Wednesday, March 11, 2015

For the Record: done nothing wrong... Dr. Mickey Nardo - 1 Boring Old Man - on #Markingson

Dr. Mickey Nardo writes a blog, 1Boring Old Man.  

"Mickey Nardo MD represents all the psychiatrists in the trenches who have had more than enough of incompetent APA leadership. He writes what is by far the best available psychiatric blog under the misleadingly modest nom-de-blog ‘1boringoldman.’ Dr. Nardo is definitely not boring and by my standards is not that old. Anyone who regularly reads his blog will agree that he lives up only to the last part of the title — he is indeed a mensch."

done nothing wrong…

Posted on Tuesday 10 March 2015

In the case of Dan Markingson at the University of Minnesots, you might recall that in spite of the university senate voting to have that case investigated, the President ordered only an investigation of the research program "looking forward", not the case itself [too deep to ignore…]. I guess we thought that the University President had done a bit of sleight of hand yet again [almost inevitable…]. But, sometimes things are bad enough to over-ride any attempts at diversion. The report came in last week, and it was a scathing indictment:

by Jennifer Couzin-Frankel
March 2015

A damning report on how the University of Minnesota [UM] protects volunteers in its clinical trials concludes that researchers inadequately reviewed research studies across the university and need more training to better protect the most vulnerable subjects. It also found that a “climate of fear” existed in the Department of Psychiatry, where concerns about clinical trials first surfaced.

The 97-page report, released 27 February, was prepared by a group of six experts appointed by the Association for the Accreditation of Human Research Protection Programs. It comes after years of complaints by some UM faculty members, led by bioethicist Carl Elliott. They charged that the school and its doctors failed to protect 27-year-old Dan Markingson, who died by suicide while enrolled in a psychiatric drug trial in 2004. They also expressed grave concerns about how Markingson’s death was investigated. [More on that case is here and here.[

Recently, Elliott’s crusade began having an impact. In December 2013, the UM Faculty Senate called for an independent review of current practices in clinical trials. The administration agreed to open its records to outsiders. Although the review did not look back at history, it nonetheless had plenty to say about how the university handles trials, which bring in millions of dollars from drug companies along with much prestige.

“[T]he external review team believes the University has not taken an appropriately aggressive and informed approach to protecting subjects and regaining lost trust,” the authors write. They examined protocols from 20 active trials as well as minutes from meetings of the institutional review board [IRB]. Many IRB members, the panel noted, did not regularly attend meetings from January to July 2014. “[T]here were no individuals on the IRB during this time period with expertise in adult hematology, oncology and transplant, cardiology, surgery, or neurology, although those fields taken together represented over 300 protocols. There was only one psychiatrist on the IRB, despite the fact that the Psychiatry Department submitted 85 protocols for review during the time period examined.” That doctor attended only four of the 26 medical IRB meetings at which new protocols were reviewed. “This departure not only contravenes the University’s own policy of having at least one member with ‘primary professional expertise in a scientific field relevant to the type of research reviewed by that panel,’ but also prompts concern about the quality of review.”

Fueling those concerns, the authors noted that the IRB spent an average of 3 to 5 minutes discussing each protocol, and there was “little discussion of the risks and benefits to subjects.” Most of the protocol changes the IRB asked researchers to make addressed administrative issues such as misspellings or adding standard language to a consent form. Requests by researchers running trials to modify who was eligible for a study—“changes that may increase or decrease risks to subjects—were almost always approved without any documentation of related discussion,” the authors write. “The review process, as documented in the minutes, does not reflect a meaningful discussion of the risks and benefits of research protocols and the necessary steps taken to protect human subjects in the face of scientific or ethical concerns”…

Surely ethics refers to more than a code of conduct, or the rules of right and wrong, or even the letter of the law. It comes from the word ethos, the culture of a place, and should offer a compass for navigating situations where there are no standing rules or precedents – something more felt than transcribed, something conveyed by example rather than memoranda or training manual. And when I’ve read about this case, their response has always been, "We did nothing wrong," but my mind always inserts, "And you didn’t do anything right either." I thought the external reviewers were most at the center when they said this about the ethosthey encountered in their investigation:

In interviews, some University personnel described considerable “fatigue” related to 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.” Most striking was the commonly conveyed sense of doubt in leadership’s commitment to human subjects protection. The widespread characterization of a few researchers in the Department of Psychiatry as “untrustworthy” and as creating a “culture of fear” in relation to efforts to enhance the protection of research subjects was of major concern to the external review team.
Dan’s hospitalization was from 2003 to 2004. Around the same time, Allen Jones happened onto TMAP and blew a whistle. Jon Juriedini in Australia first wrote the JAACAP about Paxil Study 329 in 2003. Charlie Nemeroff got busted for the first instance of his unacknowledged COI around that time. These instances turned out to be the tip of an iceberg. It was as if the traditional medical ethics had been invaded by the ethos of commerce, that patients had become subjects to be recruited for clinical trials designed to sell drugs, and marketing had become the strong undertow that was pulling everything out to sea.

While Bioethicist Carl Elliot has lead the struggle to get action on the Markingson case, he hasn’t been alone. His colleague, Leigh Turner, has also been involved, and spoke up in the faculty meeting Friday where this report was released [seeResearch methods under fire]:

We’re acting as though this report is news, but in fact there’s been several years where concerns have been brought forward in very detailed, concrete ways,” he said at the meeting. Turner said University leadership hasn’t adequately responded to problems he says have been happening within the program for years, and he questioned University President Eric Kaler’s commitment to repair the program’s current state.
Even that sounds like an understatement. University President Eric Kaler, Psychiatry Chairman Charles Schulz, and researcher Stephen Olson have obstructed previous efforts for over a decade, sticking with the "done nothing wrong" refrain.

"We did nothing wrong" is a legal standard – the standard by which we define criminal behavior in a free society based on the rule of law. An ethical standard is different. For one thing, in medicine, it is impossible to do "nothing wrong." But beyond that, an ethical standard has to do with maintaining an ethos, a culture. In a Clinical Trial of a new medication, it’s incumbent on the trialist to be vigilant that the subject’s health and medical care is not compromised by participation.

In the case of Dan Markingson and the University of Minnesota, that ethos was betrayed down the line by …
  • the design and purpose of the C.A.F.E. study
  • the oversight function of the Institutional Review Board
  • the recruitment and inclusion of Dan Markingson
  • his ongoing psychiatric care
  • the subsequent responses of Institution
While we can never know how Dan might have fared had he been treated outside the Clinical Trial environment, we can easily see that the ethical imperatives that even allow these Clinical Trials were globally deficient in the case. And it’s equally apparent that the officials of the Institution in charge show little understanding of their ethical obligations, even when repeatedly reminded by the faculty of their own Department of Bioethics.

Carl Elliot, Leigh Turner, Mike Howard, and Dan’s mother, Mary Weis, have done something remarkable. They’ve moved rhetorical deliberations about medical ethics out if the ivory towers of academia; breathed a new life into them with this paradigmatic real world case; and taken their campaign to the streets. Likewise, the external reviewers appointed by the the Association for the Accreditation of Human Research Protection Programs who were given only a restricted scope of inquiry [too deep to ignore…almost inevitable…a paradigm…] were still able to identify fundamental deficiencies in the Clinical Trial Program at the University of Minnesota, even after a decade of opportunity to make needed changes since Markingson’s death. Elliot’s team and these reviewers have obviously "done something right."

But there’s much that remains. This is a local victory, but it addresses problems we all know have a much broader scope. So will this instance lead to a general investigation of the Institutional Review Board system to insure it providesfunctional oversight rather than simply signing off? Is there a mechanism to shut down Clinical Research programs that don’t create an appropriate ethos with theethical imperatives that protect the subjects under study? And there’s one topic that isn’t even touched here: Should we even allow Clinical Trials that are undertaken for commercial purposes [like C.A.F.E.] that have no real medical/scientific value [experimercials]? While we can stand in awe of the energy it has taken for Carl Elliot’s group to get this far, there are going to have to be a lot more people devoted to "doing something right" to generalize their campaign…

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