Reeling from a decade-long series of investigations and allegations after the suicide of a psychiatric research patient, the University of Minnesota (UM) in Minneapolis is now facing a proposed state law that would assign oversight for its psychiatric drug research program to an independent ombudsman’s office.

The action is just the latest in a tumultuous series of events that began with the 2004 suicide of Dan Markingson, who was enrolled in a psychiatric drug trial at the university at the time he took his life. (For more information, see related story in this issue.)

Markingson’s suicide resulted in lawsuits and a series of independent and state investigations, opening a national dialogue on the recruitment of mentally ill patients into clinical trials. The university has not been able to escape the long shadow of the incident, which has morphed into an indictment of leadership and accountability at UM and the state Board of Regents.

In that regard, the proposed oversight law comes on the heels of a recent announcement by state legislative auditor James Nobles that he would investigate the university for a third time. In a scathing report issued last year, Nobles made the recommendation for the state ombudsman oversight after concluding that, “a primary problem uncovered by our review is past and current university leadership that is defensive, insular, and unwilling to accept criticism about the Markingson case either from within or outside the university.”1

While stating that directly linking the suicide to the drug study was impossible given Markingson’s mental illness, the state report said that the case “raises serious ethical issues and numerous conflicts of interest, which university leaders have been consistently unwilling to acknowledge. They have repeatedly claimed that clinical research at the university meets the highest ethical standards and dismissed the need for further consideration of the Markingson case by making misleading statements about past reviews. This insular and inaccurate response has seriously harmed the University of Minnesota’s credibility and reputation.”

IRB member testifies

The university is opposing the ombudsman oversight bill, arguing that sufficient oversight and ongoing improvements are now in place to protect human subjects research. However, a current member of the university’s IRB spoke in favor of the bill at an April 5, 2016, hearing of the state House of Representatives Committee on Higher Education Policy and Finance.

“Investigations and reviews indicate serious ongoing problems with research compliance in the department of psychiatry,” said Niki A. Gjere, RN, a clinical nurse specialist at the university and IRB member. “A lack of meaningful oversight has contributed to these ongoing problems. We hear from university leaders that everything is better now. We’re spending money to improve research processes, we have oversight boards and a compliance office. … Even though [Markingson] died in 2004, reports continue to identify a pervasive pattern of serious noncompliance with regulations for protecting human subjects. These serious problems are sustained and firmly embedded. This bill would give the ombudsman office the needed authority for oversight now, without waiting for years to see improvement in the psychiatry department. We need a formalized advocacy process for people participating in department of psychiatry drug studies.”

The sponsor of the bill, state Rep. Cindy Pugh, said she wanted to believe that the university was taking all appropriate actions, but couldn’t “un-hear” concerns being expressed by faculty members like Gjere. As proposed, the bill would charge the state Office of Ombudsman for Mental Health and Developmental Disabilities to monitor the treatment of individuals participating in drug trials at the university’s department of psychiatry.

“I responded with this bill not only to ensure that we the legislature are doing our part at holding the university accountable, but that we are providing Minnesotans with the highest level of assurance of patient protections within human drug studies conducted at the [psychiatric] department,” Pugh said.

A panel of legal and ethical experts commissioned by the university after a faculty vote for an independent investigation of psych research programs concluded last year that, “there are significant problems with core functions of the human research protections program, including IRB review, investigator education, practices related to consent to research, and the effective coordination of administrative oversight, clinical care, and research.”2

The report observed that some university personnel described considerable “fatigue” of 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,’” the panel reported. “Most striking was the commonly conveyed sense of doubt in leadership’s commitment to human subjects protection.”

UM lists positive steps

In testimony3 at a state senate hearing last year after both Nobles’ findings and the independent report, university President Eric W. Kaler emphasized several actions being taken to correct the problems. He conceded the university IRB should have done a more extensive review of the original study in which Markingson was enrolled and is now committed to improvement.

“While the IRB carried out a minimal review, in hindsight the IRB should have investigated more thoroughly at the time,” Kaler stated. “To the extent the [university’s] descriptions of what the IRB did has been misleading, I apologize. While we disagree with some of Mr. Nobles’ findings, we must get better in caring for our most vulnerable patients.”

According to Kaler, the university’s corrective actions in response to both the independent panel and the state investigation include the following:

  • Suspended enrollment in all department of psychiatry interventional drug studies — those that are active or awaiting approval — until they are reviewed by an independent IRB.
  • Created a task force to plan the implementation of the external review panel recommendations.
  • Engaged an independent IRB to work with the university’s post-approval monitoring process to examine other clinical studies that target vulnerable populations, and to ensure they are meeting best practices.
  • Appointed a Community Oversight Board of external experts in human subjects research and research ethics to ensure best practices are used.

Reiterating some of these efforts at the hearing on the proposed ombudsman bill, Brian Herman, PhD, vice president of research at the university, argued that the additional level of oversight is not needed.

“We recognize the value of working with the ombudsman office when issues arise under its purview,” Herman told the legislative committee. “We sought their involvement in the past and recently we asked for [their] assistance in filling openings in the institutional review board. Today the University of Minnesota research participants — including the department of psychiatry — are subject to oversight from a number of organizations. I think it’s important that you hear that, despite what you may think, the university’s oversight of its human subject research protections is actually reviewed by a number of different outside entities.”

The university is accredited by the Association for the Accreditation of Human Research Protection Programs (AAHRPP), has an internal department conducting regularly scheduled audits, and has established a community oversight board to advise the university on best practices on research participants, Herman said.

“A large number of those individuals on the oversight board [have] expertise in interacting with individuals with impaired decision-making capacity,” he said. “Lastly, as you know, the office of the legislative auditor is now conducting a follow-up review to their review last year. So our position is we believe that these avenues of oversight combined with our current professional relationship with the ombudsman [office] represents sufficient monitoring of the university’s research work that utilizes human participants.”

Herman also reminded the committee that IRBs are accountable to federal law under the Common Rule and any state action would have to be consistent with those overriding regulations.

Simmering tension

In a seemingly minor matter that revealed some of the acrimony beneath the surface, one member of the House committee questioned whether the university administration made sufficient efforts to allow concerned faculty members to meet recently with a visiting consultant on psychiatric research. An outspoken critic of the university’s handling of the fallout from the Markingson case, Carl Elliott, MD, PhD, associate professor in the university’s Center for Bioethics, said he was told there was not time for him to meet in person with the consultant, but he could talk to him by phone — which he did.

“This is very concerning to me,” responded state Rep. Connie Bernardy. “We hear testimony and commitments and promises from the University of Minnesota and they don’t get followed through. I’ll speak for myself: I expect those commitments to be followed through and it raises issues to me — what are the other things that we are being told that are actually being followed through on?”

“The lack of honesty and truthfulness by the university administration has been a big issue from the beginning and it was identified in last year’s legislative auditor’s report,” Elliott testified.

Having been at the university since 1997, Elliott has seen the entire saga unfold and called the university to account in addressing research problems that he now fears may go beyond the psychiatry department.

“I was on the IRB myself when I first arrived here,” he tells IRB Advisor. “Part of what disturbs me about the entire affair — and I actually think some things have improved with our research oversight program — is that the criticisms of our research oversight program and the gaps [reported in the investigations] were so serious and so severe that you are left wondering, can you actually trust our research and oversight program to flag issues if they are occurring in other departments?”

Elliott was skeptical that the measures taken by the university have sufficiently addressed the research protection issues, saying the ombudsman oversight bill should be enacted to fulfill the recommendation for action in the state’s investigation.

“The reason the university is opposing it — and the reason I think it is a good idea — is that it would be external monitoring,” he says. “If you go back and look at the legislative auditor’s report they say the disturbing part of the entire affair is the continued series of misleading statements by the university administration, their defensive attitude, and their unwillingness to consider any kind of external criticism. [They have been] attempting desperately to deflect criticism for 11 years. Those very people are not going to admit their own actions [are] at the root of the problems.”

REFERENCES

  1. Nobles, J. Office of the Legislative Auditor, State of Minnesota. A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case. Special Review: March 19, 2015: http://bit.ly/1xjI5IB.
  2. Kaler, EW. University of Minnesota Office of the President. “Beyond reproach:” Testimony about Legislative Auditor’s Report to Senate Committee. March 19, 2015: http://bit.ly/1WfmlsD.
  3. Donahue A, Frumin M, Rachlin J, et al. An External Review of the Protection of Human Research Participants at the University of Minnesota with Special Attention to Research with Adults Who May Lack Decision-Making Capacity. Final Report: February 23, 2015: http://www.research.umn.edu/news/documents/final_report.pdf.