In December 2009, the Anesthesia & Analgesia journal published a study by Joachim Boldt, a prominent German anesthesiologist, but a few readers raised questions about the data and, after some digging around by the editor, the article was retracted last October. Now, though, a state medical association in Germany, where the research was supposedly conducted, investigated a long list of studies attributed to Boldt and released some startling findings.

To wit, Boldt failed to take a required step: there was no evidence that he obtained Institutional Review Board approval to conduct research for 92 articles - count ‘em, 92. As you might imagine, this suggests dozens more retractions may be in the offing and further reviews have been under way, according to this letter from the editors of 11 medical journals who vowed to do their utmost to uphold ethical research conduct, as first reported by Retraction Watch (which has been following this case).

After the article in Anesthesia & Analgesia was retracted, the hospital where he worked also convened a committee to review the research. The upshot? There were no original patient data or lab data to support the findings; a solution cited in the study had not been used since 1999 and had not been delivered to the cardiac operating rooms for many years; Boldt admitted forging signatures of his co-authors on a copyright transfer form submitted to the journal, and the coauthors denied participating in the fabrication. Bottom line: “There is no convincing evidence that this study was performed at all.”

To quote Steve Shafer, the editor of Anesthesia & Analgesia, all this was “unglaublich,” or unbelievable. And the episode has raised some sobering questions about oversight of so-called investigator-initiated trials in Germany and, perhaps, elsewhere. As noted in some newly published editorials in the journal (see this, this and this), there is a disconnect.

The hospital where Boldt conducted his research, Klinikum Ludwigshafen, does not have its own IRB, or ethics committee as they are called in Germany. This explains why it took Shafer several months to determine who was responsible for overseeing ethical research at the Klinikum Ludwigshafen hospital. In fact, there is only one IRB in the entire state of Rheinland-Pfalz in which the hospital is located, and it is run by the state medical association, or LÄK-RLP. And the LAK-RLP does not have the authority or procedures to investigate a study site for fraud. The LÄK reviews protocols.

Unlike in the US, there are no private IRBs in Germany that are authorized to approve trials, according to Shafer. Yet existing IRBs, which are known in Germany as ethics committees, do not control the research activities of physicians directly, do not police research conduct, and do not have authority to inspect trial sites or perform investigations, unless authorized by the executive administration of a respective hospital, as noted in one of the editorials.

To Shafer, this is a recipe for fraud. “It’s intrinsic to the way the German system is set up. In the US, there are thousands of IRBs. But there are only 54 IRBs in all of germany. There is no system of private IRBs there,” he tells us. “Other than major universities, it would be overseen by a regional authority. So I think this (kind of fraud) can happen anywhere in that it is a potential problem anyplace where there is no overall body to look after ethical research, but where research is farmed out.”

And he worries similar shenanigans could occur in the US. For instance, an investigator could pursue research at a US hospital or clinic, which does not have its own IRB, by falsely claiming that approval was granted by a for-profit IRB. But he worries that there would be no standard form of oversight unless or until a problem was alleged.

“The same thing could happen in the United States, don’t delude yourself. They just tick the box – yeah, I got IRB approval — but do they have to submit an approval letter from the IRB chair? As journal editors we all ask, have you got ethics approval? They write back and say yes and we take it at face value that they are not lying to us,” Udo Schuklenk, editor of Bioethics and Developing World Bioethics, tells Retraction Watch.

As for Boldt, he may have violated the Code of Deontology, which says investigators are obliged to seek the advice or vote of their local ethics committee before starting biomedical research. He already lost his job at the hospital, where he chaired the Clinic of Anaesthesiology and Intensive Care, and if found guilty of violating the code, he faces a fine of 100,000 Euros, or about $136,000.

By the way, Anesthesia & Analgesia is the same journal that previously was forced to retract fraudulent papers as a result of the infamous Scott Reuben case, which you can read about here.

pic thx to The Star