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Weiye Loh

News Clips: Pinning down acupuncture: It's a placebo - 0 views

  • some doctors seem to have embraced even disproven remedies. Take, for instance, a review of acupuncture research that appeared last July in the New England Journal of Medicine. This highly respected journal is one of the most widely read by doctors across specialities.In Acupuncture For Chronic Low Back Pain, the authors reviewed clinical trials done to assess if acupuncture actually helps in chronic low back pain. The most important meta-analysis available was a 2008 study involving 6,359 patients, which 'showed that real acupuncture treatments were no more effective than sham acupuncture treatments'.
  • The authors then editorialised: 'There was nevertheless evidence that both real acupuncture and sham acupuncture were more effective than no treatment and that acupuncture can be a useful supplement to other forms of conventional therapy for low back pain.'
  • First, they admit that pooled clinical trials of the best sort show that real acupuncture does no better than sham acupuncture. This should mean that acupuncture does not work - full stop. But then they say that both sham and real acupuncture work as well as the other and thus is useful. Translation: Please use acupuncture as a placebo on your patients; just don't let them know it is a placebo.
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  • I should add that I am not criticising TCM per se. Only acupuncture, a facet of TCM, albeit its most dramatic, is being scrutinised here. Chinese herbology must be analysed on its own merits.Interestingly, although acupuncture may be TCM's poster boy today, the Chinese physician in days of yore would have looked askance at it. Instead, his practice and prestige were based upon his grasp of the Chinese pharmacopoeia.
  • Acupuncture was left to the shamans and blood letters. After all, it was grounded, not in the knowledge of which herbs were best for what conditions, but astrology.
  • In Giovanni Maciocia's 2005 book, The Foundations Of Chinese Medicine: A Comprehensive Text For Acupuncturists And Herbalists, there is a chart showing the astrological provenance of acupuncture. The chart shows how the 12 main acupuncture meridians and the 12 main body segments correspond to the 12 Houses of the Chinese zodiac.
  • In Chinese cosmology, all life is animated by a numinous force called qi, the flow of which mirrors the sun's apparent 'movement' during the year through the ecliptic. (The ecliptic is the imaginary plane of the earth's orbit around the sun).Moreover, everything in the Chinese zodiac is mirrored on Earth and in Man. This was taught even in the earliest systematised TCM text, the Yellow Emperor's Canon Of Medicine, thus: 'Heaven is covered with constellations, Earth with waterways, and man with channels.'This 'as above, so below' doctrine means that if there is qi flowing around in the imaginary closed loop of the zodiac, there is qi flowing correspondingly in the body's closed loop of imaginary meridians as well.
  • Note that not only is acupuncture astrological in origin but also the astrology is based on a model of the universe which has the earth at its centre. This geocentric model was an erroneous idea widely accepted before the Copernican revolution.
  • So should doctors check the daily horoscopes of their patients?
Weiye Loh

The Decline Effect and the Scientific Method : The New Yorker - 0 views

  • On September 18, 2007, a few dozen neuroscientists, psychiatrists, and drug-company executives gathered in a hotel conference room in Brussels to hear some startling news. It had to do with a class of drugs known as atypical or second-generation antipsychotics, which came on the market in the early nineties.
  • the therapeutic power of the drugs appeared to be steadily waning. A recent study showed an effect that was less than half of that documented in the first trials, in the early nineteen-nineties. Many researchers began to argue that the expensive pharmaceuticals weren’t any better than first-generation antipsychotics, which have been in use since the fifties. “In fact, sometimes they now look even worse,” John Davis, a professor of psychiatry at the University of Illinois at Chicago, told me.
  • Before the effectiveness of a drug can be confirmed, it must be tested and tested again. Different scientists in different labs need to repeat the protocols and publish their results. The test of replicability, as it’s known, is the foundation of modern research. Replicability is how the community enforces itself. It’s a safeguard for the creep of subjectivity. Most of the time, scientists know what results they want, and that can influence the results they get. The premise of replicability is that the scientific community can correct for these flaws.
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  • But now all sorts of well-established, multiply confirmed findings have started to look increasingly uncertain. It’s as if our facts were losing their truth: claims that have been enshrined in textbooks are suddenly unprovable. This phenomenon doesn’t yet have an official name, but it’s occurring across a wide range of fields, from psychology to ecology. In the field of medicine, the phenomenon seems extremely widespread, affecting not only antipsychotics but also therapies ranging from cardiac stents to Vitamin E and antidepressants: Davis has a forthcoming analysis demonstrating that the efficacy of antidepressants has gone down as much as threefold in recent decades.
  • the effect is especially troubling because of what it exposes about the scientific process. If replication is what separates the rigor of science from the squishiness of pseudoscience, where do we put all these rigorously validated findings that can no longer be proved? Which results should we believe? Francis Bacon, the early-modern philosopher and pioneer of the scientific method, once declared that experiments were essential, because they allowed us to “put nature to the question.” But it appears that nature often gives us different answers.
  • At first, he assumed that he’d made an error in experimental design or a statistical miscalculation. But he couldn’t find anything wrong with his research. He then concluded that his initial batch of research subjects must have been unusually susceptible to verbal overshadowing. (John Davis, similarly, has speculated that part of the drop-off in the effectiveness of antipsychotics can be attributed to using subjects who suffer from milder forms of psychosis which are less likely to show dramatic improvement.) “It wasn’t a very satisfying explanation,” Schooler says. “One of my mentors told me that my real mistake was trying to replicate my work. He told me doing that was just setting myself up for disappointment.”
  • In private, Schooler began referring to the problem as “cosmic habituation,” by analogy to the decrease in response that occurs when individuals habituate to particular stimuli. “Habituation is why you don’t notice the stuff that’s always there,” Schooler says. “It’s an inevitable process of adjustment, a ratcheting down of excitement. I started joking that it was like the cosmos was habituating to my ideas. I took it very personally.”
  • The most likely explanation for the decline is an obvious one: regression to the mean. As the experiment is repeated, that is, an early statistical fluke gets cancelled out. The extrasensory powers of Schooler’s subjects didn’t decline—they were simply an illusion that vanished over time. And yet Schooler has noticed that many of the data sets that end up declining seem statistically solid—that is, they contain enough data that any regression to the mean shouldn’t be dramatic. “These are the results that pass all the tests,” he says. “The odds of them being random are typically quite remote, like one in a million. This means that the decline effect should almost never happen. But it happens all the time!
  • this is why Schooler believes that the decline effect deserves more attention: its ubiquity seems to violate the laws of statistics. “Whenever I start talking about this, scientists get very nervous,” he says. “But I still want to know what happened to my results. Like most scientists, I assumed that it would get easier to document my effect over time. I’d get better at doing the experiments, at zeroing in on the conditions that produce verbal overshadowing. So why did the opposite happen? I’m convinced that we can use the tools of science to figure this out. First, though, we have to admit that we’ve got a problem.”
  • In 2001, Michael Jennions, a biologist at the Australian National University, set out to analyze “temporal trends” across a wide range of subjects in ecology and evolutionary biology. He looked at hundreds of papers and forty-four meta-analyses (that is, statistical syntheses of related studies), and discovered a consistent decline effect over time, as many of the theories seemed to fade into irrelevance. In fact, even when numerous variables were controlled for—Jennions knew, for instance, that the same author might publish several critical papers, which could distort his analysis—there was still a significant decrease in the validity of the hypothesis, often within a year of publication. Jennions admits that his findings are troubling, but expresses a reluctance to talk about them publicly. “This is a very sensitive issue for scientists,” he says. “You know, we’re supposed to be dealing with hard facts, the stuff that’s supposed to stand the test of time. But when you see these trends you become a little more skeptical of things.”
  • the worst part was that when I submitted these null results I had difficulty getting them published. The journals only wanted confirming data. It was too exciting an idea to disprove, at least back then.
  • the steep rise and slow fall of fluctuating asymmetry is a clear example of a scientific paradigm, one of those intellectual fads that both guide and constrain research: after a new paradigm is proposed, the peer-review process is tilted toward positive results. But then, after a few years, the academic incentives shift—the paradigm has become entrenched—so that the most notable results are now those that disprove the theory.
  • Jennions, similarly, argues that the decline effect is largely a product of publication bias, or the tendency of scientists and scientific journals to prefer positive data over null results, which is what happens when no effect is found. The bias was first identified by the statistician Theodore Sterling, in 1959, after he noticed that ninety-seven per cent of all published psychological studies with statistically significant data found the effect they were looking for. A “significant” result is defined as any data point that would be produced by chance less than five per cent of the time. This ubiquitous test was invented in 1922 by the English mathematician Ronald Fisher, who picked five per cent as the boundary line, somewhat arbitrarily, because it made pencil and slide-rule calculations easier. Sterling saw that if ninety-seven per cent of psychology studies were proving their hypotheses, either psychologists were extraordinarily lucky or they published only the outcomes of successful experiments. In recent years, publication bias has mostly been seen as a problem for clinical trials, since pharmaceutical companies are less interested in publishing results that aren’t favorable. But it’s becoming increasingly clear that publication bias also produces major distortions in fields without large corporate incentives, such as psychology and ecology.
  • While publication bias almost certainly plays a role in the decline effect, it remains an incomplete explanation. For one thing, it fails to account for the initial prevalence of positive results among studies that never even get submitted to journals. It also fails to explain the experience of people like Schooler, who have been unable to replicate their initial data despite their best efforts
  • an equally significant issue is the selective reporting of results—the data that scientists choose to document in the first place. Palmer’s most convincing evidence relies on a statistical tool known as a funnel graph. When a large number of studies have been done on a single subject, the data should follow a pattern: studies with a large sample size should all cluster around a common value—the true result—whereas those with a smaller sample size should exhibit a random scattering, since they’re subject to greater sampling error. This pattern gives the graph its name, since the distribution resembles a funnel.
  • The funnel graph visually captures the distortions of selective reporting. For instance, after Palmer plotted every study of fluctuating asymmetry, he noticed that the distribution of results with smaller sample sizes wasn’t random at all but instead skewed heavily toward positive results.
  • Palmer has since documented a similar problem in several other contested subject areas. “Once I realized that selective reporting is everywhere in science, I got quite depressed,” Palmer told me. “As a researcher, you’re always aware that there might be some nonrandom patterns, but I had no idea how widespread it is.” In a recent review article, Palmer summarized the impact of selective reporting on his field: “We cannot escape the troubling conclusion that some—perhaps many—cherished generalities are at best exaggerated in their biological significance and at worst a collective illusion nurtured by strong a-priori beliefs often repeated.”
  • Palmer emphasizes that selective reporting is not the same as scientific fraud. Rather, the problem seems to be one of subtle omissions and unconscious misperceptions, as researchers struggle to make sense of their results. Stephen Jay Gould referred to this as the “shoehorning” process. “A lot of scientific measurement is really hard,” Simmons told me. “If you’re talking about fluctuating asymmetry, then it’s a matter of minuscule differences between the right and left sides of an animal. It’s millimetres of a tail feather. And so maybe a researcher knows that he’s measuring a good male”—an animal that has successfully mated—“and he knows that it’s supposed to be symmetrical. Well, that act of measurement is going to be vulnerable to all sorts of perception biases. That’s not a cynical statement. That’s just the way human beings work.”
  • One of the classic examples of selective reporting concerns the testing of acupuncture in different countries. While acupuncture is widely accepted as a medical treatment in various Asian countries, its use is much more contested in the West. These cultural differences have profoundly influenced the results of clinical trials. Between 1966 and 1995, there were forty-seven studies of acupuncture in China, Taiwan, and Japan, and every single trial concluded that acupuncture was an effective treatment. During the same period, there were ninety-four clinical trials of acupuncture in the United States, Sweden, and the U.K., and only fifty-six per cent of these studies found any therapeutic benefits. As Palmer notes, this wide discrepancy suggests that scientists find ways to confirm their preferred hypothesis, disregarding what they don’t want to see. Our beliefs are a form of blindness.
  • John Ioannidis, an epidemiologist at Stanford University, argues that such distortions are a serious issue in biomedical research. “These exaggerations are why the decline has become so common,” he says. “It’d be really great if the initial studies gave us an accurate summary of things. But they don’t. And so what happens is we waste a lot of money treating millions of patients and doing lots of follow-up studies on other themes based on results that are misleading.”
  • In 2005, Ioannidis published an article in the Journal of the American Medical Association that looked at the forty-nine most cited clinical-research studies in three major medical journals. Forty-five of these studies reported positive results, suggesting that the intervention being tested was effective. Because most of these studies were randomized controlled trials—the “gold standard” of medical evidence—they tended to have a significant impact on clinical practice, and led to the spread of treatments such as hormone replacement therapy for menopausal women and daily low-dose aspirin to prevent heart attacks and strokes. Nevertheless, the data Ioannidis found were disturbing: of the thirty-four claims that had been subject to replication, forty-one per cent had either been directly contradicted or had their effect sizes significantly downgraded.
  • The situation is even worse when a subject is fashionable. In recent years, for instance, there have been hundreds of studies on the various genes that control the differences in disease risk between men and women. These findings have included everything from the mutations responsible for the increased risk of schizophrenia to the genes underlying hypertension. Ioannidis and his colleagues looked at four hundred and thirty-two of these claims. They quickly discovered that the vast majority had serious flaws. But the most troubling fact emerged when he looked at the test of replication: out of four hundred and thirty-two claims, only a single one was consistently replicable. “This doesn’t mean that none of these claims will turn out to be true,” he says. “But, given that most of them were done badly, I wouldn’t hold my breath.”
  • the main problem is that too many researchers engage in what he calls “significance chasing,” or finding ways to interpret the data so that it passes the statistical test of significance—the ninety-five-per-cent boundary invented by Ronald Fisher. “The scientists are so eager to pass this magical test that they start playing around with the numbers, trying to find anything that seems worthy,” Ioannidis says. In recent years, Ioannidis has become increasingly blunt about the pervasiveness of the problem. One of his most cited papers has a deliberately provocative title: “Why Most Published Research Findings Are False.”
  • The problem of selective reporting is rooted in a fundamental cognitive flaw, which is that we like proving ourselves right and hate being wrong. “It feels good to validate a hypothesis,” Ioannidis said. “It feels even better when you’ve got a financial interest in the idea or your career depends upon it. And that’s why, even after a claim has been systematically disproven”—he cites, for instance, the early work on hormone replacement therapy, or claims involving various vitamins—“you still see some stubborn researchers citing the first few studies that show a strong effect. They really want to believe that it’s true.”
  • scientists need to become more rigorous about data collection before they publish. “We’re wasting too much time chasing after bad studies and underpowered experiments,” he says. The current “obsession” with replicability distracts from the real problem, which is faulty design. He notes that nobody even tries to replicate most science papers—there are simply too many. (According to Nature, a third of all studies never even get cited, let alone repeated.)
  • Schooler recommends the establishment of an open-source database, in which researchers are required to outline their planned investigations and document all their results. “I think this would provide a huge increase in access to scientific work and give us a much better way to judge the quality of an experiment,” Schooler says. “It would help us finally deal with all these issues that the decline effect is exposing.”
  • Although such reforms would mitigate the dangers of publication bias and selective reporting, they still wouldn’t erase the decline effect. This is largely because scientific research will always be shadowed by a force that can’t be curbed, only contained: sheer randomness. Although little research has been done on the experimental dangers of chance and happenstance, the research that exists isn’t encouraging
  • John Crabbe, a neuroscientist at the Oregon Health and Science University, conducted an experiment that showed how unknowable chance events can skew tests of replicability. He performed a series of experiments on mouse behavior in three different science labs: in Albany, New York; Edmonton, Alberta; and Portland, Oregon. Before he conducted the experiments, he tried to standardize every variable he could think of. The same strains of mice were used in each lab, shipped on the same day from the same supplier. The animals were raised in the same kind of enclosure, with the same brand of sawdust bedding. They had been exposed to the same amount of incandescent light, were living with the same number of littermates, and were fed the exact same type of chow pellets. When the mice were handled, it was with the same kind of surgical glove, and when they were tested it was on the same equipment, at the same time in the morning.
  • The premise of this test of replicability, of course, is that each of the labs should have generated the same pattern of results. “If any set of experiments should have passed the test, it should have been ours,” Crabbe says. “But that’s not the way it turned out.” In one experiment, Crabbe injected a particular strain of mouse with cocaine. In Portland the mice given the drug moved, on average, six hundred centimetres more than they normally did; in Albany they moved seven hundred and one additional centimetres. But in the Edmonton lab they moved more than five thousand additional centimetres. Similar deviations were observed in a test of anxiety. Furthermore, these inconsistencies didn’t follow any detectable pattern. In Portland one strain of mouse proved most anxious, while in Albany another strain won that distinction.
  • The disturbing implication of the Crabbe study is that a lot of extraordinary scientific data are nothing but noise. The hyperactivity of those coked-up Edmonton mice wasn’t an interesting new fact—it was a meaningless outlier, a by-product of invisible variables we don’t understand. The problem, of course, is that such dramatic findings are also the most likely to get published in prestigious journals, since the data are both statistically significant and entirely unexpected. Grants get written, follow-up studies are conducted. The end result is a scientific accident that can take years to unravel.
  • This suggests that the decline effect is actually a decline of illusion.
  • While Karl Popper imagined falsification occurring with a single, definitive experiment—Galileo refuted Aristotelian mechanics in an afternoon—the process turns out to be much messier than that. Many scientific theories continue to be considered true even after failing numerous experimental tests. Verbal overshadowing might exhibit the decline effect, but it remains extensively relied upon within the field. The same holds for any number of phenomena, from the disappearing benefits of second-generation antipsychotics to the weak coupling ratio exhibited by decaying neutrons, which appears to have fallen by more than ten standard deviations between 1969 and 2001. Even the law of gravity hasn’t always been perfect at predicting real-world phenomena. (In one test, physicists measuring gravity by means of deep boreholes in the Nevada desert found a two-and-a-half-per-cent discrepancy between the theoretical predictions and the actual data.) Despite these findings, second-generation antipsychotics are still widely prescribed, and our model of the neutron hasn’t changed. The law of gravity remains the same.
  • Such anomalies demonstrate the slipperiness of empiricism. Although many scientific ideas generate conflicting results and suffer from falling effect sizes, they continue to get cited in the textbooks and drive standard medical practice. Why? Because these ideas seem true. Because they make sense. Because we can’t bear to let them go. And this is why the decline effect is so troubling. Not because it reveals the human fallibility of science, in which data are tweaked and beliefs shape perceptions. (Such shortcomings aren’t surprising, at least for scientists.) And not because it reveals that many of our most exciting theories are fleeting fads and will soon be rejected. (That idea has been around since Thomas Kuhn.) The decline effect is troubling because it reminds us how difficult it is to prove anything. We like to pretend that our experiments define the truth for us. But that’s often not the case. Just because an idea is true doesn’t mean it can be proved. And just because an idea can be proved doesn’t mean it’s true. When the experiments are done, we still have to choose what to believe.
Weiye Loh

Unwise to criticise alternative medicine, says SMA - 0 views

  • While Western-trained doctors do warn their patients about the risk and safety profile of what they prescribe and voice their opinions on various kinds of alternative medicine to their patients, it is another thing to advocate that the local medical profession collectively criticise alternative medicine groups.
  • This is especially so when doctors and alternative medicine practitioners are seen to be competitors and criticising alternative medicine can be construed as self-serving.
  • Dr Ho's column on Saturday failed to take SMA's proposal to amend the SMC ethical code in context. When the current code was introduced, TCM practitioners and acupuncturists were not state-registered. They are now. We do not think doctors will refer widely to TCM practitioners even if the code is amended. However, patients do request from their doctors medical reports and summaries when they seek care from TCM practitioners. The present code disallows such formal communication. Amending the code will facilitate better communication between a patient's various caregivers so that the patient's interest is best served.
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  • The SMA does not encourage its members to refer to alternative medicine practitioners. But we have to be realistic. They exist and are here to stay. Most public hospitals already offer acupuncture services. Several have TCM clinics on their premises. Continuing this "iron curtain" of no formal communication between doctors and alternative medicine practitioners is impractical and anachronistic.
  • Finally, many alternative medicine forms are steeped in cultural and religious beliefs, such as TCM and ayurvedic medicine. From the perspective of safeguarding social cohesion in Singapore, getting the local medical profession to collectively criticise various alternative medicine modalities is unwise.
  • In Singapore's social context, journalists should not try to pit one group of caregivers against another. It is best for an impartial and respected body such as the Government to step forward to decide what is safe and unsafe for patients. Dr Abdul Razakjr Omar Honorary Secretary Singapore Medical Association (SMA)
Weiye Loh

SMA's confusing suggestion - 0 views

  • Regardless of whether a physician is state-sanctioned, Western-trained or trained traditionally, he must be viewed with considerable caution if he does not practise methods of healing based on proper evidence by any standards.
  • SMA's suggestion that medical practitioners be allowed to refer to practitioners of traditional Chinese medicine (TCM) and acupuncturists is nothing short of wholesale endorsement of their methods. Most TCM practitioners perform acupuncture, which we now know is about as effective as a placebo. This alone should make us ask whether patients are served well by a referral to a TCM practitioner. What is especially curious is that while the SMA suggests letting doctors sign referrals to TCM practitioners, it does not encourage its members to do so and does not think doctors will do so widely. If that is SMA's view, why fiddle with the status quo and confuse doctors and the public with such mixed messages?
  • While tolerance precludes outright criticism by doctors of alternative medicine, we should not endorse non- evidence-based therapeutic modalities.
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