Bioethics Forum Essay
Getting By with a Little Help from Your Friends
If the mutilated body of one of your research subjects is discovered in a blood-soaked bathroom, who should investigate the death? If you want to be cleared of blame, it’s useful if the investigation is led by a colleague from your own department. If you were being paid by a drug company to recruit that subject into a research study, it’s best if your colleague is getting a paycheck from the same company. Best-case scenario: your colleague is on the university’s “conflict of interest” committee, too, just in case anyone raises questions.
Let me back up and explain. In 2004, a young man named Dan Markingson committed a violent suicide while a research subject in an AstraZeneca-sponsored study of antipsychotic drugs – the so-called CAFÉ study — at the University of Minnesota. The CAFÉ study was plagued by ethical problems, ranging from coercion and corruption to incompetent medical care. For years, stunned critics have challenged the University of Minnesota officials to justify the troubling study and the actions of its researchers, but those officials have simply refused to debate the issue, claiming that the University of Minnesota has already been exonerated.
A central piece of the exoneration claim has come from the (then) general counsel for the university, Mark Rotenberg. In 2010 Rotenberg issued a statement saying that the university’s institutional review board (IRB) had reviewed Markingson’s suicide, and that not only had the IRB found no fault with any university faculty members, it had also found no causal link between the CAFÉ study and Markingson’s suicide. Rotenberg repeated this claim in November 2012, when the Minnesota Board of Social Work issued a number of damning findings egarding Jean Kenney, the study coordinator for the CAFÉ study. Yet during this time Rotenberg never produced an IRB review. In fact, no one at the university ever provided any evidence that the IRB conducted more than a routine, administrative “continuing review” of the CAFÉ study, much less any evidence that the IRB exonerated the researchers from blame for Markingson’s death.
For some years I have doubted the claim that the IRB looked seriously into Markingson’s suicide. The main reason for doubting that claim is a 2007 deposition by Richard Bianco, the head of research protection at the university at the time of Markingson’s death. In that deposition, Bianco testified that neither the IRB nor anyone else at the university had ever investigated the death. His testimony is unambiguous. In response to the question, “Has the university done any investigation into the death of Dan Markingson?” Bianco replied, “No.” When Bianco was asked, “To the best of your knowledge, did anyone at the IRB, at the University of Minnesota, or anyone under your office investigate this case, actually look at the records and see the court documents that I’m describing, and if so, could you give me the name of that person?” He replied, “Not to my knowledge.”
For months now, I have been filing Data Practices Act requests to the university. First I asked for any review the IRB conducted. Later, when the university admitted that there was “no written IRB report” on Markingson’s death, I asked for the minutes of the meetings in which Markingson’s death was discussed. Last Friday, six weeks after my latest request, the university finally gave me the redacted minutes of those IRB meetings. It is now clear why the university has not been eager to make those minutes public. The conflicts of interest on the IRB are astonishing.
The IRB panel that reviewed the serious adverse event report of Markingson’s death was chaired by psychiatrist David Adson. As a faculty member in the Department of Psychiatry, Adson was a colleague of Stephen Olson, the principal investigator of the CAFÉ study. He reported to Charles Schulz, the Chair of the Department of Psychiatry and a co-investigator on the CAFÉ study. Adson was also the director of the Ambulatory Research Center, which housed the CAFÉ study. According to his CV, Adson chaired the IRB Panel from 1998 through 2005, which suggests that not only did he chair the panel when it received the report of Markingson’s death, but he was also chair when the IRB approved the CAFÉ study in 2002. And while it is possible, of course, that Adson recused himself from the IRB meetings in which the CAFÉ study was discussed, there is no suggestion of a recusal in the minutes.
If these personal conflicts of interest are not enough, consider the financial conflicts. According to a public database maintained by the Minnesota Board of Pharmacy, Adson has received more than $650,000 in consulting, research, and speaking fees from the pharmaceutical industry from 2002 to 2010. In 2004, the year when the IRB received word of Markingson’s suicide, Adson reportedly received $5,200 as “compensation for services” to AstraZeneca, the sponsor of the CAFÉ study. The next year, when he was still IRB chair, he received $16,884 from AstraZeneca. In total, AstraZeneca paid Adson over $149,000. Adson also received payments from Merck, Forest, Bristol Myers-Squibb, Pfizer, Wyeth, Sanofi-Aventis, and GlaxoSmithKline.
How could a person with such significant financial ties to the pharmaceutical industry be allowed to chair an IRB panel? Wouldn’t the university’s Conflict Review and Management Committee consider this a serious conflict of interest? For an answer to that question, you might well ask Adson himself. According to his CV, he was a member of the Academic Health Center Conflict Review and Management committee from 1998 until 2008.
No one should be surprised by this — and not simply because the University of Minnesota has papered over controversial conflicts of interest for years. This claim of IRB review of the Markingson case is just one of many supposed “exonerations” of the university that have fallen apart under scrutiny – such as the claim of exoneration by a county court, and by the Minnesota Attorney General, and by the Board of Medical Practice. In fact, this is not even the first time that Adson’s financial ties to the pharmaceutical industry have been questioned. As the St. Paul Pioneer Press reported in 2007, Adson served as the clinical leader of a controversial Eli Lilly-funded state program aimed at influencing the prescribing choices of Minnesota psychiatrists. Critics charged that Lilly’s antipsychotic, Zyprexa, benefited from the program at the expense of its competitors. Two years later, Lilly paid $1.42 billion to settle civil and criminal fraud charges for illegally marketing that drug.
Will this latest finding make any difference? Probably not. Here at the University of Minnesota, no one will respond to complaints like these. In the past I’ve tried everyone from the Research Integrity Office and the Research Consultation Service to the president of the university. Any complaint about the Markingson case is turned over to the Office of the General Counsel, which responds with a boilerplate denial of responsibility. This, of course, is a recipe for research abuse.
Carl Elliott, a Hastings Center Fellow, is a professor at the Center for Bioethics at the University of Minnesota. His most recent book is White Coat, Black Hat: Adventures on the Dark Side of Medicine.
Posted by Susan Gilbert at 10/18/2013 10:48:12 AM |