Jeanette McCarthy, MPH, PhD and Shervin Kamkar, MS
The genetic testing landscape has changed dramatically in the past decades and continues to evolve as different delivery models and markets are being explored. In this post, we’ll discuss how the genetic testing industry has developed and some of the recent industry trends and factors impacting its growth.
A Brief History of Genetic Testing
Prior to the 1990s genetic testing was really confined to rare Mendelian (single gene) diseases. But the early-mid 90s saw the discovery of genes underlying Mendelian forms of common diseases like breast cancer, colon cancer and others, opening the door to genetic testing for Mendelian forms of these common diseases.
For the next two decades, commercial genetic test providers were limited to those holding patents on key genes. That all changed in 2013 when the Supreme Court of the United States ruled that genes could not be patented. This opened the market, prompting dozens of companies to begin offering genetic tests across a wide range of indications.
Today there are >75,000 health-related genetic testis on the market for medical applications across the lifespan. Even before a child is born, preconception carrier testing is helping parents who carry recessive Mendelian disease variants with family planning to avoid passing these variants on to their children. In the prenatal setting, non-invasive testing for chromosomal abnormalities is reducing the need for risky expensive procedures like amniocentesis. Newborns and children alike are benefiting from diagnostic whole genome sequencing for undiagnosed rare diseases. In adults, diagnostic, predisposition and pharmacogenomic testing are informing treatment and even preventing disease in family members.
Genetic testing for common, polygenic diseases and traits has lagged behind. By the early 2000s, convincing genetic associations drawn from candidate gene approaches, such as the relationship between APOE and Alzheimer disease, Factor V and venous thromboembolism and others, were scarce. That all changed in the mid-2000s, with the introduction of genome-wide association studies (GWAS). GWAS has been successfully applied to hundreds of common, complex traits where it can identify genetic variants with small effects. The genotyping arrays used for GWAS were soon commercialized by several companies, who began offering single variant genetic tests for a variety of common traits and diseases of interest to consumers.
Today, the health-related genetic testing market is dominated by tests for rare chromosomal abnormalities, classical Mendelian diseases and Mendelian forms of common diseases (like hereditary cancers). Pharmacogenomic testing has also become widely available, but increased FDA scrutiny of these tests is certain to impact uptake. Relatively few companies offer single variant tests for common, polygenic diseases. However, newer polygenic risk scores for common diseases are beginning to enter the market, with several commercial labs, including Ambry and Myriad Genetics, offering these tests for health risk assessment.
Delivery Models for Genetic Testing
The traditional physician-initiated model serves patients with or at risk of disease. Healthcare providers make the decision to pursue genetic testing for their patient and are involved in ordering a clinical-grade test from a reputable lab and delivering results to their patients, with or without the aid of a genetic counselor. Most of the major genetic testing labs operate under this model.
Direct to Consumer (DTC) or consumer-initiated testing is another model, pioneered by companies such as 23andMe, where there is no healthcare provider involvement. This traditional DTC model is not widely utilized by diagnostic companies for health-related genetic tests because the FDA requires these tests to be approved. Because of FDA oversight, DTC companies are limited in what health information they can deliver.
There is a hybrid DTC model referred to as patient-initiated testing where health care providers are still involved. There are several reputable laboratories offering clinical-grade tests who operate under this model. These companies allow patients to order the test online themselves but work closely with an independent physician network and/or genetic counselors to safeguard the ordering and delivery of results to patients.
Color Genomics pioneered this model for their hereditary cancer and cardiovascular disease tests. Veritas Genetics offers whole genome sequencing and interpretation through this model. More recently, Invitae has begun offering a limited selection of its tests through this model as well.
A related model is delivery of elective genetic analysis to healthy individuals through “executive” health/wellness clinics. These programs are currently offered through several academic medical centers including the University of California at San Francisco, the Mayo Clinic, Hudson Alpha Institute for Biotechnology, Brigham and Women’s Hospital and Mass General Hospital.
Expanding Markets for Genetic Health Tests
More and more consumers are undergoing genetic health testing outside of the traditional physician-initiated model. This expansion is being driven by testing companies carving out new markets, healthcare organizations adopting large-scale testing of their patient populations, and government-sponsored research projects.
Color Genomics is the dominant player in the employee wellness space, offering genetic testing as a health benefit to family members and employees of large companies, including Visa, Levi’s, Salesforce and many others. Voluntary testing provides confidential access to genetic tests that can help employees learn their risk of certain genetic diseases earlier, with an eye towards prevention.
Helix, who pioneered the app store for genomics, has expanded its focus to offering health-related genetic tests to large population cohorts, including Renown Health’s Healthy Nevada Project and Advent Health’s WholeMe study in Florida. Through these studies, tens of thousands of patients will have their exomes sequenced and analyzed, with some health-related results coming back to patients via the Helix portal.
The US government’s All of Us Research Program has an overall goal of enrolling one million US citizens into a research study involving genome sequencing. The intent is to deliver genetic health test results back to patients via genetic counselors. Genetic testing and return of results will be piloted next year in a subset of 20,000 enrollees.
Through these types of efforts, increasing numbers of consumers will have access to important health information outside of the context of their routine health care, posing several challenges for integrating it into their usual health care.
Ancestry Testing is the Gateway to Consumer Genomics
The direct-to-consumer (DTC) genetic testing market began to take off in the mid-2010s and has been growing at an exponential rate. Over 25 million people have taken advantage of DTC genetic testing, driven in large part by ancestry testing offered by companies like 23andMe and Ancestry.com.
In 2017, 23andMe received FDA clearance to offer its health-related tests directly to consumers, with the caveat that they are not to be used for diagnostic purposes. 23andMe is limited in its health-related offerings because the genotyping array platform it uses is not well-suited for clinical-grade diagnostic testing. Most clinical-grade tests use a combination of next-generation sequencing and Del/Dup analysis.
Last year, 23andMe tested customer interest in a deeper health-related offering, presumably based on next-generation sequencing. It’s unclear whether such a product, sold DTC, would be allowed by the FDA or not. Veritas Genetics and Helix both offer more extensive genetic analysis than 23andMe, but both utilize a hybrid DTC model for delivery of results.
Ancestry.com, with an even larger consumer base than 23andMe for genealogy testing, recently began offering tests for non-health-related traits, including finger length, birth weight, aversion to cilantro and others. This summer they announced their intention to offer health related information and presumably will be required to go through the same regulatory pathway as 23andMe. If they do, it puts consumer-driven genetic testing at the very forefront at a time where the demand for consumer genetics appears to be slowing down.
It’s not exactly clear what is driving the slow down, but it clear from sequencing giant Illumina’s latest quarterly report from Q2 of 2019 that there is weakening demand for the genotyping arrays preferred by the major DTC companies. Some speculate that the early adopter interest in DTC has peaked and lack of actionability in such tests has finally weakened overall interest.
Others believe that the recent scandal with Facebook and Cambridge Analytica have made consumers more concerned about data privacy protections and data use by DTC companies, whose revenue models depend on selling aggregated and deanonymized genomic data to pharmaceutical companies. Others are concerned that once their DNA is analyzed by a DTC company, their information could be subject to seizure by government agencies or used to discriminate them against them and their children when acquiring health insurance or life insurance.
In the summer of 2018, genetic genealogy methods were used to solve the case of the Golden State Killer using the public GEDmatch database. While this was no doubt an ingenious use of a public database and powerful example of forensic genetics, the issue has raised ethical questions about how DNA tests can indirectly be used to implicate people in crimes. Overall, the compounding effect of these issues is forcing the major DTC companies to adjust their business strategies and data policies to continue to grow.
Impact of FDA Regulation of Genetic Tests
Regulation of health-related genetic tests, the vast majority of which are run as laboratory developed tests (LDTs), has been loose and somewhat erratic. The FDA claims authority over these tests but to date has used its enforcement discretion, except in the case of DTC tests. While some might debate whether the FDA actually has authority over LDTs, it has nonetheless begun flexing its regulatory muscles, most recently over pharmacogenomic tests offered by commercial labs. While congress works to sort out the regulatory authority and pass legislation around LDT regulation (their most recent effort being the VALID Act), laboratories are bracing for scrutiny. With the FDA stepping in, there will likely be a thinning out of smaller companies, or those for whom the barrier of regulatory approval is just too great.
Data is Still King But the Consumer Must Also Benefit
It’s clear that the hunger for data, and lots of it, is still driving many commercial efforts. The premise is that through machine learning and artificial intelligence (AI), genomic data can be analyzed along with broad health metrics for a comprehensive view of an individual’s health. In the biopharma space, AI will not only drive discovery and development of novel diagnostics and therapeutics but allow drug manufacturers to monitor the efficacy of those interventions post-market, predict outcomes, and better identify participants for clinical trials.
With the European Union adopting the General Data Protection Regulation (GDPR) and the US following suit (at least at the state level) with the California Consumer Privacy Act (CCPA), companies will need to fundamentally change the way they protect consumer health data and obtain consent of use. The more established players like Apple, have been functioning as a medical data aggregator for years utilizing their iPhone to capture user information, and now 23andMe is piloting similar efforts to capture electronic health records.
In the post Facebook scandal era, health data brokers like LunaDNA, Citizen Health, Nebula, doc.ai and Seqster have emerged with a new paradigm, promising consumers ownership, transparency and control of their health data as they try to monetize those assets for research discovery efforts and clinical trials.
The ability to capture broad health metrics, including other ‘omics’ like the microbiome, environment, lifestyle, medical histories, lab tests and other ‘real world’ data is fueling business innovation while putting patients in the driver seat controlling how their data is used. The real question is who will best capture consumer’s trust and provide real value back to both researchers and individuals sharing their personal health data. There is still a lot to be proven with these “patient-centric” business models, but no doubt the consumer will start to expect a piece of the revenue pie from the data monetization strategy.
The Trajectory of Genetic Testing
It’s interesting to speculate about where genetic testing will be in the next several years. Tumor molecular profiling, including liquid biopsies for cancer treatment selection, noninvasive prenatal diagnostic testing and sequencing to diagnose rare disease are applications that have shown clear value and are gaining wider acceptance by providers and payers alike, and a foothold in medical practice. In each of these areas, the stakes are high and genetic testing has a measurable impact.
Uptake of other health-related genetic tests – for predisposition/diagnostic testing, pharmacogenomics, risk assessment - is hindered by a shifting regulatory landscape, limited reimbursement, and skepticism by healthcare providers about their validity and value. While non-physician-initiated genetic testing (through employee wellness programs, population health projects and DTC testing) is increasing, the growth might not be sustainable. Population health initiatives are finite in size, and interest in DTC testing may be waning. Moreover, genetic information flowing directly to patients may have limited value unless healthcare providers and their organizations are prepared to manage the results.
To be useful, genetic test results should be integrated into medical care. Results need to be transmitted to medical centers, and ideally integrated into the electronic health record of the patient. Software solutions for consumers to seamlessly upload and understand their genetic test results in the overall context of their health will be key.
With the increasing demand for genetic tests, the shortage of genetic counselors in the US puts tele-health providers like InformedDNA, GeneMatters, My Gene Counsel and Genome Medical at the forefront. These companies are trying to scale the support services of genetic counselors and are developing novel models to help patients address the myriad range of questions and concerns patients have. However, any sustainable model must include educated healthcare providers as well.
What’s clear is that certain applications of genetic testing are maturing faster than others, likely due to a combination of perceived value and necessity. New markets and models of delivery are being explored by pioneering companies hoping to expand their footprint. External factors including the regulatory and reimbursement landscapes, consumer and healthcare provider sentiment, and an appetite for big data remain important forces that will continue to shape the genetic testing industry.
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Contact info: jeanette@pmedadvisors.com