This research ethics series uses the story of Dan Markingson’s participation in a clinical trial of anti-psychotic drugs at the University of Minnesota, his suicide 2004 while participating on the study, and subsequent events as a case study in which to explore various aspects of clinical trial conduct. In previous posts, I’ve looked at issues of “good clinical practices” and ethics: consent, investigator responsibilities and conflicts of interest. Then I examined the university’s response and then turned to the importance of careful documentation of consent. Next, I explained how I was transformed by Dan’s story from looking at it simply as an objective case lesson in clinical trial ethics, to an advocate for an independent investigation of the University of Minnesota. In a more recent post, I shared reactions to the announcement that Mark Rotenberg, the UMN’s General Counsel, was leaving Minnesota to assume a similar post, now as Counsel and Vice-President at Johns Hopkins University. I have also asked Dr. Jeffrey Lieberman, who was Principal Investigator on the CAFE and CATIE trials, to address concerns that have been raised about the ethics and conduct of that trial. Most recently, focus was on problems with IRBs.
It’s been a busy few weeks in the Land of Denial. Despite new voices and information suggesting serious breaches in the conduct of psychiatric clinical trials at the University of Minnestota, the UMN is hunkering down, continuing to absolve itself of any wrongdoing.
IRB investigation--or lack thereof
First, Carl Elliott finally received Institutional Review Board (IRB) minutes related to Dan Markingson’s death, after numerous attempts to file Data Practices Act requests. The records released by the UMN just last month—9 years after Dan’s death—show that the IRB simply acknowledged receipt of information on May 12, 2004 that “Subject 13” had experienced a “serious adverse event” (SAE) on May 8. That’s a euphemism for “committed suicide.” Acknowledging receipt of the SAE report by the IRB is all that appears in the minutes—no report of a real investigation.
In fact, while the UMN repeatedly claims that multiple investigations have been done, each exonerating it, those claims are false based on the deposition of its own human subjects protection officer, Richard Bianco, responsible for conduct of research, which is quite damning:
Plaintiff's Question: “Has the university done any investigation into the death of Dan Markingson?”
Bianco’s response: “No.”
Question: “did anyone at the University of Minnesota, or anyone under your office investigate this case, actually look at the records...”
Bianco’s Response: “Not to my knowledge”
Question: “Nobody did that?”
Bianco’s response: “No” (p. 41)
IRB’s glaring conflict of interest
There is another very troublesome finding in the records recently obtained by Dr. Elliott. The chair of the IRB responsible for investigating Dan’s death—and chair when the study was approved, was David Adson, another psychiatrist in the same department as Drs. Schulz and Olson, the principal investigators. In the IRB minutes regarding “Subject 13’s” death, Adson states that he had no conflict of interest (COI).
If you were a junior faculty member whose future promotion and tenure prospects may have been depended on Schulz’ good will, might you be reluctant or unwilling to challenge your boss on studies he was promoting, or looking deeply into a clinical trial death on which he was co-investigator? Shouldn’t this be considered a conflict of interest and have been cause for you to recuse yourself?
If you were receiving money from Astra-Zeneca (and hoping that income stream would continue), could you really be impartial as the IRB chair reviewing their studies? According to data from the Minnesota Board of Pharmacy, Adson received $5200 from Astra-Zeneca in 2004 as “compensation for services,” and an additional $16,852 in 2005. He also received more than $15,000 in 2007 alone for speaking engagements for that pharmaceutical company. His take in 2009 was even higher. Nope. No conflict of interest. Nothing to see here. Move along.
UMN retreats into the Land of Denial
Bioethicist Leigh Turner wrote a letter to University President Kaler recently, alerting him of more possible cases of research misconduct, and then to the Board of Regents. Dr. Turner reported that other families who say that their family members have been mistreated or coerced in psychiatric research studies have approached both him and Dr. Carl Elliott.
Predictably, given we are dealing with the UMN, the response to Turner was from the University’s General Counsel, citing “facts” that have been refuted on multiple occasions, most recently by Dr. Trudo Lemmens, Chair in Health Law and Policy at the University of Toronto, below.
As Turner aptly admonishes, “Pennsylvania State University provides a powerful example of what can happen when senior university administrators fail to address allegations of wrongdoing.”
A National—and International—Disgrace
Earlier this month, Dr. Trudo Lemmens and a group of others sent a letter to UMN President Eric Kaler and the University Senate, also requesting an independent investigation. Lemmens’ letter was countersigned by 175 prominent ethicists, researchers, lawyers and academicians from the US, Canada, Europe, Africa, Asia, and Australia/New Zealand. Signatories included Susan Reverby (the historian who brought unethical syphilis experiments in Guatemala to light), members of the President’s Council on Bioethics, and former editors of the New England Journal of Medicine.
Once again, the response to this internationally requested inquiry to the President and Senate came not from them, but from the University’s General Counsel, William Donohue. Condescendingly, Donohue suggested that the writers might not be “completely familiar” with the case. In a scathing rebuttal, Lemmens responded with this table critiquing “the various alleged reviews, what they found, and why the authors and signatories of the October 21, 2013 letter call for an independent inquiry.” One of the ironies of the UMN General Counsel’s letter is that their letterhead boldly proclaims, “Driven to Discover.”
In a pointed rebuke, Lemmens reminds Donohue, and readers, that the Minnesota legislature was so appalled at the UMN clinical trial suicide, that they passed “Dan’s Law,” prohibiting a patient from giving consent to participate in a clinical drug trial,” while under a civil commitment order, specifically to eliminate the type of coercive conditions Dan was subjected to.
The University’s continual ostrich-like stance refusing to seriously address thoughtful concerns raised by people from all over the world, and asking for an independent inquiry, makes one ask, “Who is delusional now?”
In which I make my Fox News debut…
I never pictured myself in a cameo on Fox News, but agreed to an interview for a story on Dan Markingson’s death. Jeff Baillon, an investigative reporter at Fox 9 in Minneapolis, did a terrific job and Fox 9 produced a compelling video, well worth watching. There were some striking moments—the saddest of which is how frail Mary Weiss, Dan’s mother, is now and what a toll this has taken on her.
In one section of the tape (~4:40), the study coordinator, Jeanne Kenney, says that she didn’t do anything wrong—I guess that ignoring a mother’s plea that her son was deteriorating, when Mary begged in a message, “Do we have to wait until he kills himself or someone else?” for anyone to do anything, is nothing wrong in her book. Kenney went on, “’You don't just kick someone out of a study because the mother wants it to happen,’ and that “the fact that Markingson committed suicide near Mother's Day ‘was a really strong message.’” Shocking display of sensitivity by a social worker and study coordinator—who subsequently received a “corrective action” by the Minnesota Board of Social Work for dispensing medications without a license, signing medical charts fraudulently with the initials of the supervising psychiatrist and failing to adequately address concerns about Dan’s suicidal intentions. [One might still ask why the Principal Investigators on the study have not been punished.]
In a dramatic segment (~5:41), Baillon interviewed another patient who said he felt compelled to participate in a clinical trial for schizophrenia. "The study subject explained that he signed up because he felt if he didn't, he wouldn't get out of Riverside Hospital. "You know, when you're locked up in a place, you're very scared and you're willing to do whatever anyone basically suggests," he said. "I don't think I was competent to be making that decision," he added. The patient also complained that he was not treated properly when he experienced severe side effects from the study medication. Olson denied this event to Fox.
Since the story aired on Minneapolis TV, other patients have come forward with complaints. For example, “CJ” said on Change.org, “I was just horrified after viewing the news program last evening airing on the Fox channel in the Twin Cities, MN. I could have been Dan Markingson or the other person that preferred to be anonymous, as I had a very similar experience with Dr. Olson and Riverside hospital. I too was recruited for a drug study and the pressure to consent was enormous, and being extremely vulnerable at the time just added to the anxiety. Fortunately, I was able to arrange my discharge with help from my family and sought and received treatment elsewhere. I was visited everyday in my hospital room by a study staff coordinator, sometimes twice a day, and at least once everyday was pressured by Dr. Olson to enroll. I was not the only patient being harassed in this manner. This abuse has to be investigated.”
Given the repeated denials by UMN that there has been any wrongdoing in the psychiatry trials, I can understand that more patients haven’t come forward. I suspect that with a truly independent commission exploring accusations of research misconduct, more people would do so.
and my image is radically altered by UMN…
Under FOIA laws, Fox 9's Baillon obtained an internal UMN e-mail about me. After I attempted to reach Mark Rotenberg, the former General Counsel, for comment and was given the run-around, the university's senior director of communications sent out the following e-mail
about me, "I looked her up and can't tell if she's a wacko or not...I get nervous about anyone who would pay any attention to Carl."
The UMN should, indeed, be nervous since increasing numbers of medical and ethics professionals have found Dr. Elliot’s critique of UMN convincing.
The senior communications director’s dismissal of my inquiry so casually doesn’t say much for the university’s desire to seek the truth—rather, his focus appears to be on hiding their mistakes.
Why I can’t drop this story
The UMN misjudged me on another point, as well. As a researcher and infectious disease physician, I am persistent in trying to uncover answers and truth. I entered this story thinking it would be a simple, “easy weekend project” to write about the ethical lapse that occurred. Instead, slowly but surely, more transgressions became apparent and I became more and more appalled by what I saw.
The other decisive factor in shaping my opinion was transparency—Dr. Elliott has backed up everything he has said with documentation on Scribd, where anyone can see the originals of correspondence and depositions, which are often damning. The UMN has not done the same, and has instead resorted to innuendo and intimidation to stifle dissent.
I am disappointed that one observation I made to Baillon was left on the cutting room floor—that the Markingson case can provide a lifetime of learning on how not to do clinical trials. #UMNproud.
I’m thankful that my searching for justice has troubled the UMN enough to dismiss me as a “wacko,” in good company, presumably, with Dr. Lemmens and all the global academics and ethicists calling for an independent investigation, as well as the tireless Dr. Elliott.
Hopefully the UMN will grow up and realize that Disney was wrong—wishing will not make their dreams come true.
One of the things I am particularly thankful for this Thanksgiving is that there are honorable people like Carl Elliott, Mike Howard, and Mary Weiss—and their growing supporters—who fight for justice and ethics despite the personal toll doing so incurs.
For further reading, previously in this series:
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Wacko – courtesy Brian Bubonic/Flickr