January 8, 2013 | 6
In earlier posts, we’ve looked at issues of consent, investigator responsibilities, and conflicts of interest on the case of Dan Markingson’s suicide while participating in a clinical trial of anti-psychotics at the University of Minnesota. This time, we turn to the University’s response.
Not surprisingly, the University has claimed it has no responsibility for any wrongdoing—that in fact, no wrongdoing even occurred. But there are some inconsistencies in the story and unanswered questions. There is also concern over how the University has responded to criticism. We’ll examine these issues in this post.
Background regarding the University’s response
In response to the Minnesota Board of Social Work’s “corrective action” vs. Jeanne Kenney, the social worker/study coordinator who did most of the study assessments on Markingson, the UMN’s General Counsel Mark Rotenberg stated, “As we’ve stated previously, the Markingson case has been exhaustively reviewed by federal, state and academic bodies since 2004. The FDA, the Hennepin County District Court, the Minnesota Board of Medical Practice, the Minnesota Attorney General’s Office and the University’s Institutional Review Board have all reviewed the case. None found fault with the University. None found fault with any of our faculty. Most importantly, none found any causal link between the CAFE trial and the death of Mr. Markingson.”
Yet a number of UMN faculty have remaining concerns and have requested an independent investigation. Two years ago, eight faculty members in the Bioethics Department wrote Rotenberg, citing the University’s conflicts of interest in the matter. The UMN declines to reexamine the case, saying that they have been exonerated. In October 2012, Dr. Carl Elliott, Professor in the UMN Center for Bioethics, wrote Dr. Debra DeBruin, director of the Clinical Research Ethics Consultation Service for the UMN Clinical and Translational Science Institute, again requesting a review. This time Dr. Elliott expressed concern regarding human subjects protections in other trials conducted by the psychiatry department as well. As always, Dr. Elliott’s concerns were thoroughly documented. Once again, the University has turned away.
The UMN’s claim of exoneration is complicated, and not quite accurate.
The FDA’s review of Markingson case
The FDA’s review of the case seems remarkably superficial to me. Perhaps I have more information now than they had available, accounting for differences in our conclusions. You can read the 2005 FDA report of Inspector Sharon Matson here:
Dan had been involuntarily committed for being psychotic and homicidal, and was then offered a stay of commitment to a psychiatric hospital if he followed the recommendations of his physician and social worker—all of which seems very coercive and is frowned upon by both research ethics and regulations. “The HHS regulations state that “An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence” (45 CFR 46.116)
There are also special cautions about enrolling vulnerable subjects, placing additional responsibility on the IRB, with regulations requiring them to “ensure that ‘additional safeguards have been included in the study to protect the rights and welfare’ of all subjects that are ‘likely to be vulnerable to coercion or undue influence.’ The regulations include ‘mentally disabled persons’ in this category (45 CFR 46.111(b)).”
Despite these facts, the FDA inspector concluded, “There was nothing different about this subject than the others enrolled to indicate that he couldn’t provide voluntary informed consent” (p. 9).
But remember, “On November 14, 2003 Dr. Olson signed a commitment document stating that Markingson “lacks the ability to make decisions regarding such treatment [consenting to neuroleptic drugs].”
Then, “on November 21—just two days after being deemed incapable of consenting to Risperdal (anti-psychotic treatment)–Dan was suddenly determined by Jeanne Kenney, his social worker, to be capable of consenting to a clinical trial of anti-psychotic medications.” (Groat expert report)
Despite notes documenting Dan’s failure to improve on the CAFE study, Ms. Weiss’s urgent warnings about his deterioration, and Dr. Olson’s requesting Dan have an additional 6 month stay of commitment, the FDA inspector concluded that the record “does not appear to indicate a significant decline or deterioration” (page 10).
Matson notes that Dan’s court appointed caseworker, David Pettit, approved of Dan’s enrollment, but missed that Pettit had no involvement with Dan prior to enrollment, as he had not yet even been assigned to the case until 3 days later, and didn’t see him until 5 days after he was enrolled (p 15 of Pope expert report). Even the judge issuing the commitment order had not been informed by Olson that Markingson would be enrolled in the CAFE study. (p 78-9 of Olson deposition)
Matson regurgitates Olson and Kenney’s views that participating in the CAFE study gave Markingson better care than he would have received had he not participated because of much closer monitoring—frightening, if true. (p 8 of FDA inspection report). At no point does she mention disadvantages of participation, including that the protocol prohibited changing his medication or using combinations of drugs, nor were alternative options clearly outlined. The inspector also fails to note that most studies of antipsychotics exclude patients at risk of violence, but this study did not, nor did the UMN IRB object. She states that the IRB reviewed the case and “no irregularities were noted.” (p 13) (I believe this is colloquially known as the fox guarding the hen house).
Similarly Inspector Matson notes that subjects had an assessment of their ability to consent to a protocol, but does not indicate that this was administered by the same study coordinator who was in charge of recruitment. (p 14)
Perhaps I just have the benefit of having more records and depositions than Ms. Matson did but, given all the evidence that she missed and that is new since her 2005 report, one would think that the FDA would reopen this case.
University counsel Mark Rotenberg skillfully and disingenuously proclaimed of reviewers, “None found fault with the University. None found fault with any of our faculty.” This is true—but only as far as it goes.
I, like Carl Elliott before me, have not been able to find anything from the Attorney General’s office that exonerates the university.
In fact the Attorney General’s office clearly had concerns about the case. For one, the Board of Social Work, which issued the corrective action against Ms. Kenney, was represented by Assistant Attorney General Benjamin R. Garbe. They cited her undertaking tasks beyond the scope of practice of a social worker—but this was clearly done with Dr. Olson’s knowledge and support.
Deputy Attorney General Michael Vanselow also wrote Mary Weiss, “We are also willing to work with you and Jim Gottstein in regard to drafting some proposed legislation to address some of the systemic problems that contributed to your son’s death.” Such legislation was passed in 2009 and is known as “Dan’s Law.” This law prohibits recruiting most patients who are under a commitment agreement into clinical trials.
University of Minnesota’s behavior
If there is one thing the university has excelled at in this sorry story is that of creating a climate of intimidation, both towards the plaintiff, Ms. Weiss, and towards concerned faculty.
One of the things I found sickening was that in 2008, the University countersued Mary Weiss for almost $57,000 to recover their legal fees—although they did not really win their case. Instead, they hid behind the state equivalent of “diplomatic immunity.” Further, Ms. Weiss only had 10 days in which to decide whether she could afford to appeal the case and explore her options. Fortunately, all but ~$1000 of the UMN’s countersuit was dismissed by the court administrator—but Mary had to waive her right to appeal.
As Carl Elliott aptly notes, for the UMN to file a countersuit against a grieving mother who has just lost her only child in a clinical trial at the University was not only a shameful tactic, but one clearly designed to punish Ms. Weiss for her lack of deference to them. It also sends a clear and intimidating message, akin to a SLAPP, or Strategic Lawsuit Against Public Participation.
The UMN appears to be playing the same game of intimidation in its actions towards Dr. Elliott, in response to his persistent request that there be an independent inquiry, rather than one by the UMN’s own General Counsel, Mark Rotenberg, who appears to be vying to be judge, jury, and executioner in this story. In response to Elliott’s requests, “Rotenberg asked the university’s Academic Freedom and Tenure Committee to take up the question of ‘[w]hat is the faculty[’s] collective role in addressing factually incorrect attacks on particular university faculty research activities?‘ – a question that appeared both to accuse Elliott of ‘factually incorrect attacks’ and to call for some unspecified action to ‘address‘ them.”
Fortunately, Rotenberg’s heavy-handed tactics appear to have backfired. Rather than squelching Elliott, a number of faculty viewed this as another thinly-veiled attempt at intimidation. A University of Chicago Professor of Law and Philosophy, Brian Leiter, described Rotenberg’s question “a quite brazen attack on the core of academic freedom,” noting that it also illustrates “how important tenure is to protect faculty whose research adversely affects corporate interests.” Other criticism followed. In one particularly scathing post, “Should the General Counsel at the University of Minnesota Take a Sabbatical for a Refresher Course in Constitutional Law?” attorney Michael McNabb notes, “The First Amendment prohibits the government from abridging free speech. A state university may not exercise prior restraint on public discussion…neither the faculty nor the administration has the authority to restrict speech at a state university (of all places).”
At this point, we have the UMN:
- hiding behind state sovereignty protection
- denying any responsibility for the death of a clinical trial subject although the Minnesota Board of Social Work found that the coordinator, practicing under the direct supervision of a physician-investigator, performed medical assessments and procedures for which she was not qualified
-an IRB chair who states that the IRB is not responsible for protecting clinical trial subjects
-a bereaved mother who is hit with a hefty countersuit as a tactic of intimidation, and who can’t afford the cost of appeal
-a courageous and well-qualified bioethics professor, Carl Elliott, who is threatened by the UMN General Counsel for voicing his concerns
-blatant financial conflicts of interest that are seemingly swept under the carpet because of the lucrative financial benefits to the UMN
There are a number of unresolved questions in my mind. Among them:
If the social worker/study coordinator was found at fault by the Minnesota Board of Social Work, why has nothing happened to the physicians supervising her and who were responsible for her actions?
Medical assessments were done by a non-medical individual, were sometimes erroneous, and records were altered after the fact. The same coordinator and physician principal investigators (Olson and Schulz) were also involved in the CATIE trial and other NIH sponsored trials. Why have these not undergone review?
What changes, if any, have the IRB and institution made to enhance protections for vulnerable subjects?
In my concluding post, we’ll look at some of the broader implications of this study for the UMN, for NIH, and for clinical trial participation.
Bowl of antidepressants – Carsten Schertzer/Flickr
Dan Markingson photo courtesy of Mary Weiss
Seroquel samples-Judy Stone
Molecules to Medicine banner © Michelle Banks