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Controversy over U of M clinical trial has heated up again

The complicated, disturbing case of Dan Markingson, the mentally ill young man from St. Paul who committed suicide in 2004, is in the news again.

Dan Markingson committed suicide in 2004 while enrolled in a University of Minnesota clinical trial of the antipsychotic Seroquel.

The complicated and disturbing case of Dan Markingson, the mentally ill young man from St. Paul who committed suicide in 2004 while enrolled in a University of Minnesota clinical trial of the antipsychotic drug Seroquel, has become embroiled in even more controversy in recent weeks.

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Dr. Carl Elliott

Last month, University of Minnesota bioethicist Dr. Carl Elliott, who has written about the Markingson case extensively, raised concerns in his blog, Fear and Loathing in Bioethics, that the “evaluation to consent” form found in Markingon’s file appears to have been filled out in identical ways to the consent form in another patient’s file.

If the forms were filled out identically, it would mean that the patients had not been individually evaluated to determine whether they were mentally capable of giving their consent to be in the study. Markingon’s mother, Mary Weiss, has long contended that her son was incapable at the time of giving informed consent. Indeed, in the days leading up to his enrollment in the study, he had been found repeatedly incompetent of consenting to treatment.

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“Most alarming of all,” wrote Elliott, “the ‘answers’ supposedly given by the research subjects appear identical. But the new form has no date, no subject ID, no subject initials, and no mention of Unit 12, the ward in Fairview Hospital where Dan Markingson was hospitalized.”

“I find these documents so alarming that they demand an investigation,” he concluded. “How many research subjects in the Department of Psychiatry have this same form in their charts?  Were any of those subjects in studies subject to federal oversight, such as the CATIE study? Did any of those subjects suffer serious injuries or death?”

A petition for an independent investigation

Soon after Elliott raised these and other new questions about documents in Markingson’s files, Weiss launched a petition to ask Gov. Mark Dayton to appoint an independent panel of experts to investigate the university for possible research misconduct. That petition has now been signed by more than 1,000 people, including dozens of physicians, bioethicists and other medical experts.

In an article published Wednesday in the Star Tribune, the university’s chief counsel, Mark Rotenberg, said, “There is no evidence that any of [the consent forms] contained predetermined, photocopied answers.” 

Rotenberg suggested to Strib reporter Jeremy Olson that the family with the duplicate form may have downloaded it from the Internet.

That charge incensed Elliott. If that is the case, he wrote on his blog Thursday, then the university should make the redacted forms public. The controversy could be easily resolved, he stressed, if the patients’ families could compare the university’s records with their own.

“But [university officials] are not letting anyone else look at the study records,” Elliott added. “They want us to take their word for it.”

Unanswered questions

The Food and Drug Administration conducted an investigation into Markingson’s suicide in 2005; it found no evidence of wrongdoing by the university. Elliott has called the FDA report from that investigation “occasionally misleading, remarkably uncritical, and often simply baffling.”

Weiss filed a lawsuit against the university, the manufacturer of Seroquel (AstraZeneca) and the two university scientists who led the study, Drs. Charles Schulz and Stephen Olson. The suit was dismissed in 2008 with a partial summary judgment. As I’ve reported here before, the judge ruled that there was no case or statue that supported the contention that AstraZeneca — or any pharmaceutical company — had a duty to put the interest of its research subjects above those of the company. Weiss did settle a separate malpractice suit with Olson for $75,000 (an amount that Elliott reported did not cover her legal costs).

“As the controversy over this study has grown louder, the university has tried to portray it as a dispute from the distant past,” wrote Elliott in an op-ed for the Pharmalot blog earlier this week. “Nothing could be farther from the truth. We still do not know if Dan’s suicide was an isolated case. It is possible that other psychiatric research subjects at the university have been seriously harmed or mistreated. Last fall, the Minnesota Board of Social Work found that the study coordinator for the CAFÉ study (the AstraZeneca clinical trial in which Dan died) as well as the federally funded CATIE study had faked the initials of an investigator on study records, failed to inform Dan of new drug risks, failed to heed the warnings that Dan was in danger of killing himself, and had been given medical responsibilities beyond her training. If University of Minnesota officials were truly concerned about the welfare of research subjects, would they not at least want to investigate?”

This is a complex story. For a recent summary of the case and the issues involved I recommend, in addition to the links above, Dr. Judy Stone‘s series in her Scientific American blog, beginning with Part I, published last December.