But beyond the headlines, Ioannidis was shocked at the range and reach of the reversals he was seeing in everyday medical research. “Randomized controlled trials,” which compare how one group responds to a treatment against how an identical group fares without the treatment, had long been considered nearly unshakable evidence, but they, too, ended up being wrong some of the time. “I realized even our gold-standard research had a lot of problems,” he says. Baffled, he started looking for the specific ways in which studies were going wrong. 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.”

Though scientists and science journalists are constantly talking up the value of the peer-review process, researchers admit among themselves that biased, erroneous, and even blatantly fraudulent studies easily slip through it. 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.”