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CTAF Recommends Sequencing-Based Screening Tests for T21 and T18 in High-Risk Women

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The California Technology Assessment Forum has issued draft guidelines recommending the use of non-invasive prenatal trisomy tests as advanced prenatal screening tests for trisomies 21 and 18 in high-risk pregnant women.

CTAF concluded that the tests are currently not ready for use in average-risk women, or as a replacement for primary screening techniques. Additionally, it said that there is not yet enough evidence supporting the tests' ability to screen for trisomy 13.

Such tests are being marketed by Sequenom, Verinata Health, and Ariosa in the US, and by Germany's LifeCodexx in Europe.

The tests from the three US-based firms met CTAF's requirements for having the appropriate regulatory approval and scientific evidence to call trisomy 21 and 18. CTAF did not comment on LifeCodexx's test.

CTAF assesses the safety and effectiveness of emerging medical novel technologies. Insurance companies often use its recommendations to guide coverage decisions.

For trisomy 21 and 18 testing, CTAF cited published validation studies by each of the companies demonstrating high specificities and sensitivities. It also cited a cost-effectiveness analysis of Verinata's Verifi as evidence that these tests could improve health outcomes.

The cost-effectiveness analysis determined that non-invasive screening could reduce invasive diagnostic testing by 72 percent and because invasive tests carry a risk of miscarriage, it would also reduce miscarriages that are caused by such tests by 66 percent (CSN 5/2/2012).

At the time that CTAF performed its analysis, there were only two published studies that tested the technology for its ability to detect trisomy 13. Detection rate was 78.65 percent in one study and 91.7 percent in the other, and between the two studies, only 26 cases of trisomy 13 were evaluated. Thus, CTAF determined that "the ability to draw conclusions is limited by the small number of cases."

While CTAF determined that noninvasive testing for trisomy 21 and triosmy 18 meet the criteria for advanced prenatal screening, it noted that none of the published literature has yet compared this type of method to current primary screening methods such as measurements of maternal serum markers and ultrasound.

Nor can these assays replace invasive diagnostic testing for aneuploidies, because despite the tests' high sensitivity and specificity, "its accuracy is not that of the gold standard of fetal karyotyping," CTAF wrote.

"In addition, karyotyping can provide information about other conditions besides fetal aneuploidy status, whereas [circulating fetal] DNA cannot."

And although Ariosa recently published a study demonstrating the use of its test in average-risk women, CTAF concluded that "the small number of T21 and T18 cases in this study, the fact that not all pregnancies underwent karyotyping, and that not all samples could be given trisomy risk scores, limit the conclusions that can be drawn from this study."

The study suggests that the assays may have "potential utility in average risk women" and should continue to be evaluated, but "it is currently not ready for routine use in average risk women."

Ariosa CEO Ken Song told Clinical Sequencing News in an email that CTAF's recommendations represent only the "first step" in making non-invasive prenatal testing "an option for any pregnant woman."

He added that he thinks the recommendation will "help streamline access" to these tests and that "as clinical data and experience of using NIPT in the average-risk population continues to build, it should lead to near term broader coverage, support, and access."

In its guidelines, CTAF did not draw distinctions between the three different tests being offered by US companies — Sequenom's MaterniT21, which screens for T21, 18, and 13 using a shotgun sequencing strategy; Verinata's Verifi, which tests uses a similar method for the same indications; and Ariosa's Harmony Prenatal Test, which uses a targeted sequencing strategy to screen for T21 and T18.

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