Genetic testing: Counselors Desperately Needed

As genetic tests proliferate, physicians, patients, and health plans need someone to lead them through a minefield of valuable but occasionally conflicting information. Only 1 genetic counselor exists for every 650,000 people in the United States.

Abstract

Genetic tests are proliferating, and payers, PBMs, and professional societies are developing in-house expertise to fill the counseling gap. All agree that more education programs and clinical decision tools are needed. But hard questions about data validity have to be answered first if personalized medicine is to become a reality.

For the past 18 months, Quest Diagnostics has been selling a test that can detect variants of the UGT1A1 gene. Some doctors order the test for patients undergoing chemo therapy for metastatic colorectal cancer to evaluate whether they are likely to have an adverse reaction to the chemotherapy drug irinotecan (Camptosar).

A slate of experts put together by the Centers for Medicare and Medicaid Services Office of Public Health Genomics — the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group — determined recently that there is good reason to believe the test could help identify patients likely to experience such side effects as diarrhea and neutropenia.

But there’s a sizeable pitfall awaiting anyone who uses it.

If doctors decide to reduce the dosage of the drug because of test results, says the EGAPP Working Group, they could end up doing more harm than good by not providing the patient with a strong enough dose to fight the cancer.

But the group also concluded that genetic testing for Lynch syndrome, which helps to trigger colorectal cancer, is a good thing. Armed with that knowledge, someone at high risk could get the needed screening tests done early enough to allow for quick intervention.

“Our review of the evidence found that in some situations, genetic testing may be helpful, but in other situations — including some genetic tests currently used in cancer care — there is not enough evidence available to determine the balance of benefits and harms,” says Alfred Berg, MD, MPH, chair of the EGAPP Working Group.

With a wave of new genetic tests hitting the market, promising to help identify the right drug regimen for a particular patient or to illuminate an individual’s risk of disease, independent expert panels like the EGAPP Working Group are still in the early stages of considering just how useful genetic testing is. In the meantime, a broad swath of practicing physicians — as well as insurers — are relying on what is a short supply of genetic counselors and clinical geneticists to provide them with the latest guidance.

Some 3,000 certified genetic counselors and perhaps 1,000 more clinical geneticists are currently at work in the United States. Although the profession itself is far from new, the onslaught of genetic tests means that the data they work with often are. And they frequently find themselves leading physicians, patients, and insurers through a minefield of newly minted — and occasionally conflicting — information.

But while the genetic counseling profession is small, the field is far from static. Some insurers have been developing their own in-house expertise as well as contracting with genetic counseling companies. Medco, the pharmaceutical benefit manager, has decided to mount its own studies to accumulate the hard data it needs to understand how to advise its clients about genetic tests. Professional societies, meanwhile, are taking a bigger role. And some advocates urge adoption of a new set of clinical support tools that can bring practical advice directly into the clinic.

MICHAEL JUSTICE

“At the laboratory level, my job is to make sure it’s not snake oil and that there’s science behind it,” says Charles Strom, MD, PhD, medical director of Quest Diagnostic’s genetic testing center. “We don’t want to offer something that turns out to be nonsense.”

SO MANY TESTS

“Most genetic counselors work out of hospitals or physician offices,” says Steven Keiles, MS, CGC, vice president, director of genetic services at Ambry Genetics, based in Aliso Viejo, Calif., and president of the National Society of Genetic Counselors. Most major universities and children’s hospitals have genetics divisions, and hundreds of other counselors either work for laboratories or independent medical groups, Keiles says. “And some HMOs have their own genetic counselors.

“A lot of specialty medicine is moving into primary care, and the role of the counselor is to advise physicians who don’t have the resources and can’t handle this expanse of genomic medicine,” says Keiles.

In late 2007, Aetna contracted with Informed Medical Decisions, a national genetics counseling company based in Palm Springs, Calif., to counsel cancer patients whose plans included coverage for genetic testing. Humana says it’s looking into offering genetic counseling as well. And Kaiser Permanente has one of the largest internal groups of genetic advisors on hand, with five separate regional genetic centers in northern California alone.

“This new advance into personalized medicine genetics is really making its way into every branch of medicine,” says Joann Bergoffen, MD, chief of the department of genetics at the Kaiser Permanente Regional Genetics Laboratory in San Jose, Calif. “Twenty or 30 years ago, genetics was related to rare conditions. It was unknown and mystical. Now genetics is really going to touch on common diseases, and is going to make its way into general medical practice.”

Giving better advice on genetic testing will depend on getting better data on how the tests work in practice.

Many physicians acknowledge that when it comes to genetics, there is a big gap between what they know and what they should know, says Teresa Deluca, MD, MBA, at Medco.

“It’s interesting how little clinical data there are for some of these tests,” says the EGAPP Working Group’s Berg. “One of our messages is that we need better-quality research. You can go to EGAPP and get advice on a handful of things, and you can search the databases, but there’s no single place where you can get the information.”

If you were to look around the world, he says, you would find other tech-assessment efforts underway to explore the utility of genetic testing.

“The core problem is that there are hundreds, if not thousands, of tests out there,” he adds. “We’re trying to come up with models to do evidence-based reviews of different tests in different settings.”

And most practicing physicians, Berg says, are simply unaware of the latest data on these tests.

Genetic counseling grew up around single genetic tests for rare disorders. Now, says Berg, many genetic tests are supposed to be used in primary care, where you can get a test to determine whether you should get an SSRI [selective serotonin reuptake inhibitor] drug for depression or a prescription for a blood thinner. “That’s a very different kind of scenario. It’s so common that no one imagines that only genetic counselors can handle it —there just aren’t enough of them.”

A HUGE PROBLEM

It’s not unusual for Charles Strom, MD, PhD, medical director of Quest’s genetic testing center, to hear straight from physicians that they don’t think a genetic test works as billed — in part because they may rarely turn up positive. But that’s not unusual, Strom says, “especially when you consider some genetic tests turn out positive in something like 5 percent of cases.” If you do the test on a small group of patients over some months, he adds, you might not get any positives.

“At the laboratory level, my job is to make sure it’s not snake oil and that there is science behind it,” says an affable and outspoken Strom. “We tend to be pretty conservative in my shop. We don’t want to offer something that turns out to be nonsense. People trust us.”

Many physicians wouldn’t know how to contact a geneticist, says Strom. “Which is why I get a call, or it goes to one of our genetic counselors. You may say I’m biased. But I’m an MD — I’ve taken the Hippocratic oath. Sometimes I tell people that it’s really early. I’ll give them the literature on how people are using it. I can’t recommend or not recommend it. Or, if I know, I’ll say, ‘This is what I recommend.’”

Strom and about a dozen genetic advisors are on hand at Quest to field calls from physicians, and he’s acutely aware of the small number of people overall who are qualified to handle their questions.

One study found that a country should have 1 clinical geneticist per 250,000 population. Right now, in the United States, there’s just 1 per 650,000.

“I think it’s a huge problem,” he adds. “There is a dearth of people like me, less than a thousand practicing clinical geneticists. That’s a very small number.”

In the vacuum, Strom says, a growing number of physicians are turning to their professional organizations for advice.

“When we talk, no one listens. When the American College of Obstetricians and Gynecologists talks, everyone listens.

“For good or ill, there are two major motivating factors: malpractice lawsuits and professional societies. Some day, someone will die or get severely ill because he or she did not have a pharmacogenomic test that the FDA had a position on or a society had a position on, and the physician will be sued. The society will do a practice bulletin, and you’ll see a surge of adoption.

“It’s not ideal, but tort attorneys will tell you that they are at the end of the quality assurance process. These are very dangerous times for practicing physicians. There’s all this new information, and they will fall back on their societies for the standard of care.”

Often, even the experts can have a hard time navigating the evidence for a test.

“There are many, many gray areas, especially when it comes to these newer pharmacogenomics tests that look at drug response or side effects based on your genotype,” says Heather L. Shappell, MS, CGC, a certified genetic counselor and the founder of Informed Medical Decisions.

“There isn’t as much evidence,” she adds. “You see a couple of reports showing that it could be useful, and then a company starts marketing the test as if it’s proven to help make treatment decisions. This whole thing goes back to a serious issue — there is no regulation of genetic testing like there is for drugs.”

Shappell and other certified genetic counselors feel they are on much firmer footing with evaluating a person’s risk for hereditary disease. Referring to the National Comprehensive Cancer Network’s guidelines, Shappell can navigate the equation between increased risk and a sensible schedule for disease screening. A history of colon cancer in a close family situation, for example, could dictate that family members start getting colonoscopies in their early 20s, or 10 years before the age at which a family member has been diagnosed with colon cancer. For payers, that’s the kind of advice that could help prevent someone from getting more screening services than needed, as well as offer family members a chance to detect cancer when it can be most effectively treated.

Shappell’s company doesn’t do genetic counseling on pharmacogenomic tests, but it does offer consulting arrangements to help insurers sort out which of these tests are available.

“We don’t have outcomes data to really make a good decision,” she adds. “The EGAPP’s decision with the UGT1A1 test was that there was not enough [evidence] to recommend for or against its use. We need more data, and the only way to get more data is to use the tests and follow the people to see if their outcomes are affected.”

Which is what Medco is doing.

NO TIME TO LEARN

Teresa Deluca, MD, MBA, vice president of personalized medicine at Medco Health Solutions, says she talks to doctors about genetics on a regular basis. And many physicians, especially those who have been practicing medicine the longest, are quick to acknowledge a big gap between what they know and what they should know.

“A common response,” says Deluca, is ‘I know it’s there, but I don’t have time to learn it.’”

That gives Medco the opportunity to step in and provide its own advice on what the giant PBM believes is one of the most important goals in pharma today — using the right drug on the right patient at the right time. And it’s gathering outcomes data on genetic testing to back it up.

Deluca thought that most payers would have to see the data before they bought in. But she was bowled over by the response.

Currently, Medco has enrolled 100 clients in two pharmacogenomic studies on warfarin and tamoxifen. Those companies agreed to pay all the costs for the genetic tests that guide the use of both drugs for their employees.

These clients recognize the scientific value and the economic story, Deluca says. “So this is moving faster than we would have anticipated.”

If you need warfarin and your employer is one of those 100 pioneers, says Deluca, your doctor gets a call from a “research center pharmacist, trained in genomics. If the doctor approves, we will then call you and explain who is calling and why. If you agree that this is something you want to do, the lab is contacted, a swab test is sent out, and the research center pharmacist counsels the doctor on the results.” Medco tracks the response against a baseline.

“Within the first six months of a warfarin prescription, there’s a 25 percent chance of hospitalization due to bleeding or stroke. By adding genomic information, you have a better chance of getting the dose correct and preventing bleeds and strokes.

“We can see data in real time. We know when the prescription is filled or not refilled,” says Deluca, the primary investigator for both studies, which are being wrapped, reviewed, and presented to professional societies later this year.1

Medco plans to move at a deliberate pace. Later this year, says Deluca, the company will add at least one more genetic test under review to the mix, and may offer studies on up to three new genetic tests by the end of the year.

It’s still early days, though. And Deluca wasn’t at all surprised to hear about the dispute regarding Camptosar.

“It is an evolving field,” she says. As new data are delivered, “we will be able to use more of the science and less of the art of medicine with more precision” when it comes to defining the right dose of the right drug for the right patient.

FILLING THE GAP

Last fall, the American College of Medical Genomics started a public campaign urging people to start a new page on their family tree —one that tracks which relatives have been sickened by disease. Paired with DNA risk-testing, they said, disease genealogy would give each of us an inside track on the health problems that lie ahead.

“Even in our ‘high tech’ world, family history remains the most sensitive genetic test known,” said the ACMG. But the ACMG also is quick to note that there just isn’t enough expert knowledge on genetics to translate for the population as a whole.

According to a study by the United Kingdom’s Royal College of Physicians, says ACMG executive director Michael S. Watson, MS, PhD, a country should have 1 clinical geneticist per 250,000 in population. Right now, there’s 1 per 650,000 Americans.

There are three distinct areas of genetics that call for expert knowledge, he adds: Rare disease genetics, which has spawned a move to screen virtually all newborns for genetic ailments; the “middle” ground of genetics, in which specific genetic variations are linked to a significantly increased risk of disease, like BRCA gene variations in breast cancer; and “common disease genetics” linking people to an increased risk of cardiovascular disease or type 2 diabetes.

“Most breast cancer patients don’t have BRCA abnormalities,” says Watson. “They’re in a more garden-variety breast cancer group with lower genetic strength, so to speak. And because of the number of people who may have low-strength, moderate-risk genes, there aren’t enough people on the planet to see all of them.”

As a result, Watson says, the United States needs to move to increase not only the number of professional geneticists at work, but also to work at improving education in genetics for primary care doctors. But, he adds, don’t expect the average physician to take time away from his or her practice to learn.

“Physicians just don’t have much time for continuing medical education,” says Watson. “They’re rolling patients through on a rapid basis, and there is not much time left for education on something about which they may get asked questions.”

Instead, he says, it would be more beneficial to develop the kind of clinical decision support tools that could be used to guide physicians on cases as they arise, much the way the ACMG helped to develop support tools for doctors to understand the wave of newborn screening tests that have been adopted.

One option would be to advance new programs that would make it easy for doctors to compute the mathematical calculations on disease risk based on family history. And the current push for electronic medical records and more efficient healthcare under the Obama administration provides a fertile ground to plant the seeds.