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Cost Effectiveness Study Shows Sequencing-Based T21 Test Leads to Better Clinical Outcomes

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A cost-effectiveness study seeking to measure the clinical and economic impact of Verinata Health's sequencing-based Verifi test to diagnose fetal aneuploidies has found that implementing the test may reduce invasive diagnostic procedures, miscarriages caused by such procedures, and lead to a moderate cost savings.

These "non-invasive prenatal tests represent a major sea change in prenatal care for women," Susan Garfield, vice president of market access and healthcare at GfK Bridgehead, a consultancy that performed the cost-effectiveness analysis, told Clinical Sequencing News. "So, we wanted to understand what do these high sensitivity and specificity tests mean from a cost perspective … and the clinical impact of incorporating these tests."

The study, funded by Verinata and published last week in the Journal of Managed Care Medicine, found that while the economic impact was moderate, resulting in a 1 percent cost savings over the standard of care, the clinical impact was high.

The model found that the use of a sequencing-based test as a follow-up to initial screening could reduce the number of invasive diagnostic tests like amniocentesis and chorionic villus sampling by 72 percent. Additionally, because these invasive tests carry a risk for inducing miscarriages, the number of miscarriages caused by such procedures could be reduced by 66 percent if replaced with a non-invasive test. Furthermore, the study found that the sequencing-based test would identify fetal trisomy 21 in 15 percent more women than with standard of care.

While the cost-effectiveness study specifically looked at Verinata's test, Sequenom's MaterniT21 test is very similar. It also uses sequencing to detect trisomies 21, 18, and 13, and has comparable sensitivity and specificity. Sequenom management could not be reached for comment.

Currently, the standard of care for prenatal screening for aneuploidy includes a maternal serum screening in the first and/or second trimester and ultrasound in the first trimester. A second-trimester ultrasound can also detect abnormalities.

These screening tests, however, are not diagnostic, and detect between 77 percent and 86 percent of trisomy 21 cases with a false positive rate of between 3.2 percent and 5.6 percent. Second trimester screenings have a higher detection rate — between 85 percent and 94 percent — but also a higher false positive rate — between 8.5 percent and 11 percent.

As a result, women who test positive after screening are then recommended for an invasive procedure like CVS or amniocentesis, which have a sensitivities and specificities of around 99 percent.

The model developed by the Bridgehead researchers evaluated a theoretical cohort of 100,000 pregnancies. Within the standard-of-care arm, women who tested positive in the initial screening were then offered either an immediate CVS test or a second-trimester amniocentesis test. The women in the Verifi arm would still receive the initial standard of care screening, and if they tested positive would be offered the Verifi test or CVS immediately, or a second-trimester amniocentesis test.

The model took into account measured test uptake, including the fact that some women who test positive in the initial screen opt to not receive either an amnio or CVS test. Additionally, women who do opt for further testing typically chose amniocentesis over CVS — 71 percent versus 29 percent — and these rates were also incorporated into the model.

The researchers also incorporated miscarriage rates and test-induced miscarriage rates of 1 percent for CVS and 0.5 percent for amniocentesis into the model.

The model also looked at the use of the Verifi test both with a confirmatory test and without.

The biggest benefit of using Verifi, according to the researchers, is the reduction in miscarriages.

The model found that incorporating the test could reduce invasive diagnostic-induced miscarriages by 66 percent, to 20 from 60 out of 100,000 pregnancies. If an invasive procedure is not used to confirm the results of the Verifi test, that number is further reduced to 18.

Additionally, adoption of the test results in earlier and more accurate diagnoses — 15 percent more women will receive a trisomy 21 diagnosis and 2 percent more women will receive a trisomy 18 diagnosis, according to the study.

The test also reduced cost, albeit moderately. The study estimated total costs for prenatal screening and diagnosis for fetal aneuploidies to be $59,748,721 for 100,000 pregnancies under the current standard of care. Incorporating Verifi reduces that by 1 percent annually to $59,228,142.

"Normally, you would expect that level of [clinical] improvement to come at a significant cost to the healthcare system," said Garfield. So even though the reduction was modest, it was still "impressive," she said. Furthermore, as the test becomes more widely accepted and CVS and amniocentesis are not needed to confirm the results, it could result in even further cost reductions, she added.

Amniocentesis and CVS cost between $1,400 and $1,700, while the Verifi test costs $1,200.

Because the Verifi test is noninvasive, though, it might have a higher adoption rate than either CVS or amniocentesis, so further cost impacts would have to be evaluated, Garfield said.

Anthony Odibo, the director of the Division of Ultrasound and Genetics and co-director of the Fetal Care Center at Washington University School of Medicine, who began offering the Verifi test about two months ago to women whose initial screen is positive or have some other indication that they are at high risk for aneuploidy, told CSN that the results of the cost-effectiveness study are "really significant from a clinician as well as from a policy-maker perspective."

From a clinician's perspective, "if you can reduce the number of invasive procedures by about 70 percent that means you really reduce the risks a woman is exposed to during pregnancy."

Additionally, he added, "any new technology tends to be more costly, but this shows moderate cost savings."

The one potential drawback, he said, is that it is currently unclear whether insurance companies are reimbursing for the test. While he offers women the option of receiving the test, he said he does not know to what extent it's being reimbursed, since the negotiations happen between the payors, the laboratory doing the test, and the patient.

Odibo said that the test has been well-accepted by the women to whom he has offered it, and said he hopes that it will eventually replace amniocentesis and CVS.

In order for it to completely replace the invasive tests, however, it would first have to demonstrate its performance on twin pregnancies and other aneuploidies, he said.