1 Boring Old Man

Human subjects protections under fire at the University of Minnesota

SCIENCEINSIDER

by Jennifer Couzin-Frankel

March 2015

A damning report on how the University of Minnesota [UM] protects volunteers in its clinical trials concludes that researchers inadequately reviewed research studies across the university and need more training to better protect the most vulnerable subjects. It also found that a “climate of fear” existed in the Department of Psychiatry, where concerns about clinical trials first surfaced.

The 97-page report, released 27 February, was prepared by a group of six experts appointed by the Association for the Accreditation of Human Research Protection Programs. It comes after years of complaints by some UM faculty members, led by bioethicist Carl Elliott. They charged that the school and its doctors failed to protect 27-year-old Dan Markingson, who died by suicide while enrolled in a psychiatric drug trial in 2004. They also expressed grave concerns about how Markingson’s death was investigated. [More on that case is here and here.[

Recently, Elliott’s crusade began having an impact. In December 2013, the UM Faculty Senate called for an independent review of current practices in clinical trials. The administration agreed to open its records to outsiders. Although the review did not look back at history, it nonetheless had plenty to say about how the university handles trials, which bring in millions of dollars from drug companies along with much prestige.

“[T]he external review team believes the University has not taken an appropriately aggressive and informed approach to protecting subjects and regaining lost trust,” the authors write. They examined protocols from 20 active trials as well as minutes from meetings of the institutional review board [IRB]. Many IRB members, the panel noted, did not regularly attend meetings from January to July 2014. “[T]here were no individuals on the IRB during this time period with expertise in adult hematology, oncology and transplant, cardiology, surgery, or neurology, although those fields taken together represented over 300 protocols. There was only one psychiatrist on the IRB, despite the fact that the Psychiatry Department submitted 85 protocols for review during the time period examined.” That doctor attended only four of the 26 medical IRB meetings at which new protocols were reviewed. “This departure not only contravenes the University’s own policy of having at least one member with ‘primary professional expertise in a scientific field relevant to the type of research reviewed by that panel,’ but also prompts concern about the quality of review.”

Fueling those concerns, the authors noted that the IRB spent an average of 3 to 5 minutes discussing each protocol, and there was “little discussion of the risks and benefits to subjects.” Most of the protocol changes the IRB asked researchers to make addressed administrative issues such as misspellings or adding standard language to a consent form. Requests by researchers running trials to modify who was eligible for a study—“changes that may increase or decrease risks to subjects—were almost always approved without any documentation of related discussion,” the authors write. “The review process, as documented in the minutes, does not reflect a meaningful discussion of the risks and benefits of research protocols and the necessary steps taken to protect human subjects in the face of scientific or ethical concerns”…

In interviews, some University personnel described considerable “fatigue” related to what they considered unrelenting and unjustified criticism of the University’s human subjects protection program. In contrast, others expressed bewilderment and frustration that, in their view, the University has failed to understand and remedy problems stemming from and related to “Markingson.” Most striking was the commonly conveyed sense of doubt in leadership’s commitment to human subjects protection. The widespread characterization of a few researchers in the Department of Psychiatry as “untrustworthy” and as creating a “culture of fear” in relation to efforts to enhance the protection of research subjects was of major concern to the external review team.

“We’re acting as though this report is news, but in fact there’s been several years where concerns have been brought forward in very detailed, concrete ways,” he said at the meeting. Turner said University leadership hasn’t adequately responded to problems he says have been happening within the program for years, and he questioned University President Eric Kaler’s commitment to repair the program’s current state.

"We did nothing wrong" is a legal standard – the standard by which we define criminal behavior in a free society based on the rule of law. An ethical standard is different. For one thing, in medicine, it is impossible to do "nothing wrong." But beyond that, an ethical standard has to do with maintaining an ethos, a culture. In a Clinical Trial of a new medication, it’s incumbent on the trialist to be vigilant that the subject’s health and medical care is not compromised by participation.

• the design and purpose of the C.A.F.E. study
• the oversight function of the Institutional Review Board
• the recruitment and inclusion of Dan Markingson
• his ongoing psychiatric care
• the subsequent responses of Institution

Carl Elliot, Leigh Turner, Mike Howard, and Dan’s mother, Mary Weis, have done something remarkable. They’ve moved rhetorical deliberations about medical ethics out if the ivory towers of academia; breathed a new life into them with this paradigmatic real world case; and taken their campaign to the streets. Likewise, the external reviewers appointed by the the Association for the Accreditation of Human Research Protection Programs who were given only a restricted scope of inquiry [too deep to ignore…, almost inevitable…, a paradigm…] were still able to identify fundamental deficiencies in the Clinical Trial Program at the University of Minnesota, even after a decade of opportunity to make needed changes since Markingson’s death. Elliot’s team and these reviewers have obviously "done something right."