Dutch association against quackery, and genetic testing
Peter Brooks
instances of it.
http://www.bmj.com/cgi/eletters/336/7649/853
Interestingly the current supply of genetic tests to people seems a
prime candidate for exposure as quackery. I think that this article
makes some interesting points:
"
BMJ 2008;336:858-860 (19 April), doi:10.1136/bmj.39534.451458.AD
Feature
Direct to Consumer Genetic Testing
Knowing me, knowing you
Jeanne Lenzer, medical investigative journalist1, Shannon Brownlee,
senior fellow2
1 New York, 2 New America Foundation, Washington, DC
Correspondence to: J Lenzer jeanne...@gmail.com
Patients are beginning to present with not only a web diagnosis but
predictions of future disease. Jeanne Lenzer and Shannon Brownlee
examine the problems of the rise in commercial genetic testing
Do you want to Google your genes or peer into your future risks of
heart disease or cancer? Now you can, according to direct to consumer
testing companies. Gone are the days when genetic testing was limited
to doctors ordering tests for rare, but prognostically potent, single
gene disorders such as Huntington’s disease, Duchenne’s muscular
dystrophy, or cystic fibrosis. Thanks to an explosion of newly
discovered single nucleotide polymorphisms, or SNPs (pronounced
snips), companies are marketing genetic tests for traits ranging from
the mundane—eye colour and wet ear wax—to serious conditions such as
Crohn’s disease and Alzheimer’s disease.
While the global market for these tests is growing rapidly—estimated
at $730m (£366m; 463m) last year and growing by 20% annually1—evidence
that they can provide patients with clinically useful information is
lagging far behind. There is little regulatory oversight of the tests,
and even less in the way of clinical data to help doctors guide
patients who go to them carrying printouts of their genetic details.
Genetic tests and "personalised medicine" are supposed to enable
doctors to customise each patient’s care, yet there is a paucity of
studies on interventions for patients with genetic variants.
The promise being made to consumers is clear: forewarned is forearmed.
The website for deCODE genetics, based in Reykjavik, says its tests
will "help to empower individuals and their doctors." The Californian
company 23andMe, which has backing from Google and the biotech company
Genentech, provides an "odds calculator" that the company says will
allow customers to see which "health concerns are most likely to
affect a person with your genetic profile." Navigenics, also based in
California, claims its tests can provide a "roadmap to optimal health"
that can enable customers to "take action before a disorder strikes to
delay or even prevent the illness altogether." And all for a fee
ranging from $1000 to $2500.
A more likely scenario is that these tests will raise more questions
than they answer. It is unclear what consumers think they are learning
from their "genetic blueprints." Some screening tests, though non-
invasive and seemingly harmless, have been shown to trigger a cascade
of further evaluations and interventions that result in measurable
harms while providing no benefit.2 3 4 5
Although widespread genetic testing might eventually lead to well
defined risk profiles and the ability to tailor drugs to the
individual, such results may not be available for many years. In the
meantime, genetic testing poses important and largely unacknowledged
risks. As well as clinical concerns, there are questions about the
effect of the corporate partnerships that link genomic data mining
companies to electronic medical records, hospitals, and drug
companies.
Genomics revolution
Direct to consumer genetic testing has its roots in the human genome
project, which was launched in 1984 with the promise of opening
frontiers in medicine. Novel, personalised treatments would flow from
an understanding of genetic underpinnings of disease, and some experts
predict that the genomics revolution is poised to deliver information
that will allow people to make personalised lifestyle changes or
decide whether to have a child, and allow doctors to prescribe correct
drugs at correct doses.6 Linda Avey, cofounder of 23andMe, is an
advocate of personalised medicine. "We’re still using very antiquated
systems for diagnosis and for prescribing therapies. Whenever you take
a drug it’s kind of a gamble whether your body will respond
appropriately to it," she said.
Thus far, however, only a handful of genetic tests can indicate how a
patient will react to a drug, and even then, the test may lack
clinical value. For example, a working group that reviewed studies of
dosing of serotonin reuptake inhibitor drugs based on the CYP450
polymorphism concluded that there is no evidence that the test is
"useful in medical, personal, or public health decision-making."7 Even
the discovery of the genes for many single gene conditions has failed
to lead to the expected cures. For some diseases, like Huntington’s
disease and sickle cell anaemia, the prospects for treatment seem as
remote as they were before the genes were discovered.
Along with genetic information, some companies offer to calculate a
customer’s risk of developing conditions such as type 2 diabetes,
cardiovascular disease, and prostate and breast cancer. 23andMe, for
example, offers a scan of some 580 000 SNPs and a report on roughly 14
conditions for which customers might be at risk. These risk
calculations are exceedingly rough, however, as most SNPs have been
only loosely connected to any particular disease, and there are few
hard numbers that can accurately predict the contribution of a
particular polymorphism to an individual’s phenotypic risk.
A lack of data has not stopped genomics companies from capitalising on
the appealing concept of personalised medicine, starting with their
names, which include 23andMe (23 chromosomes), deCODEme, and Knome
(pronounced know me). Knome is founded by George Church, professor of
genetics at Harvard, who helped develop the first direct genomic
sequencing method. For upwards of $350 000, Knome will sequence a
customer’s entire genome. 23andMe also provides genetic information
for "entertainment" and "education" purposes, such as whether one has
genetic markers for an enhanced ability to taste bitterness or for
athleticism.
Companies are careful to acknowledge in the fine print the lack of
meaningful data. In a special message "To the Medical Community,"
23andMe acknowledges that the information it provides "is tailored to
genotypes not to individuals"—an acknowledgment that belies the claim
of personalised, clinically relevant health information. But 23andMe
cofounder Anne Wojcicki argues that people have a right to know their
genetic information and says that the company is not providing
"actionable" health information but information that is largely
intended to educate and lead to better research.
But what is it that customers are being educated about? When asked if
customers of 23andMe were under the impression that they could obtain
health information that would be useful to them, Professor Church, who
is an adviser to 23andMe, responded, "I hope not." He added,
"Education is useful, but distinct from clinically accepted
diagnoses."
Estimating risk
Nevertheless, doctors are likely to be seeing more and more patients
arriving at their doors, genomic results in hand, requesting treatment
for diseases they do not yet have or more screening tests. Most
doctors, according to a recent systematic review by RAND Health, are
"woefully underprepared" to counsel patients about genetic tests.8
According to one study cited in the review, only 5% of doctors said
they felt "confident in their ability to interpret test results."
Rather than improving health, widespread genetic testing is likely to
result in widespread anxiety. In a commentary published in JAMA,
Gilbert Welch and Wylie Burke caution that there is substantial
confusion about estimates of genetic risk.9Selection bias, they say,
can lead to "overestimates of both risks and consequences of disease."
For example, the oft cited 87% risk of cancer by the age of 70 years
among women who test positive for the BRCA1gene was derived from tests
of exceptionally high risk women who had at least four family members
with ovarian or breast cancer diagnosed before age 60 years. Far lower
estimates were obtained when the inclusion criteria for testing were
broadened.9 Another form of bias, surveillance bias, can lead to
similar exaggeration of risk when people with a certain genetic trait
choose to have more frequent testing. "The quickest way to develop
breast cancer," said Dr Welch, "is to be tested for it."
Framing risk can have a powerful effect—an effect that genomics
companies are putting to use when marketing their tests. The website
of 23andMe warns of a "1 in 8" chance of developing breast cancer, a
risk that can be expected to alarm many women. Yet a woman’s risk is
that high only once she reaches the age of 70. In the US, such risk
estimates have led many women to overestimate their chances of dying
of breast cancer, which accounts for only 3% of female deaths annually.
10
Similarly, telling men (accurately) that more than half of them will
have prostate cancer by the age of 60 years, and that men with certain
genetic variants have a four times greater risk of developing prostate
cancer than men with none of those variants (also accurate) could
understandably persuade some men to have prostate specific antigen
testing.10 But if the information is framed differently men might not
be so enthusiastic. "Only 3% of men die of prostate cancer," Dr Welch
says. Instead of telling men that they are at an 80% increased risk of
developing prostate cancer, he says, doctors should tell men that
their lifetime risk of dying from prostate cancer is 3%. "And an 80%
increase of that risk doesn’t even increase the risk to 6%."
Research benefits
The potential pay-off, for both patients and companies, lies with
pharmacogenomics, the development of new, more personalised drugs.
This requires access to huge numbers of research subjects, their
genomes, and their phenotypic (clinical) records—an extraordinarily
expensive undertaking. In a clever reversal, companies are getting
research subjects to pay—rather than be paid—to become research
subjects. Genetic testing companies’ primary source of income is fees
paid by customers. In future, they can expect to earn even more by
selling the genomic information they gather to researchers and to
biotechnology and drug companies. Customers of 23andMe sign a consent
document indicating that the company may share their genomic data
(anonymously) and that the company may sell the data to researchers.
Customers of 23andMe are asked if they would like to make their health
records available (free) to researchers to advance medical science.
Companies are planning ways to integrate genomic data with phenotypic
information from patients’ electronic records. Google, which invested
$3.9m in 23andMe, is poised to launch its online personal health
records. (The cofounder of Google, Sergey Brin, is married to Ann
Wojcicki, cofounder of 23andMe.) Ms Avey says 23andMe plans to work
with personal health record companies to enable data merger.
Although 23andMe insists it is in the business of advancing research,
its commercial appeal to the public suggests a different interest. Dr
Welch says that telling customers about their risk factors could
result in surveillance bias. "They might be conducting research," he
said, "but it won’t be goodresearch."
The potential gold mine in combining genomic and phenotypic
information is evident from the fact that at least one company, the
Coriell Institute for Medical Research in New Jersey, is offering
genetic testing to 10 000 people. The institute has partnered with
several healthcare organisations, including Cooper University
Hospital, which is offering Coriell’s free genomic screening to the
first 2000 of its 5500 employees who sign up. The response has been
"overwhelmingly positive," according to a hospital spokeswoman.
Cooper’s chief medical officer, Simon Samaha, says that the hospital
is planning training sessions for doctors, who expect an influx of
patients after the screening.
While genomic databases may lead to better drugs, integrating genomic
and phenotypic data has raised concerns about potential discrimination
by insurance companies and employers. In the US, antidiscrimination
laws vary from state to state, and there is little agreement among
payers, physicians, researchers, and patients about whether insurance
companies should have access to genomic information. Dr Samaha says
that he’s not sure that it’s wrong for insurance companies to have
access to such genomic data: "It raises a question about how open the
economy should be."
Failed regulation
Concerned with the potential for harm, advisory bodies in the US and
UK have recommended regulatory oversight of direct to consumer genetic
testing—yet national agencies in both countries have failed to act.
According to Public Citizen’s Health Research Group, a public interest
group based in Washington, DC, the 2004 draft report by the US
secretary’s advisory committee on genetics, health and society was
"notable" for its "accurate diagnosis of the manifold problems in the
oversight of genetic testing and . . . for its complete failure to
identify an appropriate treatment for these problems."11
Critics say that regulatory oversight is uneven to non-existent. There
is little oversight of clinical validity (is the genetic variant
reliably associated with the phenotypic change observed?) and clinical
utility (do enhanced surveillance, prophylactic treatment, or
lifestyle changes improve outcome?).
Even accurate detection of genetic variants is not necessarily
assured. In 1997 and 2001, US governmental groups and an earlier
advisory panel recommended proficiency testing for all laboratories
doing genetic tests—but those recommendations were simply ignored by
federal agencies.12 In an almost comical response, the Center for
Medicare and Medicaid Services, the agency responsible for ensuring
analytical validity under the Clinical Laboratory Improvement
Amendments, argued that setting laboratory standards for genetic
testing was too difficult. To prove its point, it cited the agency’s
previous difficulty in ensuring the accuracy of cervical smear
testing, which took 17 years to complete. The reason the amendments
were passed (and proficiency testing instituted) was because of
massive malpractice suits resulting from the deaths of women whose
cervical smears had been misread.12
Peter Lurie, deputy director of Public Citizen’s Health Research
Group, is disturbed by the lack of oversight of genetic testing. He
worries that the public may "assume there is the same degree of
oversight" for genetic tests as there is for tests such as a red blood
cell count. "But," he said, "they are not even remotely the same."
Similar problems plague the UK. Sir John Sulston, acting chair of the
Human Genetics Commission, which lacks regulatory authority, says that
nothing has changed since December 2007, when he wrote that direct to
consumer genetic testing is "for now, largely in the hands of
commercial test providers: the pharmaceutical companies, their
marketing departments and PR agents."13
What all this means is that testing companies are operating in a
regulatory vacuum. The steps needed to protect the public have been
clearly laid out by the various public interest groups and advisory
panels. Until national agencies act, it will be up to doctors to
handle the expected influx of questions and problems that arise from
direct to consumer genetic testing. The first step towards reducing
the chances of harm posed by widespread genetic testing is to educate
doctors and patients about the limited value and potential harms of
testing.11 12 13
Perhaps the most powerful argument for regulation comes from a
surprising source. Dietrich Stephan, cofounder and chief science
officer of Navigenics, says that his company has had discussions with
the Food and Drug Administration and determined that "right now we are
exempt from FDA regulation." But he says his company would welcome FDA
oversight because there are "a lot of charlatans and pseudoscience
occupying this space and we are ready to be regulated."
Competing interests:None declared.
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"