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As Freedman put it in The Atlantic: “80 percent of non-randomized studies (by far the most common type) turn out to be wrong, as do 25 percent of supposedly gold-standard randomized trials, and as much as 10 percent of the platinum-standard large randomized trials.” Ioannidis himself was quoted uttering some sobering words for the medical community (and the public at large): “Science is a noble endeavor, but it’s also a low-yield endeavor. 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.”

Julia and I actually addressed this topic during a Rationally Speaking podcast, featuring as guest our friend Steve Novella, of Skeptics’ Guide to the Universe and Science-Based Medicine fame. But while Steve did quibble with the tone of the Atlantic article, he agreed that Ioannidis’ results are well known and accepted by the medical research community. Steve did point out that it should not be surprising that results get better and better as one moves toward more stringent protocols like large randomized trials, but it seems to me that one should be surprised (actually, appalled) by the fact that even there the percentage of flawed studies is high — not to mention the fact that most studies are in fact neither large nor properly randomized.

The second big recent blow to public perception of the reliability of scientific results is an article published in The New Yorker by Jonah Lehrer, entitled “The truth wears off.” Lehrer also mentions Ioannidis, but the bulk of his essay is about findings in psychiatry, psychology and evolutionary biology (and even in research on the paranormal!).

In these disciplines there are now several documented cases of results that were initially spectacularly positive — for instance the effects of second generation antipsychotic drugs, or the hypothesized relationship between a male’s body symmetry and the quality of his genes — that turned out to be increasingly difficult to replicate over time, with the original effect sizes being cut down dramatically, or even disappearing altogether.

As Lehrer concludes at the end of his article: “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.”

None of this should actually be particularly surprising to any practicing scientist. If you have spent a significant time of your life in labs and reading the technical literature, you will appreciate the difficulties posed by empirical research, not to mention a number of issues such as the fact that few scientists ever actually bother to replicate someone else’s results, for the simple reason that there is no Nobel (or even funded grant, or tenured position) waiting for the guy who arrived second.

n the midst of this I was directed by a tweet by my colleague Neil deGrasse Tyson (who has also appeared on the RS podcast, though in a different context) to a recent ABC News article penned by John Allen Paulos, which meant to explain the decline effect in science.

Paulos’ article is indeed concise and on the mark (though several of the explanations he proposes were already brought up in both the Atlantic and New Yorker essays), but it doesn’t really make things much better.

Paulos suggests that one explanation for the decline effect is the well known statistical phenomenon of the regression toward the mean. This phenomenon is responsible, among other things, for a fair number of superstitions: you’ve probably heard of some athletes’ and other celebrities’ fear of being featured on the cover of a magazine after a particularly impressive series of accomplishments, because this brings “bad luck,” meaning that the following year one will not be able to repeat the performance at the same level. This is actually true, not because of magical reasons, but simply as a result of the regression to the mean: extraordinary performances are the result of a large number of factors that have to line up just right for the spectacular result to be achieved. The statistical chances of such an alignment to repeat itself are low, so inevitably next year’s performance will likely be below par. Paulos correctly argues that this also explains some of the decline effect of scientific results: the first discovery might have been the result of a number of factors that are unlikely to repeat themselves in exactly the same way, thus reducing the effect size when the study is replicated.

nother major determinant of the unreliability of scientific results mentioned by Paulos is the well know problem of publication bias: crudely put, science journals (particularly the high-profile ones, like Nature and Science) are interested only in positive, spectacular, “sexy” results. Which creates a powerful filter against negative, or marginally significant results. What you see in science journals, in other words, isn’t a statistically representative sample of scientific results, but a highly biased one, in favor of positive outcomes. No wonder that when people try to repeat the feat they often come up empty handed.

A third cause for the problem, not mentioned by Paulos but addressed in the New Yorker article, is the selective reporting of results by scientists themselves. This is essentially the same phenomenon as the publication bias, except that this time it is scientists themselves, not editors and reviewers, who don’t bother to submit for publication results that are either negative or not strongly conclusive. Again, the outcome is that what we see in the literature isn’t all the science that we ought to see. And it’s no good to argue that it is the “best” science, because the quality of scientific research is measured by the appropriateness of the experimental protocols (including the use of large samples) and of the data analyses — not by whether the results happen to confirm the scientist’s favorite theory.

The conclusion of all this is not, of course, that we should throw the baby (science) out with the bath water (bad or unreliable results). But scientists should also be under no illusion that these are rare anomalies that do not affect scientific research at large. Too much emphasis is being put on the “publish or perish” culture of modern academia, with the result that graduate students are explicitly instructed to go for the SPU’s — Smallest Publishable Units — when they have to decide how much of their work to submit to a journal. That way they maximize the number of their publications, which maximizes the chances of landing a postdoc position, and then a tenure track one, and then of getting grants funded, and finally of getting tenure. The result is that, according to statistics published by Nature, it turns out that about ⅓ of published studies is never cited (not to mention replicated!).

“Scientists these days tend to keep up the polite fiction that all science is equal. Except for the work of the misguided opponent whose arguments we happen to be refuting at the time, we speak as though every scientist’s field and methods of study are as good as every other scientist’s, and perhaps a little better. This keeps us all cordial when it comes to recommending each other for government grants. ... We speak piously of taking measurements and making small studies that will ‘add another brick to the temple of science.’ Most such bricks lie around the brickyard.”

Most damning of all, however, is the potential effect that all of this may have on science’s already dubious reputation with the general public (think evolution-creation, vaccine-autism, or climate change)

“If we don’t tell the public about these problems, then we’re no better than non-scientists who falsely claim they can heal. 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.”

Joseph T. Lapp said... But is any of this new for science? Perhaps science has operated this way all along, full of fits and starts, mostly duds. How do we know that this isn't the optimal way for science to operate?My issues are with the understanding of science that high school graduates have, and with the reporting of science.

What seems to have emerged in recent decades is a change in the institutional setting that got science advancing spectacularly since the establishment of the Royal Society. Flaws in the system such as corporate funded research, pal-review instead of peer-review, publication bias, science entangled with policy advocacy, and suchlike, may be distorting the environment, making it less suitable for the production of good science, especially in some fields.

Remedies should exist, but they should evolve rather than being imposed on a reluctant sociological-economic science establishment driven by powerful motives such as professional advance or funding. After all, who or what would have the authority to impose those rules, other than the scientific establishment itself?

But even when the perfect liver became available a few days after she was put on the list, doctors could not operate. What made Nataline different from most transplant patients, and what eventually brought her case to the attention of much of the country, was that her survival did not depend on the availability of an organ or her clinicians or even the quality of care she received. It rested on her health insurance company.

Cigna had denied the initial request to cover the costs of the liver transplant. And the insurer persisted in its refusal, claiming that the treatment was “experimental” and unproven, and despite numerous pleas from Nataline’s physicians to the contrary.

But as relatives and friends organized campaigns to draw public attention to Nataline’s plight, the insurance conglomerate found itself embroiled in a public relations nightmare, one that could jeopardize its very existence. The company reversed its decision. But the change came too late. Nataline died just a few hours after Cigna authorized the transplant.

Mr. Potter was the head of corporate communications at two major insurers, first at Humana and then at Cigna. Now Mr. Potter has written a fascinating book that details the methods he and his colleagues used to manipulate public opinion

Mr. Potter goes on to describe the myth-making he did, interspersing descriptions of front groups, paid spies and jiggered studies with a deft retelling of the convoluted (and usually eye-glazing) history of health care insurance policies.

We learn that executives at Cigna worried that Nataline’s situation would only add fire to the growing public discontent with a health care system anchored by private insurance. As the case drew more national attention, the threat of a legislative overhaul that would ban for-profit insurers became real, and Mr. Potter found himself working on the biggest P.R. campaign of his career.

Cigna hired a large international law firm and a P.R. firm already well known to them from previous work aimed at discrediting Michael Moore and his film “Sicko.” Together with Cigna, these outside firms waged a campaign that would eventually include the aggressive placement of articles with friendly “third party” reporters, editors and producers who would “disabuse the media, politicians and the public of the notion that Nataline would have gotten the transplant if she had lived in Canada or France or England or any other developed country.” A “spy” was dispatched to Nataline’s funeral; and when the Sarkisyan family filed a lawsuit against the insurer, a team of lawyers was assigned to keep track of actions and comments by the family’s lawyer.

In the end, however, Nataline’s death proved to be the final straw for Mr. Potter. “It became clearer to me than ever that I was part of an industry that would do whatever it took to perpetuate its extraordinarily profitable existence,” he writes. “I had sold my soul.” He left corporate public relations for good less than six months after her death.

“I don’t mean to imply that all people who work for health insurance companies are greedier or more evil than other Americans,” he writes. “In fact, many of them feel — and justifiably so — that they are helping millions of people get they care they need.” The real problem, he says, lies in the fact that the United States “has entrusted one of the most important societal functions, providing health care, to private health insurance companies.” Therefore, the top executives of these companies become beholden not to the patients they have pledged to cover, but to the shareholders who hold them responsible for the bottom line.