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U of M bioethicist latest to call for independent look at the school's troubling Markingson case

The complicated and troubling case of Dan Markingson — the mentally ill young man from St. Paul who committed suicide in 2004 while enrolled in a University of Minnesota clinical trial of the antipsychotic drug Seroquel — is not going away.

In fact, it’s heating up again.

Earlier this year, Markingson’s mother, Mary Weiss, along with her friend Mike Howard and University of Minnesota bioethicist Dr. Carl Elliott, launched a petition to ask Gov. Mark Dayton to appoint an independent panel of experts to investigate the university for possible research misconduct. That petition has now been signed by more than 3,400 people from around the world, including dozens of physicians, bioethicists and other medical experts.

In October, more than 170 leading academic scholars in research ethics, bioethics, health law and biomedical research (including the former editors of several prominent medical journals and a co-founder of the Hastings Center, a leading nonpartisan bioethics research institution) sent a letter to the U of M Faculty Senate, asking it “to take the moral responsibility of a public institution seriously, and to explicitly endorse and request the establishment of a fully independent, transparent, and detailed inquiry” into Markingson’s death.

“Mr. Markingon’s death and the way the CAFÉ study [the one in which Markingson was enrolled] was conducted raise substantial concerns about the enrollment of vulnerable and potentially incompetent research subjects in clinical trials, the appropriateness of specific informed consent and capacity assessment procedures in mental health research, the potential impact of conflicts of interest on the behavior of clinical investigators and university administrators, the qualifications of research personnel, and the overall integrity of medical research at major medical schools and their hospitals,” wrote Trudo Lemmens, a professor of health law and policy at the university of Toronto, and his co-signatories.

Then, last Sunday, KMSP-TV reporter Jeff Baillon ran a long investigative segment on the Markingson case. In his report, he included the comments of an anonymous man who recounted how he had felt pressure while receiving care at the U of M’s Riverside Hospital to participate in a study run by the university for a pharmaceutical company, even after he complained to the study’s investigators that the experimental drug he was receiving was causing severe headaches, blurred vision and abdominal pain — symptoms so severe that he thought of committing suicide.

The medical director of that study, Dr. Stephen C. Olson — the same psychiatrist who oversaw Dan Markingson’s clinical trial — told Baillon in an email that the man in the TV newscast had never reported severe headaches or blurred vision to him.

In a letter sent Tuesday to the U of M's medical community, Dr. Aaron Friedman, the dean of the university's medical school, said Baillon's report was "full of inaccuracies and unsubstantiated claims," although he did not detail them. He also claimed that the Markingson case has been investigated by the Food and Drug Administration, the Hennepin County District Court, the Board of Medical Practice, and the university and its general counsel office. "None of these reports found a link between the clinical drug trial and Dan Markingsons [sic] unfortunate death," Friedman added.

The claim that the case has been fully investigated has been strenuously challenged, however, by the bioethicists and others who have been calling for an independent investigation. As an accompaniment to the letter sent to the U of M's Faculty Senate in October, Lemmens compiled a detailed overview of the previous "reviews" of the Markingson case. The annotated document makes the argument that any investigations that have occurred to date have been superficial at best.

To better understand all this recent activity surrounding the Markingson case, MinnPost spoke earlier this week with U of M bioethicist Leigh Turner. He has called for the university to launch an independent investigation and is a signator to both the petition and the letter sent last month to the Faculty Senate. He also recently wrote to university officials to alert them to other allegations of U of M psychiatric research misconduct that have come to his attention. The following is an edited version of that interview.

MinnPost: You’ve always supported your colleague Carl Elliott’s call for the university to conduct an independent investigation into the Dan Markingson case. But why have you decided in recent months to take an even more visible role?

Leigh Turner: One of my concerns has been Carl. I’ve tried to be supportive, but there was a point where I came to realize that I hadn’t done as much as I could or should. I think it puts him in a very dangerous and difficult position if he’s seen as the only faculty member — particularly the only faculty member in bioethics — who is taking on and challenging an entire university administration. That’s a terrible burden for any one faculty member to have to confront.

So it’s been a conscious decision on my part to go from being a supportive person to being more visible and vocal. I want to show he has support within the Center for Bioethics and within the Academic Health Center, and more generally.

MP: What actions have you taken?

Leigh Turner
Leigh Turner

LT: Over the summer I sent three letters to President [Eric] Kaler and then one to William Donahue [the U of M’s general counsel] after I got a response from him, and then, more recently, additional letters to Kaler and the Board of Regents.

The really unsettling thing for me is that, as a result of the letters I sent this summer, I began hearing from additional Minnesotans who have [described] very similar experiences in psychiatric clinical trials here at the University of Minnesota. I don’t feel completely sideswiped by them because I know Carl has received those kinds of messages for some time now. I’ve also seen a number of things on the Internet where people have posted comments and offered descriptions of a family member’s care. So I can’t say it comes completely out of the blue. But they are unnerving. I find them profoundly disturbing.

This university has never conducted a detailed, thorough, independent investigation of Dan Markingson’s death, and now here are what seem to be a number of individuals coming forward with remarkably similar stories.

MP: One of those individuals spoke to Jeff Baillon in his KMSP report, but the man declined to be identified. Are any of the people who contacted you willing to come forward and talk about their experiences in public?

LT: I don’t have a good answer to that. I feel somewhat ambivalent to the extent that I should provide details. It’s clear from writing to both President Kaler and to the Board of Regents that I was willing to say I had been contacted, and I was willing to [describe] the general lines of this information in terms of the parallels being made to Dan Markingson, the extremely critical remarks being made about university psychiatrists, and [the individuals’] concerns over the care that was provided. But I don’t think it’s an appropriate thing for me to be handing over communications and providing names of people to the senior administration when it’s clear that all of this information will go directly to the general counsel.

This is a university that has repeatedly demonstrated great reluctance to conduct anything that I think would be a recognizable, fair, independent assessment. I don’t know if people will feel comfortable coming forward and describing their accounts and giving detailed information about them.

MP:  How is this case, as well as the administration’s handling of it, affecting the U of M’s reputation?

LT: In my letter, I mention reputational damage. If there was some sort of paper trail instead of getting these platitudes from the general counsel, if there was a document — a 60- or 70-page, very detailed careful assessment of Dan Markingson’s death and the allegations about the CAFÉ trial and the care he received — and if it was clear that the university had been rigorous in investigating those allegations, then I think people within the university and academics outside the university would have greater appreciation for the sense that the university had made a genuine attempt to understand what had taken place.

But that document doesn’t exist. There is nothing in the public domain suggesting that any such investigation has occurred. What is happening is more and more people are becoming aware of Dan Markingson’s death and the ethical and legal issues related to the CAFÉ study and possibly to related studies.

MP: Even after almost a decade.

LT: Yes. In some respects, this is old news. And yet there are all these unanswered questions. It’s not something that has gone away. It’s not something that is stuck in the past. I think we’re already seeing signs of the damage to the University of Minnesota and its reputation. And I wouldn’t be surprised to see that worsen.

MP: How is that damage manifesting itself?

LT: It’s coming up in different kinds of way. One is the increased willingness [of individuals] to sign the petition. And then there are [the discussions] at academic conferences and events. People are clearly concerned and have critical things to say about the university. It raises questions in terms of the research governance at the university. And I do think people find the response of senior administration just mystifying. You have the dean of medicine, Aaron Friedman, and William Donahue, the general counsel, always acting as the spokespersons, and always responding with the same kind of package of claims: “These various bodies have investigated. There’s no need for additional investigation.”

But they never actually answer the many criticisms that are out there.

MP: In your most recent letter to the Board of Regents and President Kaler, you raise the analogy of the Penn State sexual abuse scandal. Can you explain what you mean by that analogy?

LT: The biggest thing for me is, I don’t know how this story ends. In the Penn State case, criminal charges were filed against several senior university administrators. They were extremely serious charges. There’s nothing comparable here at the University of Minnesota. So [the analogy] is more of a warning flare than a clear parallel.

The analogy I see is that [Penn State] was an institution that had numerous opportunities to investigate, to do something. In 1998, there was a complaint filed about [assistant football coach] Jerry Sandusky engaging in sexual assault. There was a criminal investigation and it ended up being dropped. There were people at the very apex of power at that institution — the president of the university, a vice president, the head coach — who knew what had taken place, and they didn’t do anything meaningful with it. They didn’t alert authorities. They didn’t contact police. They didn’t take advantage of that knowledge.

The same thing happened three years later, in 2001. Once again, they had access to information, but they didn’t act on it. And then what ends up happening? There is a criminal investigation, there is a grand jury indictment, and it’s absolutely devastating to the university. One reason it is devastating is that it appears that very senior people within that institution were communicating about the subject, knew about it and did nothing meaningful with that information. They didn’t take the steps that they should have taken.

The [U of M’s] Board of Regents and senior administrators have been contacted numerous times now with questions about the care Dan Markingson received and the CAFÉ study. Their attention has also been drawn to additional allegations about research misconduct. If there is ever an independent investigation, and if that investigation finds that research misconduct has occurred — and I’m not saying that is a known outcome, far from it — but if that does occur, it will cause enormous damage to this institution. Because questions will be asked: Why was the senior administration so opposed to a thorough independent investigation? Why was the response always that everything necessary has been done and that there’s no need to look at this again?

So I am concerned that these various attempts to warn and alert them and encourage them to investigate have been so systematically repudiated. We’ll have to see what ends up unfolding. But my concern is that a number of very prominent individuals have taken a very firm stand on this, and it’s a stand that could, in time, prove to be wrong. And that would cause extraordinary damage.

MP: Why else should Minnesotans be concerned about the Dan Markingson case and the issues surrounding it?

LT: There are a number of people in the community who will have a son or daughter or other family member who will end up with mental illness and have quite serious mental health problems. There are many places where such individuals can go, but the University of Minnesota-affiliated medical facilities are one likely destination for them. If that occurs, whether people are being seen as patients outside clinical trials or whether they are being seen as research subjects within clinical trials, it’s really important that they’re provided with the highest quality of clinical care and that that care meets all ethical and legal standards.

Obviously, lots of people who have mental illness can still make informed choices about their care. It’s important to not make broad generalizations. But, at the same time, within that larger population there is a subset of people who will have extremely limited and impaired decision-making capacity. It’s very important that everything possible is done to ensure that they’re not being treated in any kind of coercive way, to ensure that they are receiving a high standard of care and a very respectful kind of care. It’s also important to make sure that if they can’t make choices themselves, that the concerns of their family members are given very serious consideration and not dismissed or trivialized.

The various comments I’ve seen on the Internet and the messages I’ve received suggest a fairly aggressive approach [at the U of M] to recruiting research subjects. [Patients are being approached and asked] to participate in a clinical trial, and then, when they don’t express interest, are being asked again and again and again. It’s important that asking people to participate in clinical trials doesn’t turn into something coercive and heavy-handed. That’s something that the university, the clinician-investigators themselves and the [Institutional Review Board] all need to take very seriously and ensure doesn’t happen. Because you don’t want people feeling compelled to enter clinical studies.

Also, when you have things like involuntary commitment orders, it’s very important for people to understand that there’s not going to be anything like the threat of commitment to compel them to participate in a clinical study. I’m not saying that has occurred. I don’t want to make libelous remarks based on limited evidence, but it’s the kind of broad ethical and legal issue that needs to be taken seriously.

MP:  You’ve also expressed concerned about who is speaking for the university on this issue.

LT: No one seems to have any great objection to the general counsel always being the official spokesperson for the university. I think that’s because people just don’t spend much time thinking about it. But I think there is this ongoing massive conflict of interest taking place, and it’s one that is being promoted by the university administration. When there are questions about ethical and legal issues related to a case like that of Dan Markingson, when there are additional possible incidents of research misconduct, there is a role for the general counsel in terms of settling with individuals, in terms of representing and defending the university in court. But it’s not realistic to think that people who are tasked with minimizing the cost of settlement to the university can also conduct a fair and thorough and independent investigation.

I don’t think people have given enough thought to the fact that we have a general counsel’s office that is operating on both sides of the fence. It shouldn’t be doing that. There needs to be somebody else responding to these concerns.

MP: You’ve also raised the issue of trust.

LT:  Yes. I think there’s a larger trust issue here. I think that for all parties there is a lot to be gained by conducting a rigorous, expansive, fair and independent investigation. I think that would be of value not just to Mary Weiss and Mike Howard and Carl Elliott. It would also help clear the air about the conduct of psychiatric clinical trials at this university [and about the] two clinician-investigators who often come up in media reports, Stephen Olson and Charles Schultz. A thorough investigation — an independent investigation — needs to look carefully at the criticisms and allegations that have been brought against them. Serious criticisms have been raised. A thorough investigation would provide some sort of meaningful response.

This is what we have now: We have a situation where we have serious criticisms, serious allegations. But because the university’s response is always “We’re not going to answer” and “Investigations have already occurred,” it means they never really respond to the criticisms. And so the criticisms remain. You’re left in this kind of ongoing permanent state of limbo where there seems to be a long list of serious criticisms that are swirling around and never addressed in any kind of effective, substantive way. You end up with something that never comes to an end. There’s always this conclusion that never arrives.

* * *

Leigh’s letters to university officials and their responses have been posted on Scribd. For background on Dan Markingson’s case, I recommend a 2008 investigative report that appeared in the Pioneer Press or a 2010 article published by Elliott in Mother Jones. For details about more recent developments in the case, Ed Silverman at the Pharmalot blog has provided a handy summary. Elliott also provides frequent updates about the case on his Fear and Loathing in Bioethics blog. You can watch Baillon's KMSP report here.

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Comments (5)

Very good article

I have been concerned about this matter for some time, also.

Dr. Mickey Nardo - a well respected semi-retired psychiatrist - has recently written two pieces on his facetiously named blog, One Boring Old Man.

I highly recommend them to interested parties.

"Bigger than Minnesota:

link: http://ow.ly/r5Lyh

and

"The rightest of causes"

link: http://ow.ly/r5LFR

The links are to the pieces as highlighted on my blog The Periodic Table. Many of the points highlighted have been mentioned for years on the blog.

Some illustrative examples:

"What happened several days later defies understanding. In Minnesota, committed patients can be offered another option, a stay of commitment, and avoid being confined to a mental institution as long as they agree to comply with the treatment program laid out by their psychiatrist. Dan was offered the stay if he would enroll in the CAFE clinical trial [Comparison of Atypicals in First Episode] in which he would be randomized to take either Seroquel, Zyprexa, or Risperdal. The absurdities were everywhere. He had been declared unable to "make decisions regarding his treatment," yet he was allowed to sign a consent form to be in the study. It was a maintenance study yet Dan had not responded. And he had written those notes above. After a few weeks, he was transferred to a halfway house that hardly addressed his lethality. The outcome parameter of the study was how many patients voluntarily discontinued the medication, yet Dan was court ordered to take the medication as a condition of his stay of commitment."

"Everything’s wrong with this case. The CAFE study was an AstraZeneca experimercial conceived to counter Seroquel’s poor showing in the NIMH CATIE study. The rigid design didn’t allow the flexibility needed in treating first episode psychotic illness, particularly one like Dan’s. Dan was no candidate for the trial on any count for obvious reasons, not the least of which was being required to take a medication in a study measuring patients’ rate of voluntary discontinuation of medication. He’s the kind of case where non-response to a first choice of medication would’ve dictated trying others, adding anxiolytics [forbidden by CAFE protocol], and considering a drug reserved for refractory psychosis."

"I think Dan’s care was outrageous, and reaches to the heart of doing clinical trials for pharmaceutical marketing rather than to answer genuine scientific questions. I question whether the trial should’ve been done at all. In the case where it was done, I’m sure that Dan didn’t belong in it. And I can’t get around thinking that his being enrolled was to meet recruitment goals. Had he chosen to stop the medication [the outcome parameter], he faced "recommitment," something he didn’t want. His mother’s desperate attempts to withdraw him were ignored."

" I urge you to consider supporting Carl Elliot’s efforts no matter where your opinions fall. He’s going after the rightest of causes…"

"absurdities that I [and everyone else] mentioned; allowing a patient declared incompetent to suddenly become competent to sign on to a trial; putting someone whose mind was filled with the kind of thoughts listed in an earlier post [the rightest of causes…] on a blinded, fixed dose of medication; moving him to a halfway house when there’s no evidence that he was halfway anywhere; ignoring his mother’s concerns; putting him in a study measuring how long people stay on a medication when he was essentially sentenced to keep taking it; etc. Those things are obvious."

"Another thing that lingered was the clip in the video where the clinical coordinator said she "‘didn’t do anything that was wrong or against the law.’ She said Mary Weiss was very controlling. ‘You don’t just kick someone out of a study because the mother wants it to happen.’ Kenny said Dan was doing well. ‘The guy had pretty many stressors going on. Mom was very much interfering with things.’ Kenny said that the fact that Dan committed suicide near Mother’s Day ‘was a really strong message.’" And then there was this remark from the University’s Senior Director of Communication about Scientific American writer Judy Stone, "I looked her up and can’t tell if she’s a whacko or not. I get nervous about anyone who would pay attention to Carl."

It’s the lack of engagement of Dan that haunts me in this story – from AstraZeneca, to Dr. Olson, to the clinical coordinator, to the university – or the implication that his mother was being a royal pain, or that she had something to do with his suicide, or that Judy Stone was a "whacko," or that Carl Elliot doesn’t deserve to be listened to, or even that "it’s a tragedy, not a scandal." Who was engaged with Dan – the young man who was living among telepaths, mind readers, and hybrids, absent emotional attachments?

So:
The CAFE Study was driven by commercial interests rather than to gain medical knowledge.

It was a maintenance study for patients who had responded to medications. Dan had been admitted several days before with a florid psychosis of several months’ duration. There is no evidence that he responded to treatment. There was nothing "maintenance" about his case.

He was a success story for the trial because he hadn’t stopped the medication. That was a complete sham, because he couldn’t stop the medication under threat of commitment.

His clinical condition certainly didn’t improve over the ensuing six months. If anything, he was deteriorating.

But neither burnout or understaffing appear to be the case here. This is something else that shouldn’t ever be in the mix – corporate greed. And in this case, it filtered down to the people doing the clinical trial itself and resulted in negligence in medical care, failing to engage the case at hand. It is a scandal that deserves full investigation and exposure, at a minimum – and maybe its days in court. Finally, Dan’s Law is bigger than Minnesota…

-----------

Sorry to go on so long. But this case has been on my mind for quite some time.

What EXACTLY is it going to take for my university to step forward, take responsibility, and see that things like this don't happen again?

I am not #umnproud. I am #umn ashamed, sorry to say.

William B. Gleason
University of Minnesota faculty and alum

Hit 'em in the pocketbook

I won't give them any more money, and I will respond to all solicitations from the Alumni Association with the reason why they got no money from me.

I urge others to do the same.

What about the University's IRB ?

See http://www.thehastingscenter.org/Bioethicsforum/Post.aspx?id=6582&blogid... for a rundown of the conflicts of interest in the University's Independent Review Board (IRB) in the Markingson matter.

The University's IRB is personally, professionally and financially so thoroughly compromised, it's not possible to take any of their decisions or actions seriously.

There is nothing independent about this IRB.

Thanks for this fantastic interview

While Carl Elliot has done much to draw out the way this story seems so appalling on its face, this thoughtful interview with Leigh Turner forces those who care about the eroding reputation of the University to face the reality of how strangely, clumsily and ineffectively the administration has behaved.

From a PR standpoint this is a disaster, and it makes the parties refusing to engage look more inept at every step. I keep waiting for the reply that says something more than "this has been investigated over and over, there's nothing to see here" and it never comes. Does the U of M have a communications department? Because if they are involved they should all be fired.

I remain surprised that the governor with his decent nose for things that stink, hasn't yet been willing to say something.

Thanks for this.

Jean Kenney's comments should

Jean Kenney's comments should actually trigger another complaint filed with the Board of Social Work. What she failed to mention is the fact that on May 13, 2004, two days beyond "Mothers Day," Dan was scheduled back into court by the recommendation of Stephen Olson to have another 6 months tacked onto his civil commitment. Dan thought he was going back to California in May. Funny, the CAFE' study ran for 52 weeks and that's exactly what Dan's civil commitment would have done. Kenny's lack of professionalism and concern for the client (Dan) is disgusting.