Monday, June 23, 2014

For the Record: A necessary audit of University of Minnesota drug research



"It is time to eradicate this stain on the reputation of 
a splendid university."

Arne Carlson, former governor of Minnesota 



The announcement by the legislative auditor that he will be reviewing the drug-testing program at the University of Minnesota is welcome news. Most of the concerns revolve around the suicide of an enrollee, Dan Markingson, in May 2004. However, the ongoing problems center on large amounts of money being afforded universities by drug companies in return for extensive testing of experimental drugs on human subjects. At best, it brings together a problematic mixture of conflicts of interest and human tragedy.

Over the span of the program, it has drawn considerable negative press, including headlines in the Star Tribune in August 1993 — “University kept silent for 4 years on research misconduct by Garfinkel” (Dr. Barry Garfinkel was convicted and sent to prison) — and continuing to May of this year, when Science magazine published a lead article analyzing the Markingson case and continuing issues.”

During this time, Dr. Carl Elliott, a professor in the Department of Bioethics, and his colleague, Dr. Leigh Turner, have been critical of the oversight of this program, including the various reports that cleared the university of wrongdoing. A large and distinguished cadre of doctors, researchers and scientists from the United States, as well as Canada and New Zealand, has joined in this criticism. As a result of the publicity, Elliott and Turner continue to receive calls from parents and families of enrollees declaring their concerns over mistreatment, failure to protect the harmed and misinformation given to potential subjects. This has been verified by a local TV investigation.

Unfortunately, instead of this compelling matter being resolved internally, the debate has continued to spill out to the public, drawing national media attention from the likes of the New York Times and the Boston Globe.

The legislative auditor now has the opportunity to conduct a thorough and professional audit of this operation covering the past 10 years. It is imperative for the well-being of all concerned that his report be exhaustive and credible in order that the necessary changes are instituted. This means that inherent conflicts of interest be closely monitored, that the integrity of the study be improved and that the subjects be fully protected.


This audit should involve:

1) A thorough review of the finances, including the number of studies, payments to doctors and clinicians, administrative costs, etc.

2) An examination of the conflicts of interest built into the process. This should include a background inspection of all program personnel as well as those who serve on an oversight board. Transparency should be the rule.

3) A disclosure of the number of tests, enrollees, injuries and deaths.

4) A full understanding of the oversight process, commencing with the Board of Regents. Are its members independent of management? How do they manage dissent involving management, faculty and/or the public? Why did they not intercede, particularly knowing the ills of the past involving criminal misconduct and continuing with public reports of ongoing concerns relative to the care of enrollees?

5) That the legal and human rights of the enrollee are fully protected and that the family is involved. This includes upfront disclosure of all needed information, professional monitoring and care, if harm is caused.



Logic would indicate that certain areas of management require more oversight than others, particularly when significant money comes from drug companies for testing on humans. Somehow, that special attention appears not to have been there, even when respected members of the faculty raised red flags.

I am most hopeful that the legislative auditor not only will deal with these concerns but also will come forth with standards that will significantly improve independent oversight and be fully protective of our enrollees, who all too often are our most vulnerable citizens. It is time to eradicate this stain on the reputation of a splendid university.

Sunday, May 18, 2014

For the Record: U Flunks on Rigorous Core Courses - Professor Eva von Dassow





"Housework is a breeze. Cooking is a pleasant diversion. Putting up a retaining wall is a lark. But teaching is like climbing a mountain."  Fawn Brodie
My colleague, Professor Eva von Dassow,  has graced these pages before. Her comments to the University of Minnesota Board of Regents went modestly viral - twenty-five thousand views, and are still worth considering.  They may be found here:

When Professor von Dassow Speaks, Hopefully Somebody Will Listen...




The following material is reprinted with the permission of the author and the Minneapolis Star-Tribune where it was first published.



Counterpoint: U flunks on rigorous core courses

May 16, 2014

Article by: EVA VON DASSOW 


Readers may be interested in what faculty members at the University of Minnesota think of the curricular requirements celebrated for their breadth and rigor by Vice Provost Robert McMaster in a recent counterpoint article (“Quality of curriculum at U is second to none,” April 26).

McMaster, describing our set of liberal-education requirements as “comprehensive,” states that “all students must complete seven courses in what we call the core”; he then lists 11 categories of requirements.

There is in fact no set of core courses. Rather, hundreds of courses have been submitted by individual faculty members for approval to meet one or another of the LE requirements. The mechanism for obtaining approval is to write a proposal claiming that the course does this and adding similar claims to the syllabus; proposal and syllabus are submitted to the Council on Liberal Education. If the council finds the right words on the proposal and syllabus, the course is certified as meeting the selected liberal-education requirement. (You can see how many courses meet which requirements here: http://tinyurl.com/UMNOneStop.)

Thus no student need ever take, for example, a course in history. Students can satisfy the liberal-education requirement in “historical perspectives” by taking any course, in any college, that has been certified as meeting this requirement. Same with “mathematical thinking” and the other nine requirements. All of the approved courses may be fine components of a liberal education, but then, what university course isn’t?

Faculty members submit courses for liberal-education certification under duress, in effect, because if we don’t, our courses will get insufficient enrollment, inasmuch as students are constrained to choose courses that meet requirements. Many of us nonetheless find it absurd to be required to prove that a history course is a history course, a math course is a math course, and so on. The chorus of faculty discontent with this structure of requirements has reached such a pitch as to provoke a movement to change it.

Of the university’s student learning outcomes, McMaster says faculty members use them “to make certain our undergraduates are indeed learning, and this learning is measured.” Indeed, for every undergraduate course, faculty members are required to claim that it meets one of seven prescribed outcomes.

One would think the desired outcome of studying anatomy is to learn anatomy, that of studying Arabic to learn Arabic and so forth throughout the course catalog. But the student learning outcomes were intentionally written to be so broad that at least one of them could be construed to apply to any course or subject — including nonacademic ones.

Our athletics programs could make a sound case that, through their participation in a sport, student-athletes meet the learning outcomes McMaster lists. Surely members of the football team “can identify, define and solve problems,” in practice and in play; they “can locate and critically evaluate information,” with lightning rapidity on the field; they “have mastered a body of knowledge,” namely, about football; and they can and must “communicate effectively” to play as a team. And “this learning is measured,” all right, game by game.

Though we may decry the liberal-education requirements as a travesty of liberal education and the learning outcomes as vacuous (a view not universally held; after all, we’re a university), the faculty still teach what we say we teach — anatomy, Arabic, Hebrew, history, math and so forth. What guarantees that students learn, or rather, how is anyone to know whether they did?

For a century or so, grades have been used as a proxy for assessing student achievement. Yet we all know of colleagues who just give all students As and Bs, because it’s much easier to do that than to conduct a true assessment and risk the trouble that can ensue. Those easy As are failing our students, while making the job ever harder for those of us who keep trying to uphold standards and grade accordingly.

No wonder employers are dismayed to find that, for all the tuition graduates have paid, they often lack either skills or knowledge. This is what results from emphasizing requirements instead of subjects, metrics over substance, credentials in place of learning and graduation rates over education.


Eva von Dassow is associate professor of classical and Near Eastern studies at the University of Minnesota. The views expressed here are her own.

Monday, April 21, 2014

For the Record: Important questions remain unanswered in U of M Markingson case




Dale Hammerschmidt, MD, FACP, is an emeritus professor, Division of Hematology, Oncology and Transplantation, University of Minnesota Department of Medicine. 


As we were waiting for our first patients of the morning to be checked in, a colleague and I discussed his experience at a university-wide committee meeting the previous day. He reported vigorous criticism of the University of Minnesota Medical School (and certain Medical School faculty), centered upon the deaths of research subjects in clinical trials. Particularly prominent in the discussion was the suicide a decade ago of Dan Markingson, a patient who became a subject in a comparative trial of newer antipsychotic agents. My colleague perceived this as old news, a lack of understanding of the realities of research into the treatment of life-threatening illnesses, and at a certain level an attack on clinical investigation by faculty from outside the Medical School.
I’m sympathetic to his perception, but I also think there are substantive reasons that the Markingson case continues to cause concern; there are questions raised by it that have never had a satisfying (public) resolution.
Some of the concerns involve the conduct of the study at this site, some involve the study design more broadly, some involve Markingson’s specific experience, and some involve the fundamental issues in conducting research involving the care of vulnerable persons. When these different themes get lumped together, an accusatory tone and defensiveness may get in the way of learning from the events.
Accordingly, I’ll not spend much time here on allegations of site-specific misconduct; I’ve never reviewed that part of the record in detail, and I don’t have much to add. I will register my disappointment, however, at the university’s response. On several occasions, we have been told that the university and its investigators have been “exonerated,” because the attorney general chose not to prosecute and the federal oversight bodies (FDA and OHRP) did not effect any sanctions. I think that most faculty members understand that a decision not to prosecute is quite a few steps shy of “exoneration,” and I think most faculty members would like to see a higher behavioral standard than “freedom from felony prosecution.”
On several occasions, it has been suggested that an outside review panel be convened, to review the case and study in detail; these suggestions have not been taken seriously (at least until very recently), which I think is unfortunate. The careful review of serious misadventures is one of our important tools for improving clinical practice; it should also be one of our key tools for improving research practice. Even if no misconduct is found and no weakness in human subjects’ protection is found, a thorough and independent review would show that the university is taking the matter seriously, rather than sweeping it under the carpet.
Looking beyond the narrow concerns of misconduct per se, there are several questions we might ask that I think are very important:
  • Markingson was in an unusual situation, known as “stay of commitment;” that is, a court had ruled in favor of his commitment, but stayed its implementation as long as he co-operated in treatment and did well. Technically, he was his own legal consent authority, but he was demonstrably vulnerable and by definition compromised in his ability to give consent. Routine ethical guidelines and federal regulations* provide that there be special protections for vulnerable research subjects; we might thus ask: Were there adequate protections in place for this vulnerability? What would be the best sort of protections to use in this sort of circumstance in the future?
  • A fellow on a stay of commitment is in a dependent position with respect to his treating psychiatrist – the stay is conditioned on co-operation with therapy. This could have a coercive effect if the treating psychiatrist is also the one inviting the patient’s participation in a clinical trial or the one conducting the clinical trial. Here we might ask: Were there adequate protections against this adverse influence? In fact, can there ever be adequate protections for the situation (must the person inviting study enrollment be someone uninvolved in the patient’s care)?
  • Because the commitment was stayed, no family member was named as a guardian or decisional surrogate for Markingson, and none had clear legal status with respect to his care. That set the stage for tension (a mild word) when a family member was concerned that he was not doing well on his randomly-assigned therapy. So another question: Were there adequate provisions in place for a response to family concerns? Is there a way that such a scenario can be planned for in the design of this sort of study? Might the person most likely to have been named guardian have been a good choice to serve as a special advocate (as part of the special protections)?
  • The study was a drug-company-sponsored comparison among newer (but not experimental) drugs useful in managing major psychiatric illnesses. The interests of the sponsor and the best interests of the participating patients can come into conflict in such a study. An additional concern: Did the incentive structure of the study militate unreasonably against code-breaking or crossing over when a patient was not doing well? In  fact, one might well ask if it is ever appropriate for a clinical study comparing competing products in vulnerable subjects to be conducted by the sponsor of one of the products.
If we ask questions like these honestly and critically, we may not like all the answers. We may have to admit that we could do a lot better; we may have to admit that there are circumstances where we really don’t know what’s best. But that’s how we move forward. And improving our research practices is far preferable to abandoning our efforts.

*45 CFR §46.111(b) [Criteria for the approval of research]: When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as … mentally disabled persons …, additional safeguards have been included in the study to protect the rights and welfare of these subjects.
*Identical wording appears in the FDA regulations at 21 CFR §56.111(b)


Tuesday, March 25, 2014

For the Record: The Silence of the Bioethicists #markingon





Well, Clarice - have the lambs stopped screaming?




My colleague Leigh Turner writes in Health in the Global Village:




Silence from the Bioethicists



University of Minnesota Bioethicists Remain Silent as a Research Scandal Unfolds

For four years, my colleague Carl Elliott has made an extraordinary effort to help Dan Markingson’s mother, Mary Weiss, and her friend, Mike Howard, fight for justice by calling for an independent investigation of alleged psychiatric research misconduct at the University of Minnesota. During this time, many faculty members at the University have become involved in challenging university officials’ refusal to conduct a credible inquiry. Numerous faculty members signed a petition that asks Governor Dayton to establish a panel tasked with investigating Markingson’s death. Last December the Faculty Senate passed the “Resolution on the matter of the Markingson case.”  Bill Gleason has for years written about Dan Markingson and pressed for an inquiry into possible research misconduct.  Kirk Allison  organized a campus screening of Off Label, a documentary that addresses the Markingson case. I have written to President Kaler, the Board of RegentsGovernor Mark Dayton, and Minnesota’s Attorney General, and urged them to investigate Markingson’s death and related allegations of psychiatric research misconduct.

University faculty – myself included – should have done more to hold senior administrators accountable. Still, there has been some dissent at an institution ruled by officials who refuse to investigate disturbing reports of possible research misconduct.  Acknowledging these critical voices, I am struck by the silence of my colleagues at the Center for Bioethics.  The faculty members who should have been most vocal in response to allegations of research misconduct at our own institution have remained silent.

Jeremy Olson and Paul Tosto first reported Dan Markingson’s death in 2008.  Elliott’s Mother Jones article, “Making a Killing,” was published in 2010.  Since then, there has been extensive news coverage of alleged research misconduct at the University.  During this period, faculty members at the Center for Bioethics have never had a meaningful discussion addressing Markingson’s death; the possibility that serious psychiatric research misconduct occurred at our university; and university officials’ repeated refusals to support a credible investigation.  There seems to be an unspoken yet collective understanding within the Center for Bioethics that it is taboo to discuss Dan Markingson’s death and related allegations of psychiatric research misconduct. The silence is deafening.     

University officials have responded to Elliott’s investigative work and whistle-blowing by attempting to frame him as a lone, self-promoting, rogue employee who twists facts and uses this “unfortunate tragedy” to advance his own interests.  My bioethicist colleagues have done little to counter this institutional script.  Remaining silent, they have allowed university administrators to isolate, insult, and attempt to intimidate Elliott.

Mark Rotenberg

Despite former General Counsel Mark Rotenberg’s misleading claims  in reply to Elliott’s article in Mother Jones and subsequent blog posts, at no point did bioethics faculty members at the University ever challenge Rotenberg and demand credible responses.  Rotenberg has made many inaccurate assertions about the Markingson case. Faculty members at the Center for Bioethics have never demanded better responses from senior university officials.

Justin Paquette and Brian Lucas         

When Justin Paquette, a public relations representative for the University’s Academic Health Center, claimed that Elliott’s “unfounded logic” and “personal crusade against our psychiatry department” amounted to “fiction” motivated by Elliott’s interest in “marketing” his books, bioethicists at the University did not respond to Paquette’s ad hominem attacks.  I was among those who should have immediately condemned Paquette’s ugly exercise in character assassination.  Faculty members in bioethics also remained silent when Brian Lucas, another public relations employee, speculated about whether Judy Stone, author of numerous pieces critical of the university’s handling of the Markingson case, is “a wacko.”      

Aaron Friedman

Aaron Friedman, former dean of the medical school and vice president for health services, has on  numerous occasions  dismissed Elliott’s concerns and supported Stephen Olson and Charles Schulz, two psychiatrists at the center of allegations of psychiatric research misconduct.  In an Op-Ed, Friedman writes, “as Elliot (sic) clamors for more examination, he seems to feel no responsibility to accurately report what has already been done.”  Friedman’s commentary accuses Elliott of making “unfounded accusations” and providing a “selective and distorted narrative.” Friedman’s diatribe went unchallenged by faculty members at the bioethics center.  

Tim Mulcahy, Aaron Friedman, Mark Rotenberg, and the Academic Freedom and Tenure Committee

In 2011, two University Vice Presidents, Aaron Friedman and Tim Mulcahy, attended a meeting of the Academic Freedom and Tenure Committee and explored ways to silence or challenge Elliott.  They were there as  a question former General Counsel Mark Rotenberg posed at another committee meeting.  “What,” Rotenberg had asked, “is the faculty[’s] collective role in addressing factually-incorrect attacks on particular University faculty research activities?”  Minutes from the meeting suggest that the purpose of the vice presidents’ time with the Academic Freedom and Tenure Committee was to explore ways of restricting Elliott’s academic freedom and sanctioning him for making what they alleged were inaccurate claims.  I was the only one of Elliott’s colleagues from the Center for Bioethics to attend the committee’s next meeting and ask whether Rotenberg’s comment was a dog whistle call to restrict Elliott’s academic freedom.  While Karen-Sue Taussig, an anthropologist, and philosophers Valerie Tiberius, Ken Waters, and Naomi Scheman attended the meeting and  offered robust support for Elliott’s academic freedom and right to call for an investigation, despite the principles at stake there was no additional representation from the Center for Bioethics.    

Debra DeBruin and Steven Miles

Even when directly asked to investigate, faculty members at the Center have refused to address allegations of psychiatric research misconduct. Debra DeBruin and Steve Miles have both served as directors of the University’s clinical research ethics consultation service.  Despite being requested to conduct an inquiry into Markingson’s death and examine the adequacy of human subject protections in the Department of Psychiatry, both DeBruin and Miles refused to investigate.     

The Letter to the Board of Regents

The only exception to the collective silence at the Center for Bioethics has been single letter that was sent to the Board of Regents.  In November 2010, eight faculty members wrote to the Regents and called for an investigation of the Markingson case. Notably, however, Jeffrey Kahn, then the director of the Center for Bioethics, did not sign the letter.  Debra DeBruin, then the associate director and now director of the Center for Bioethics, did not sign the letter.  Steven Miles and Susan Wolf, two of the Center’s most senior and prominent bioethicists, did not sign the letter. Throughout a serious research scandal, bioethicists who claim they are concerned with justice, protecting the vulnerable, and responsible governance of human subjects research have remained silent.  

The University’s Power Structure

It takes little insight into the power structure of the University to understand why faculty members at the bioethics center remain silent. Anyone paying attention to President Kaler, former Vice President Aaron Friedman, former  Vice President Mulcahy, former General Counsel Mark Rotenberg, and current General Counsel William Donohue would have noticed that senior officials all dismiss calls for an investigation of psychiatric research misconduct.  To publicly call for an investigation is to swim against the institutional tide.  It is much easier to keep quiet than to confront the university’s most powerful administrators.   

Silence in the Face of Injustice

When does remaining silent during a research scandal lead to complicity in wrongdoing?  Will collective silence from bioethicists prompt blunt questions concerning why the University of Minnesota has a Center for Bioethics? Might collective silence diminish bioethics as an area of study by suggesting that bioethicists, when confronted with allegations of misconduct at their own institution, do little more than defer to authorities? What happens if an investigation at some point determines that serious research misconduct has occurred at the University of Minnesota and most bioethicists at the Center for Bioethics here said and did nothing rather than confront wrongdoing?

Contemporary bioethicists look at the Tuskegee research scandal and question why so many individuals chose to remain silent in the face of wrongdoing.  “It was a different time, a different place,” we say, and congratulate ourselves on the progress we assume we’ve made.  We look at the past and we think we are distinguishable from people who responded to injustice with silence and indifference.  But doesn’t the silence of those who have voices and could choose to use them for good bind past to present and connect us to what we thought we had surpassed?
 
The Silence of the Bioethicists”, an earlier version of this post, appeared March 24, 2014 on the blog, Impact Ethics.





Wednesday, March 19, 2014

For the Record: Judge's decision on Brenny vs. U Minnesota Regents




...the university violated the state’s Human Rights Act prohibition of discrimination against a person on the basis of sexual orientation. [The judge] awarded Brenny a maximum of $334,000 for lost wages based on the university’s conduct, plus another maximum of $25,000 for mental anguish.

Richard Brenny, Katie Brenny’s father, said Tuesday he didn’t realize how badly she was suffering until hearing her testimony. When she told him at the time how bad it was, “I just couldn’t believe it,” he said. “The whole system failed,” he said. “And all the people involved are gone.”


He said he hopes the U has corrected the problems his daughter faced or is at least working toward a solution.

(Star-Tribune)



Additional Background:







  








And what did the University of Minnesota have to say about losing this discrimination suit?

In response to the ruling, university spokesman Chuck Tombarge said, “With due respect to the court, we are disappointed with the decision and will closely review the findings, conclusions and order, and determine the appropriate next steps.”

Not "We are very sorry."

Not "This never should have happened."

Not "We will be taking steps to see that this does not happen again."

In a word: despicable.