The Decline Effect and the Scientific Method
Published on January 10th, 2011 | by Harmonist staff20
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 drugs, sold under brand names such as Abilify, Seroquel, and Zyprexa, had been tested on schizophrenics in several large clinical trials, all of which had demonstrated a dramatic decrease in the subjects’ psychiatric symptoms. As a result, second-generation antipsychotics had become one of the fastest-growing and most profitable pharmaceutical classes. By 2001, Eli Lilly’s Zyprexa was generating more revenue than Prozac. It remains the company’s top-selling drug.
But the data presented at the Brussels meeting made it clear that something strange was happening: 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.
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.
For many scientists, 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.
Jonathan Schooler was a young graduate student at the University of Washington in the nineteen-eighties when he discovered a surprising new fact about language and memory. At the time, it was widely believed that the act of describing our memories improved them. But, in a series of clever experiments, Schooler demonstrated that subjects shown a face and asked to describe it were much less likely to recognize the face when shown it later than those who had simply looked at it. Schooler called the phenomenon “verbal overshadowing.”
The study turned him into an academic star. Since its initial publication, in 1990, it has been cited more than four hundred times. Before long, Schooler had extended the model to a variety of other tasks, such as remembering the taste of a wine, identifying the best strawberry jam, and solving difficult creative puzzles. In each instance, asking people to put their perceptions into words led to dramatic decreases in performance.
But while Schooler was publishing these results in highly reputable journals, a secret worry gnawed at him: it was proving difficult to replicate his earlier findings. “I’d often still see an effect, but the effect just wouldn’t be as strong,” he told me. “It was as if verbal overshadowing, my big new idea, was getting weaker.” 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.”
Schooler tried to put the problem out of his mind; his colleagues assured him that such things happened all the time. Over the next few years, he found new research questions, got married and had kids. But his replication problem kept on getting worse. His first attempt at replicating the 1990 study, in 1995, resulted in an effect that was thirty per cent smaller. The next year, the size of the effect shrank another thirty per cent. When other labs repeated Schooler’s experiments, they got a similar spread of data, with a distinct downward trend. “This was profoundly frustrating,” he says. “It was as if nature gave me this great result and then tried to take it back.” 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.”
Schooler is now a tenured professor at the University of California at Santa Barbara. He has curly black hair, pale-green eyes, and the relaxed demeanor of someone who lives five minutes away from his favorite beach. When he speaks, he tends to get distracted by his own digressions. He might begin with a point about memory, which reminds him of a favorite William James quote, which inspires a long soliloquy on the importance of introspection. Before long, we’re looking at pictures from Burning Man on his iPhone, which leads us back to the fragile nature of memory.
Although verbal overshadowing remains a widely accepted theory—it’s often invoked in the context of eyewitness testimony, for instance—Schooler is still a little peeved at the cosmos. “I know I should just move on already,” he says. “I really should stop talking about this. But I can’t.” That’s because he is convinced that he has stumbled on a serious problem, one that afflicts many of the most exciting new ideas in psychology.
One of the first demonstrations of this mysterious phenomenon came in the early nineteen-thirties. Joseph Banks Rhine, a psychologist at Duke, had developed an interest in the possibility of extrasensory perception, or E.S.P. Rhine devised an experiment featuring Zener cards, a special deck of twenty-five cards printed with one of five different symbols: a card was drawn from the deck and the subject was asked to guess the symbol. Most of Rhine’s subjects guessed about twenty per cent of the cards correctly, as you’d expect, but an undergraduate named Adam Linzmayer averaged nearly fifty per cent during his initial sessions, and pulled off several uncanny streaks, such as guessing nine cards in a row. The odds of this happening by chance are about one in two million. Linzmayer did it three times.
Rhine documented these stunning results in his notebook and prepared several papers for publication. But then, just as he began to believe in the possibility of extrasensory perception, the student lost his spooky talent. Between 1931 and 1933, Linzmayer guessed at the identity of another several thousand cards, but his success rate was now barely above chance. Rhine was forced to conclude that the student’s “extra-sensory perception ability has gone through a marked decline.” And Linzmayer wasn’t the only subject to experience such a drop-off: in nearly every case in which Rhine and others documented E.S.P. the effect dramatically diminished over time. Rhine called this trend the “decline effect.”
Schooler was fascinated by Rhine’s experimental struggles. Here was a scientist who had repeatedly documented the decline of his data; he seemed to have a talent for finding results that fell apart. In 2004, Schooler embarked on an ironic imitation of Rhine’s research: he tried to replicate this failure to replicate. In homage to Rhine’s interests, he decided to test for a parapsychological phenomenon known as precognition. The experiment itself was straightforward: he flashed a set of images to a subject and asked him or her to identify each one. Most of the time, the response was negative—the images were displayed too quickly to register. Then Schooler randomly selected half of the images to be shown again. What he wanted to know was whether the images that got a second showing were more likely to have been identified the first time around. Could subsequent exposure have somehow influenced the initial results? Could the effect become the cause?
The craziness of the hypothesis was the point: Schooler knows that precognition lacks a scientific explanation. But he wasn’t testing extrasensory powers; he was testing the decline effect. “At first, the data looked amazing, just as we’d expected,” Schooler says. “I couldn’t believe the amount of precognition we were finding. But then, as we kept on running subjects, the effect size”—a standard statistical measure—“kept on getting smaller and smaller.” The scientists eventually tested more than two thousand undergraduates. “In the end, our results looked just like Rhine’s,” Schooler said. “We found this strong paranormal effect, but it disappeared on us.”
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! Hell, it’s happened to me multiple times.” And 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 1991, the Danish zoologist Anders Møller, at Uppsala University, in Sweden, made a remarkable discovery about sex, barn swallows, and symmetry. It had long been known that the asymmetrical appearance of a creature was directly linked to the amount of mutation in its genome, so that more mutations led to more “fluctuating asymmetry.” (An easy way to measure asymmetry in humans is to compare the length of the fingers on each hand.) What Møller discovered is that female barn swallows were far more likely to mate with male birds that had long, symmetrical feathers. This suggested that the picky females were using symmetry as a proxy for the quality of male genes. Møller’s paper, which was published in Nature, set off a frenzy of research. Here was an easily measured, widely applicable indicator of genetic quality, and females could be shown to gravitate toward it. Aesthetics was really about genetics.
In the three years following, there were ten independent tests of the role of fluctuating asymmetry in sexual selection, and nine of them found a relationship between symmetry and male reproductive success. It didn’t matter if scientists were looking at the hairs on fruit flies or replicating the swallow studies—females seemed to prefer males with mirrored halves. Before long, the theory was applied to humans. Researchers found, for instance, that women preferred the smell of symmetrical men, but only during the fertile phase of the menstrual cycle. Other studies claimed that females had more orgasms when their partners were symmetrical, while a paper by anthropologists at Rutgers analyzed forty Jamaican dance routines and discovered that symmetrical men were consistently rated as better dancers.
Then the theory started to fall apart. In 1994, there were fourteen published tests of symmetry and sexual selection, and only eight found a correlation. In 1995, there were eight papers on the subject, and only four got a positive result. By 1998, when there were twelve additional investigations of fluctuating asymmetry, only a third of them confirmed the theory. Worse still, even the studies that yielded some positive result showed a steadily declining effect size. Between 1992 and 1997, the average effect size shrank by eighty per cent.
And it’s not just fluctuating asymmetry. 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.”
What happened? Leigh Simmons, a biologist at the University of Western Australia, suggested one explanation when he told me about his initial enthusiasm for the theory: “I was really excited by fluctuating asymmetry. The early studies made the effect look very robust.” He decided to conduct a few experiments of his own, investigating symmetry in male horned beetles. “Unfortunately, I couldn’t find the effect,” he said. “But 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.” For Simmons, 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.
Read the enitre New Yorker article, here.