Report takes the University of Minnesota to task for its efforts to protect human subjects.

Report takes the University of Minnesota to task for its efforts to protect human subjects.

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Human subjects protections under fire at the University of Minnesota

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.”

The outsiders made other observations. Although the university is in the process of enhancing training in basic human subjects protections for researchers, which the authors praised, they remained concerned that beyond basic instruction, “there are currently no human subjects protections training requirements for investigators, including those working with high-risk or vulnerable populations.”

Along those lines, the authors touched on some of the central issues raised in the Markingson case: Dan Markingson agreed to enroll in a trial while committed involuntarily to the hospital, raising questions about his ability to consent, and the lead researcher on the trial was also his treating psychiatrist. Although vulnerable individuals like Markingson often participate in clinical trials, the authors of the review worried that Minnesota had not drawn lessons from that case. “We found only a single instance where consideration of the dual and potentially conflicting role of treating psychiatrist/investigator was addressed,” they noted. And, they added, “the external review team found no evidence that the University, Fairview [Hospital], and its investigators have taken steps to ensure a broader understanding of the implications of this very fraught situation” of enrolling patients who have been involuntarily committed into trials.

A death during a clinical trial, possibly attributed to it, is every university’s nightmare. Elliott and a widening circle of others were harsh and relentless in their criticism, the reviewers acknowledge. The university’s response, they suggest, has been “assuming a defensive posture. In other words, in the context of nearly continuous negative attention, the University has not persuaded its critics (from within and outside the University) that it is interested in more than protecting its reputation and that it is instead open to feedback, able to acknowledge its errors, and will take responsibility for deficiencies and their consequences.” In the Department of Psychiatry, faculty and staff told the reviewers that they work in “a ‘culture of fear,’ ” and “[t]hey provided stories of intimidation by researchers and fear of retaliation should staff voice opposition to practices that were of concern.”

As the report creates ripples across campus, the Faculty Senate is preparing to meet this Friday with University President Eric Kaler and the authors of the report. Kaler released a statement Friday thanking the outside reviewers for their advice. He stressed that they looked at a “small fraction of our clinical research enterprise,” involving individuals with diminished decision-making capacity. “[C]onsistent with our charge to them, the panel’s view and subsequent analysis was limited,” he noted. (The authors described their report as covering protection of human research participants at UM with “special attention” to adults who may lack decision-making capacity.)

Kaler expressed hope that with the advice of the authors, UM could enhance its research protections. “The panel has provided us with a clear road map for making our program truly exceptional,” he wrote in his statement. “[T]he University of Minnesota has the opportunity to become a national model against which all other research institutions could be measured.” Senior administrators said in a statement that they hope to develop an “action plan” to respond to the report within 60 days.

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