, Natera’s stock fell more than 7%, but had recovered much of its value by mid-morning Wednesday.
“Natera fully supports FDA communication regarding NIPT and has long believed that educating patients and healthcare providers about the strengths and limitations is critical to patient care,” the company said in a statement. .
Myriad, another test maker, said it would support a role for the FDA in regulating lab-developed tests. Labcorp said it appreciates the FDA’s guidance on this and that “screening tests should be followed by diagnostic tests where appropriate.”
Other major test makers, including Quest and BioReference Laboratories, did not immediately return requests for comment.
The Times review included a review of 17 brochures from companies that sell prenatal screenings. At the time, 10 of the brochures did not mention that a false positive could occur. Mr. Gutierrez reviewed some of the documents and described them as “problematic” and “misleading”.
“Many labs that offer these tests claim the tests are ‘reliable’ and ‘highly accurate’, providing ‘peace of mind’ to patients,” the agency wrote, citing examples published by The Times in January. “The FDA is concerned that these claims are not supported by strong scientific evidence.”
After reviewing the scientific literature, the agency said that while prenatal screening tests “generally work well at ruling out disorders”, they are less reliable when they show positive results. The most reliable positive results are for Down syndrome. For rarer genetic conditions, caused by small missing fragments of chromosomes called microdeletions, the agency has found that a positive screening result can be a false positive between 70% and 98% of the time.
Their findings are consistent with the Times article, which identified five microdeletion screens for which approximately 85% of positive results are false positives.
“It’s a strong response,” said Liz Richardson, who leads The Pew Charitable Trusts Health Care Products Project and has authored reports calling for regulation of prenatal testing. “In my view, this still places a great burden on consumers and health care providers to know how to interpret these tests, when really the onus is on the company to communicate truthfully and not misleadingly. ,” she added.
“While this is a helpful first step, I think what is needed is more comprehensive reform of FDA oversight of these tests, as well as other lab-developed tests. .”
A bill to provide additional scrutiny is currently in Congress. The VALID Act is a bipartisan bill in both houses that would give the FDA the power to regulate lab-developed tests the same way it regulates diagnostic tests. The bill will go to committee this spring.
In a statement, Representative Chip Roy of Texas, one of the authors of the Congressional letter and opponent of abortion, applauded the FDA advice as “another step toward protecting life.”
“Parents deserve full information when making complicated medical decisions for their children, especially when these tests may be a matter of life and death,” he said.
Susan C. Beachy contributed to the research.