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发帖数: 2136 | 1 Why Almost Everything You Hear About Medicine Is Wrong
http://www.newsweek.com/2011/01/23/why-almost-everything-you-he
If you follow the news about health research, you risk whiplash. First
garlic lowers bad cholesterol, then—after more study—it doesn’t. Hormone
replacement reduces the risk of heart disease in postmenopausal women, until
a huge study finds that it doesn’t (and that it raises the risk of breast
cancer to boot). Eating a big breakfast cuts your total daily calories, or
not—as a study released last week finds. Yet even if biomedical research
can be a fickle guide, we rely on it.
But what if wrong answers aren’t the exception but the rule? More and more
scholars who scrutinize health research are now making that claim. It isn’t
just an individual study here and there that’s flawed, they charge.
Instead, the very framework of medical investigation may be off-kilter,
leading time and again to findings that are at best unproved and at worst
dangerously wrong. The result is a system that leads patients and physicians
astray—spurring often costly regimens that won’t help and may even harm
you.
(Gallery: Medical Breakthroughs: The Good and the Bad)
It’s a disturbing view, with huge im-plications for doctors, policymakers,
and health-conscious consumers. And one of its foremost advocates, Dr. John
P.A. Ioannidis, has just ascended to a new, prominent platform after years
of crusading against the baseless health and medical claims. As the new
chief of Stanford University’s Prevention Research Center, Ioannidis is
cementing his role as one of medicine’s top mythbusters. “People are being
hurt and even dying” because of false medical claims, he says: not
quackery, but errors in medical research.
This is Ioannidis’s moment. As medical costs hamper the economy and impede
deficit-reduction efforts, policymakers and businesses are desperate to cut
them without sacrificing sick people. One no-brainer solution is to use and
pay for only treatments that work. But if Ioannidis is right, most
biomedical studies are wrong.
In just the last two months, two pillars of preventive medicine fell. A
major study concluded there’s no good evidence that statins (drugs like
Lipitor and Crestor) help people with no history of heart disease. The study
, by the Cochrane Collaboration, a global consortium of biomedical experts,
was based on an evaluation of 14 individual trials with 34,272 patients.
Cost of statins: more than $20 billion per year, of which half may be
unnecessary. (Pfizer, which makes Lipitor, responds in part that “managing
cardiovascular disease risk factors is complicated”). In November a panel
of the Institute of Medicine concluded that having a blood test for vitamin
D is pointless: almost everyone has enough D for bone health (20 nanograms
per milliliter) without taking supplements or calcium pills. Cost of vitamin
D: $425 million per year.
Ioannidis, 45, didn’t set out to slay medical myths. A child prodigy (he
was calculating decimals at age 3 and wrote a book of poetry at 8), he
graduated first in his class from the University of Athens Medical School,
did a residency at Harvard, oversaw AIDS clinical trials at the National
Institutes of Health in the mid-1990s, and chaired the department of
epidemiology at Greece’s University of Ioannina School of Medicine. But at
NIH Ioannidis had an epiphany. “Positive” drug trials, which find that a
treatment is effective, and “negative” trials, in which a drug fails, take
the same amount of time to conduct. “But negative trials took an extra two
to four years to be published,” he noticed. “Negative results sit in a
file drawer, or the trial keeps going in hopes the results turn positive.”
With billions of dollars on the line, companies are loath to declare a new
drug ineffective. As a result of the lag in publishing negative studies,
patients receive a treatment that is actually ineffective. That made
Ioannidis wonder, how many biomedical studies are wrong?
His answer, in a 2005 paper: “the majority.” From clinical trials of new
drugs to cutting-edge genetics, biomedical research is riddled with
incorrect findings, he argued. Ioannidis deployed an abstruse mathematical
argument to prove this, which some critics have questioned. “I do agree
that many claims are far more tenuous than is generally appreciated, but to
‘prove’ that most are false, in all areas of medicine, one needs a
different statistical model and more empirical evidence than Ioannidis uses,
” says biostatistician Steven Goodman of Johns Hopkins, who worries that
the most-research-is-wrong claim “could promote an unhealthy skepticism
about medical research, which is being used to fuel anti-science fervor.”
Even a cursory glance at medical journals shows that once heralded studies
keep falling by the wayside. Two 1993 studies concluded that vitamin E
prevents cardiovascular disease; that claim was overturned by more rigorous
experiments, in 1996 and 2000. A 1996 study concluding that estrogen therapy
reduces older women’s risk of Alzheimer’s was overturned in 2004.
Numerous studies concluding that popular antidepressants work by altering
brain chemistry have now been contradicted (the drugs help with mild and
moderate depression, when they work at all, through a placebo effect), as
has research claiming that early cancer detection (through, say, PSA tests)
invariably saves lives. The list goes on.
Despite the explosive nature of his charges, Ioannidis has collaborated with
some 1,500 other scientists, and Stanford, epitome of the establishment,
hired him in August to run the preventive-medicine center. “The core of
medicine is getting evidence that guides decision making for patients and
doctors,” says Ralph Horwitz, chairman of the department of medicine at
Stanford. “John has been the foremost innovative thinker about biomedical
evidence, so he was a natural for us.”
Ioannidis’s first targets were shoddy statistics used in early genome
studies. Scientists would test one or a few genes at a time for links to
virtually every disease they could think of. That just about ensured they
would get “hits” by chance alone. When he began marching through the
genetics literature, it was like Sherman laying waste to Georgia: most of
these candidate genes could not be verified. The claim that variants of the
vitamin D–receptor gene explain three quarters of the risk of osteoporosis?
Wrong, he and colleagues proved in 2006: the variants have no effect on
osteoporosis. That scores of genes identified by the National Human Genome
Research Institute can be used to predict cardiovascular disease? No (2009).
That six gene variants raise the risk of Parkinson’s disease? No (2010).
Yet claims that gene X raises the risk of disease Y contaminate the
scientific literature, affecting personal health decisions and sustaining
the personal genome-testing industry.
Statistical flukes also plague epidemiology, in which researchers look for
links between health and the environment, including how people behave and
what they eat. A study might ask whether coffee raises the risk of joint
pain, or headaches, or gallbladder disease, or hundreds of other ills. “
When you do thousands of tests, statistics says you’ll have some false
winners,” says Ioannidis. Drug companies make a mint on such dicey
statistics. By testing an approved drug for other uses, they get hits by
chance, “and doctors use that as the basis to prescribe the drug for this
new use. I think that’s wrong.” Even when a claim is disproved, it hangs
around like a deadbeat renter you can’t evict. Years after the claim that
vitamin E prevents heart disease had been overturned, half the scientific
papers mentioning it cast it as true, Ioannidis found in 2007.
The situation isn’t hopeless. Geneticists have mostly mended their ways,
tightening statistical criteria, but other fields still need to clean house,
Ioannidis says. Surgical practices, for instance, have not been tested to
nearly the extent that medications have. “I wouldn’t be surprised if a
large proportion of surgical practice is based on thin air, and [claims for
effectiveness] would evaporate if we studied them closely,” Ioannidis says.
That would also save billions of dollars. George Lundberg, former editor of
The Journal of the American Medical Association, estimates that strictly
applying criteria like Ioannidis pushes would save $700 billion to $1
trillion a year in U.S. health-care spending.
Of course, not all conventional health wisdom is wrong. Smoking kills, being
morbidly obese or severely underweight makes you more likely to die before
your time, processed meat raises the risk of some cancers, and controlling
blood pressure reduces the risk of stroke. The upshot for consumers: medical
wisdom that has stood the test of time—and large, randomized, controlled
trials—is more likely to be right than the latest news flash about a single
food or drug. |
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