As consumer demand increases for medical laboratory testing services that bypass the supervision of primary care doctors, clinical laboratories may be affected
Direct-to-consumer (DTC) genetic testing organizations and telecommunications companies in South Korea are collaborating to help consumers stay informed of their health status by sending lab test results directly to their mobile devices without requiring physician involvement. What can labs in the West learn from these developments?
Founded in 2015, NGeneBio provides smartphone-based healthcare services for individuals who solicit genetic testing. Through the partnership, KT plans to combine its knowledge of artificial intelligence (AI) and cloud computing with NGeneBio’s genetic decoding expertise to “provide services such as tailored health management (diet and exercise therapy) services, and storage and management of personal genome analysis information.”
No Doctors Involved?
Outside of genealogy, the general intent of DTC genetic testing is to equip consumers with certain genetic data that may help them manage their healthcare without requiring visits to their healthcare provider. The healthcare information provided through the NGeneBio venture will include data delivered directly to customers’ smartphones on the status of their:
skin,
hair,
nutrition, and
muscular strength.
According to an article in Korean business news publication Pulse, “Genetic test services in Korea are restricted to some 70 categories, such as the analysis of the risk of hair loss, high blood pressure, and obesity.”
Last September, Pulse reported, Korean mobile carrier SK Telecom Co. announced a similar partnership with Macrogen Inc. to introduce a mobile app-based DNA testing service called “Care8 DNA.” To utilize this service, consumers order a DNA test kit, take a saliva sample via mouth swab, and then send the kit to a clinical laboratory for analysis. Users typically receive their test results on the Care8 DNA app (available from both Google Play and Apple’s App Store) within a few weeks.
The service costs ₩8,250 South Korean won ($7.36 US) per month. A one-year subscription to the service costs ₩99,000 won or $88.36 US. The Care8 DNA app features 29 testing services, including:
skin aging,
possibility of hair loss,
resistance to nicotine,
the body’s recovery speed after exercise,
and more.
Along with those results, consumers can receive personalized health coaching guidance from professionals like nutritionists and exercise physiologists to improve their overall wellbeing, Pulse noted.
KoreaTechToday reports that the Macrogen/SK Telcom Care8 DNA app (above) “links the consumer immediately to a gene testing company instead of going through a medical institute first. BIS Research [a marketing research and intelligence company located in Freemont, Calif.] estimates the global direct-to-consumer (DTC) gene test market would increase to ₩7.6 trillion won in 2028.” That is more than $6.7 billion US dollars. Such a shift toward DTC home testing would likely have a huge financial impact on clinical laboratories that process genetic tests as well as the healthcare providers who order them. (Photo copyright: SK Telecom Co.)
In February 2019, Macrogen became the first company in South Korea to take advantage of the government’s relaxed regulations on DTC genetic testing, Korea Biomedical Review reported. In addition to the basic services offered through the Care8 DNA app, Macrogen’s DTC tests also can cover 13 diseases, including:
Other Korean Genetic Testing Companies Adding DTC Services
“Industry officials think DTC genetic tests should include testing for diseases,” an industry official told Korea Biomedical Review in April. “There will be more companies who make these attempts.”
“A DTC genetic test is a contactless healthcare service suitable for the COVID-19 era. The expansion of detailed test items allows users to comprehensively check nutrients, obesity, skin, hair, eating habits, and exercise characteristics at one time,” an official at Theragen Bio told Korea Biomedical Review. “We expect that our service will attract more attention from consumers.”
What Can Be Learned?
Countries in Asia—particularly South Korea, Japan, and Taiwan—are among the fastest adopters of new technology in the world. Thus, it can be instructive to see how their consumers use healthcare differently than in the West, and how those users embrace new technologies to help them manage their health.
It is not certain how all this will impact clinical laboratories and genetic doctors in the western nations. Direct-to-consumer genetic testing has had its ups and downs, as Dark Daily reported in multiple e-briefings.
Nevertheless, these developments are worth watching. Worldwide consumer demand for genetic home testing, price transparency, and easy access to test results on mobile devices is increasing rapidly.
At-home genetic test kits face scrutiny for providing information that may provide consumers with an incomplete picture of their genetic health risks and ancestry
Genetic testing for disease risk and heritage are hugely popular. But though clinical laboratory and pathology professionals understand the difference between a doctor-ordered genetic health risk (GHR) test and a direct-to-consumer (DTC) genetic test, the typical genetic test customer may not. And misunderstanding the results of a DTC at-home genetic test can lead to confusion, loss of privacy, and potential harm, according to Consumer Reports.
To help educate consumers about the “potential pitfalls” of at-home DTC testing kits offered by companies such as Ancestry and 23andMe, Consumer Reports has published an article, titled, “Read This Before You Buy a Genetic Testing Kit.” The article covers “four common claims from the manufacturers of these products, whether they deliver, and what to know about their potential pitfalls.”
Are Genetic Ancestry Tests Accurate?
Ancestry and 23andMe are the DTC genetic test industry leaders, with databases of genetic information about 18 million individuals and 10 million individuals respectively. According to a Consumer Reports survey, as of October 2020 about one in five Americans had taken a DTC genetic test. Reported reasons for doing so included:
66% of respondents wanted to learn more about their ancestry.
20% wanted to locate relatives.
18% wanted to learn more about their health.
11% wanted to learn if they have or are a carrier for any medical conditions.
3% wanted to get a medical test they could not get through their doctor.
Though DTC genetic tests remain popular, Consumer Reports is now warning consumers to view the genealogical or medical insights gleaned through these tests with caution. “If you go in there thinking that this test is going to tell you who you are, you’re going to be wrong,” Wendy Roth, PhD (above), Associate Professor of Sociology at the University of Pennsylvania, told the publication. (Photo copyright: University of Pennsylvania.)
As Consumer Reports notes, doctor-ordered genetic health risk (GHR) testing typically aims to answer a specific question about a patient’s risk for a certain disease. DTC at-home genetic testing, on the other hand, examines a “whole range of variants that have been linked—sometimes quite loosely—to a number of traits, some not related to your health at all.
“Think of it this way: When your doctor orders genetic testing, it’s akin to fishing for a particular fish, in a part of the ocean where it’s known to live,” Consumer Reports noted, “A DTC test is more like throwing a net into the ocean and seeing what comes back.”
In its article, Consumer Reports addressed four common DTC genetic test claims:
The Tests Can Find Far-Flung Relatives: While the tests can unearth people in its database whom you might be related to, 9% of respondents in the Consumer Reports survey discovered unsettling information about a relative.
Testing Can Uncover Where Your Ancestors Are From: Genetic tests may show the percentage of your DNA that comes from Europe or Asia or Africa, but accuracy depends on how many DNA samples a company has from a particular region. As genetic test manufacturers’ reference databases widen, a customer’s genetic ancestry test results can “change over time.” Also, finding a particular variation in genetic code does not definitively place someone in a specific region, or ethnic or racial group.
Genetic Tests Can Reveal Your Risk for Certain Diseases: Testing companies such as 23andMe are authorized by the Food and Drug Administration (FDA) to offer physician-mediated tests, which are analyzed in a federally-certified clinical laboratory. However, test results may provide a false sense of security because DTC tests look for only select variants known to cause disease.
The Tests Can Tell What Diet Is Best for You: Incorporating genetic information into diet advice has the potential to be transformative, but the science is not yet there to offer personalized nutritional advice.
Consumer Reports pointed to a 2020 study published in the MDPI journal Nutrients, titled, “Direct-to-Consumer Nutrigenetics Testing: An Overview,” which evaluated 45 DTC companies offering nutrigenetics testing and found a need for “specific guidelines” and “minimum quality standards” for the services offered. For example, the study authors noted that more than 900 genetic variants contribute to obesity risk. However, weight-loss advice from DTC test companies was based on a “limited set of genetic markers.”
In the Consumer Reports article, Mwenza Blell, PhD, a biosocial medical anthropologist and Rutherford Fellow and NUAcT Fellow at Newcastle University in the United Kingdom, said “genetic ancestry tests are closer to palm reading than science.”
Seattle Cancer Care Alliance and an Associate Professor of Oncology at the University of Washington, fears consumers “miss important limitations on a test’s scope” or “misunderstand critical nuances in the results.”
Cheng says the ability to use flexible or health savings accounts (HSAs) to cover the cost of 23andMe’s GHR assessments, as well as the FDA’s approval of 23andMe’s Personal Genome Service Pharmacogenetic Reports test on medication metabolism, may have added to the confusion.
“This may further mislead people into thinking these tests are clinically sound. Again, they are not,” Cheng wrote.
As an oncologist, Cheng is particularly concerned about consumer GHR testing for heritable cancer risk, which screen for only a handful of genetic variants.
“The results are inadequate for most people at high risk of cancers associated with inherited mutations in BRCA1 or BRCA2 genes, including families whose members have experienced ovarian cancer, male breast cancer, multiple early breast cancers, pancreatic cancer, or prostate cancer,” Cheng wrote. “Put simply, this recreational test has zero value for the majority of people who may need it for true medical purposes.”
DTC genetic health-risk assessments may one day lead to consumers collecting samples at home for tests that aid in the diagnosis of disease. In the meantime, clinical laboratory professionals can play a role in educating the public about the limitations of current DTC genetic test offerings.
By offering DTC preventative gene sequencing, hospital leaders
hope to help physicians better predict cancer risk and provide more accurate
diagnoses
Two Boston health systems, Brigham and Women’s Hospital and Massachusetts General Hospital (MGH), are the latest to open preventative gene sequencing clinics and compete with consumer gene sequencing companies, such as 23andMe and Ancestry, as well as with other hospital systems that already provide similar services.
This may provide opportunities for clinical laboratories. However, some experts are concerned that genetic sequencing may not be equally available to patients of all socioeconomic classes. Nor is it clear how health systems plan to pay for the equipment and services, since health insurance companies continue to deny coverage for “elective” gene sequencing, or when there is not a “clear medical reason for it, such as for people with a long family history of cancer,” notes STAT.
Therefore, not everyone is convinced of the value of gene sequencing to either patients or hospitals, even though advocates tout gene sequencing as a key element of precision medicine.
Is Preventative Genetic Sequencing Ready for the Masses?
Brigham’s Preventive Genomics Clinic offers comprehensive DNA sequencing, interpretation, and risk reporting to both adults and children. And MGH “plans to launch its own clinic for adults that will offer elective sequencing at a similar price range as the Brigham,” STAT reported.
The Brigham and MGH already offer similar gene sequencing services as other large health systems, such as Mayo Clinic and University of California San Francisco (UCSF), which are primarily used for research and cancer diagnoses and range in price depending on the depth of the scan, interpretation of the results, and storage options.
However, some experts question whether offering the
technology to consumers for preventative purposes will benefit anyone other
than a small percentage of patients.
“It’s clearly not been demonstrated to be cost-effective to promote this on a societal basis,” Robert Green, MD, MPH, medical geneticist at Brigham and Women’s Hospital, and professor of genetics at Harvard, told STAT. “The question that’s hard to answer is whether there are long-term benefits that justify those healthcare costs—whether the sequencing itself, the physician visit, and any downstream testing that’s stimulated will be justified by the situations where you can find and prevent disease.”
Additionally, large medical centers typically charge more
for genomic scans than consumer companies such as 23andMe and Ancestry. Hospital-based
sequencing may be out of the reach of many consumers, and this concerns some
experts.
“The idea that genomic sequencing is only going to be
accessible by wealthy, well-educated patrons who can pay out of pocket is
anathema to the goals of the publicly funded Human Genome Project,” Jonathan
Berg, MD, PhD, Genetics Professor, University of North Carolina at Chapel
Hill, told Scientific
American.
And, according to the American Journal of Managed Care, “It’s estimated that by 2021, 100 million people will have used a direct-to-consumer (DTC) genetic test. As these tests continue to gain popularity, there is a need for educating consumers on their DTC testing results and validating these results with confirmatory testing in a medical-grade laboratory.”
This is why it’s critical that clinical laboratories and
anatomic pathology groups have a genetic testing and gene sequencing strategy,
as Dark
Daily reported.
David Bick, MD, Chief Medical Officer at the HudsonAlpha Institute for Biotechnology and Medical Director of the Smith Family Clinic for Genomic Medicine, told Scientific American, “there’s just more and more interest from patients and families not only because of 23andMe and the like, but because there’s just this understanding that if you can find out information about your health before you become sick, then really our opportunity as physicians to do something to help you is much greater.”
In an article he penned for Medium, Robert Green, MD, MPH (shown above counseling a patient), medical geneticist at Brigham and Women’s Hospital and professor of genetics at Harvard, wrote, “The ultimate aim of our Genomes2People Research Program is to contribute to the transformation of medicine from reactive to proactive, from treatment-oriented to preventive. We are trying to help build the evidence base that will justify societal decision to make these technologies and services accessible to anyone who wants them, regardless of means, education or race and ethnicity.” (Photo copyright: Wall Street Journal.)
Is Preventative Genomics Elitist?
As large medical centers penetrate the consumer genetic
testing market some experts express concerns. In a paper he wrote for Medium,
titled, “Is Preventive Genomics Elitist?” Green asked, “Is a service like this
further widening the inequities in our healthcare system?”
Green reported that while building the Preventive Genomics Clinic at Brigham, “we … struggled with the reality that there is no health insurance coverage for preventive genomic testing, and our patients must therefore pay out of pocket. This is a troubling feature for a clinic at Brigham and Women’s Hospital, which is known for its ties to communities in Boston with diverse ethnic and socioeconomic backgrounds.”
Most of Brigham’s early genetics patients would likely be “well-off,
well-educated, and largely white,” Green wrote. “This represents the profile of
typical early adopters in genetic medicine, and in technology writ large. It
does not, however, represent the Clinic’s ultimate target audience.”
More Data for Clinical Laboratories
Nevertheless, preventive genomics programs offered by large
health systems will likely grow as primary care doctors and others see evidence
of value.
Therefore, medical laboratories that process genetic
sequencing data may soon be working with growing data sets as more people reach
out to healthcare systems for comprehensive DNA sequencing and reporting.
This is not the first time genetic-testing company Orig3n has been scrutinized by state and federal investigators over its business practices
It’s not often that multiple employees of a clinical laboratory company go public with criticism about the quality of their lab company’s tests. But that is what is happening at Orig3n. Problems at the Boston-based genetic testing company were the subject of an investigative report published by Bloomberg Businessweek (Bloomberg).
In September, Bloomberg reported that 17 former Orig3n employees said the company’s Deoxyribonucleic acid (DNA) tests sometimes failed to deliver the intended results or were often contaminated or inaccurate. The individuals had been employed by the company as managers, lab technicians, software engineers, marketers, and salespeople between 2015 and 2018.
The former employees claimed that Orig3n “habitually cut
corners, tampered with or fabricated results, and failed to meet basic
scientific standards,” Bloomberg reported. The individuals also stated
that advice intended to be personalized to individual consumers’ genetic
profiles was often just generic information or advice that had no scientific
basis.
According to Bloomberg, the individuals also alleged
that Orig3n’s lab was careless in its handling of genetic samples in several
ways, including:
Multiple samples being labeled with the same
barcode;
DNA and blood samples for stem cell bank
misplaced or mixed up;
No controls to ensure accuracy;
Handling methods that could lead to
contamination; and
Fabricating results when a test outcome was
unclear.
The former employees also stated that “Orig3n ran tests without proper authorization in its lab at the 49ers’ stadium, and that managers regularly compelled them to write positive reviews of Orig3n’s tests on Amazon.com and Google to offset waves of negative feedback,” Bloomberg reported.
“Accurate science didn’t seem to be a priority. Marketing
was the priority,” said a former lab technician who spoke with Bloomberg
on the condition of anonymity. Orig3n denied the accusations in a statement,
describing them as “grossly inaccurate,” and claimed the former employees were
simply disgruntled.
“In some cases, former employees are former employees for a reason,” Orig3n Chief Executive Officer Robin Smith told Bloomberg. “We’ve found after employees are gone that they have not done things appropriately.”
In 2018, NBC Chicago(NBC) conducted an investigation into various consumer DNA testing kits. NBC sent DNA samples to several different testing companies. This included non-human samples, which NBC’s investigators had obtained from a female Labrador Retriever.
With the exception of Orig3n, all of companies identified
the DNA as non-human and did not process the kits. Orig3n did, however, process
the canine DNA. It then returned a seven-page analysis that suggested the
subject of the sample “would probably be great for quick movements like boxing
and basketball, and that she has the cardiac output for long endurance bike
rides or runs,” NBC reported.
This would be funny if it weren’t so concerning.
Following reports that it had processed dog DNA, Orig3n stated
it had made changes and improvements to the company’s testing methodologies. Smith
also stated Orig3n’s lab protocols had been improved as well.
“Sometimes we look at the accuracy of things and go, ‘Man,
that’s not working,’” Smith told Bloomberg. “Our approach and our
philosophy is [sic] to constantly improve the products.”
Serious Accusations of Clinical Laboratory Malfeasance
Founded in 2014 with the intent of creating the world’s largest stem cell bank, by 2016, Boston-based Orig3n had refocused its attention on the burgeoning field of direct-to-consumer DNA testing. On its website, Orig3n sells several DNA-testing kits with varying costs.
Orig3n’s attempt to offer free genetic tests to large numbers of people at a professional sporting event in the fall of 2017 may be what caught the attention of federal investigators and led to a deeper investigation. Dark Daily previously covered this controversy, which centered around Orig3n’s plan to distribute free genetic testing kits to fans at a Baltimore Ravens football game.
In that situation, state and federal healthcare regulators blocked the giveaway over concerns about protected health information (PHI). Now, Orig3n is being accused of questionable business practices by 17 of its former employees.
The former employees’ statements that the company’s genetic
testing lab did not follow appropriate test protocols—and that it allegedly
mishandled specimens and even reported false test results—are serious
allegation of malfeasance and warrants an investigation.
Pathologists and clinical laboratory managers know that patient
harm can potentially result from inaccurate genetic test results if used for
clinical purposes. Dark Daily will continue to follow the investigation
into Orig3n.
Low prices to encourage consumers to order its WGS service is one way Veritas co-founder and genetics pioneer George Church hopes to sequence 150,000 genomes by 2021
By announcing an annotated whole-genome sequencing (WGS) service to consumers for just $599, Veritas Genetics is establishing a new price benchmark for medical laboratories and gene testing companies. Prior to this announcement in July, Veritas priced its standard myGenome service at $999.
“There is no more comprehensive genetic test than your whole genome,” Rodrigo Martinez, Veritas’ Chief Marketing and Design Officer, told CNBC. “So, this is a clear signal that the whole genome is basically going to replace all other genetic tests. And this [price drop] gets it closer and closer and closer.”
Pathologists and clinical laboratory managers will want to watch to see if Veritas’ low-priced, $599 whole-genome sequencing becomes a pricing standard for the genetic testing industry. Meanwhile, the new price includes not only the sequencing, but also an expert analysis of test results that includes information on more than 200 conditions, Veritas says.
“The focus in our industry is shifting from the cost of sequencing genomes to interpretation capabilities and that’s where our secret sauce is,” said Veritas CEO Mirza Cifric in a news release. “We’ve built and deployed a world class platform to deliver clinically-actionable insights at scale.” The company also says it “achieved this milestone primarily by deploying internally-developed machine learning and AI [artificial intelligence] tools as well as external tools—including Google’s DeepVariant—and by improving its in-house lab operations.”
The myGenome service offers 30x WGS, which Veritas touts in company documentation as the “gold standard” for sequencing, compared to the less-precise 0.4x WGS.
The myGenome service is available only in the United States.
Will Whole-Genome Sequencing Replace Other Genetic Tests?
Veritas was co-founded by George Church, PhD, a pioneer of personal genomics through his involvement with the Harvard Personal Genome Project at Harvard Medical School. In a press release announcing the launch of myGenome in 2016, Veritas described its system as “the world’s first whole genome for less than $1,000, including interpretation and genetic counseling.”
Church predicts that WGS will someday replace other genetic tests, such as the genotyping used by personal genomics and biotechnology company 23andMe.
“Companies like 23andMe that are based on genotyping technology basically opened the market over the last decade,” Martinez explained in an interview with WTF Health. “They’ve done an incredible job of getting awareness in the general population.”
However, he goes on to say, “In genotyping technology, you
are looking at very specific points of the genome, less than half of one
percent, a very small amount.”
Martinez says Veritas is sequencing all 6.4 billion letters
of the genome. And, with the new price point, “we’re closer to realizing that
seismic shift,” he said in the news release.
“This is the inflection point,” Martinez told CNBC.
“This is the point where the curve turns upward. You reach a critical mass when
you are able to provide a product that gives value at a specific price point.
This is the beginning of that. That’s why it’s seismic.”
Rodrigo Martinez (above), Veritas’ Chief Marketing and Design Officer, told CNBC, “The only way we’re going to be able to truly extract the value of the genome for a healthier society is going to be analyzing millions of genomes that have been sequenced. And the only way we can get there is by reducing the price so that more consumers can sequence their genome.” Photo copyright: Twitter.)
Payment Models Not Yet Established by Government, Private
Payers
However, tying WGS into personalized medicine that leads to actionable diagnoses may not be easy. Robin Bennett, PhD (hon.), a board certified senior genetic counselor and Professor of Medicine and Medical Genetics at UW School of Medicine, told CNBC, “[Healthcare] may be moving in that direction, but the payment for testing and for services, it hasn’t moved in the preventive direction. So, unless the healthcare system changes, these tests may not be as useful because … the healthcare system hasn’t caught up to say, ‘Yes, we support payment for this.’”
“Insurers are looking for things where, if you get the
information, there’s something you can do with it and that both the provider
and the patient are willing and able to use that information to do things that
improve their health,” Phillips told CNBC. “Insurers are very interested
in using genetic testing for prevention, but we need to . . . demonstrate that
the information will be used and that it’s a good trade-off between the
benefits and the costs.”
Sequencing for Free If You Share Your Data
Church may have an answer for that as well—get biopharmaceutical companies to foot the bill. Though Veritas’ new price for their myGenome service is significantly lower than before, it’s not free. That’s what Nebula Genomics, a start-up genetics company in Massachusetts co-founded by Church, offers people willing to share the data derived from their sequencing. To help biomedical researchers gather data for their studies, Nebula provides free or partially-paid-for whole-genome sequencing to qualified candidates.
“Nebula will enable individuals to get sequenced at much
lower cost through sequencing subsidies paid by the biopharma industry,” Church
told BioSpace.
“We need to bring the costs of personal genome sequencing close to zero to
achieve mass adoption.”
So, will lower-priced whole-genome sequencing catch on?
Perhaps. It’s certainly popular with everyday people who want to learn their
ancestry or predisposition to certain diseases. How it will ultimately affect
clinical laboratories and pathologists remains to be seen, but one thing is
certain—WGS is here to stay.
