Princess Health and Two New Independent Reports on the Death of Dan Markingson, But Now What Will Happen? . Princessiccia
anechoic effect AstraZeneca atypical anti-psychotics clinical trials conflicts of interest manipulating clinical research research subjects suppression of medical research University of MinnesotaYears after his death, there is now a little more clarity about the clinical trial in which Dan Markingson was enrolled when he died. Whether this clarity will have any impact remains to be seen.
We most recently posted about the aftermath of Mr Markingson's death here, (and see posts in 2013 here, and in 2011 here.) Very briefly, Mr Markingson was an acutely psychotic patient enrolled in a drug trial sponsored by Astra Zeneca at the University of Minnesota. His enrollment was said to be voluntary although at the time he enrolled he had been under a stayed order that could have involuntarily committed him to care. Despite his mother's ongoing and vocal concerns that he was not doing well on the study drug and under the care of trial investigators, he continued in the trial until he died violently by his own hand. After his death, his mother Mary Weiss, friend Mike Howard, and University of Minnesota bioethics professor Carl Elliott campaigned for a fair review of what actually happened. University managers not only rebuffed their concerns, but harshly criticized Professor Elliott, and ended up reprimanding him for "unprofessional conduct."
Two New Reports
In the last few weeks, two new independent reports on the case appeared. Both vindicated the concerns and questions raised by Mary Weiss, Mike Howard, and Prof Elliott.
Association for Accreditation of Human Research Protection
One, called for by the University of Minnesota faculty senate, was by the Association for Accreditation of Human Research Protection, and said that the university left research subjects "susceptible to risks that otherwise would be avoidable" (see this Minneapolis Star-Tribune article.) Furthermore, according to a post in the Science Insider blog from the American Association for the Advancement of Science, it said,
Also, it said the university has been
Finally, it noted a "climate of fear" in the Department of Psychiatry.
Office of the Legislative Auditor for the State of Minnesota
The second report, available in full here,was from the Office of the Legislative Auditor for Minnesota. If anything, it was more damning. Its summary included,
It seemed to affirm in detail nearly all of Weiss', Howard's and Elliott's concerns. It recommended that the University should suspend new psychiatric drug trials until the problems it identified were remedied (see Star-Tribune article here.)
Vindication, but Will It Lead to Progress?
Taken together, these reports vindicate the work of Mr Markingson's mother, friend, and academic watchdog Professor Elliott and their supporters. As the Star-Tribune reported,
The Minnesota Post added the response of Professor Elliott and a colleague,
It appears there a several major remaining questions.
What Were the Underlying Causes?
Although both reports went into some detail about what happened to Mr Markingson, they seemed not to dwell on why it happened. They did not seem to address relevant contextual factors, policies, and decisions. For example, the report by the Office of the Legislative Auditor included,
However, as we and many others more erudite have discussed frequently, clinical research that evaluates products or services made by the commercial sponsors of the research has proven to be highly susceptible to manipulation by these sponsors to increase the likelihood that the results will serve marketing purposes, and suppression if the manipulation fails to produce the wanted results. Commercial sponsors often strongly influence the design, implementation, analysis and dissemination of clinical research. Often their influence is mediated by financial relationships with individual researchers and with academic institutions who seem more and more beholden to outside sponsors, that is, by conflicts of interest. The report by the Auditor noted pressures, including financial pressures on the physician who ran the study in which Mr Markingson was a subject to enroll more patients and keep them enrolled. To protect patients better in the future, in my humble opinion the relationships among commercial sponsors, academic medical institutions, and individual researchers need further consideration. Is the easy money supporting research coming from commercial firms with vested interests in the outcome of that research really worth the risks of biased results, hidden results, and to research subjects?
Will Anything Change and Will Anyone be Held Accountable?
Once these two reports were delivered, it now seems to be up to university managers to make needed changes. In general, these are the same managers who are described above as so "defensive," who not only ignored complaints, but appeared to try to silence those who complained. If they are left in charge, why should we expect them to make any meaningful changes? Instead, should they not be held accountable for their actions?
Will the University Cease Hostilities Against Dr Elliott?
Again, as noted above, university managers did not merely disagree with Professor Elliott. They disparaged him, appeared to try to intimidate him, and reprimanded him. It seems at the very least he is owed an apology. So far, nothing in the news coverage suggests he has or will receive one.
Will Anyone Notice?
So far, this case has gotten good coverage in Minnesota media. However, it has largely been ignored in the national media. Beyond Minnesota, I could only find mention in some blogs, e.g., in PharmaLot by Ed Silverman, and in Forbes by Judy Stone. I have seen nothing in any US medical or health care journal, although the British Medical Journal did cover it in a news feature. This case clearly has global implications, and ought to be considered one of the most important cases illustrating the perils of commercially sponsored human research, but it remains proportionately anechoic.
Summary
The latest reports seem only to confirm that clinical research at major academic institutions has gone way off track. It now seems that in their haste to bring in external funding, university administrators and the academic researchers who are beholden to them have sadly neglected the protection of their own patients. As we have said ad infinitum, true health care reform would turn leadership of health care organizations over the people who understand and are willing to uphold the mission of health care, and particularly willing to put patients' and the public's health, and the integrity of medical education and research when applicable, ahead of the leaders' personal interests and financial gain.
ADDENDUM (25 March, 2015) - See also numerous posts by Professor Elliott on the Fear and Loathing in Bioethics blog, by Bill Gleason in the Periodic Table blog, and by Mickey Nardo on the 1BoringOldMan blog.
ADDENDUM (30 March, 2015) - Note that after receiving offline comments, I changed the first paragraph to emphasize the clarity is about the trial, rather than the patient's death, and second paragraph to clarify that the order to commit was stayed.
We most recently posted about the aftermath of Mr Markingson's death here, (and see posts in 2013 here, and in 2011 here.) Very briefly, Mr Markingson was an acutely psychotic patient enrolled in a drug trial sponsored by Astra Zeneca at the University of Minnesota. His enrollment was said to be voluntary although at the time he enrolled he had been under a stayed order that could have involuntarily committed him to care. Despite his mother's ongoing and vocal concerns that he was not doing well on the study drug and under the care of trial investigators, he continued in the trial until he died violently by his own hand. After his death, his mother Mary Weiss, friend Mike Howard, and University of Minnesota bioethics professor Carl Elliott campaigned for a fair review of what actually happened. University managers not only rebuffed their concerns, but harshly criticized Professor Elliott, and ended up reprimanding him for "unprofessional conduct."
Two New Reports
In the last few weeks, two new independent reports on the case appeared. Both vindicated the concerns and questions raised by Mary Weiss, Mike Howard, and Prof Elliott.
Association for Accreditation of Human Research Protection
One, called for by the University of Minnesota faculty senate, was by the Association for Accreditation of Human Research Protection, and said that the university left research subjects "susceptible to risks that otherwise would be avoidable" (see this Minneapolis Star-Tribune article.) Furthermore, according to a post in the Science Insider blog from the American Association for the Advancement of Science, it said,
[T]he external review team believes the University has not taken an appropriately aggressive and informed approach to protecting subjects and regaining lost trust,
Also, it said the university has been
assuming a defensive posture. In other words, in the context of nearly continuous negative attention, the University has not persuaded its critics (from within and outside the University) that it is interested in more than protecting its reputation and that it is instead open to feedback, able to acknowledge its errors, and will take responsibility for deficiencies and their consequences.
Finally, it noted a "climate of fear" in the Department of Psychiatry.
Office of the Legislative Auditor for the State of Minnesota
The second report, available in full here,was from the Office of the Legislative Auditor for Minnesota. If anything, it was more damning. Its summary included,
the Markingson case raises serious ethical issues and numerous conflicts of interest, which University leaders have been consistently unwilling to acknowledge. They have repeatedly claimed that clinical research at the University meets the highest ethical standards and dismissed the need for further consideration of the Markingson case by making misleading statements about past reviews. This insular and inaccurate response has seriously harmed the University of Minnesota�s credibility and reputation.
It seemed to affirm in detail nearly all of Weiss', Howard's and Elliott's concerns. It recommended that the University should suspend new psychiatric drug trials until the problems it identified were remedied (see Star-Tribune article here.)
Vindication, but Will It Lead to Progress?
Taken together, these reports vindicate the work of Mr Markingson's mother, friend, and academic watchdog Professor Elliott and their supporters. As the Star-Tribune reported,
'Over the past eleven years the University of Minnesota has made us feel as if we have no voice, no rights and absolutely nothing remotely called justice,' wrote Mike Howard, a close friend to Markingson�s mother, in a letter in the audit. 'This report is the first step toward accountability.'
The Minnesota Post added the response of Professor Elliott and a colleague,
'It�s nice to have an independent confirmation of what we�ve been telling the university for five years, but which they have refused to listen to,' he told MinnPost on Thursday.
Elliott said he is not convinced, however, that Kaler and other university leaders are going to take responsibility for what happened in the Markingson case � or take the necessary steps to fix the problem going forward.
'One of the most worrying findings in the report was the widespread belief on campus that the university leadership doesn�t care about human study subjects,' he said.
Leigh Turner, another U bioethicist who has also been outspoken about the issues raised by the Markingson case, expressed similar concerns. 'Can we expect reform from the very people who have done nothing for the past several years?' he said in a phone interview.
'I hope there�s some change,' he added. 'But the fact that [Markingson died in 2004] and it�s now 2015, I think hope has to be tempered with a dose of realism. There are some very powerful forces interested in minimizing the findings and suggesting that there are only minor things that need to be done.'
It appears there a several major remaining questions.
What Were the Underlying Causes?
Although both reports went into some detail about what happened to Mr Markingson, they seemed not to dwell on why it happened. They did not seem to address relevant contextual factors, policies, and decisions. For example, the report by the Office of the Legislative Auditor included,
We understand that the University of Minnesota has been and should continue to be an institution that delivers not only high quality medical care but also engages in cutting edge medical research� research that does pose risks to human subjects. In addition, we do not question the appropriateness of the University obtaining money from pharmaceutical and other medical companies to support that research. However, in every medical research study�whether supported with public or private money�the University must always make the protection of human subjects its paramount responsibility.
However, as we and many others more erudite have discussed frequently, clinical research that evaluates products or services made by the commercial sponsors of the research has proven to be highly susceptible to manipulation by these sponsors to increase the likelihood that the results will serve marketing purposes, and suppression if the manipulation fails to produce the wanted results. Commercial sponsors often strongly influence the design, implementation, analysis and dissemination of clinical research. Often their influence is mediated by financial relationships with individual researchers and with academic institutions who seem more and more beholden to outside sponsors, that is, by conflicts of interest. The report by the Auditor noted pressures, including financial pressures on the physician who ran the study in which Mr Markingson was a subject to enroll more patients and keep them enrolled. To protect patients better in the future, in my humble opinion the relationships among commercial sponsors, academic medical institutions, and individual researchers need further consideration. Is the easy money supporting research coming from commercial firms with vested interests in the outcome of that research really worth the risks of biased results, hidden results, and to research subjects?
Will Anything Change and Will Anyone be Held Accountable?
Once these two reports were delivered, it now seems to be up to university managers to make needed changes. In general, these are the same managers who are described above as so "defensive," who not only ignored complaints, but appeared to try to silence those who complained. If they are left in charge, why should we expect them to make any meaningful changes? Instead, should they not be held accountable for their actions?
Will the University Cease Hostilities Against Dr Elliott?
Again, as noted above, university managers did not merely disagree with Professor Elliott. They disparaged him, appeared to try to intimidate him, and reprimanded him. It seems at the very least he is owed an apology. So far, nothing in the news coverage suggests he has or will receive one.
Will Anyone Notice?
So far, this case has gotten good coverage in Minnesota media. However, it has largely been ignored in the national media. Beyond Minnesota, I could only find mention in some blogs, e.g., in PharmaLot by Ed Silverman, and in Forbes by Judy Stone. I have seen nothing in any US medical or health care journal, although the British Medical Journal did cover it in a news feature. This case clearly has global implications, and ought to be considered one of the most important cases illustrating the perils of commercially sponsored human research, but it remains proportionately anechoic.
Summary
The latest reports seem only to confirm that clinical research at major academic institutions has gone way off track. It now seems that in their haste to bring in external funding, university administrators and the academic researchers who are beholden to them have sadly neglected the protection of their own patients. As we have said ad infinitum, true health care reform would turn leadership of health care organizations over the people who understand and are willing to uphold the mission of health care, and particularly willing to put patients' and the public's health, and the integrity of medical education and research when applicable, ahead of the leaders' personal interests and financial gain.
ADDENDUM (25 March, 2015) - See also numerous posts by Professor Elliott on the Fear and Loathing in Bioethics blog, by Bill Gleason in the Periodic Table blog, and by Mickey Nardo on the 1BoringOldMan blog.
ADDENDUM (30 March, 2015) - Note that after receiving offline comments, I changed the first paragraph to emphasize the clarity is about the trial, rather than the patient's death, and second paragraph to clarify that the order to commit was stayed.
