Has the Time Arrived to Incorporate Genetic Testing Into Health Care?

Use of genetic information in health care is not new. Genome-wide association studies (GWAS), next-generation sequencing (NGS), and pharmacogenetics all incorporate different facets of genomics with the purpose of identifying abnormalities linked with disease risk, increasing understanding of disease pathogenesis, and identifying which patients respond best to certain treatments. 

Apart from these methodologies most commonly used in scientific research, average Americans may be more familiar with “recreational genetics,” or services offered by companies like 23andMe that provide insights on everything from one’s genealogical background to cilantro taste aversion.

However, in an age where personal data are considered one of the hottest products on the market, not only are companies looking to profit from one’s digital footprint, but the rise in popularity of direct-to-consumer genetic testing permits the commoditization of perhaps the most private, personal information—an individual’s genetic makeup.

Projections estimate that in the next 4 years, this market will reach a $1.9 billion valuation.

Capitalizing on this trend, more and more companies are taking recreational genetics a step further to offer genetic tests that yield potentially lifesaving information in the form of risk of disease development based on the presence of certain genetic features.

And at the same time that consumers may be coming into their providers’ offices with data they purchased themselves, payers and providers are trying to determine how to more easily incorporate genetic screening into standard care.

This effort is spearheaded by organizations like Helix, which works with health system partners, and Color, whose tests include access to physician support.

On the surface, the idea of estimating personalized risk for disease marks a key step in precision medicine and health autonomy, not to mention important implications for population health, as disease predisposition screening can help drive early intervention and prevention initiatives.

But despite the myriad of promises offered on the individual and population levels, serious questions regarding cost, data protection, and access to follow-up care arise alongside the boom of personal genetic testing.

Ethical Questions Meet Gray Areas

At the most basic level, gaining knowledge of an increased risk of a certain disease or outcome can lead to lifestyle improvements or behavior modifications. However, simply identifying a gene or mutation that is associated with an increased risk of a condition does not mean an individual will necessarily develop that condition, and for some, the stress of that knowledge can have its own consequences.

One popular area of genetic screening is prenatal testing, where doctors usually decide which conditions are included in tests. A recent New York Times article documented the sagas that pregnant women underwent after completing a genetic test to identify their children’s risks of developing serious disorders.

Such prenatal tests initially just screened for Down syndrome and were successful in that effort. But recently, screenings for rarer conditions have permeated the market.

Putting aside the emotional decisions that must be made when an expectant mother finds out her child is at a heightened risk of a potentially shortened life span, reporters at the Times found that, among some tests, “for every 15 times they correctly find a problem, they are wrong 85 times.”

Because rare disorders are just that—rare—the diversity of data used to assess associations with these diseases can be limited, and testing accuracy may suffer due to false positives. The reporting of test performance data varies by company, with some basing claims on studies involving only 1 or 2 pregnancies with the condition in question.

According to experts, there is no threshold for how often a test needs to yield a positive result correctly to be worth offering, and one obstetrician likened the practice to “running mammograms on kids,” the Times reported.

When it comes to personal risk assessment via genetic testing, the disease, if present, may be in such an early stage that, if detected, it prompts questions on treatment efficacy, care value, and excess cost. Furthermore, should genetic testing identify an increased risk or presence of a disease, individuals with limited access to health resources or who are underinsured may find themselves in a predicament, unsure of where to seek or how to afford the necessary follow-up care.

“It’s not enough to just learn one day that you have a predisposition to a particular disease or have a pharmacogenomic result that means you shouldn’t be prescribed a certain medication,” said Carolyn Neuhaus, PhD, a research scholar at The Hastings Center during an online discussion on the “All of Us” Research Program.

These pieces of information need to be integrated into electronic health records, Neuhaus explained. “You have to have providers who have the training on how to utilize that information properly in clinical care,” in addition to infrastructure in place to translate these findings into meaningful benefits and improved health care, she added.

The National Institutes of Health's "All of Us" program is the first government study to return individualized genetic data to participants and aims to enroll more than 1 million individuals. Neuhaus is also a principal investigator on 2 projects concerning the research program.

One key goal of “All of Us” is to include a very diverse population to address the challenge of racial homogeneity seen in many genomic research studies.

A regularly utilized source of genetic data is the UK Biobank, which includes over 500,000 British residents recruited between 2006 and 2010. According to a 2019 analysis, of the 487,000 participants for whom genome-wide array data were assayed, 88% self-identified as being of White British ethnic background and another 6% as other White background.

To diversify the pool of individuals from which disease risks can be ascertained and predicted with greater certainty, it follows that more people will need to be screened. However, with higher rates of screening, new questions merit answers:

• Will individuals be required to share test results with health care providers or blood relatives?
• If this practice becomes part of routine clinical care, who will cover the costs of genetic screening?
• Should this service be contracted out, will individuals trust private companies with their personal genetic data?
• How will providers choose which company to use?
• How will findings be interpreted, and who will filter out superfluous data?
• What happens to that excess data?
• Should there be an age limit on who can be screened?

The American Journal of Managed Care^® (AJMC^®) recently spoke with one company aiming to fill these gaps.

Providing Actionable Genetic Information

The human genomic data set “is the only data set in health care that doesn’t change,” said James Lu, MD, PhD, cofounder and CEO of Helix, in an interview with AJMC^®. 

Working with its partners, which include Renown Health, Mayo Clinic, and Advent Health, Helix’s goal is to overcome some of the hurdles of genetic testing outlined above and take advantage of this fixed metric to improve individual and population health.

“If you can turn [a genomic data set] into a digital resource for health care, it enables providers, patients, and health care systems to benefit from having the data to manage disease, detect diseases earlier, and help prevent severe outcomes,” Lu said.

Although the company used to offer testing to the public, individuals looking to get screened by Helix now must be at least 18 years old and members of one of its health system partners, as the company's main focus is enabling systems to conduct screening well and at scale, as opposed to just empowering single individuals.

Paramount to the group’s mission is the system of providers in place who are ready to act should screening turn up signals of a heightened disease risk. Helix is unique in that it prepares physicians to receive the information via education and automation to make sure every patient who gets screened receives the right outcomes.

Findings are also directly linked back to a patient’s medical record to mitigate care gaps, ensure follow-up, and truly prevent disease—distinguishing the process from just a “feel-good exercise,” Lu explained. This way, patients will not be burdened with unactionable knowledge.

The screening is paid for by the health systems, and patients do not pay any out-of-pocket costs. In addition, the company works to reduce the challenges inherent in some genetic tests by only screening for what’s been defined by the CDC as “the most actionable set of genes.”

Helix does generate a large data set covering all 20,000-plus genes, but “we only slice that data set and use it as needed,” Lu said.

Specifically, the Helix Health Test only returns results on the first 11 genes encompassing 3 conditions: hereditary breast and ovarian cancer, which are caused by mutations in BRCA1 or BRCA2 genes; Lynch syndrome, which is related to colon cancer and associated with mutations in mismatch-repair genes; and familial hypercholesterolemia, which contributes to an increased risk of heart disease or stroke.

“Those 3 diseases have been chosen by the CDC because (1) early identification saves lives; (2) it's clearly very actionable, in that providers should be able to treat them; and (3) it's very clear what a mutation means,” Lu said.

“We prepare the physicians just to return on these sets of genes initially,” he added, “and then you can come back and use that data over and over again as a digital asset to help that patient in other questions.”

Tackling Privacy Concerns

Identifying risk of a potentially fatal disease may instill pause in some individuals, who are wary insurance companies may see this scenario as one similar to the preexisting condition debate and raise insurance rates once an abnormality is found.

But according to Lu, protections outside of the Affordable Care Act are in place to prevent such practices.

Citing the Genetic Information Nondiscrimination Act of 2008, Lu outlined how employers and health insurance cannot discriminate against individuals for having genetic information.

When an individual finds out risk information and the disease is prevented or manifests, “they should be protected from any sort of discrimination from a health insurance perspective,” he said. “That said, there's always work to be done in this space. And I think, at a broad scale, privacy legislation that protects genetic information is going to be important as this becomes standard of care.”

Expounding on potential patient privacy concerns, Lu stressed the notion of individual ownership over one’s data that helps drive Helix’s work. Once an individual gets sequenced at Helix, they can manage their data by sharing it between health systems, downloading it, or even deleting it.

“We spend a lot of time thinking about, ‘How do we make our systems and our interactions more secure and more private for our individuals?’” Lu said, not just for the company’s success but also to build trust with patients.

Future Trends

From a broader perspective, the use of genetic screening can potentially lead to improvements in population health and health equity and cut down on health care costs. When specific populations are identified as being at greater risk of a disease, targeted treatments will lead to better response rates and less health care waste, in theory.

In one recent example, researchers were also able to dramatically speed up the rate at which rare genetic diseases were diagnosed using nanopore genome sequencing.

“Although most critical care decisions must be made in hours, traditional testing requires weeks and rapid testing requires days,” they wrote in The New England Journal of Medicine.

Of 12 patients studied between December 2020 and May 2021 in 2 California hospitals, researchers were able to obtain an initial genetic diagnosis for 5 patients, with the shortest time recorded at 7 hours and 18 minutes.

This rapid turnaround could be crucial for critically ill patients. “You can not only make care better, and help patients more, but do it cheaper, save money, save the system money,” study author and Stanford cardiologist Euan Ashley, MB, ChB, DPhil, told STAT News.

About a half teaspoon of blood was used for each patient’s genetic sequencing, and researchers were able to sequence up to 48 DNA samples from a single patient at once. They then used cloud computing to analyze data and scan sequences for mutations that could explain a patient’s symptoms.

One caveat in this example is that the sequencing technologies used were not cheap, and insurance companies currently have different policies when it comes to covering genetic testing.

As reflected in the case series outlined, use of genomics in the health care system is fairly limited, according to Lu, and when it comes to care of large-scale populations, it’s underutilized.

“The way we think about it is how can you leverage that data in combination with other data sets to either identify patients early for preventive care, risk stratify patients for different levels of care, [or use] pharmacogenetics to help make decisions around the appropriate types of therapeutics for care,” he said.

Increasing access to these tests will help integrate them into standard care and improve overall population outcomes, Lu explained. By doing so, cost savings will be achieved via quality improvement and closing care gaps, thus reducing total cost of care. This drive can also broaden sample diversity and enhance interpretation capability, he added.

Looking ahead, researchers and public health officials would do well to take advantage of the impact that COVID-19 has had on advancing the public’s understanding of sequencing, not only from an individual perspective but from a genetic epidemiological perspective as well.

“The amount of people talking about sequencing now, pre- and post pandemic, has been like a sea change,” Lu said. “If you thought back to the early days of the COVID-19 pandemic, it was actually sequencing that enabled us to design tests. It was sequencing of what was then an unknown virus posted to the scientific commons that enabled the test manufacturers to build the first PCR [polymerase chain reaction] test.”

This increased familiarity with sequencing-based technologies will enhance our ability to respond to and look at new variants not only of COVID-19, but of the flu and other viruses, he contended.

However, it would be remiss to ignore the large roles that environmental factors and social determinants of health play in forecasting one’s disease susceptibility. Recent calls to increase health equity have largely focused on these modifiable risk factors that can be improved through measures like policy changes.

As Neuhaus noted, “Inequitable systems of care provision cannot be undone by genomic research alone.”

“There's a place, I think, for researchers, whether it's in the ethics and public health and qualitative research side, or people on the genetics and biomedical research side, to say, ‘Yes, we are doing the work that will sort of catalyze and create the knowledge that is needed to reduce health disparities. But we can't do that, we can’t actually deliver on that alone,’” she added.

Outside factors like exposure to pollution, individual health habits, insurance status, and geographic location all influence disease risks, and for some, addressing these root causes of disparities will also result in tangible benefits.

But as technology and treatment advancements continue to progress in the 21st century, and with the hindsight now gained from the COVID-19 pandemic, there’s no doubt genomics will play a big role in 2022 and beyond, despite some unresolved challenges.

Genomics “is going to be as impactful to medicine as, say, radiology was,” Lu said. Diagnostic testing, population genomic approaches, and viral surveillance mark just a few areas of recent progress, and “we think we’re just at the beginning.”