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Expanding Beyond Germline Tests, NIH GTR Lists Multi-Analyte Algorithm Assay; Planning for Exome Dx


Originally published May 20.

NEW YORK (GenomeWeb) – The US National Institutes of Health's Genetic Testing Registry officially expanded its scope this spring from listing diagnostics that gauge germline mutations associated with inherited diseases and pharmacogenetic tests to including assays that gauge somatic gene markers.

To date, the GTR includes approximately 400 registered labs that have submitted more than 17,000 tests, mostly for germline targets. In recent months, labs have added 128 tests that gauge somatic targets, as well as several hundred next-generation sequencing tests. And this week, Genomic Health announced that healthcare providers can also find information about its Oncotype DX breast cancer recurrence test on the registry. The company touted it as the first multi-analyte algorithm-based cancer diagnostic to be featured on GTR.

The NIH began developing the GTR in 2010 in an attempt to create a single and more complete repository of genetic tests. The GTR precursor, GeneTests, only listed tests for Mendelian disorders. The GTR, managed by NIH's National Center for Biotechnology Information, started off listing only germline tests for Mendelian disorders and PGx tests, but is now steadily expanding its scope to include all varieties of genetic tests.

The NIH enabled the GTR to be able to accept somatic test listings in September, and since then, NIH officials had been working with labs that want to list such tests. When rolling out a new feature like this for the site, GTR very much depends on early adopter labs that are willing "to roll up their sleeves" and work out the development issues with NIH, according to Wendy Rubinstein, director of the registry. Genomic Health played that early adopter role when it came to open GTR up for inclusion of somatic tests.

Since last year, Genomic Health has worked with the NIH to add capabilities to the GTR, so that the registry could better handle the types of data that would need to be submitted on so-called multi-analyte algorithm based assays (MAAA), such as Oncotype DX. "Adding somatic tests is a new development. There is a lot that's in common with the germline tests, but we've had to make sure that [we're ready for] the type of data that all the labs are going to send in," Rubinstein told PGx Reporter.

"Genomic Health was willing to work with us to fill out a test record very deeply, fill in every single field, and submit types of data we hadn't seen before," she said. For example, the GTR needed to add terms to describe whether the multi-analyte somatic tests were for disease "monitoring" or "prognosis," which doesn't come up that often for germline tests. Rubinstein noted that although Genomic Health's Oncotype DX is the first somatic MAAA listed on the GTR, the site also lists a germline breast cancer susceptibility test developed by Phenogen Sciences Laboratories, called BREVAGen, that would fall into this test category.

"As new discoveries about the human genome continue to inspire medical innovations, we are proud to showcase how well-designed validation and utility studies can be translated into a practice-changing test like Oncotype DX," Phil Febbo, Genomic Health's CMO, told PGx Reporter. "This is also another way to make the wealth of information confirming the value of Oncotype DX accessible by healthcare providers and patients who are seeking accurate, credible information about genomic tools."

The global genetic testing market is growing at breakneck speed and is projected to be valued at just under $2 billion by next year, but the rapidly expanding molecular testing field makes it a challenge for healthcare providers to keep abreast of new tests and emerging technologies.

"The GTR is really there for clinicians to come to our site and order tests," Rubinstein said. "And we have to make sure it is simple and easy for labs to submit data, for example, by using a new spreadsheet which accommodates all of the fields." In this regard, GTR has developed advanced search functions that allow users to find specific tests using different terms, such as "somatic" and "germline," without knowing the brand name of the test.

As they expand the scope of GTR, NIH officials in recent months have been reaching out to test makers that are members of the interest group AdvaMedDx, large reference labs, and developers of NGS-based tests, inviting companies to submit data on tests that are not listed on the site and on tests that would require new development in order to be listed on the site. NIH officials keep a close watch on how the genetic testing field is changing, and often the tests listed on the GTR can provide a good barometer. For example, Rubinstein noted that despite the relatively recent emergence of an advanced sequencing panel cleared by the US Food and Drug Administration, approximately 8 percent of the molecular tests on the site use NGS.

"With the growing use of genomics in cancer, there is a need for transparency and accessibility to the clinical and scientific data supporting each assay," Genomic Health's Febbo said. "The GTR provides a public resource for investigators, healthcare providers, and patients."

Still, listing a test on the GTR is voluntary, and getting labs to invest the time to create accurate and informative listings on their tests can require some encouragement. A few years ago, while the NIH was building the GTR, the agency estimated it would take each submitter 30 minutes to input data in the 31 minimal fields for one test and 2.5 hours to fill in the optional sections. The NIH further estimated that if the average submitter input information for 12.2 tests, the overall hourly burden per respondent will be 36.6 hours annually if all fields are completed.

With updates to GTR submissions methods, such as the use of spreadsheets that automatically upload to the site, the time commitment for labs may be reduced. NIH wasn’t able to provide updated figures by press time.

"It takes a lot for a lab to say, 'OK, I have the time and resources to devote to this," Rubinstein reflected. "Because you know what's happened to these labs in the last couple of years. They're really being hit hard with requirements to submit evidence on new codes and their reimbursement has been cut."

The next area of focus for NIH will be to figure out how to list whole-genome and exome sequencing tests. "We're starting to design what an actual test registration of an exome would look like," Rubinstein said. "So, we've started to talk to people about that and ask our advisors about that."

Separately, NIH's ClinVar database and the GTR have been using a common database, which is allowing synergies between the two resources. The NIH announced last year that it would build a public, annotated database of variants across the human genome using standardized classification methods, called the Clinical Genome Resource (ClinGen). ClinVar is the centralized repository of genotype-phenotype information for ClinGen, and currently includes more than 100,000 submissions on more than 18,000 genes and 100,000 gene variations.

Rubinstein explained that NCBI centrally tracks GTR and ClinVar submitters. "We're now doing new development, so when they come in through one or the other, the common data elements can be shared. Laboratories can designate submitter permissions for their staff so the experience will be smoother as well," she said. "We have highlighted in [the] GTR who the ClinVar submitters are, but we're going to make that more prominent as well."