NEW YORK (GenomeWeb) – In switching from a noninvasive prenatal test that ran on next-generation sequencing technology to one that runs on a microarray, Roche's Ariosa Diagnostics aims to speed up its turnaround time and lower its costs, while maintaining accuracy, according to the company.
The firm recently evaluated the clinical performance of its microarray-based Harmony test, which analyzes aneuploidies in chromosomes 21, 18, and 13, in 799 pregnant women, in a study published in Prenatal Diagnosis. The test identified 107 out of 108 trisomy 21 cases, 29 out of 30 trisomy 18 cases, and 12 out of 12 trisomy 13 cases. Specificity was 100 percent for all three trisomies.
In addition, the firm compared the results of the microarray-based test to previous clinical studies of its test when it was based on NGS.
Comprehensively, Ariosa found that combined with nine previously published clinical performance studies, sensitivities were 99.3 percent, 97.4 percent, and 93.8 percent for trisomies 21, 18, and 13, respectively, while specificities were all greater than 99.9 percent.
For comparison, Sequenom advertises that its NGS-based MaterniT21 Plus test has sensitivities of 99.1 percent, 99.9 percent, and 91.7 percent and specificities of 99.9 percent, 99.6 percent, and 99.7 percent, for trisomies 21, 18, and 13, respectively.
The study, along with the previously published clinical studies, demonstrate the firm's proprietary assay and analysis, known as Digital Analysis of Selected Regions (DANSR) and Fetal-Fraction Optimized Risk of Trisomy Evaluation (FORTE), respectively, "across a couple of quantitative platforms," Ariosa Chief Medical Officer Tom Musci told GenomeWeb.
"We wanted to show another dataset using our custom array and link that to performance across multiple studies and put it all together," he said.
Ariosa, which was bought by Roche last year, previously published a study comparing the NGS approach with the microarray approach and found that the microarray approach was more accurate and faster.
However, Musci said that this newer study goes a step further in that it is a blinded cohort. "The other paper was really about showing the same samples split between the two platforms and showing some of the technical issues and benefits," he said. This study was designed to show "clinical effectiveness."
Just under 800 pregnant women were included in the cohort from centers in Sweden, the UK, and the US. All women either had diagnostic testing or were followed to birth, and the newborns were evaluated for aneuploidies.
Testing was performed in Ariosa's laboratory. Ariosa's Harmony test analyzes only chromosomes 21, 18, and 13 using its custom targeted assay, DANSR. The products of the assay are then hybridized to a custom array — Affymetrix's GeneTitan multi- channel instrument. The firm then uses its FORTE algorithm to calculate risk scores. Samples with a 1 percent or higher score are classified as high risk and samples with a risk score below 1 percent are classified as low risk. In addition, Ariosa also calculates the fraction of fetal DNA in a sample by analyzing 576 SNPs.
In the study, the women's median age was 36 years, and on average, women were getting the test at 16 weeks gestation. Of the 799 pregnancies, 759 were singletons and 40 were twins. Five women had become pregnant from in vitro fertilization.
From the 799 samples, eight, or 1 percent, did not have enough fetal DNA to calculate a risk score. For the remainder, the median fetal fraction per sample was 13.8 percent.
The test classified all 641 euploid pregnancies correctly as low risk. Of the 108 samples clinically diagnosed with trisomy 21, one was missed. Of the 30 samples diagnosed as trisomy 18, the Harmony test classified 29 of them as high risk. Ariosa subsequently re-examined the pure fetal DNA to which it had access. Its test still found the sample to be euploid, suggesting that the clinical diagnosis of trisomy 18 may have been incorrect, the authors wrote.
Musci said that thus far customers' response to the switch to a microarray from NGS analysis has been positive. "The labs see a lot of advantages," he said.
"We've achieved faster turnaround times, which has made a clinical impact, while keeping at least the same accuracy," he added.
In its previous study, the firm found that analysis via microarray could be done in 7.5 hours versus 56 hours using NGS.
Clinically, Musci said that using the microarray-based test, results can be delivered as quickly as 36 hours of sample receipt.
Ariosa is also in the process of bringing its Harmony test through CE-IVD clearance. Already, its FORTE algorithm is CE-marked, and Musci said the company would have "additional announcements around CE-IVD" in the coming months.
The company is also "actively considering" bringing the test through US Food and Drug Administration clearance, Musci said. He declined to say definitively whether this was a goal of the company, but said that "it fits into our overall commitment to bringing this test forward and broadening access."
In addition, Roche's acquisition of Ariosa has been a "positive development" given the company's experience in the diagnostic space, Musci said.
Ariosa has also recently begun licensing its technology to labs in other countries so that they can run the test in their own labs, which "a lot of our large customers have an interest in doing," Musci said. In addition, "enabling regional laboratories has certainly boosted market share in those regions and is generally attractive for both patients and clinicians to have it close," he said. Achieving CE-IVD registration will help further that process of enabling labs to perform the test themselves. Last month, the company licensed its test to Sonic Healthcare, which will make Harmony available in Australia and the UK.
Ariosa's goal has always been to deliver a test that women can use regardless of their pregnancy risk at a low cost. It pursued a targeted strategy focusing on just the three chromosomal abnormalities for this reason, and unlike Sequenom never required ordering physicians to specify characteristics of the pregnancy that made it high risk as a reason for ordering the test. Previously, Ariosa had contracted with some as an in-network provider to offer its test for $795. A recent study sponsored by Ariosa found that when NIPT is offered to the general population it is more economical than first trimester screening when it costs $453 or less.
Musci declined to disclose the current price of its test and whether it offered it at the $453 rate that was determined to be cost effective, but he said that customer pricing varies depending on factors such as test volume and the term of the contract.