NEW YORK (GenomeWeb) – Recognizing that a growing number people are choosing to buy genetic testing online instead of waiting for their doctors to order it for them, PerkinElmer and NorthShore University HealthSystem this week announced that they, too, are exploring the consumer genomics market.
"We recognize that access to genetic information still remains an issue, and for a growing number of people, their first touch point to getting genetic information is through novel ways of delivery," said Peter Hulick, director of NorthShore's Center for Personalized Medicine.
Driven largely by interest in ancestry genetic testing, it is now estimated that 12 million people have purchased services from a consumer genomics firm, and more than half of those people became first-time customers last year. "Partnering with companies like Helix helps to bridge the gap between traditional medicine and this new avenue for genetic risk assessments," Hulick said.
PerkinElmer and NorthShore have partnered with personal genomics firm Helix in an effort to expand consumers' ability to access health-related insights online. The online genomics marketplace launched by Helix in 2017 employs a model whereby Helix sequences customers' exomes once, enabling app developers to interpret portions of the data to serve different consumer interests.
At the end of 2017, the marketplace featured around 35 products that interpreted customers' genomic data for recreational purposes, and in the context of their health, fitness, nutrition, family, and ancestry. The company said last month that it intends to use an anticipated $200 million in raised funds to increase the number of apps in its marketplace this year to around 50, focusing particularly on health-related apps.
The latest announcement from PerkinElemer and NorthShore are in line with that strategy. The first app PerkinElmer is developing with Helix will report pathogenic and likely pathogenic variants in 59 genes that the American College of Medical Genetics and Genomics (ACMG) had identified as actionable, disease-linked biomarkers. NorthShore will apply the genetic risk score developed by Jianfeng Xu, NorthShore's VP of translational research, to report a polygenic prostate cancer risk score. Both partners hope to follow up these initial offerings with additional apps.
The partnership with Helix comes as PerkinElmer, a company specializing in newborn screening and high-throughput, next-generation sequencing for rare inherited diseases, is expanding its whole-genome and -exome sequencing capabilities. Last year, the company's PerkinElmer Genetics unit started offering WES and WGS for diagnosing genetic diseases in newborns and then extended WGS services to healthy children of families who are customers of ViaCord, its cord blood and tissue banking business.
Market research conducted as part of those offerings indicated that adults were very interested in knowing actionable genetic testing results, information that would allow them to be more proactive about their health. "Parents particularly are more inquisitive and curious about getting their genome sequenced before extending it out to their children," said Madhuri Hegde, VP and chief scientific officer for lab services within PerkinElmer Diagnostics.
Since joining PerkinElmer at the end of 2016 from Emory Genetics Laboratory, Hegde has focused on expanding the company's footprint in clinical next-generation sequencing and readying a proprietary variant evaluation pipeline called the Ordered Data Interpretation Network. The pipeline automates aspects of the variant classification process, but because it's set up in an "ordered format," Hegde explained that experts in data curation also review the accumulated evidence on the variants at different stages of the curation process.
Because WES or WGS approaches will detect numerous variants, correct interpretation is a particularly critical piece of the testing process, particularly in a consumer-facing product. Hegde said her team has spent a lot of time setting up the curation and interpretation infrastructure at PerkinElmer.
Analysis of public variant databases such as ClinVar has shown classification calls taken from the published literature or the gene catalog Online Mendelian Inheritance in Man tend to overcall variants as pathogenic that upon reevaluation turn out benign. "We all know even in BRCA1 and BRCA2 genes there are truncating variants that are not pathogenic. They're actually benign," Hegde said as an example. "We want to avoid these kinds of errors."
To address this issue, PerkinElmer's interpretation pipeline grabs information on variants from the literature and makes automated calls. "But we don't go by that," Hegde said. The final classification calls are ultimately made by American Board of Medical Genetics and Genomics-certified experts who investigate the variant against all the available evidence.
NorthShore, meanwhile, will enter the Helix marketplace with a SNP-based prostate cancer genetic risk score that tells individuals if they are at heightened risk for the disease compared to the general population. "Much of the genetic risk for cancers is not captured by single genes" that are known to significantly increase an individual's chances of getting the disease, such as BRCA1 and BRCA2, said Hulick. As such, there has been growing interest in looking at polygenic risk scores, where individual SNPs confer a small risk, but in the aggregate, they have an impact large enough to influence patient management.
The performance of the genetic risk score has been evaluated in prostate cancer and it has shown to be an independent predictor of risk, and that it can supplement family history to better identify high-risk patients. Hulick believes the risk score could help advance tailored prostate cancer screening approaches, not just for those at high risk but also for those at lower risk compared to the general population. NorthShore is conducting studies to explore the risk score's utility in this regard.
NorthShore has also been working with a number of clinical labs, including Invitae and Ambry Genetics, to explore different channels for commercializing the risk score, and the Helix marketplace offers another avenue. However, NorthShore's app through Helix will not tell customers if they harbor other risk factors associated with prostate cancer, including high-penetrance mutations in genes such as BRCA2.
"So, that's where it's important that as part of this ordering process [for the app] there will be a screening questionnaire, physician review, and availability of genetic counseling, because it may be a better first step to first do germline testing for hereditary cancer risk genes, and then [genetic risk score] testing," Hulick noted.
PerkinElmer and NorthShore both said that they're still figuring out the details around how results will be communicated to consumers. However, in general, when customers purchase health-related apps on the Helix marketplace, they fill out a questionnaire to determine if testing is appropriate for them.
For example, PerkinElmer's product reporting on pathogenic variants in 59 gene is not intended for people with known risk factors of an inherited disease, including a family history of an illness, or those with a diagnosed genetic condition who'd benefit from more comprehensive evaluation. The customer questionnaire will try to parse who can receive testing and who can't. Physicians who are part of a third-party network — who are familiar with the product but aren't the individual's own doctor — will review the questionnaire to determine which orders to approve and which to deny.
If approved, the analysis is performed and results are reported to customers directly via the partner's app or website. Customers are then free to discuss the results with the partner organization, their own doctor, or receive genetic counseling, which is provided at no additional cost for health-related apps on Helix.
Although Helix and its partners have maintained that this model appropriately involves healthcare professionals, the third-party network physicians employed to review and approve test orders don't necessarily have a relationship with the patient. As such, this type of consumer-facing testing model has been criticized as a way to avoid triggering the US Food and Drug Administration, which in 2013 took a hard stance against 23andMe's health-related direct-to-consumer offerings and only recently started authorizing access to certain reports after the company submitted its tests for review.
Even when 23andMe relaunched the DTC offering for certain genetic health risk tests last year with FDA authorization, many in the clinical genetics community felt that such testing should not be offered without the involvement of a knowledgeable expert, because there is a risk that people could get an incomplete picture of their genetic predisposition for serious diseases. ACMG issued a statement in this regard and pointed out to GenomeWeb that FDA's authorization goes against its practice guidelines for APOE4 testing for Alzheimer's risk and hereditary hemochromatosis.
Reflecting on PerkinElmer's plans to develop an app to report pathogenic variants in 59 genes, ACMG CEO Mike Watson noted that the group has a committee in charge of maintaining the list of actionable genes. "As more data come in and new treatments continue to become available, not only will additional genes be added to the list, but some could be removed," he noted.
Moreover, he pointed out that most of the information on genetic diseases comes from clinically affected people who seek out medical care and tend to be more severely affected. "Data on how tests perform in screening in asymptomatic people is only developing now," Watson said, adding that the ACMG stands by its position that ordering and interpretation of such tests benefits from the involvement of trained and experienced providers.
Hegde was careful to differentiate PerkinElmer's goals in entering the consumer genomics space from companies that offer direct-to-consumer genetic testing for traits like ear wax quality and ancestry. "This is not a DTC product. We realize this cannot be a DTC product, and we're not interested in doing that," Hegde said with regard to the app for reporting the 59 genetic variants. "This is a true diagnostic test."
Hulick also maintained that the physician review process enables identification of information in the test order, such as family history or criteria laid out in expert guidelines, that would flag individuals who should not receive information through the app.
Meanwhile, the Helix app will extend strategies that NorthShore has already employed within its patient community. For example, through the NorthShoreConnect app patients can message their doctors, manage prescriptions, and view lab results. The health system has also put together videos to help patients understand what certain test results mean.
Similarly, NorthShore and PerkinElmer will develop genetic counseling bots and educational videos to support Helix customers.