Research fraud from Japan

Science seems to have the full article from its magazine available on line about the remarkably extensive fraudulent medical research of one Yoshihiro Sato in Japan.  (He has since committed suicide, as did another researcher found to have committed fraud in stem cell research.)    This is not a topic I normally follow, but the way other researchers detect problems in this field, and sometimes just accept improbably explanations initially, is interesting.   For example:

Avenell's own quest began in 2006, when she was combing through dozens of papers for a review evaluating whether vitamin D reduces the risk of bone fractures. In two papers by Sato, she stumbled on a weird coincidence. They described different trials—one in stroke victims, the other in Parkinson's disease patients—but the control and study groups in both studies had the exact same mean body mass index. Looking further, she quickly found several other anomalies. She decided not to include Sato's studies in her analysis.

She wasn't the first to notice something was off. In a 2005 Neurology paper, Sato claimed that a drug named risedronate reduces the risk of hip fractures in women who have had a stroke by a stunning 86%. In a polite letter to the journal, three researchers from the University of Cambridge in the United Kingdom noted that the study was "potentially of great importance," but marveled that the authors had managed to recruit 374 patients in just 4 months.

Two years later, a letter in what was then the Archives of Internal Medicine was less polite. A study of male stroke patients published by Sato had managed to enroll 280 patients in just 2 months; another one, of women with Alzheimer's disease, recruited a staggering 500 in an equally short period. Sato claimed to have diagnosed all of the Alzheimer's patients himself and done follow-up assessments of all 780 patients every 4 weeks for 18 months. Both studies had very few dropouts, and both showed risedronate, again, to be a resounding success. "We are deeply concerned whether the data provided by Sato et al are valid," Jutta Halbekath of Arznei-Telegramm, a Berlin-based bulletin about the drug industry, and her co-authors wrote. Sato apologized in a published response and claimed the study had been conducted at three hospitals, not one. "The authors did not describe this fact, the reason being that these hospitals were reluctant to have their names in the article," he wrote. He didn't name the other hospitals or explain why they wanted to remain anonymous. The journal apparently accepted the explanation.

The letter's authors also spotted a troubling pattern. In addition to the two papers in the Archives of Internal Medicine, they found 11 further studies by Sato, published elsewhere, that tested whether sunlight, vitamin D, vitamin K, folate, and other drugs could reduce the risk of hip fractures. All but two reported "extremely large effects with significant results," they noted. But the Archives of Internal Medicine didn't want to point fingers at other journals. "You may allude to your concern that other papers have similar concerns," its editors warned Halbekath, "but we cannot allow you to mention those other papers by journal name."

By now, several researchers had raised red flags and waved them for everyone to see—and then everybody moved on. "The trail just went cold," Avenell says.

Remarkably, the article goes onto note that Japan is an unusually popular country for bad medical research, and the culture of respect seems to be part of the problem:

Sato's fraudulent work has propelled him to No. 6 on Retraction Watch's list of researchers who have racked up the most retractions. At the top is Japanese anesthesiologist Yoshitaka Fujii, with 183 retractions; his frequent co-author Yuhji Saitoh, also from Japan, is at 10th place, while Japanese endocrinologist Shigeaki Kato is No. 8. Iwamoto is at No. 9. That means half of the top 10 are Japanese researchers. Yet only about 5% of published research comes from Japan. What explains the number of prolific Japanese fraudsters?

Michiie Sakamoto, who is leading another investigation at Keio University, into Iwamoto's studies in animals, says it has to do with respect. "In Japan, we don't usually doubt a professor," he says. "We basically believe people. We think we don't need strict rules to watch them carefully." As a result, researchers faking their results may be exposed only after they have racked up many publications.

Outside researchers may also be less likely to question anomalous results from Japan. Several early critics of Sato's work say they thought at first that his unusual results might be due to something uniquely Japanese. One case in point: In 2003, Sato published a study on data from 40 patients with a very rare affliction named neuroleptic malignant syndrome, collected over 3 years. In a letter to the journal, a U.K. neurologist said he and his colleagues "could only recall two such cases in living memory"—but instead of casting doubt on the study, they said it was interesting that the syndrome seemed so prevalent in Japan.

But none of that explains why Sato decided to embark on his fraud—and nobody seems to be able to shed much light on that question. "Given the number of papers he published, he must have spent a very large amount of time on them," Bolland says. "I don't understand what his gain was. … There must have been some reason to do it." The Keio University panel is just as puzzled. "We discussed this a lot in the committee," Saya says. It might have been like a hobby, he suggests. A thrill. Saya uses the word "otaku," a Japanese term often applied to people who read manga obsessively.

The article also explains how big a problem such bad research is - it has a real cascading effect on other studies and policies.

Pretty fascinating...