Dan Markingson (November 25, 1976 – May 8, 2004) was a man from St. Paul, Minnesota who died by suicide in an ethically controversial psychiatric research study at the University of Minnesota. For nearly eleven years, University of Minnesota officials defended the conduct of its researchers, despite significant public criticism,Matt Lamkin, "Will the U review or whitewash a research subject's death?" Star Tribune (Minneapolis), December 18, 2013.Arne Carlson,"Markingson case: University of Minnesota can't regain trust under current leadership," Star Tribune (Minneapolis), April 13, 2015. numerous news reports,Paul Tosto and Jeremy Olson, "The death of subject 13." Pioneer Press (St. Paul), May 18, 2008.Jennifer Couzin-Frankel, "A Lonely Crusade," Science, May 23, 2014;344(6186):793–7Carl Elliott, "The Deadly Corruption of Clinical Trials." Mother Jones, September/October 2010, 54–63.Jeff Baillon, "Nurse questions integrity of U of M drug researchers," Fox 9 News (KMSP), May 19, 2014.Andy Mannix, "Charles Schulz under Scrutiny for Seroquel Study Suicide," City Pages, February 2, 2011. and pressure for an external investigation.Leigh Turner, "The U of M should thoroughly investigate issues in the Markingson case," MinnPost, March 11, 2014.Judy Stone, "A Clinical Trial and Suicide Leave Many Questions: Part 6: The Run-Around, or Why I Now Call for an Independent Investigation of University of Minnesota," Scientific American Molecules to Medicine blog, March 26, 2013.Public Citizen, Health Research Group, Public letter to President Eric Kaler, June 16, 2014.Office of the Legislative Auditor, State of Minnesota, A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case , March 19, 2015. In March 2015, an investigation by a state watchdog agency found a number of major ethical violations in the case, including serious conflicts of interest and financial incentives, poor oversight of the study, pressure on Markingson to join the study while he was in a highly vulnerable state, and a series of misleading public statements by university officials.Susan Perry, "U of M Suspends Enrollment in Psychiatric Drug Trials in the Wake of Scathing Report on Markingson Case," MinnPost, March 20, 2015. Shortly afterward, the university suspended recruitment into psychiatric research studies. On April 9, 2015, Charles Schulz, MD, announced his resignation as Chair of the Department of Psychiatry.Jeremy Olson, "U psychiatry chief steps down in wake of research criticism," Star Tribune (Minneapolis), April 13, 2015.

Because of the many ethical issues involved in Markingson's story, it is now used as a case study in many university bioethics courses.Alex Friedrich, "U's handling of drug study suicide earns an 'F' among peers," Minnesota Public Radio News, April 23, 2015.

Markingson and the CAFÉ study

Dan Markingson was raised in St. Paul, Minnesota by his mother, Mary Weiss, and earned a degree in English literature from the University of Michigan. In the summer of 2003, when he was 26 years old, Markingson was living in Los Angeles, where he hoped to become a screenwriter. During a visit to Los Angeles, Weiss became alarmed at changes in her son's behavior that suggested he was seriously mentally ill. She persuaded him to return to St. Paul. On November 12, 2003, Markingson spoke about an apocalyptic "storm" in which he would be required to murder people, including his mother. As a result, he was admitted to a locked psychiatric unit at Fairview University Medical Center. His treating physician was Dr. Stephen Olson, an associate professor in the University of Minnesota's Department of Psychiatry.Office of the Legislative Auditor, State of Minnesota, A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case, March 19, 2015, p. 5.

After starting Markingson on risperidone, an antipsychotic drug, Olson wrote in support of a petition for an involuntary commitment order that would send Markingson to Anoka Metropolitan Regional Treatment Center, a long-term state psychiatric hospital.Office of the Legislative Auditor, State of Minnesota, A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case, March 19, 2015, p. 5. A judge granted the commitment order on November 17, 2003.In the Matter of the Civil Commitment of Daniel Markingson, State of Minnesota, County of Dakota, Court File PX-03-10465, November 17, 2003. Two other clinicians examined Markingson as part of the commitment process and both noted Markingson's extremely disordered thinking.K. Geister, Report of Pre-petition Screening Team Re: Daniel Markingson, Respondent. November 17, 2003.J. Jacobson, Report of Examiner. Dakota County Court File No. PX-03-10. November 19, 2003. Shortly afterward, Olson requested that the court grant Markingson a stay of commitment, which permitted Markingson to avoid involuntary confinement at Anoka as long as he agreed to abide by the Fairview University Medical Center treatment plan. A judge granted that request on November 20, 2003.In the Matter of the Civil Commitment of Dan Markingson, Respondent, State of Minnesota, County of Dakota, File No. PX-O3-10465, November 20, 2003.

Rather than simply treating Markingson, however, Olson asked Markingson to enroll in the AstraZeneca-sponsored CAFÉ study, which compared three atypical antipsychotic drugs. The CAFÉ study was a year-long, double-blinded study aimed at patients experiencing their first episode of psychosis.J.P. McEvoy, J.A. Lieberman, et al. "Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison, American Journal of Psychiatry. 2007 July; 164(7):1050–60.

On November 21, 2003, one day after the stay of commitment was granted, Jean Kenney, a study coordinator, had Markingson sign an informed consent form for the CAFÉ study when his mother, Mary Weiss, was not present. Weiss strongly objected to her son's enrollment in the research study, but her objections were dismissed.Carl Elliott, "The Deadly Corruption of Clinical Trials," Mother Jones, September/October 2010, p. 57.

Two weeks later, Markingson was discharged to Theo House, a residential facility for the mentally ill in St. Paul. He was required to sign an aftercare agreement stating that he understood that he could be returned to involuntary confinement if he failed to take his study medication or keep his CAFÉ study appointments.Aftercare agreement for Dan Markingson, December 8, 2003.

Over the course of the next five months, Mary Weiss became convinced that Markingson's condition was deteriorating and tried repeatedly to have him removed from the CAFÉ study.Office of the Legislative Auditor, State of Minnesota, A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case, March 19, 2015, pp. 17–18. She warned the University of Minnesota research team that Markingson was in danger of suicide. On April 11, 2004, she left a voice mail message for the study coordinator, Jean Kenney, asking "Do we have to wait until he kills himself or anyone else before anyone does anything?"Office of the Legislative Auditor, State of Minnesota, A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case, March 19, 2015, p. 17. On May 8, Markingson killed himself with a box cutter, nearly decapitating himself. Laboratory tests later revealed that he had been taking quetiapine, produced by AstraZeneca.NMS Labs, Toxicology Report, Patient name: Dan Markingson, Minnesota Regional Medical Examiner's Office, February 14, 2008.Carl Elliott, "The Deadly Corruption of Clinical Trials," Mother Jones, September/October 2010, p. 58.

Responses to Markingson's death

The University of Minnesota Institutional Review Board received a serious adverse event report from Olson, but did not review any medical records or interview anyone other than Olson.Office of the Legislative Auditor, State of Minnesota, A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case, March 19, 2015, pp. 3, 20–22. On July 22, 2005, the Food and Drug Administration issued an Establishment Inspection Report. The FDA inspector, Sharon Matson, found no violations.Sharon Matson. FDA Establishment Inspection Report, Stephen Olson MD. Report no. FEI 3004927371. July 22, 2005.

However, an investigation by the state Ombudsman for Mental Health and Mental Retardation found several areas of concern.Jo Zillhardt, Office of the Ombudsman for Mental Health and Mental Retardation, Medical Review Subcommittee, letter on death of Dan Markingson, June 17, 2005. In a letter on June 17, 2005, the Ombudsman's office pointed out that patients under a civil commitment (involuntary commitment) order are especially vulnerable and need special protection. The letter also noted a conflict of interest, since Olson had served as both Markingson's treating physician and the principal investigator of the study into which he recruited Markingson.

In January, 2007, Mary Weiss filed a lawsuit against the University of Minnesota, but a Hennepin County judge ruled that the university had statutory (or discretionary) immunity. The judge allowed a malpractice suit against Olson to proceed, which was settled for $75,000.Office of the Legislative Auditor, State of Minnesota, A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case, March 19, 2015, p. 8. The University of Minnesota then filed a notice to assess costs against Mary Weiss, demanding $57,000.Board of Regents of the University of Minnesota and Institutional Review Board, Notice of Taxation of Costs and Bill of Costs and Disbursements, State of Minnesota, County of Hennepin, Court File 27 CV-07-1679, April 29, 2008. The university agreed to drop the demand if Weiss agreed not to appeal the immunity ruling.Office of the Legislative Auditor, State of Minnesota, A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case, March 19, 2015, p. 8.

The Markingson case was first brought to public attention when the St. Paul Pioneer Press published a 3-part series in May 2008.Paul Tosto and Jeremy Olson, "The death of subject 13." Pioneer Press (St. Paul), May 18, 2008. The Pioneer Press series raised concerns about the financial ties Olson and his CAFÉ study co-investigator, Charles Schulz, the Chair of the Department of Psychiatry, had to AstraZeneca and other pharmaceutical companies. It also noted that recruitment into the CAFÉ study had increased dramatically after the University of Minnesota had established a special unit for psychotic patients called Station 12 in which every patient was evaluated for potential recruitment into a research study.

In 2009, the Minnesota state legislature passed "Dan's Law," which placed significant restrictions on the ability of psychiatrists to recruit patients under civil commitment (involuntary commitment) orders into psychiatric drug studies.Laws of Minnesota 2009, chapter 58; codified as Minnesota Statutes, 253B.095, subdivision 1(d)(4) and (e).Jeremy Olson, "Minnesota House, Senate Unanimously Pass Limits on Researchers' Use of Mentally Ill Patients," Pioneer Press (St. Paul), May 8, 2009.