The story has been updated to include comments from Counsyl.Â
SAN FRANCISCO (GenomeWeb) – Earlier this month, Quest Diagnostics launched an expanded carrier screening test that uses next-generation sequencing to screen for 22 heritable diseases. Quest's offering is the latest entry in the growing market of NGS-based carrier screening tests that includes providers such as Good Start Genetics, Counsyl, and GenePeeks.
The NGS-based carrier screening market has grown rapidly over the last few years, as sequencing costs have declined and demand for such information has grown. Individuals now have a range of options for testing — from tests for only cystic fibrosis to panels that cover hundreds of disorders.
Quest's QHerit expanded carrier screening test will be applicable for any couple considering having a child, said Felicitas Lacbawan, executive medical director for advanced diagnostics at Quest Diagnostics.
In addition, the QHerit test builds on more than 10 years' experience by Quest of offering more limited, ethnic-specific carrier screening panels and single-disease tests. "The physicians and healthcare workers we serve wanted more expanded panels," Lacbawan said. And, as a large reference laboratory that already serves one out of two physicians and has 2,000 patient service centers throughout the country, Quest thinks that its test will have broad reach.
Quest uses next-generation sequencing on Illumina's MiSeq instrument for the majority of the disorders. For Fragile X, it uses PCR and Sanger sequencing, and for spinal muscular atrophy, it uses quantitative PCR to determine copy number status of the SMN1 gene. Fragile X, which is a repeat expansion disorder, and SMA are both difficult to detect via NGS, Lacbawan said, due to the short read lengths.
In addition, Quest will continue to offer its single-gene carrier tests. "Some clinicians want to use our older tests, so even though QHerit was created because of suggestions from customers, we won't be discontinuing any of the other tests," she said.
Lacbawan said that Quest chose which disorders to include on its panel based largely on recommendations from the American College of Obstetricians and Gynecologists, as well as other key opinion leaders.
In February, ACOG issued an opinion on the use of expanded carrier screening and included 22 disorders that it said met its recommended criteria for being included on a panel. Quest's QHerit panel includes the majority of those disorders.
Quest's offering is somewhat middle-of-the-road when it comes to the number of disorders it analyzes. On the upper end of the spectrum is GenePeeks, whose test looks at around 1,000 monogenic disorders that manifest in childhood. The company primarily markets to fertility clinics and includes a proprietary method called Virtual Progeny Analysis, whereby it predicts disease phenotypes of couples based on their test results.
Taking a more conservative approach is Good Start Genetics, which breaks down its carrier screening panel into common, pan-ethnic disorders, ethnicity-specific hemoglobinopathies, and disorders that are most common among Ashkenazi Jewish populations. It enables patients and physicians to select which disorders to include on their panel. Good Start Genetics, though, is focused not only on fertility clinics, but markets its test to the Ob-Gyn community. It also has a marketing partnership with Roche Diagnostics and sells its test through Amazon.
Molecular diagnostic firm Counsyl offers a carrier screening test that is more comprehensive than Good Start Genetics' but not quite as large as GenePeeks' test. Recently, it expanded its Foresight carrier screening test to include more than 175 conditions, up from 94 in a previous version. The company said that its scientists evaluated more than 600 disorders, but ultimately settled on around 175 that would be the most actionable and removed some genes previously included but that the company ultimately classified as having "mild" severity or that the firm found had "questionable clinical utility due to reduced penetrance based on our experience in screening patients," James Goldberg, chief medical officer at Counsyl, said in an email.
Such differences among the tests result in price differences and variability in insurance coverage. GenePeeks' test, for instance, is not in-network with payors and the company said last month that it would offer it at an introductory price of $950.
By contrast, Quest said that it estimated that for 75 percent of its patients, the QHerit test would be covered by insurance and patients would have out-of-pocket costs of $25 or less. Good Start Genetics has contracts with payors that include 130 million covered lives. Counsyl is also an in-network provider for many large national payors and has around 250 million lives covered under contract.
Mount Sinai Health System spinout Sema4 also offers several options for carrier screening: an expanded panel that includes more than 200 disorders; a standard panel that includes just cystic fibrosis, SMA, and Fragile X; as well as an Ashkenazi Jewish-specific panel. Pathway Genomics, too, offers carrier screening for more than 120 conditions.
Counsyl's Goldberg said that the growth in expanded carrier screening, which is due in part to reduced costs for sequencing, enables patients who previously would not have been tested to gain access: "providers can offer screening to patients of all ethnicities," he said. That's important, he said, citing a previous study by Counsyl that found that "for some ethnicities, such as East Asian and Middle Eastern, carrier screening guidelines were potentially missing more than 90 percent of pregnancies affected by serious hereditary conditions."
However, the wide and ever-growing number of tests on the market has caused some concerns and is what prompted ACOG to issue guidance on how to use such tests.
"Patients have the ability now to choose no testing or testing for hundreds of disorders that they may never have even considered before," said Britton Rink, an Ob-Gyn on ACOG's genetics committee. Rink said that has led to both the opportunity for couples to get valuable information as well as the possibility for confusion.
ACOG's opinion stops short of recommending expanding carrier screening for everyone, although it says that such tests are "acceptable strategies." It does recommend offering screening for cystic fibrosis and SMA for all patients, and Fragile X for patients with a family history. And, for expanded carrier screening panels, ACOG recommends certain criteria when deciding what conditions to include. For instance, conditions should have a carrier frequency of one in 100 or greater, a well-defined phenotype, and be serious and early-onset disorders.
The purpose of the opinion "was to provide some information and guidance to providers that they could use when counseling patients," Rink said.
She said her main concern was that patients would receive expanded carrier screening without being properly informed about the test, the potential results, and what those results would mean. Because panel-based testing is now comparable in price to testing for a single disorder, she worries patients who may just want cystic fibrosis testing may opt for a larger panel that includes cystic fibrosis, but also 50 other disorders, because it is the same price. "And some conditions may have variable expressivity or poorly defined frequencies," she said, which makes it "hard to calculate residual risk and makes me worry that patients' understanding is not truly an informed consent."
Nonetheless, she said, the rapid expansion of genomic testing "reflects where we are in modern medicine. It allows patients to have the option of more information that they may want to make reproductive choices."