The University of Minnesota needs stronger measures to protect people participating in its scientific research, according to an outside review that found “inconsistent and inadequate” practices to prevent vulnerable patients from being coerced into clinical studies.
The review, released Friday, strikes at the same issues critics raised about the recruitment of Dan Markingson, a man with schizophrenia who died by suicide in 2004 while participating in a U drug study. Markingson was enrolled by a psychiatrist who had been treating him and advising a judge whether the young man needed to be committed to an institution.
The report, paid for by the university and conducted by the Association for the Accreditation of Human Research Protection Programs, found that the university’s lapses had left research subjects “susceptible to risks that otherwise would be avoidable.”
“Some research subjects, by virtue of impairment or incapacity, may be unable to fully protect their own interests at the point of study enrollment and during the course of research participation,” according to the review. The university, it said, gave “inadequate attention” to the issue.
Researchers were poorly equipped to deal with unstable patients whose ability to consent to research fluctuated, for example. The researchers also were inconsistent in determining when guardians or others could consent on patients’ behalf.
The report did credit the university for a “thoughtful” overhaul of the policies and training for its Institutional Review Boards, which oversee the safety and appropriateness of research involving humans. But it recommended the use of clinical gatekeepers who could provide unbiased, hands-on observation to make sure patients are safe.
In a letter also released Friday, University President Eric Kaler and vice president for research Brian Herman said the U would assemble a plan for responding to the report within 60 days.
“Measuring the difference between our current research program and our commitment to becoming beyond reproach was the charge given to the independent review panel,” they said. “Now, we will be accountable for taking action.”
In an interview, Herman pledged an immediate correction to one finding — that subordinates in some cases are reviewing the soundness and safety of their boss’ research. Reviewers found five instances, which they described as conflicts.
The review was commissioned by the U’s Faculty Senate in late 2013 following media coverage of Markingson’s recruitment into the so-called CAFE study, which was funded by drugmaker AstraZeneca to compare three antipsychotic drugs, and his subsequent death.
Many believed that lingering questions from the Markingson case had harmed faculty recruitment and retention.
“Frankly, the whole reason we pressed so hard for this, is we feel like there is a cloud over the university that affects all of us who work there,” said Karen-Sue Taussig, an anthropology professor.
Relatives blamed the university for recruiting Markingson when he was delusional. They argued that a psychiatrist, Dr. Stephen Olson, held too much sway as both a recruiter and caregiver, and that the doctor was unmoved when the family said Markingson was getting worse during the study and needed to be withdrawn from it.
The Legislature has since made it unlawful for doctors to recruit their own patients into their own drug studies.
Carl Elliott, a U bioethics professor and outspoken critic of the school’s conduct in the Markingson case, said the review vindicates his concerns. “The PR line of the university has always been that this is an old case. We’ve been cleared repeatedly, and we’ve fixed everything. Now it turns out they haven’t fixed anything.”
The Psychiatry Department received stinging criticism, including that its human subjects protections do “not reflect the best efforts of a University of this caliber.” Fairview Health clinical staff members also told the reviewers privately that they lacked trust in two U psychiatrists and worried that research recruiting tactics were too aggressive.
The doctors’ names were redacted from the public version of the review, which recommended that one receive supervision and training in leadership and in protecting human subjects.
University officials have been incredulous over the continued attention to the Markingson case, which was reviewed years ago by the U.S. Food and Drug Administration (FDA) and Minnesota’s mental health ombudsman. The university also was excused from a lawsuit by Markingson’s mother; Olson, the psychiatrist, settled the case.
More attention is coming. A preliminary investigation by Minnesota’s legislative auditor is due in March, and one lawmaker recommended delaying regent appointments until then. Former Gov. Arne Carlson has pressed for legislative hearings, accusing university officials of “concocting fiction” that the Markingson case was thoroughly reviewed.
“Nobody has pressed them to tell when, where and how these investigations were conducted,” he said. “And where are your findings?”
University officials recently acknowledged that FDA investigators were back on campus last fall, meeting with Olson, though the precise subject wasn’t disclosed.