The Food and Drug Administration in April issued a safety communication to patients and health care providers about the risk of false results from prenatal blood tests that look for fetal genetic abnormalities. According to a New York Times investigation, these tests “have gone from laboratory experiments to an industry that serves more than a third of the pregnant women in America.”
Worse still, the newspaper found that noninvasive prenatal testing (NIPT) for five rare genetic conditions can return false positive results 80% to 93% of the time.
Yet, because of a loophole in federal policy, FDA does not review the accuracy of these products or their marketing, and the labs are not required to report key information about their performance to the agency. This lack of oversight can expose patients to serious harm.
“False positive rates cause a great deal of stress and anxiety for patients,” Dr. Marta Kolthoff, director of medical genetics at West Penn Hospital in Pittsburgh, recently told The Pew Charitable Trusts.
That was the case for Meri Horn and Avi Gelboim when they were expecting their first child in 2015. Their obstetrician offered the New Yorkers a test that could determine the baby’s sex, the couple said, but they were never warned that the results would include statements—many of them unreliable—about their child’s risk of having serious genetic abnormalities.
“When my doctor called me with the results that the test showed a positive result for Angelman syndrome, I was devastated,” Horn told Pew. The extremely rare disorder causes developmental delays, speech and balance issues, and seizures.
“My doctor did not truly understand what a positive result indicated … and therefore could not accurately answer our questions,” she said.
“It was easily one of the worst moments in my life,” Gelboim added.
The couple’s obstetrician referred them to a genetic counselor, who advised Horn to undergo an amniocentesis to confirm the result. Fortunately, after several difficult and anxiety-filled weeks, they learned that the test’s results for Angelman syndrome were false; Horn later gave birth to a healthy baby boy.
Their experience, similar to those of too many expectant couples, underscores the need for additional action. FDA’s safety communication will help parents and their doctors better use prenatal tests and understand the results, but it’s not enough. Indeed, NIPT products are not the only tests slipping through the regulatory cracks. That’s why Congress must strengthen the agency’s authority to ensure the reliability and safety of all clinical tests used to guide medical care for millions of Americans each year.
NIPT products belong to a class of tests known as lab-developed tests (LDTs). Despite often serving the same clinical needs as commercially manufactured tests, LDTs do not undergo FDA review because they fit within the definition of the current loophole: They are developed and used in the same lab. This made sense in 1976, when today’s regulatory scheme was established, but since then, LDTs, like NIPT products, have evolved and their uses have expanded significantly.
Under the outdated rules, developers of NIPT products and other LDTs do not need to demonstrate to FDA—or any other regulator—that their products accurately and reliably detect the diseases or conditions for which they’re designed. Health care providers and test makers also are not required to report to FDA when tests deliver inaccurate results that harm patients—for example, if expectant parents make important decisions that affect the outcome of a pregnancy based on inaccurate information. In addition, labs do not need to submit labels and marketing claims to the agency to ensure that their marketing language is supported by data. In contrast, manufactured test kits and their makers’ claims are subject to FDA review, and reporting cases of harm to patients is required.
In the case of NIPT products, Kolthoff said, most providers receive information about the tests from manufacturers that does not include statistical context and that makes it more difficult for physicians and patients to understand and reliably evaluate test results.
“A lot of the marketing aimed at patients by these labs emphasizes reassurance, ease, and other positive aspects of NIPTs. There is very little information about the significance if an abnormality is detected,” Kolthoff said. “There should be oversight from the FDA like any other test or medical product.”
Congress can help by passing meaningful diagnostics reform—as spelled out in the Verifying Accurate Leading-edge IVCT Development (VALID) Act—as part of pending FDA user fee legislation. Lawmakers must pass such a bill this fall to maintain normal functioning at the agency. This carefully negotiated, bipartisan measure would balance safety and innovation by directing FDA to review high-risk LDTs before they are used on patients while continuing to exempt low-risk tests. It also would oblige all test developers to register their products with the agency, report when patients are harmed because of faulty tests, and provide information around their tests’ performance and evidence in support of their appropriate clinical use.
Enacting this legislation would be a significant win for public health, modernizing the 46-year-old approach governing the market today. The VALID Act reflects years of diligent work and compromise by a diverse set of stakeholders, including patient groups, health care providers, labs, medical device manufacturers, and many others. Taking that into account, Congress should act quickly to build on this progress and ensure that FDA has the tools needed to protect Americans from inaccurate tests.
Michael Dobias leads research and advocacy efforts for The Pew Charitable Trusts’ health care products project.