Dan Markingson wasn't himself.
He feared evil spirits were after him. He described experiences with aliens in his apartment. He was convinced that the Illuminati would soon call on him to murder people - perhaps even his own mother - and he was not afraid to do it.
In November 2003, Markingson's mother, Mary Weiss, committed him to the psychiatric wing of Fairview Medical Center on the University of Minnesota's campus. There, Markingson volunteered to participate in a clinical study for an experimental anti-psychotic drug funded by AstraZeneca, called a Cafe study.[jump]
On May 8, 2004, Markingson ended his own life at age 26.
Markingson's suicide may have been prevented if not for a pattern of serious potential ethical violations on part of U of M researchers, according to eight faculty members from the college's bioethics department. These alleged violations include a doctor recruiting a patient mentally unfit to volunteer for the study, conflict-of-interest relationships with U of M researchers conducting studies funded by Big Pharma, and clinical studies designed with an innate bias to churn out positive results.
The eight faculty members sent a letter to the U of M's Board of Regents last week calling for an independent investigation into the events surrounding Markingson's suicide.
"It's not a casual thing," says Leigh Turner, an associate professor who co-authored the letter. "Those of us who signed the letter are faculty members here, and I think if we thought this was handled in an effective, responsible way in-house, we wouldn't have sent it."
Carl Elliott, another co-author of the letter, first became interested in the Markingson case in 2008 after reading an investigative series about it in the Pioneer Press.
Elliott was shocked at what appeared to be a series of critical ethical issues that began as soon as Weiss checked her son into Fairview.
According to the article, Markingson's doctor -- the same person who urged him to volunteer for the AstraZeneca-funded study -- was also the study's principal investigator.
When Markingson signed up for the Cafe study, Weiss was not present. She attempted to remove her son from the study when she discovered what had happened -- the experimental drug was risky for Markingson, and Weiss wanted standard treatment -- but doctors refused to listen.
Fairview's Institutional Review Board, the in-house committee charged with looking out for the safety of patients involved in research studies, never intervened in the case. Instead, the board trusted that Markingson's doctors were operating with his best interest in mind.
Elliott was also surprised that very few of his colleagues at the U of M shared his dismay. When he started asking around, it seemed that most had not seen or even heard about the article. Senior faculty at the U told Elliott that the story was slanted, and shouldn't be taken seriously, he says.
But Elliott wasn't convinced. He began researching the case himself.
"The more I looked into it, the more I started to feel it was even worse than the Pioneer Press made it seem," says Elliott.
Elliott wrote a follow-up article on his findings, "The Deadly Corruption of Clinical Trials," which appeared in Mother Jones earlier this year.
From the article:
The danger lies not just in the particular circumstances that led to Dan's death, but in a system of clinical research that has been thoroughly co-opted by market forces, so that many studies have become little more than covert instruments for promoting drugs. The study in which Dan died starkly illustrates the hazards of market-driven research and the inadequacy of our current oversight system to detect them.
Elliott thought the piece would direct the U of M's attention to what appeared to be many alarming questions that had so far gone unanswered.
Instead, the college's lead counsel, Mark Rotenberg, penned a response statement dismissing many of the article's allegations. Rotenberg pointed out that Markingson's death had been examined by federal and state entities already.
"None found fault with the University, none found fault with the involved faculty, and none found any causal link between the Café trial and the unfortunate death of Dan Markingson," wrote Rotenberg.
The statement didn't satisfy Elliott and the other seven bioethics faculty members who authored last week's letter.
The letter asks that the Regents appoint a panel of investigators with no ties to the U of M to conduct a thorough examination of the case.
"Patients participating in research studies at the University of Minnesota need to be confident that the university is doing everything it can to protect them from harm," states the letter.
Elliott hopes the Regents listen to the letter's request and initiate the investigation. He fears what could happen if the U of M takes no further action.
"Nothing has been done to eliminate the problems that led to Dan Markingson's suicide," says Elliott.
Here's the letter in full:
Board of Regents University of Minnesota 600 McNamara Alumni Center 200 Oak Street SE University of Minnesota Minneapolis, Minnesota 55455-2020
November 23, 2010
Dear Members of the Board:
On May 8, 2004, a young man named Dan Markingson committed suicide in a psychiatric research study at the University of Minnesota. The study was sponsored by the pharmaceutical company, AstraZeneca. Over the past two years, articles in the St. Paul Pioneer Press and Mother Jones magazine have suggested an alarming series of ethical violations and lapses with that study which, if true, suggest serious problems in the way that clinical research is conducted and overseen at the university. Those ethical violations include: recruiting a mentally ill, possibly incompetent subject into a research study while he was under an involuntary commitment order; large financial conflicts of interest on the part of the university researchers conducting the study; a payment structure for the study which included financial incentives to recruit and retain subjects rather than provide them with standard therapy; an allegedly biased study design aimed at generating positive results for AstraZeneca rather than investigating a genuine scientific question; the failure of university researchers to address the legitimate concerns of Mr. Markingson's mother, Mary Weiss, who warned that her son was suicidal and who attempted for months to have him removed from the study as his mental condition deteriorated; the apparent development of a specialized unit in Fairview Hospital designed to identify severely mentally ill subjects for recruitment into research studies; and finally, a failure of the institutional oversight system for protecting human subjects of research. Although the University of Minnesota and AstraZeneca were cleared of blame by an FDA investigator in 2005, we believe that the problems outlined in the Pioneer Press and Mother Jones articles are serious enough to warrant further investigation. These reports raise troubling questions that to date have not been addressed in our university's response to the death of Mr. Markingson. Patients participating in research studies at the University of Minnesota need to be confident that the university is doing everything it can to protect them from harm. For this reason, we respectfully request that the Board of Regents appoint an impartial panel of experts in research ethics and university governance of medical research to investigate the Markingson case, particularly any larger structural or financial conditions that might have played a role in his death and which may still be putting patients at risk. Given the ongoing controversy over conflicts of interest in the Academic Health Center, we believe that it is important that panel members come from outside the University of Minnesota and have no financial or professional relationships to the researchers responsible for the study in which Mr. Markingson died. While it is understandable that some of our colleagues will have little interest in revisiting this case and the ethical issues it raises, we are persuaded that there is a disturbing and unjustifiable gap between how our university has responded to this death and the careful, critical investigation it warrants. We therefore seek your intervention in this matter.
Carl Elliott MD PhD Professor, Center for Bioethics and Departments of Pediatrics and Philosophy
Dianne Bartels, RN, MA, PhD Assistant Professor, Center for Bioethics and Department of Medicine
Joan Liaschenko, RN, PhD, FAAN Professor, Center for Bioethics and School of Nursing
Mary Faith Marshall, PhD Professor, Center for Bioethics and Department of Family Medicine and Community Health
John Song, MD, MPH, MAT Associate Professor, Center for Bioethics and Department of Medicine
Leigh Turner, PhD Associate Professor, Center for Bioethics and School of Public Health and College of Pharmacy
Susan Craddock PhD Chair, Department of Gender, Women, and Sexuality Studies and Affiliate Faculty Member, Center for Bioethics
Joan Tronto PhD Professor, Department of Political Science and Affiliate Faculty Member, Center for Bioethics