Why Almost Everything You Hear About Medicine Is Wrong

Why Almost Everything You Hear About Medicine Is Wrong

by Sharon Begley, Newsweek, January 24, 2011

"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.

It’s a disturbing view, with huge implications 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...."

As much as 90 percent of the published medical information that doctors rely on is flawed

Lies, Damned Lies, and Medical Science - Magazine - The Atlantic

"Much of what medical researchers conclude in their studies is misleading, exaggerated, or flat-out wrong. So why are doctors—to a striking extent—still drawing upon misinformation in their everyday practice? Dr. John Ioannidis has spent his career challenging his peers by exposing their bad science."

"...Though the results of drug studies often make newspaper headlines, you have to wonder whether they prove anything at all. Indeed, given the breadth of the potential problems raised at the meeting, can any medical-research studies be trusted?

That question has been central to Ioannidis’s career. He’s what’s known as a meta-researcher, and he’s become one of the world’s foremost experts on the credibility of medical research. He and his team have shown, again and again, and in many different ways, that much of what biomedical researchers conclude in published studies—conclusions that doctors keep in mind when they prescribe antibiotics or blood-pressure medication, or when they advise us to consume more fiber or less meat, or when they recommend surgery for heart disease or back pain—is misleading, exaggerated, and often flat-out wrong. He charges that as much as 90 percent of the published medical information that doctors rely on is flawed. His work has been widely accepted by the medical community; it has been published in the field’s top journals, where it is heavily cited; and he is a big draw at conferences. Given this exposure, and the fact that his work broadly targets everyone else’s work in medicine, as well as everything that physicians do and all the health advice we get, Ioannidis may be one of the most influential scientists alive. Yet for all his influence, he worries that the field of medical research is so pervasively flawed, and so riddled with conflicts of interest, that it might be chronically resistant to change—or even to publicly admitting that there’s a problem....

[Ioannidis] goes on to suggest that an obsession with winning funding has gone a long way toward weakening the reliability of medical research....

In poring over medical journals, he was struck by how many findings of all types were refuted by later findings....

And before long he discovered that the range of errors being committed was astonishing: from what questions researchers posed, to how they set up the studies, to which patients they recruited for the studies, to which measurements they took, to how they analyzed the data, to how they presented their results, to how particular studies came to be published in medical journals.

This array suggested a bigger, underlying dysfunction, and Ioannidis thought he knew what it was. “The studies were biased,” he says. “Sometimes they were overtly biased. Sometimes it was difficult to see the bias, but it was there.” Researchers headed into their studies wanting certain results—and, lo and behold, they were getting them. We think of the scientific process as being objective, rigorous, and even ruthless in separating out what is true from what we merely wish to be true, but in fact it’s easy to manipulate results, even unintentionally or unconsciously. “At every step in the process, there is room to distort results, a way to make a stronger claim or to select what is going to be concluded,” says Ioannidis. “There is an intellectual conflict of interest that pressures researchers to find whatever it is that is most likely to get them funded.”....

How should we choose among these dueling, high-profile nutritional findings? Ioannidis suggests a simple approach: ignore them all.

For starters, he explains, the odds are that in any large database of many nutritional and health factors, there will be a few apparent connections that are in fact merely flukes, not real health effects—it’s a bit like combing through long, random strings of letters and claiming there’s an important message in any words that happen to turn up. But even if a study managed to highlight a genuine health connection to some nutrient, you’re unlikely to benefit much from taking more of it, because we consume thousands of nutrients that act together as a sort of network, and changing intake of just one of them is bound to cause ripples throughout the network that are far too complex for these studies to detect, and that may be as likely to harm you as help you. Even if changing that one factor does bring on the claimed improvement, there’s still a good chance that it won’t do you much good in the long run, because these studies rarely go on long enough to track the decades-long course of disease and ultimately death....

“The odds that anything useful will survive from any of these studies are poor,” says Ioannidis—dismissing in a breath a good chunk of the research into which we sink about $100 billion a year in the United States alone.

And so it goes for all medical studies, he says. Indeed, nutritional studies aren’t the worst. Drug studies have the added corruptive force of financial conflict of interest....

Nature, the grande dame of science journals, stated in a 2006 editorial, “Scientists understand that peer review per se provides only a minimal assurance of quality, and that the public conception of peer review as a stamp of authentication is far from the truth.”...

Doctors may notice that their patients don’t seem to fare as well with certain treatments as the literature would lead them to expect, but the field is appropriately conditioned to subjugate such anecdotal evidence to study findings. Yet much, perhaps even most, of what doctors do has never been formally put to the test in credible studies, given that the need to do so became obvious to the field only in the 1990s, leaving it playing catch-up with a century or more of non-evidence-based medicine, and contributing to Ioannidis’s shockingly high estimate of the degree to which medical knowledge is flawed. That we’re not routinely made seriously ill by this shortfall, he argues, is due largely to the fact that most medical interventions and advice don’t address life-and-death situations, but rather aim to leave us marginally healthier or less unhealthy, so we usually neither gain nor risk all that much.

Medical research is not especially plagued with wrongness. Other meta-research experts have confirmed that similar issues distort research in all fields of science, from physics to economics (where the highly regarded economists J. Bradford DeLong and Kevin Lang once showed how a remarkably consistent paucity of strong evidence in published economics studies made it unlikely that any of them were right). And needless to say, things only get worse when it comes to the pop expertise that endlessly spews at us from diet, relationship, investment, and parenting gurus and pundits. But we expect more of scientists, and especially of medical scientists, given that we believe we are staking our lives on their results. The public hardly recognizes how bad a bet this is. The medical community itself might still be largely oblivious to the scope of the problem, if Ioannidis hadn’t forced a confrontation when he published his studies in 2005....

[His] bigger worry, he says, is that while his fellow researchers seem to be getting the message, he hasn’t necessarily forced anyone to do a better job. He fears he won’t in the end have done much to improve anyone’s health. “There may not be fierce objections to what I’m saying,” he explains. “But it’s difficult to change the way that everyday doctors, patients, and healthy people think and behave.”...

What [doctors are] not trained to do is to go back and look at the research papers that helped make these drugs the standard of care. “When you look the papers up, you often find the drugs didn’t even work better than a placebo. And no one tested how they worked in combination with the other drugs,” she says. “Just taking the patient off everything can improve their health right away.” But not only is checking out the research another time-consuming task, patients often don’t even like it when they’re taken off their drugs, she explains; they find their prescriptions reassuring.

In fact, the question of whether the problems with medical research should be broadcast to the public is a sticky one in the meta-research community. Already feeling that they’re fighting to keep patients from turning to alternative medical treatments such as homeopathy, or misdiagnosing themselves on the Internet, or simply neglecting medical treatment altogether, many researchers and physicians aren’t eager to provide even more reason to be skeptical of what doctors do—not to mention how public disenchantment with medicine could affect research funding. Ioannidis dismisses these concerns. “If we don’t tell the public about these problems, then we’re no better than nonscientists who falsely claim they can heal,” he says. “If the drugs don’t work and we’re not sure how to treat something, why should we claim differently? Some fear that there may be less funding because we stop claiming we can prove we have miraculous treatments. But if we can’t really provide those miracles, how long will we be able to fool the public anyway? The scientific enterprise is probably the most fantastic achievement in human history, but that doesn’t mean we have a right to overstate what we’re accomplishing.”...

But as long as careers remain contingent on producing a stream of research that’s dressed up to seem more right than it is, scientists will keep delivering exactly that.

“Science is a noble endeavor, but it’s also a low-yield endeavor,” he says. “I’m not sure that more than a very small percentage of medical research is ever likely to lead to major improvements in clinical outcomes and quality of life. We should be very comfortable with that fact.” "

The secret about drugs is that they only work in about half of the people who take them

Making Personalized Medicine Pay - BusinessWeek:

"The dirty little secret about drugs is that they only work in about half of the people who take them. So says an educational nonprofit called the Personalized Medicine Coalition, and many drug executives concede as much. Of the $292 billion spent in the U.S. on prescription drugs in 2008, as much as $145 billion went to medications that didn't help individual patients, said Jerel Davis, project manager at McKinsey, at a recent conference. And billions more are being spent to treat adverse drug reactions and other complications. "When you look at the data, it's shocking," says Dr. Robert S. Epstein, chief medical officer at Medco Health Solutions (MHS), a $51 billion company that manages drug prescriptions for 60 million Americans.

Researchers know how to solve this problem. First, figure out the differences between those patients who respond to a drug and those who don't, then treat only to those who will benefit. But this personalized medicine approach 'has been slower to develop than we thought 10 years ago,' says Richard K. Schatzberg, CEO of Generation Health, a startup that offers targeted medicine services. Lack of enthusiasm in the drug industry is a big reason; companies would lose billions of dollars if only those who actually benefit were to use such blockbuster drugs as antidepressants, arthritis medicines, and cholesterol pills...."

Does the Vaccine Matter?

Does the Vaccine Matter? - The Atlantic (November 2009):

"[S]ome flu experts are challenging the medical orthodoxy and arguing that for those most in need of protection, flu shots and antiviral drugs may provide little to none....

When Lisa Jackson, a physician and senior investigator with the Group Health Research Center, in Seattle, began wondering aloud to colleagues if maybe something was amiss with the estimate of 50 percent mortality reduction for people who get flu vaccine, the response she got sounded more like doctrine than science. “People told me, ‘No good can come of [asking] this,’” she says. “‘Potentially a lot of bad could happen’ for me professionally by raising any criticism that might dissuade people from getting vaccinated, because of course, ‘We know that vaccine works.’ This was the prevailing wisdom.”

The history of flu vaccination suggests other reasons to doubt claims that it dramatically reduces mortality. In 2004, for example, vaccine production fell behind, causing a 40 percent drop in immunization rates. Yet mortality did not rise. In addition, vaccine “mismatches” occurred in 1968 and 1997: in both years, the vaccine that had been produced in the summer protected against one set of viruses, but come winter, a different set was circulating. In effect, nobody was vaccinated. Yet death rates from all causes, including flu and the various illnesses it can exacerbate, did not budge...

The most vocal—and undoubtedly most vexing—critic of the gospel of flu vaccine is the Cochrane Collaboration’s Jefferson, who’s also an epidemiologist trained at the famed London School of Tropical Hygiene, and who, in Lisa Jackson’s view, makes other skeptics seem “moderate by comparison.” Among his fellow flu researchers, Jefferson’s outspokenness has made him something of a pariah....

“Tom Jefferson has taken a lot of heat just for saying, ‘Here’s the evidence: it’s not very good,’” says Majumdar. “The reaction has been so dogmatic and even hysterical that you’d think he was advocating stealing babies.” Yet while other flu researchers may not like what Jefferson has to say, they cannot ignore the fact that he knows the flu-vaccine literature better than anyone else on the planet. He leads an international team of researchers who have combed through hundreds of flu-vaccine studies. The vast majority of the studies were deeply flawed, says Jefferson. “Rubbish is not a scientific term, but I think it’s the term that applies.” Only four studies were properly designed to pin down the effectiveness of flu vaccine, he says, and two of those showed that it might be effective in certain groups of patients, such as school-age children with no underlying health issues like asthma. The other two showed equivocal results or no benefit.

Flu researchers have been fooled into thinking vaccine is more effective than the data suggest, in part, says Jefferson, by the imprecision of the statistics....

As with vaccines, the scientific evidence for Tamiflu and Relenza is thin at best. In its general-information section, the CDC’s Web site tells readers that antiviral drugs can “make you feel better faster.” True, but not by much. On average, Tamiflu (which accounts for 85 to 90 percent of the flu antiviral-drug market) cuts the duration of flu symptoms by 24hours in otherwise healthy people. In exchange for a slightly shorter bout of illness, as many as one in five people taking Tamiflu will experience nausea and vomiting. About one in five children will have neuropsychiatric side effects, possibly including anxiety and suicidal behavior....

Why, then, has the federal government stockpiled millions of doses of antivirals, at a cost of several billion dollars? And why are physicians being encouraged to hand out prescriptions to large numbers of people, without sound evidence that the drugs will help? The short answer may be that public-health officials feel they must offer something, and these drugs are the only possible remedies at hand. “I have to agree with the critics the antiviral question is not cut-and-dried,” says Fauci. “But [these drugs are] the best we have.” The CDC’s Nancy Cox also acknowledges that the science is not as sound as she might like, but the government still recommends their use. And as with vaccines, she considers additional randomized placebo-controlled trials of the antiviral drugs to be “unethical” and thus out of the question....

The annals of medicine are littered with treatments and tests that became medical doctrine on the slimmest of evidence, and were then declared sacrosanct and beyond scientific investigation. In the 1980s and ’90s, for example, cancer specialists were convinced that high-dose chemotherapy followed by a bone-marrow transplant was the best hope for women with advanced breast cancer, and many refused to enroll their patients in randomized clinical trials that were designed to test transplants against the standard—and far less toxic—therapy. The trials, they said, were unethical, because they knew transplants worked. When the studies were concluded, in 1999 and 2000, it turned out that bone-marrow transplants were killing patients. Another recent example involves drugs related to the analgesic lidocaine. In the 1970s, doctors noticed that the drugs seemed to make the heart beat rhythmically, and they began prescribing them to patients suffering from irregular heartbeats, assuming that restoring a proper rhythm would reduce the patient’s risk of dying. Prominent cardiologists for years opposed clinical trials of the drugs, saying it would be medical malpractice to withhold them from patients in a control group. The drugs were widely used for two decades, until a government-sponsored study showed in 1989 that patients who were prescribed the medicine were three and a half times as likely to die as those given a placebo....

As it stands, more than 50 percent of health-care workers say they do not intend to get vaccinated for swine flu and don’t routinely get their shots for seasonal flu, in part because many of them doubt the vaccines’ efficacy....

“There’s no worse place to go than the hospital during flu season,” says Majumdar. Those who don’t have the flu are more likely to catch it there, and those who do will spread it around, he says. “But we don’t tell people this.”

All of which leaves open the question of what people should do when faced with a decision about whether to get themselves and their families vaccinated. There is little immediate danger from getting a seasonal flu shot, aside from a sore arm and mild flu-like symptoms. The safety of the swine flu vaccine remains to be seen. In the absence of better evidence, vaccines and antivirals must be viewed as only partial and uncertain defenses against the flu. And they may be mere talismans. By being afraid to do the proper studies now, we may be condemning ourselves to using treatments based on illusion and faith rather than sound science."

Pharmaceuticals In Our Water Supplies

Pharmaceuticals In Our Water Supplies

Pharmaceuticals In Our Water Supplies
Are “Drugged Waters” a Water Quality Threat?

By Arizona Water Resource, July-August 2000, Volume 9, Number 1

Developed to promote human health and well being, certain pharmaceuticals are now attracting attention as a potentially new class of water pollutants. Such drugs as antibiotics, anti-depressants, birth control pills, seizure medication, cancer treatments, pain killers, tranquilizers and cholesterol-lowering compounds have been detected in varied water sources.

Where do they come from? Pharmaceutical industries, hospitals and other medical facilities are obvious sources, but households also contribute a significant share. People often dispose of unused medicines by flushing them down toilets, and human excreta can contain varied incompletely metabolized medicines. These drugs can pass intact through conventional sewage treatment facilities, into waterways, lakes and even aquifers. Further, discarded pharmaceuticals often end up at dumps and land fills, posing a threat to underlying groundwater.

Farm animals also are a source of pharmaceuticals entering the environment, through their ingestion of hormones, antibiotics and veterinary medicines. (About 40 percent of U.S.-produced antibiotics are fed to livestock as growth enhancers.) Manure containing traces of such pharmaceuticals is spread on land and can then wash off into surface water and even percolate into groundwater.

Along with pharmaceuticals, personal care products also are showing up in water. Generally these chemicals are the active ingredients or preservatives in cosmetics, toiletries or fragrances. For example, nitro musks, used as a fragrance in many cosmetics, detergents, toiletries and other personal care products, have attracted concern because of their persistence and possible adverse environmental impacts. Some countries have taken action to ban nitro musks. Also, sun screen agents have been detected in lakes and fish.

Researchers Christian G. Daughton and Thomas A. Ternes reported in the December issue of “Environmental Health Perspectives” that the amount of pharmaceuticals and personal care products entering the environment annually is about equal to the amount of pesticides used each year.

Concern about the water quality impacts of these chemicals first gained prominence in Europe, where for over a decade scientists have been checking lakes, streams, and groundwater for pharmaceutical contamination. American officials and scientists are taking note, with two recent U.S. professional organizations — the National Ground Water Associations and the American Chemical Society — addressing the issue at their annual meetings this summer.

What risk does chronic exposure to trace concentrations of pharmaceuticals pose to humans or wildlife? Some scientists believe pharmaceuticals do not pose problems to humans since they occur at low concentrations in water. Other scientists say long-term and synergistic effects of pharmaceuticals and similar chemicals on humans are not known and advise caution. They are concerned that many of these drugs have the potential of interfering with hormone production. Chemicals with this effect are called endocrine disrupters and are attracting the attention of water quality experts.

To some scientists the release of antibiotics into waterways is particularly worrisome. They fear the release may result in disease-causing bacteria to become immune to treatment and that drug-resistant diseases will develop.

Scientists generally agree that aquatic life is most at risk, its life cycle, from birth to death, occurring within potentially drug-contaminated waters. For example, anti-depressants have been blamed for altering sperm levels and spawning patterns in marine life. Most studies of pharmaceutical and pharmaceutically active chemicals in water have mostly focused on aquatic animals.

Read the entire article

The Indiana Jones of the medicine world

The Indiana Jones of the medicine world
"Chris Kilham is a medicine hunter -- a sort of Indiana Jones of the plant world. Hired by companies that market herbal remedies for ailments ranging from the common cold to depression, Kilham has spent the past decade roaming remote areas of the globe in search of the next best botanical."

Read the entire article