COMMENTS DUE TODAY: FDA considering regulating cell free DNA testing

FDA_Blue_LogoThe FDA is considering regulating laboratory developed tests (“LDTs”). MaterniT21, verifi, Harmony, and Panorama are all LDTs. Today is the last day to submit comments to the FDA. Here’s mine on why the FDA should regulate LDTs.

Below is the comment I have posted at the FDA’s website:


Non-invasive prenatal screening (“NIPS”) tests cell free DNA in a pregnant woman’s bloodstream for genetic conditions that her fetus may have. All NIPS tests are laboratory developed tests (“LDTs”), and since entering the market, regulation has been called for.

The International Society for Prenatal Diagnosis stated that “[t]he current absence of specific guidelines for quality control and quality assurance for cfDNA screening is a serious concern.” A sting operation in the Fall of 2014 demonstrated how much these measures were needed, with NIPS labs reporting results that a fetus had a genetic condition from blood samples of women who were not even pregnant. 

The American College of Medical Genetics & Genomics statement “encourage[d] providers of NIPS technology to make serious efforts to provide the more clinically relevant metrics.” If anything, the labs have moved away from this, and instead companies like Sequenom highlight how they report their test results as “positive” or “negative;” this is contrary to every professional medical organization’s guidelines, which emphasize the need for patients to understand that NIPS has false positives and false negatives. 

The result is that a technology that is supposed to provide information is instead providing misinformation, with dire results.

Relying on the marketing materials given to them by the laboratories, practitioners are incorrectly advising their patients that NIPS is “99+%” accurate–no NIPS test provides that much certainty. Women, though, are relying on this misinformation and terminating their pregnancies, in one case even where a diagnostic test proved the NIPS result was a false positive, as reported in December 2014 in the Boston Globe by the New England Center for Investigative Reporting.

This mass confusion is only expected to grow on a larger scale as the laboratories push to have their tests offered to all women, not just those already at a higher-probability for having a child with a genetic condition.

Medical advisors to Illumina, the maker of verifi, and Ariosa, the maker of Harmony, have called for their tests to be offered to all patients. This despite those same professionals’ own research having shown that the tests are not reliable in low-risk populations. In the case of verifi, its report in the New England Journal of Medicine (NEJM) showed a screen-positive was a true positive less than 50% of the time. This prompted the Society for Maternal-Fetal Medicine to issue a statement emphasizing the need for limiting NIPS per the guidelines to high-risk populations.

But the profit-incentive is pushing the labs to call for a wider offering.

Researchers at Harvard and Massachusetts General Hospital raised concerns about NIPS moving ahead of the evidence: “T]he diffusion of [NIPS] into routine prenatal care may be occurring too quickly. Professional societies do not recommend these tests for normal-risk pregnancies because their clinical utility in the general population is not well established. … [NIPS] testing seems to be drifting into routine practice ahead of the evidence.”

Further, this expansion of misinformation and lack of evidence will increase in 2015 as other laboratories offer their own version of NIPS or a licensed version of verifi without publishing any clinical data on their respective tests’ accuracy.

The NIPS labs have had years to address these concerns raised by professional societies, researchers, ethicists, and their own research. They have chosen not to self-regulate, but instead push for wider expansion with more confusing representations of their tests’ accuracy. Having been given the chance, it is now time for the FDA to impose regulation on these labs in order to ensure quality standards are being met and accurate information is delivered with NIPS testing.

Should the FDA choose to regulate, then the FDA should require the laboratories to also report the additional information recommended to accompany a test result for a genetic condition.

Professional guidelines have long recommended that women receive accurate information about the tested-for condition and referral to support resources whenever a test result is reported. In 2008, this was codified into federal law with the Prenatally & Postnatally Diagnosed Conditions Awareness Act. Increasingly, states are passing laws requiring medical professionals to provide accurate information about Down syndrome and referral to local support groups. These are the materials provided by the National Center for Prenatal & Postnatal Down Syndrome Resources. Currently, Ariosa and Natera have offered these materials to their provider networks, but the materials need to be sent with each screen-positive result, regardless of which lab performs the test.

Patient information materials are part of the information to be delivered with accurate NIPS test results, which the FDA could bring about by regulating the LDTs offering NIPS.

The time is now to do so.


If you agree with the concerns raised by this comment, I hope you will submit your own comment to the FDA–but you must do so today. Feel free to cut-and-paste this comment and submit it yourself at this link.

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