U of M faculty members call for an investigation into death of research subject

Dan Markingson was deemed incompetent. Then, days later, he was deemed competent enough to take part in a research study that ultimately netted the U of M hundreds of thousands of dollars-and possibly led to Markingson’s violent death.

Now, more than six years after the suicide of the 26-year-old Minnesota man, eight faculty members at the University of Minnesota are calling for an independent investigation into the gruesome death that occurred while Markingson was part of a U of M research study.

“There are serious questions about this case that need to be answered,” says Dr. Leigh Turner, an associate professor of bioethics and signatory on a letter to the Board of Regents calling for an investigation. “How much did [financial] incentives have a role in Markingson being enrolled in the study, even despite significant concerns of his mother?” Turner wants to know. “And why was [Markingson’s] consent even sought when just days before he was deemed incompetent?”

The letter calls for an independent investigation into Markingson’s death and for the U, a top-research institution already tainted by stories outlining serious conflict of interest and threats to academic freedom, to examine its conflict of interest policy and ensure safeguards are in place to protect its research subjects.

Markingson lacked “capacity to make decisions”

In 2003 Markingson was enrolled in a psychiatric drug study against his mother’s wishes. Two separate parties had deemed Markingson mentally incompetent when he was admitted to the U of M’s Fairview Medical Center on November 12 after Markingson’s mom, Mary Weiss, called the police after he threatened to slit her throat.

Just months before that incident in St. Paul, Weiss had become seriously concerned about the mental state of her son, a celebrity-tour-bus driver in L.A. Weiss went to visit him that summer. He told her a hole burnt in his carpet was from aliens and that a secret world order had called for him to kill people in a storm. Seriously worried for his safety, she convinced him to move back to Minnesota, but only after pretending to be a “guardian angel” spirit of his dead grandmother who suggested the “storm” was starting in Minnesota.

At the hospital only a few months later, in a document signed by Dr. Stephen Olson, an associate professor of psychiatry at the U of M, Markingson was deemed incompetent and ordered to a state mental institution. At the time, Olson noted, Markingson “lack[ed] the capacity to make decisions regarding such treatment.”

Days later, under orders of a judge and Olson, Markingson was granted a “stay of commitment,” an option in Minnesota where patients can avoid involuntary commitment to a mental institution as long as they follow a treatment plan. This gave Markingson only two options: Go involuntarily to a state hospital, or commit to a treatment plan to be ordered by Olson.

Olson’s treatment plan for Markingson consisted of enrolling him in a blind clinical trial sponsored by the pharmaceutical company AstraZeneca. Markingson’s mother was not present to offer consent. She believes her son was coerced by Olson to sign up for the study.

In early May of that same year, while still enrolled in the blind study for Seroquel despite his mother’s repeated attempts to remove him and her fear that he would hurt himself or others, Markingson stabbed himself to death with a box cutter in the bath tub of a halfway house.

Questions of serious ethical violations

The eight signatories want the U to investigate whether Olson’s financial interests played a role in Markingson’s diagnosis and inclusion in the study, and his resulting death.

According to a 2008 story in the Pioneer Press: “Olson had been searching for recruits for more than a year. The study required a very specific and elusive person – a schizophrenic experiencing his first symptoms. Markingson fit that profile.” The University was in danger of losing the study. Finding new research subjects was essential to continued funding, the story says.

Weiss, however, objected to her son’s inclusion in the clinical trial, and she was surprised by Olson’s diagnosis of schizophrenia. Her son had been previously diagnosed with bipolar disorder. The schizophrenia diagnosis was new.

Weiss had repeatedly and unsuccessfully called for her son to be removed from the study, including making multiple phone calls and sending five letters to the doctors. She cited an increase in her son’s erratic behavior and inner rage. She worried her son would kill himself or someone else. She received only one response, from Dr. Charles Schulz, the chairman of the U’s psychiatry department. “It was not clear to me how you thought the treatment team should deal with this issue,” he wrote in a letter.

The study, according to an article by U of M professor Dr. Carl Elliott in Mother Jones, barred subjects from being  being taken off their assigned drug. It also required them to stay on the drug for an entire year. Taking Markingson off the drug would’ve resulted in a loss of funding.

The U of M received $327,000 for this study, Turner notes. And for each person enrolled the University received an additional $15,000. Some of that money went directly to the psychiatry department-and some directly to Olson’s salary.

Between 2002 and 2008, Olson and Schulz had earned a combined $811,045 from pharmaceutical companies, and $261,364 of that came directly from AstraZeneca. According to the 2008 Pioneer Press story, “Four experts hired by Weiss’ attorneys agreed that Olson had an ethically questionable position – as the gatekeeper over Markingson’s commitment, as his treating psychiatrist, and as the researcher with a financial incentive to enroll patients.”

Elliott, a bioethics professor at the U of M who also wrote a story about the case for Mother Jones, says the letter to the Regents is not an accusation, but a call for an investigation into the claims raised by experts and the U faculty. “There are lots of questions about this,” Elliot says. “And no one at the U has, as far as I know, looked into this.”

Elliott says of most serious concern to him are the financial conflicts of interest and that just days after deeming Markingson incompetent, Olson determined without documentation and without Markingson’s mother present that Markingson was competent enough to consent to a research study.

“It’s not clear how Olson or how his study coordinator evaluated his competence,” Elliot says, “because Mary Weiss wasn’t there when it happened.” Elliott is hoping how Olson determined Markingson’s competence will be revealed in an independent investigation.

FDA “ignores conflict of interest”

In 2005 the Food and Drug Administration investigated the conduct of Olson, who was Markingson’s only doctor when he was enrolled in the research study. The FDA’s study cleared Olson of wrongdoing. However, Elliott and the signatories note that that the FDA investigation did not include questions of serious ethical violations.

“There is nothing about conflict of interest in that report,” Elliott notes. “The conclusion [by the investigator] was that [Markingson] was mentally competent. Yet he was so mentally dangerous that he needs to be involuntarily committed? How can an FDA investigator look at that and say there is nothing to suggest he is incompetent?”

In addition, most clinical trials exclude patients who are at risk of homicide or suicide. This study only excluded those at risk of suicide, which Markingson later became. Elliott wonders how someone admitted to the hospital threatening to kill someone could be included in a research study that normally bars violent subjects.

Elliott has made numerous attempts to reach the FDA about his questions and concerns. He says he is continuously stonewalled and the FDA refuses to answer any questions.

“A system has failed”

Dr. Mary Faith Marshall has been involved with human-subject protection policy initiatives for more than a decade. The U of M bioethics professor signed the letter to the Board of Regents because of what she says were serious lack of protections for Markingson. “Any time a human subject dies in a research project it’s a signal or a sign that the system has failed,” she says.

“There was a failure of the monitoring system,” Marshall adds. “There were, I think, some conflicts of interest at play. And there were coercive elements.”

After the death of Jesse Gelsinger, a research subject who died during a clinical trial for gene therapy at the University of Pennsylvania, Marshall was asked to chair the National Human Research Protections Advisory Committee, which recommended, in 2002, that all research subjects be awarded the same protections, regardless of private of federal funding. Marshall notes that had this been a federally-funded study-which is regulated by the Office of Human Resource Protections-it likely would have been shut down.

“The University agrees, regardless of federal or private funding, we are going to use the same standard to protect subjects,” Marshall says. In theory, the U uses the same standard for all studies. That includes ensuring that research subjects are capable to make decisions, are not coerced into a study, and understand the impact of the study. But even with those ethical safeguards in place, universities and researchers aren’t prone to the same regulations and repercussions when a study is funded with private dollars.

The OHRP was asked to investigate the case and determine whether Markingson was competent in voluntarily submitting to the study. “If I were a member of the site-visit team, I certainly would be looking into this,” Marshall says.

But the office declined to look into the matter because the study was funded with private dollars. Currently, there is no system in place to ensure that privately funded research follows the same guidelines as federally funded studies. Still, Marshall says, it is then the U’s responsibility to look into the case and determine if ethical violations were committed in the death of Markingson.

“Voluntariness is an essential component of decisional capacity for any research subject,” Marshall says. “And there was little evidence to suggest he had any voluntariness… It’s a shame that the federal government doesn’t think they can make a for-cause visit where someone has been killed in a study with private funding.”

More conflicts of interest for the U

In the wake of the “Troubled Waters” scandal, in which University Relations officials yanked a film’s premiere after it had raised concerns of the larger agricultural community, U faculty and staff have continued to raise questions about conflicts of interest. Letters to the Board of Regents suggest and call for investigations by independent committees into why the film was pulled by a non-academic department.

Matt McGeachy, a student representative to the Board of Regents, recently put together a document outlining student concerns about conflict of interests at the University. He included in his draft concerns over “Troubled Waters” censorship and the Markingson case. However McGeachy says that last Monday the Board of Regents Office nixed that section in the report, suggesting, according to McGeachy, “that it was inappropriate for inclusion.” McGeachy plans to edit and resubmit the draft for inclusion next semester.

Turner and Elliott hope the Board doesn’t similarly dismiss the letter signed by eight faculty members calling for an investigation into the Markingson case.

“This is the court of last appeal,” Elliott said. “The U  has known about this case for a long time. And the response was to follow with legal action against Mary Weiss.”

After Weiss filed a wrongful death lawsuit against the U of M, the U turned around and filed a lawsuit against Weiss to collect $57,000 in legal fees.

“To me, that’s shameful,” Elliott says. “I am embarrassed that even happened. This is a woman whose son died. Do people actually know that this man died? And do they know that the U’s response to the lawsuit was to file an action against the dead man’s mother to prevent her from filing any further lawsuits? I really hope that the answer isn’t silence this time.”

Elliott says he and the other signatories are waiting on a response from the Board of Regents.