Major fraud probe of Japanese anesthesiologist Yoshitaka Fujii may challenge retraction record

We have learned that a widely published Japanese anesthesiologist is under investigation by his university over concerns that he engaged in repeated fraud for decades that has tainted roughly 180 articles—many of which may be retracted as a result.

In a related move, the journal Clinical Therapeutics is retracting papers by the researcher, Yoshitaka Fujii, most recently of Toho University, in Tokyo. Judy Pachella, managing editor of the journal, confirmed the retractions but would not state how many papers were affected. Clinical Therapeutics published 17 articles by Fujii, between 2003 and 2010.

Many of Fujii’s papers involved trials of drugs to treat postoperative nausea and vomiting (PONV), a significant side effect of surgery. He was not heavily cited, according to Thomson Scientific’s Web of Knowledge, although some of his studies were cited by several dozen other papers.

The bulk of Fujii’s papers appeared in the anesthesia literature, and in particular the Canadian Journal of Anesthesia, which has published at least 39 of his articles. The investigation was triggered last spring when Fujii submitted a manuscript to the journal containing what appeared to be plagiarism.

Sources familiar with the investigation said that Toho University is preparing to release a statement about Fujii’s misconduct, as early as tomorrow. It is unclear if Fujii is still employed by the institution; an email sent to his university account bounced back. [See update at end.]

Although the scope of the deception might prove to be shocking, it likely will come as no surprise to some in the anesthesia community. In 2000, a group of researchers led by Peter Kranke, of the Department of Anaesthesia and Critical Care at University of Würzburg Hospital, in Germany, challenged the veracity of Fujii’s studies in a letter to the journal Anesthesia & Analgesia.  Its title: “Reported data on granisetron and postoperative nausea and vomiting by Fujii et al. are incredibly nice!”

Kranke and his colleagues analyzed 47 of Fujii’s papers, published between 1994 and 1999, on the treatment of postoperative nausea and vomiting with granisetron.

With increasing amazement, we noticed that the results reported by Fujii et al. are incredibly nice and we became skeptical when we realized that side effects were almost always identical in all groups.

They concluded that “there must be an underlying influence causing such incredibly nice data.”

Fujii, who at that time was affiliated with the University of Tsukuba Institute of Clinical Medicine, in Ibaraki, dismissed the implied accusation in a response that the journal published alongside Kranke’s letter. In many of his trials, he wrote,

we found that several patients who had received granisetron experienced mild headache and that an incidence of headache was approximately 10%. Consequently, an incidence of headache seems to be identical, but it was true. How much evidence is required to provide adequate proof about antiemetics’ adverse events introduced recently by several investigators?

Christian C. Apfel, an expert on PONV and a co-author of the letter by Kranke, said he has been disappointed that the anesthesiology journals did not retract any of the papers his critique cited, and that they other journals continued to publish Fujii’s studies despite what he considered to be clear evidence of fabrication. “The likelihood that the data are true, as we calculated, is something like less than one seven in a billion,” said Apfel, of the University of California, San Francisco Medical Center.

In a follow-up study published in 2001 in Acta Anaesthesiologica Scandinavica, Apfel, Kranke and colleagues conducted a meta-analysis of Fujii’s studies of granisetron and showed that his trials demonstrated efficacy for the drug that was well outside what other groups were finding. Although the recommended dose of granisetron is 1 mg, Fujii’s papers said that amount was ineffective. Rather, the papers said, 3 mg worked—and remarkably well. On average, Apfel said, Fujii’s studies indicated that the drug was three times as effective as any other antiemetic:

The data for effectiveness are off the charts.

However, Apfel noted, Fujii’s findings likely did not affect patient care in the United States.

If Fujii’s data had an impact, people would have used 3 mg. But people didn’t.

Apfel even wrote to the FDA, its Japanese counterpart and the Japanese Society of Anesthesiologists to warn them about Fujii’s results—but received either no reply or a cursory acknowledgment of his concerns. The FDA could not immediately confirm for Retraction Watch whether regulators had received Apfel’s letter or responded to it.

Steven L. Shafer, editor-in-chief of Anesthesia & Analgesia, which published 24 of Fujii’s papers, said the case began in earnest last spring after the researcher submitted a manuscript to the CJA. Shafer said he agreed to analyze the statistics in the manuscript, and reached the conclusion that there was a very high probability of fraudulent data.

The journal corresponded with Fujii, asking for a copy of the ethical approval form for the study. What they got back was unsatisfactory.

The editors then contacted Fujii’s clinical institution and were informed that not only were the data fabricated, but that Fujii had not obtained approval to conduct such a study. (He published a similar paper in Anesthesia & Analgesia in 2003, prior to Shafer’s arrival as editor.)

Anesthesia & Analgesia will be posting a letter to readers online. Shafer apologized for what he called his journal’s “inadequate response” to the 2000 letter challenging Fujii’s results:

Publication of the letter was appropriate, but the lack of institutional follow-up was not appropriate. It was similarly inappropriate to publish additional manuscripts by Fujii when the allegations of fraud were unresolved.

Anesthesia & Analgesia published 11 articles by Fujii after the 2000 letter that alleged improprieties in his data, Shafer noted. Shafer said he would issue expressions of concern for all of Fuji’s papers in his journal.

This case is the latest in a string of recent misconduct scandals involving anesthesiologists, in the United States and abroad. In 2009, journals were forced to retract nearly two dozen papers by Scott Reuben, a Massachusetts pain specialist, who fabricated data and eventually spent six months in federal prison for health care fraud.

That was followed last year by revelations that Joachim Boldt, a critical care specialist in Germany, had failed to receive ethics approval for many of his clinical trials. To date, journals have retracted nearly 90 of his papers. Boldt also may have fabricated data in at least one study, a 2010 article in Anesthesia & Analgesia. In fact, it was Shafer’s response to that paper that led to the massive retractions.

Another retraction of Fujii’s work will be coming from Otolaryngology—Head and Neck Surgery, said Richard Rosenfeld, editor in chief of the journal. The study, “Antiemetic efficacy of low-dose midazolam in patients undergoing thyroidectomy,” was published electronically in December 2010. In January 2012, Fujii contacted the journal to say that he had obtained ethics approval to conduct the research after starting the trial and wanted to withdraw the paper, Rosenfeld said:

We notified our publisher, SAGE, at the time this came in and have tried to obtain additional clarification from Dr. Fujii.  No response has been received,” said Dr. Rosenfeld, who has asked SAGE to pull the article “since there is no doubt at this point of an ethical violation.

We’ll continue to update what is obviously a rapidly moving story.

Update, 10:30 p.m. Eastern, 3/7/12: Toho University has posted a statement, “Disciplinary Decision concerning Dr. Yoshitaka Fujii,” to its website. Fujii was apparently fired on February 29. The statement refers to a list of nine papers that will be retracted, but there’s no list on the page. It also claims that Fujii requested the retractions himself, but that’s not our understanding of how things happened:

Since all of Dr Fujii’s clinical studies appeared in these 9 publications were conducted at Ushiku Aiwa General Hospital, which has no relation to his research activity in Toho University, the investigation committee contacted the head of the Ushiku Aiwa General Hospital. As far as the head of the hospital knows, there was only one clinical study listed by Dr. Fujii as having been conducted at the hospital. Eight of the nine clinical studies were conducted without any ethics committee’s approval, and this was judged sufficient to decide that 8 of his publications (No. 2 to 9) should be retracted since they did not conform to the global standard of ethics for clinical studies. After the investigation, the committee asked Dr. Yoshitaka Fujii and his co-author, Dr. Michiyo Itakura, to explain the whole circumstances. Dr. Fujii admitted that the clinical studies were done without any ethics committee’s approval. Dr. Itakura, however, was not involved in this misconduct. Dr. Yoshitaka Fujii sent letters of retraction to the affected journals. We organized a disciplinary committee and decided that a disciplinary dismissal was appropriate for Dr. Fujii, effective from February 29, 2012. Dr. Fujii has already been dismissed from Toho University.

Masaru Kuroda, M.D. & Ph.D.
Dean
Toho University Faculty of Medicine

Our attempts to reach Kuroda today were unsuccessful.

Note: A version of this story also appears at AnesthesiologyNews.com, where one of us (AM) is editor. Please see an update here.