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Next act in genomics: the consumer orders

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Karen Titus

April 2019—For years, laboratories have chafed against testing being, literally and figuratively, an out-of-sight, out-of-mind transaction. Now a new, highly visible era in genetics may be pushing testing the other way, into the hands of consumers who value entertainment as well as medical information. Anyone who wants to write a book about this shift has a ready-made title: From Basement to Big Top.

It’s not that clinical testing is becoming an actual circus. But ever since the first consumer genetic tests entered the market in 2007—in a nonphysician-ordered, SNP array technology way—labs, physicians, and regulatory agencies have had plenty to juggle. Today that includes relatively affordable sequencing, DNA ancestry searches, and patient empowerment. Throw in a little Silicon Valley verve, and we arrive at the present: presumably healthy consumers who want a peek at their own genetic profiles.

Some call this consumer-directed testing. Others prefer consumer-facing testing.

Jill Hagenkord, MD, adds a few more to the mix. Dr. Hagenkord, chief medical officer at Color Genomics, refers to direct-to-consumer and easy-access testing, placing them both in the category of consumer genomics.

Dr. Jill Hagenkord (right) with Wendy McKennon, vice pres-ident of product and user experience, at Color Genomics. “We’re all part of this first group of clinical pathologists and laboratories that are actually doing real consumer genetics,” Dr. Hagenkord says. (Photo courtesy of Cindy Charles)

Whatever the phrase, the shift is striking. Patient-centered care sounds almost quaint. With consumers pulling up their own chairs to the table—or rather, a digital screen—even the phrase “test menu” takes on a different tone. Menus aren’t being handed only to clinicians who order for themselves and patients, like a well-heeled gentleman announcing “The lady will have. . . .” The lady can do her own ordering, thank you very much.

When she gives talks on the subject, Dr. 
Hagenkord makes a point of differentiating between nonclinically valid information—“ancestry, eye color, fun stuff”—and tests that are clinically valid. She notes that with their ability to sequence a genome or exome, consumer labs have the option of including “infotainment” genetic information as well as clinically valid information. The infotainment piece, she says, engages consumers and can increase their genetic literacy, as well as drive family health discussions.

Matthew Ferber, PhD, agrees. He’s the director of Mayo Clinic GeneGuide, a genetic testing experience that lets consumers initiate the test; Mayo’s hook, so to speak, is education.

Mayo has partnered with PWN Health, a physician provider and genetic counseling network licensed in all 50 states, and Helix, which performs the actual sequencing. Dr. Ferber, a clinical molecular geneticist who is also co-director of Mayo’s clinical genomics laboratory and founder of the institution’s clinical genome sequencing center, uses the term near-consumer testing to describe the service.

GeneGuide launched at the end of last September, after a roughly two-year development period. “We felt there was an opportunity for Mayo to do it in a very responsible way,” says Dr. Ferber.

It’s crucial, he says, for consumers to know exactly what they will and won’t get out of the experience (a word that pops up a lot in these conversations). GeneGuide is not aimed at people looking for a diagnosis, but rather at increasing genomic literacy; it does so by including topics such as autosomal recessive diseases, pharmacogenomics, and complex disease. “It’s purely educational,” Dr. Ferber says. The goal is to get people excited about learning, starting with their own DNA. This in turn should lead to deeper conversations about health with family members and physicians, he says.

Mayo advertises on social media and online radio stations but has taken steps to prevent a floodgates-have-opened scenario that many fear. When a consumer purchases a kit online ($199.99, plus $9.95 standard shipping), that triggers a qualification questionnaire that is reviewed by PWN Health. Just because a consumer orders a test doesn’t mean it’s appropriate—you can probably order sushi at a truck stop, too, but that doesn’t make it right.

A pregnant woman can order the GeneGuide test, for example, but will need to acknowledge she understands that the test is not diagnostic and that comprehensive carrier screening is available elsewhere. If a consumer says they are affected by any of the conditions covered by GeneGuide (including as part of their family history), they can’t order the test; instead, they are directed to see their personal physician and pursue diagnostic testing. Likewise, the test is not deemed appropriate for someone who has had a bone marrow transplant or a liver transplant.

Once they’re collected, samples are sent directly to Helix for sequencing.

Mayo receives an alert when sequencing has been completed and will download the portion of data required to drive the GeneGuide interpretation engine. Dr. Ferber reviews the results and interpretations and signs out the reports. These results go first to PWN Health, which does its own review. PWN Health may reach out to patients and schedule a genetic counseling session in the event of a troubling finding—two cystic fibrosis alterations, say, or a positive malignant hyperthermia variant. Only after everyone is comfortable will Mayo release the data to the consumer on its app, says Dr. Ferber.

GeneGuide is not meant to compete with clinical 
 diagnostics, Dr. Ferber says. Its limited menu is meant to whet the appetite of consumers. Testing is divided into four categories:

  • Carrier screening: cystic fibrosis, GJB2-related hearing loss, MCAD deficiency, and sickle cell disease.
  • Medication response: over-the-counter ibuprofen and omeprazole metabolism, and pseudocholinesterase deficiency and malignant hyperthermia susceptibility. The latter two were chosen after discussions with Mayo anesthesiologists. Says Dr. Ferber: “They felt like having that data was as good as having a piece of family history data in a pre-op visit. That level of information, coming from an educational experience like this, would be of value to consumers as well.”
  • Disease risk: age-related macular degeneration, atrial fibrillation, coronary artery disease, and venous thrombo–
embolism.
    All four entail genetic risk but are also influenced by environment, gender, and lifestyle, Dr. Ferber says. Mayo portrays individual risks using a beaker analogy that shows consumers the changing water levels as risks are added/reduced. In many cases, the genetic risks are relatively minor compared with other factors, he notes. With CAD, for example, “If you’re a smoker, that’s a bigger risk than the independent genetic factors that are included within the test. People need to know that.” He and his fellow “nerds are quite happy with how we did this,” he says with a laugh. “I’m eager to see post-market surveys to see if consumers are enjoying this as much as we did in the lab as we built it.”
  • Health traits: alcohol flush reaction, atopic dermatitis, and lactase persistence.

These are not Mayo’s “sweet spots,” Dr. Ferber concedes, but these common traits were included to potentially provide consumers with an a-ha! moment.

Once it completes the sequencing, Helix stores the data on its secure server. “This is important,” says Dr. Ferber. Even though Helix is doing whole exome sequencing, Mayo Clinic GeneGuide has access only to the data being tested for in the GeneGuide kit.

Down the road, the additional data might prove important. And since the test started with the consumer, later follow-up might be easier when, say, a new variant is reclassified—the consumer can be reached directly and quickly. Or, as Dr. Ferber puts it, “The report isn’t just for the physician anymore.”

While waiting for results, users can peruse education modules that cover a range of topics, including genetic fundamentals, heredity, precision medicine, and common familial diseases. Clearly Mayo deems this information important, but Dr. Ferber admits the material continues to be tweaked—based on early returns, he says, consumers appear to be quite focused on their test results, and perhaps a little less so on education.

And for a dose of fun and learning (Dr. Ferber’s words), GeneGuide also offers an interactive pedigree drawing tool, similar to what’s used in professional medical settings, but in a simpler version. Consumers can fill out and edit an electronic survey; users can toggle between a consumer view and a physician view. Dr. Ferber sees several advantages to this flexible approach. First, it keeps the language consistent, without overwhelming patients or oversimplifying matters for professionals. It also helps with accuracy. His clinical colleagues, he says, tell him that patients often inadvertently provide inaccurate information during an office visit. It also encourages patients to include other relatives. “It’s not just you and your doctor and maybe a significant other in the room, trying to recall all this stuff. This allows you to fill out this information while sitting on your couch, in the comfort of your own home.” Ideally, he adds, it will be possible to link individual pedigrees to patients’ EHRs, though this goal is a ways off. “It’s a great idea, but a complex one,” he says.

David Bick, MD, chief medical officer and a faculty investigator at HudsonAlpha, has been keeping a close watch on the field. He’s a coauthor (as are Drs. Hagenkord and Ferber) of an article (Lu JT, et al. J Mol Diagn. 2019;21[1]:3–12) that looked at consumer genomics, including a framework for evaluating analytical and interpretive components of the tests. “The concept for the article was hatched maybe two years ago, when we all realized that elective genomic testing”—Dr. Bick’s preferred phrase—“was becoming extremely widespread. We were saying this is clearly happening—there’s no doubt about that. Let’s do it in a responsible way.”

Adds Dr. Hagenkord: “We’re all part of this first group of clinical pathologists and laboratories that are actually doing real consumer genetics. None of this is hypothetical to us. We run into expected and unexpected problems every day, and we’re starting to amass enough of a knowledge base to help” with future guidelines. The authors noted, for example, that testing in elective settings, in a low-risk population, needs to control false-positive rates in a way that’s different from the diagnostic setting.

Dr. Bick is also associate laboratory director of HudsonAlpha’s Clinical Services Laboratory, which provides a fee-for-service whole genome sequencing and pharmacogenetics test called Insight. About three years ago the company started the Smith Family Clinic for Genomic Medicine (Dr. Bick is the medical director), which uses genomics in regular patient care for those with rare and undiagnosed diseases. When the standard practice of medicine didn’t return an answer, Dr. Bick explains, the next step would entail using whole genome sequencing. Medical history, family history, physical exam results, and medical records from the patient’s personal physician are all sent to the laboratory with the sample. “The laboratory has a lot of clinical information to help them look at the genome and personalize the results to the individual,” he says, adding, “This is what patients/consumers want: a test result that reflects their personal medical situation.”

When he gave talks about this approach, he says, he would invariably be approached by someone who expressed interest in having their own genome sequenced, even though they had no known genetic condition.

For a long time, says Dr. Bick, “We said no—that’s not what we’re focused on. But literally, we got so many requests for this, we said, ‘Why are we telling people that they can’t have their genome analyzed? Why is that? If they want to pay for their own testing, then it should be possible.’”

The ultimate goal, he says, is to identify risk in people who are ostensibly healthy. “What’s happening over and over again,” Dr. Bick says, “is the realization that restricting genetics to people who have some obvious, in-your-face problem leaves out a lot of people who could benefit.”

Of the approximately 50 patients who’ve had their sequencing done, several have been found to have an unexpected variant that suggested a different approach to, say, colorectal cancer screening. Dr. Bick calls this a primary result, related to the individual’s medical problem(s).

Sequencing also yields secondary results, which may lead to disease in the future. One patient was interested in a possible genetic clue to his Parkinson’s disease; no link was found, but he did have a pathogenic variant in BRCA2, which prompted discussions with his sons and granddaughters about possible inheritance.

The clinic also offers carrier status testing. In this case, says Dr. Bick, consumers see the information as a gift of sorts for their children and grandchildren. (The self-pay approach tends to self-select older clients, he says.)

In the case of the pharmacogenetics testing, the clinic tests for 89 different drugs with pharmacogenetic variants. Patients may not currently be on any of the drugs, but having the information available may be useful if they’re prescribed one, he says. “The time you need a pharmacogenetics test is the day before the doctor orders the drug for you.” In one case, an individual who was on Plavix (clopidogrel) was found to have a DNA variant that interfered with his ability to convert the drug into its active form; he subsequently switched to a different platelet inhibitor.

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