NIH program could lead to new diagnostic biomarkers for clinical laboratory tests across a more diverse segment of US population
In another milestone in the US National Institutes of Health’s (NIH) plan to gather diverse genetic information from one million US citizens and then use that data to inform clinical care in ways consistent with Precision Medicine, the NIH’s All-of-Us Research Program announced in a news release it has “begun returning personalized health-related DNA results” to more than 155,000 study participants.
In addition, those participants who request them will receive genetic reports that detail whether they “have an increased risk for specific health conditions and how their body might process certain medications.”
The All-of-Us program, which began enrolling people in 2018, is one of the world’s largest—if not the largest—project of its kind. It could result in more than a million human whole genome sequences to drive medical research and speed discoveries. Study findings, for example, may produce new biomarkers for clinical laboratory tests and diagnostics.
In 2020, the All-of-Us program “had begun releasing genetic results for ancestry and a small number of nonclinical genetic traits,” according to GenomeWeb. Now, the program is taking on the greater challenge of sharing health-related genetic test results directly with its participants.
“We really wanted to make sure that we are providing a responsible return to our participants,” Anastasia Wise, PhD, All-of-Us Program Director for the Genetic Counseling Resource, told GenomeWeb. “They might get information that’s unexpected,” she explained.
So far, about 10,000 people received the NIH’s invitation and 56% have shown interest in receiving their genetic test results, GenomeWeb noted.
“Knowledge is powerful,” said Josh Denny, MD (above), Chief Executive Officer, NIH All-of-Us Research Program, in an NIH news release. “By returning health-related DNA information to participants, we are changing the research paradigm, turning it into a two-way street—fueling both scientific and personal discovery that could help individuals navigate their own health,” he added. The NIH’s research could lead to new clinical laboratory precision medicine diagnostics for chronic diseases across a more diverse segment of the US population. (Photo copyright: National Institutes of Health.)
Two Types of Genetic Health Reports
Study participants who provided a blood sample and gave their consent to receiving genomic information may also receive a Hereditary Disease Risk report that includes 59 genes and genetic variants linked to serious and “medically actionable” health conditions.
About 3% to 5% of participants will have findings suggesting a high risk for a genetic disease such as breast and ovarian cancers as indicated by BRCA1 and BRCA2 genes, Medical Xpress reported.
“I kind of shudder to think about what could happen if I hadn’t known this [finding that she has the BRCA2 gene],” said Rachele Peterson, All-of-Us Chief of Staff, who spoke to the Associated Press about her receiving own Hereditary Disease Risk report.
Participants can also choose to receive an All-of-Us Medicine and Your DNA report with insights on seven genes that affect how specific medications are metabolized. This pharmacogenetics report is important for those who could learn, for example, that they have a 50% to 60% greater risk of a second heart attack when they continue to take the standard medication, as opposed to a different medication, Medical Xpress noted.
“The information on metabolizing medication can be particularly important for people who need treatment after a heart attack,” Josh Denny, MD, Chief Executive Officer, NIH All-of-Us Research Program, told Medical Xpress.
“Such transparency of genetic information about a massive group—as well as the genetic information on individuals—can be used to improve patient care and clinical outcomes,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.
“The program provides a roadmap for other healthcare organizations to follow. And this is useful strategic knowledge for clinical laboratory leaders to understand and incorporate into their plans to support precision medicine with genetic testing and whole human genome sequencing,” Michel added.
Rich Genetic Data Across a More Diverse Population
As to its goal to reflect national diversity, NIH reported about 80% of All-of-Us participants reside in communities that have been unrepresented in medical research, and that 50% are part of a racial or ethnic minority group.
By combining this information into a single database, the MVP promises to advance knowledge about the complex links between genes and health, according to an MVP news release.
Researchers tapping All-of-Us and MVP data may ultimately produce enlightening and impactful study findings, which could enable clinical laboratories to perform new diagnostic precision medicine tests that identify diseases early and save lives.
Encouraging patients—even children—to be more directly involved in their own medical care may reduce the burden on healthcare workers and might even help those clinical laboratories struggling to hire enough phlebotomists to collect specimens
Researchers at Emory University School of Medicine have concluded a study which found that school-aged children can successfully use a nasal swab to obtain their own SARS-CoV-2 test specimens. This may come as a surprise to hospital and clinical laboratory personnel who have performed nasal swabbing for COVID-19 tests. Some people, adults included, find the procedure so uncomfortable it brings tears.
And yet, after being shown a 90-second how-to video and given a handout with written instructions and pictures, 197 Atlanta children who had COVID-19 symptoms between July and August of 2021 performed their own self-swabbing. A healthcare worker then collected a second swabbed sample. All samples were submitted to a clinical laboratory for PCR analysis.
The Emory study provides another example of how the healthcare system is engaging patients to be directly involved in their own medical care. Results of the study could positively impact clinical laboratories facing a shortage of personnel, as well as schools where children have to take repeated COVID-19 tests with the assistance of trained professionals.
In a study with 197 school-age children, researchers at Emory University School of Medicine found that children could self-swab themselves for COVID-19 testing after watching a 90-second instructional video. Clinical laboratory leaders who are short on personnel may find these results intriguing. (Photo copyright: Emory University.)
How Did the Children Do?
The self-collected swabs and those collected by a healthcare worker agreed 97.8% of the time for a positive result and 98.1% of the time for a negative result. The analysis showed that both collection methods identified the 44% of symptomatic kids who were positive for COVID-19.
“Seeing how closely the results line up between the children and trained healthcare workers is a strong indicator that these age groups are fully capable of swabbing themselves if given proper instruction,” said Jesse Waggoner, MD, an Assistant Professor of Infectious Diseases with the Emory University School of Medicine and one of the lead authors on the study, in an Emory University press release.
A higher percentage of children age eight and under needed assistance, such as more instruction before correctly completing self-collection—21.8% compared to 6.1% for children older—but SARS-CoV-2 detection among the two age groups did not differ.
Does FDA Approve of Self-Swabbing?
The US Food and Drug Administration (FDA) has not authorized COVID-19 tests that include self-swabbing by children under age 14. However, data from the Emory study, published in JAMA, is now available to test manufacturers seeking authorization for pediatric self-collection.
“Pediatric self-swabbing will support expanded testing access and should make it even easier to test school age populations with fewer resources,” said Tim Stenzel, MD, PhD, Director of the Office of In Vitro Diagnostics at the FDA, in the Emory statement. “This study furthers our knowledge of test accuracy with these types of samples and provides test manufacturers with data to support their EUA (Emergency Use Authorization) requests to the FDA.”
Self-swabbing versus Clinical Laboratory Worker
While it has been longstanding medical practice to have healthcare workers collect samples for respiratory tract infection testing, the Emory researchers suggest that allowing children to collect their own COVID-19 samples could be one way to reduce the burden of a shortage of healthcare workers.
The researchers also believe pediatric self-swabbing would expand access to diagnostic tests and make it easier to test school-age populations.
“Every minute of a healthcare worker’s time is at a premium,” said senior study author Wilbur Lam, MD, Professor of Pediatrics and Biomedical Engineering, Emory University and Georgia Tech, in a National Institutes of Health (NIH) press release. “Why not allow a kid to self-swab? It’s a win-win! They would rather do it themselves and it frees up the healthcare worker to do other things,” he added.
In 2020, a Stanford University School of Medicine study published in JAMA showed test samples collected by adults who swabbed their own nasal passages were as accurate as those collected by healthcare workers. This study involved 30 participants who had previously tested positive for COVID-19.
Though the Emory University and Stamford University studies were small, they agreed in their findings which is significant. Clinical laboratory executives and pathologists should expect this trend toward direct-to-consumer and other forms of self-testing to continue, even among young patients.
Although there are healthcare providers who see the potential in microbiome testing, many clinical laboratories are not yet ready to embrace microbiome-based testing
In an unlikely string of events, no less than Nordstrom, the national department store chain, announced in September that it would offer microbiome-based test claimed to “check gut health.” Apparently, its customers were interested in this clinical laboratory test, as the Nordstrom website currently indicates that the “Health Intelligence Test Kit by Viome” is already sold out!
What does it say about consumer interest in clinical laboratory self-testing that Nordstrom has decided to offer at-home microbiome tests to its store customers? Can it be assumed that Nordstrom conducted enough marketing surveys of its customers to determine: a) that they were interested in microbiome testing; and b) they would buy enough microbiome tests that Nordstrom would benefit financially from either the mark-up on the tests or from the derived goodwill for meeting customer expectations?
Whatever the motivation, the retail giant recently announced it had partnered with Viome Life Sciences to sell Viome’s microbiome testing kits to its customers online, and in 2022, at some Nordstrom retail locations. These tests are centered around helping consumers understand the relationship between their microbiome and nutrition.
Pathologists and clinical laboratories will want to track Nordstrom’s success or failure in selling microbiome-based assays to its consumers. Microbiomics is in its infancy and remains a very unsettled area of diagnostics. Similarly, Viome, a self-described precision health and wellness company that conducts mRNA analysis at scale, will need to demonstrate that its strategy of developing precision medicine diagnostics and therapeutics based on the human microbiome has clinical relevance.
Helping Consumers with ‘Precision Nutrition’
In a September news release, Viome founder and CEO Naveen Jain, a serial entrepreneur, said, “Both Viome and Nordstrom believe that true health and beauty start from within. There is no such thing as a universal healthy food or healthy supplement. What is right for one person can be wrong for someone else, especially when it comes to nutrition which is key to human longevity and vitality. Precision nutrition is the future!”
“Precision medicine seeks to improve the personalized treatment of diseases, and precision nutrition is specific to dietary intake. Both develop interventions to prevent or treat chronic diseases based on a person’s unique characteristics like DNA, race, gender, health history, and lifestyle habits. Both aim to provide safer and more effective ways to prevent and treat disease by providing more accurate and targeted strategies.
“Precision nutrition assumes that each person may have a different response to specific foods and nutrients, so that the best diet for one individual may look very different than the best diet for another.
“Precision nutrition also considers the microbiome, trillions of bacteria in our bodies that play a key role in various daily internal operations. What types and how much bacteria we have are unique to each individual. Our diets can determine which types of bacteria live in our digestive tracts, and according to precision nutrition the reverse is also true: the types of bacteria we house might determine how we break down certain foods and what types of foods are most beneficial for our bodies.”
Medical Laboratory Testing, not Guessing
Viome Life Sciences is a microbiome and RNA analysis company based in Bellevue, Wash. The test kit that Nordstrom is selling is called the Health Intelligence Test. It is an at-home mRNA test that can provide users with some insights regarding their health. Consumers use the kit to collect blood and fecal samples, then return those samples to Viome for testing.
In a press release announcing its collaboration with Nordstrom, Viome said, “In a world overwhelmed by information relating to diet and supplement advice, Viome believes in testing, not guessing and empowering its users with actionable insights. To date, Viome has helped over 250,000 individuals improve their health through precision nutrition powered by microbial and human gene expression insights.”
Nordstrom began offering Viome’s Health Intelligence Test kit for $199 on its website starting in September. As of this writing and noted above, the kits are sold out. Nordstrom plans to stock the kit in select stores starting in 2022.
Viome’s Health Intelligence Test kit (above) looks at the microbiome to determine gut health, cellular health, healthy aging, immune health, and stress responses. Test results offer consumers personalized nutritional suggestions and recommendations for supplements, probiotics, and prebiotics based on an individual’s biology. Test are performed by Viome’s own clinical laboratories and results sent directly to Nordstrom’s customers. (Photo copyright: Viome Life Sciences.)
Individuals who purchase the test submit blood and stool samples to Viome’s lab which performs an analysis of gene activity patterns in the user’s cells and microbiome. Viome provides the results to consumers within two to three weeks.
“This partnership is a giant step towards making our technology more accessible, so people can understand what’s right for their unique body,” Jain said in the news release. “We are inspired each day by the incredible changes our customers are seeing in their health including improvements in digestion, weight, stress, ability to focus, and more.”
According to the news release, Viome conducted blind studies earlier this year that revealed significant successes based on their precision nutritional approach to wellness. Study participants, Viome claims, improved their outcomes to four diseases through nutrition:
Is Microbiome Diagnostics Testing Ready for Clinical Use?
Microbiomics is a relatively new field of diagnostics research. Much more research and testing will be needed to prove its clinical value and efficacy in healthcare diagnostics. Nevertheless, companies are offering microbiomics testing to consumers and that has some healthcare providers concerned.
In the GeekWire article, David Suskind, MD, a gastroenterologist at Seattle Children’s Hospital and Professor of Pediatrics at the University of Washington, described Viome’s study methodology as “questionable,” adding, “I think this is a very interesting and exciting space and I do think there are definite potential implications, down the road. [However] we are not there in terms of looking at microbiome and making broad recommendation for individuals, as of yet.”
Will at-home clinical laboratory testing kits that analyze an individual’s microbiome someday provide data that help people lead healthier lives and ward off diseases? That’s Jain’s prediction.
In an article published in Well+Good, Jain said, “COVID-19 has, of course, been such a dark time, but one positive that did come from it is that more people are taking control of their own health. I really believe that the future of healthcare will be delivered not at the hospital, but at home.”
If this collaboration between Nordstrom and Viome proves successful, similar partnerships between at-home diagnostics developers and established retail chains may become even more common. And that should be on the radars of pathologists and clinical laboratories.
All-of-Us program is free to participants and provides data to more than 800 research studies for cancer, COVID-19, Alzheimer’s, and other diseases; findings will lead to new biomarkers for clinical laboratory tests
It is hard to say no to free. At least that is what the National Institutes of Health (NIH) is counting on to help increase the size and diversity of its database of genetic sequences. The NIH’s All-of-Us Research Program is offering free genetic testing for all participants in the program, as well as free wearable Fitbits for those selected to provide lifestyle and behavior data.
Many pathologists and clinical laboratory managers know that this group of researchers hope to build a database of more than one million genetic sequences to better understand “how certain genetic traits affect underrepresented communities, which could greatly affect the future of customized healthcare,” CBS affiliate 8 News Now reported.
“Customized healthcare” is a euphemism for precision medicine, and genetic sequencing is increasingly playing a key role in the development of personalized diagnostics and therapeutics for cancer and other deadly diseases.
In “VA’s ‘Million Veterans Program’ Research Study Receives Its 100,000th Human Genome Sequence,” Dark Daily described how the NIH’s All-of-Us program was launched in 2018 to aid research into health outcomes influenced by genetics, environments, and lifestyle. At that time, the program had biological samples from more than 270,000 people with a goal of one million participants.
Matthew Thombs, Senior Project Manager of Digital Health Technology at Scripps Research in La Jolla, Calif., joined the All-of-Us program after losing a family member “to a condition I believe could have been managed with changes to their lifestyle,” he told 8 News Now.
“What we are building will empower researchers with the information needed to make such conclusions (about possible need to change lifestyles) and forever alter how diseases are treated,” he added. “I hope that what we are doing here will help my son grow up in a world where healthcare is more of a priority, and many of the ailments we see today are things of the past.”
Such genetic testing could discover biomarkers for future personalized clinical laboratory diagnostics and drug therapies, a key aspect of precision medicine.
The photo above shows an All-of-Us participant being prepped to provide a biological sample for genetic testing. According to Matthew Thombs, Senior Project Manager of Digital Health Technology at Scripps Research, “participants can provide as much or as little information as they like, every single data point matters.” The collected data is shared anonymously with more than 800 research studies for COVID-19, Alzheimer’s, cancer, and other diseases, 8 News Now reported. (Photo copyright: KLAS-TV.)
Scripps Research Integrates Mobile Health Technology into All-of-Us Program
A critical aspect of the NIH’s research is determining how people’s behavior combined with their genetics may predispose them to certain diseases. Nonprofit research institution Scripps Research is working with the NIH’s All of Us Research Program to enroll and collect biological samples from one million US residents.
In addition, Scripps is fitting study participants with wearable mobile health devices to capture data on their habits and lifestyles.
“Until now, the treatment and prevention of disease has been based on a ‘one-size-fits-all’ approach, with most therapeutics tailored for the ‘average patient’. However, advances in genomic sequencing, mobile health technologies, and increasingly sophisticated informatics are ushering in a new era of precision medicine. This new approach takes into account differences in people’s genes, environment, and lifestyles giving medical professionals resources to design targeted treatments and prevention strategies for the individual,” Scripps states on its website.
Can wearable fitness devices and related data contribute to research on genetics and healthcare outcomes? Scripps aims to find out. It has fitted 10,000 people in the All-of-Us program with Fitbit devices (Fitbit Charge 4 tracker or Fitbit Versa 3 smartwatch) at no cost. Since February, Scripps has distributed 10,000 Fitbit wearable devices through the All-of-Us program.
“By sharing information about their health, habits, and environment, participants will help researchers understand why people get sick or stay healthy,” the Scripps website adds.
The Scripps researchers plan to analyze how the people use the wearable devices. They are also accumulating data about participants’ physical activity, heart rate, sleep, and other health metrics and outcomes “as part of the broader All of Us program,” a Scripps news release explained.
“This is the first time All of Us is distributing devices to participants. Our goal is to better understand how participants engage during research studies in order to continually improve user experience and participation. We also expect to learn more about how wearable data may inform the personalization of healthcare,” said Julia Moore Vogel, PhD, Director of The Participant Center at the All of Us Research Program at Scripps Research, in the news release.
All-of-Us Program Records ‘Significant Progress in Participant Diversity’
As of June, the NIH has enrolled 386,000 participants into the All-of-Us program, with 278,000 consenting to all of the program’s steps. Eighty percent of biological samples in the collection are from people in communities that have been under-represented in previous biomedical research an NIH new release noted. According to the NIH, that gives the All-of-Us research program “the most diverse dataset.”
What will all this research ultimately bring to clinical laboratories? Who knows? Nevertheless, if federal institutions like the NIH and non-profit research companies like Scripps believe precision medicine is worth investing in, then the All-of-Us program is worth watching.
A diverse database of a million genetic sequences combined with lifestyle and behavioral data may lead to new and improved personalized diagnostics and drug therapies.
As many clinical laboratory scientists know, gene sequencing technology continues to become faster, more accurate, and less expensive per whole human genome sequenced
In February, Dark Daily reported that Personalis, Inc. (NASDAQ:PSNL) had delivered its 100,000th whole human genome sequence to the US Department of Veterans Affairs Million Veterans Program (VA MVP). Now, the Menlo Park, Calif.-based cancer genomics company has topped that achievement by delivering its 125,000 whole human genome sequence!
“This represents another important landmark for both the program and for Personalis,” said John West, Chief Executive Officer, Personalis, in a news release. “We congratulate the VA MVP for reaching this important milestone.
“We strongly believe that the research projects being performed today will enable precision medicine in healthcare systems in the future across a wide range of disease areas,” he added. This is a positive development for clinical laboratories, as personalized medicine services require a lab to sequence and interpret the patient’s DNA.
Personalis was contracted with the US federal government to perform genetic research in 2012 and has delivered 50,000 genomes to the VA MVP during the past twelve months.
The Personalis and VA MVP researchers seek to gain a better understanding of how genetic variants affect health. Before the COVID-19 pandemic hit the US, the VA was enrolling veterans in the Million Veterans Program at 63 VA medical centers across the country. There are currently about 830,000 veterans enrolled in the venture and the VA is expecting two million veterans to eventually sign up for the sequencing project.
“As a global leader in genomic sequencing and comprehensive analytics services, Personalis is uniquely suited to lead these population-scale efforts and we are currently in the process of expanding our business operations internationally,” West added.
According to the press release, “the VA MVP provides researchers with a rich resource of genetic, health, lifestyle, and military-exposure data collected from questionnaires, medical records, and genetic analyses. By combining this information into a single database, the VA MVP promises to advance knowledge about the complex links between genes and health.”
NIH All of Us Research Program Supports Precision Medicine Goals Another genetic research project being conducted by the US National Institutes of Health (NIH) is the All of Us Research Program. Using donated personal health information from thousands of participants, the NIH researchers seek to “learn how our biology, lifestyle, and environment affect health,” according to the program’s website.
“We’re changing the paradigm for research,” said Josh Denny, MD (above), Chief Executive Officer of the All of Us Research Program, in an NIH news release. “Participants are our most important partners in this effort, and we know many of them are eager to get their genetic results and learn about the science they’re making possible. We’re working to provide that valuable information in a responsible way,” he added. Clinical laboratories may soon see new precision medicine biomarkers derived from this type of research. (Photo copyright: Vanderbilt University.)
The All of Us Research Program intends to have at least one million US participants take part in the research. The researchers hope to help scientists discover new knowledge regarding how biological, environmental, and behavioral factors influence health, and to learn to tailor healthcare to patients’ specific medical needs, a key component of precision medicine.
Participants in the project share personal information via a variety of methods, including surveys, electronic health records, and biological samples.
A Better Sampling of Under-Represented Communities
Since opening enrollment in 2018, more than 270,000 people have contributed blood, urine, and saliva samples to the All of Us Research Program. More than 80% of the participants come from communities that are traditionally under-represented in biomedical research.
“We need programs like All of Us to build diverse datasets so that research findings ultimately benefit everyone,” said Brad Ozenberger, PhD, Genomics Program Director, All of Us, in the NIH news release. “Too many groups have been left out of research in the past, so much of what we know about genomics is based mainly on people of European ancestry. And often, genomic data are explored without critical context like environment, economics, and other social determinants of health. We’re trying to help change that, enabling the entire research community to help fill in these knowledge gaps.”
The All of Us Research Project’s analysis of the collected data includes both whole-genome sequencing (WGS) and genotyping and is taking a phased approach in returning genetic data to participants.
Participants initially receive data about their genetic ancestry and traits. That is followed later by health-related results, such as how their genetic variants may increase the risk of certain diseases and how their DNA may affect their reaction to drug therapies.
Genetic researchers hope programs like these will lead to improved in vitro diagnostics and drug therapies. Genetic sequencing also may lead to new diagnostic and therapeutic biomarkers for clinical laboratories.
