Posted on behalf of David Cyranoski.
In May 2004 Daniel Markingson, a patient with schizophrenia in an anti-psychotic drug trial at the University of Minnesota in Minneapolis, “stabbed himself to death in the bathtub with a box cutter, ripping open his abdomen and nearly decapitating himself,” as a magazine article would report six years later.
Controversy has rumbled since the story broke in May 2008. Should Markingson have been in the trial in the first place? Should he have been removed from it earlier? Were those running the trial negligent and, if so, does the university share responsibility?
The university has consistently denied wrongdoing. Critics, mainly bioethicists, have maintained that there are many unresolved issues. On 5 December, the university faculty senate agreed that there was a need for investigation into the way the university handles clinical research — but the ambiguous wording of its official statement has started another round of debate about how it will proceed.
The study, begun in March 2002 and sponsored by AstraZeneca, compared the tolerability and efficacy of three antipsychotic drugs that were already on the market. Stephen Olson, a psychiatry professor at the university, enrolled Markingson, his patient. Markingson’s condition deteriorated until his suicide.
Markingson’s mother, Mary Weiss, who had been trying to remove her son from the study for months, sued the university, Olson, the drug company and other parties. The court dismissed the various claims raised on legal grounds (“statutory immunity”) except for testimony that Olson failed to monitor Markingson’s compliance with the drug protocol and withheld information on risks and benefits of other treatments. This led him “to enter a drug study in which he was inadequately monitored, untreated, with this lack of treatment causing his psychosis to persist, thus causing his death by ritualistic, psychotic, suicide”.
In April 2008, Weiss and Olson settled out of court for US$75,000. University administrators have themselves called this a “nominal” fee, and Weiss told Mother Jones magazine in the 2010 article that it would not cover her own legal expenses. She also said that she agreed to a settlement only after the university threatened to sue her for court fees — a highly unusual request in the US legal system.
The university administration has since insisted that the case was closed, pointing to the court ruling and to other “examinations”, such as those by the US Food and Drug Administration and the Minnesota Board of Medical Practice.
Bioethicists, however, continue to argue that, legal considerations aside, the university should establish responsibility, particularly about whether Markingson had been coerced into entering the trial and whether doctors missed warning signs. They point to Olson’s conflict of interest in enrolling his own patient in a study by which he stood to gain financially, and the fact that Olson had testified that Markingson “was mentally ill and lacked the capacity to make decisions regarding his medical treatment” a week before getting his informed consent to put him in the trial.
On 14 November, a letter to the Faculty Consultative Committee accompanied by 175 signatures of bioethicists, psychiatrists and legal experts, argued that each of the reviews that the university used to defend itself was either flawed or misinterpreted into suggesting that there was no wrongdoing. The letter called for an independent investigation.
The faculty senate resolution passed on 5 December calls for just that: “an independent and transparent examination”. The resolution says that “previous investigations did not address the broader question of whether the university’s procedures, practices and policies governing clinical research on human subjects, some of them changed since the Markingson case, reflect both best practices in clinical research on human subjects and the faculties high ambitions for ethical behavior”. The resolution passed 67 to 23.
Carl Elliott, a bioethicist at the university who has been pushing in vain for a re-investigation for years, was happily surprised to see member after member speaking in support of the measure at the senate hearing. He was also surprised to see Olson, who had generally shied away from making public statements about the case, step up to the microphone to defend himself with what Elliott considers a questionable comparison. Olson said: “Cancer patients die in cancer studies all the time, and it’s not a surprise that people with mental illness will die in a trial of mental illness.”
But will this new investigation put the matter to rest? The resolution specified an investigation of “current” practices and makes no explicit reference to re-opening the Markingson case, although it mentions it as the trigger for its investigation and it includes a clause noting the special demands for “oversight of clinical research involving adult participants with diminished functional abilities” — a clear reference to Markingson.
On 10 December, university president Eric Kaler told the Minnesota Daily, a student-run newspaper, that he is “willing to take the advice of the Senate and the panel”, with the goal of airing “out clearly and very publicly what we do and have a panel of external experts validate that and be sure we are doing this absolutely as well as can be done”. But, he added, it will not examine the Markingson case: “It’s not a review of the Markingson case; it’s a review of what we are doing now and what we’re going to do moving forward.”
The next day, on 11 December, Trudo Lemmens, a professor of health law and policy at the University of Toronto in Canada, and five of the other authors behind the petition, wrote to Kaler to tell him that their concerns would be met only if “the investigation covers problems in the Markingson case and examines whether other similar cases exist”.
Whether the Markingson case gets the thorough look Lemmens and others hope for might hinge on whether the committee is truly independent.