[Ip-health] As sequencing moves into clinical use, insurers balk
elizabeth.rajasingh at keionline.org
Thu Jun 19 12:20:59 PDT 2014
BY JULIE STEENHUYSEN
CHICAGO Thu Jun 19, 2014 11:29am EDT
(Reuters) - Aimee Robeson just wants an answer.
Her son, Christian, was born in 2010 with multiple, mysterious syndromes
that leave him unable to speak, chew, or walk on his own.
Initial genetic tests failed to provide a diagnosis. Aimee's hopes are now
pinned on a new test called exome sequencing that searches all the
protein-making genes for glitches that could explain Christian's condition.
Once strictly the domain of research labs, gene-sequencing tests
increasingly are being used to help understand the genetic causes of rare
disease, putting insurance companies in the position of deciding whether to
pay the $5,000 to $17,000 for the tests.
As use of the new technology has grown, a number of insurers, including
Blue Cross Blue Shield, have reacted by putting the brakes on
reimbursement, according to interviews with researchers, diagnostic experts
and insurance executives. Insurers are demanding proof that the results
will lead to meaningful treatments among the estimated 2 million Americans
with a serious, undiagnosed disease, still an unlikely prospect in the
majority of cases.
Genetics experts say that sequencing more than doubles the chances that
families get a diagnosis, and saves spending on multiple tests of single
genes. Even if no treatment is found, the tests can also end hugely
expensive medical odysseys as parents frantically search for the cause of
their child’s furtive illness.
Until the reimbursement issue is resolved, some smaller diagnostics players
will likely stay on the sidelines, leaving the field to early adopters of
the technology such as Ambry Genetics and Bio-Reference Laboratories'
GeneDx. And families short on resources like the Robesons will be left
scrambling for funding.
UNRAVELING RARE DISEASE
Howard Jacob was the first to use gene-sequencing tools to unravel the
mystery of a rare disease in 2009, leading to a bone marrow transplant that
saved a little boy named Nic Volker.
Five years later, Jacob's molecular genetics lab at the Medical College of
Wisconsin has done more than three dozen whole genome sequences, a test
that reads the more than 3 billion letters that make up the human genetic
code. They have sequenced 400 whole exomes, tests that look only at the
protein-making segments of DNA known as exons, which represent 2 percent of
the genome but account for 85 percent of disease-causing mutations.
Baylor College of Medicine in Houston, Texas, has handled 3,500
exome-sequencing cases since it started offering the test in 2011. A study
of its first 250 cases showed whole exome sequencing identified the
disease-causing gene in 25 percent of cases. Since the findings were
published last October, the rate has increased to 28 percent as the list of
known mutations has grown, said Dr. Christine Eng, who directs Baylor's
Whole Genome Sequencing Laboratory.
Eng said insurance companies initially paid for most of the tests, but as
volume has increased, more claims are getting denied. "There are some
companies that are saying out and out, we won't cover this test."
Dr. Allen Bale, director of the DNA Diagnostic Lab at Yale School of
Medicine in Connecticut, has seen a 500 percent increase in orders for
exome sequencing since 2011. The lab does about 750 whole exome tests a
year, and there, too, reimbursement is becoming an issue.
Bale said Medicare does not cover the tests. Other insurers pay enough so
the lab can break even.
"There's a lot of testing we're doing that's getting denied. We appeal it,"
he said. "A lot of time that works, but it's case by case."
LACK OF EVIDENCE
Although gene sequencing is still far from mainstream, its rapidly dropping
cost - which has fallen from $3 billion for the first gene map in 2003 to
as little as $1,000 this year - has made the tests increasingly attractive.
In cases like Christian’s, doctors say it offers a more comprehensive way
to diagnose unexplained syndromes, replacing the guessing game in which
tests are ordered based on what they think the problem might be.
Insurers are not yet convinced.
Dr. Julie Kessel, who directs coverage policy for Cigna, said sequencing
requests were scarcely noticed five years ago. Now, "they're very, very
much on the radar." Cigna generally does not cover whole genome or whole
exome sequencing unless there is a clear clinical reason.
Last August, one of the industry’s biggest players, Blue Cross Blue Shield,
issued a report saying exome sequencing might pinpoint the genetic cause of
disease in up to half of patients, but only a fraction of those will be
able to use that as guidance because treatments don't exist yet. Since
then, Blues plans in Louisiana, North Carolina and Pennsylvania have deemed
exome sequencing "investigational," meaning not eligible for coverage.
Christian's own insurance company, Pennsylvania Medicaid provider UPMC for
You, "didn't budge at all," Aimee Robeson said. The family hired an
attorney and appealed, but lost. The company wanted proof the test would
offer a benefit. Christian’s geneticist wrote a letter listing reasons it
might, but the judge wasn't swayed.
Insurers say their objections stem from a lack of evidence that the tests
can improve patient care.
There are some celebrated examples that it can, such as the Volker case or
Noah and Alexis Beery of California, whose genetic defect left them with
health problems similar to cerebral palsy. Genome sequencing led to highly
effective treatments to replace the missing neurotransmitters that were
causing their symptoms.
In most cases, however, finding a treatment "is vanishingly rare because
we're only just making these discoveries," said Dr. Teri Manolio of the
National Human Genome Research Institute, a part of the National Institutes
At Aetna Inc, Dr. James Cross, vice president of national medical policy
and operations, said sequencing has gotten ahead of the evidence.
Traditionally the company has made coverage decisions based on the
individual test and whether it affects patient outcomes, he said. "With
sequencing, you've got a lot of information that we don't have that kind of
For Ambry Genetics, the first commercial lab to offer whole exome
sequencing, insurance coverage is "all over the map" for the company's
$5,800 test, said billing director Marsha McDonagh. She works with Blue
Cross, Cigna, Aetna, UnitedHealthcare and several Medicaid plans, among
others. "The ones least receptive right now are the Blues," she said.
Consultant Stephane Budel of DeciBio believes the reimbursement issue is
stifling competition among diagnostics providers. Industry players range
from those just ramping up, such as MolecularHealth and Selah Genomics, to
midsize companies such as Ambry and GeneDx and giants such as Illumina and
Thermo Fisher Scientific's Life Technologies.
"There's definitely a number of smaller players that are waiting for this
to be sorted out," said Budel. He believes insurers' concerns will fall
away as sequencing costs continue to fall in the next few years. "There is
very little doubt it is going to become standard of care."
Even without treatments, a diagnosis gives parents the ability to make
better-informed family-planning decisions and puts a stop to repeated
testing that can cost tens of thousands of dollars.
"There's a monumental relief with diagnosis. It changes everything," said
Dr. Richard Gibbs, director of the Baylor Human Genome Sequencing Center,
who sequenced the Beery twins.
Andrea Smith of Winthrop Harbor, Illinois, realized her son Ethan had a
serious problem when a virus turned his urine "the color of Coca-Cola."
With her next boy, Chase, a virus caused kidney failure; the same happened
with her youngest child, Norah. A fourth had no symptoms.
Doctors suspected a genetic form of atypical hymolytic-uremic syndrome, a
kidney disorder. Their case was so compelling that doctors at Children's
Hospital of Wisconsin offered to sequence Norah's genome, funded by a
They learned that three of her children inherited the disorder, and the
fourth is a carrier. But testing also showed the defect could be corrected
with a kidney transplant. Smith says it's too early to consider that option
for her children, but she's glad to know she has one.
Aimee Robeson may soon get an answer as well. Members of her church are
paying the $7,000 for Christian's test.
"I'm relieved it's getting done," Aimee said. "I want to make sure if there
is anything that I could do for my son, that I did it."
Perl Fellow, Knowledge Ecology International
1621 Connecticut Ave. NW, Suite 500
Washington, DC 20009
*elizabeth.rajasingh at keionline.org <elizabeth.rajasingh at keionline.org>* |
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