Wednesday, May 27, 2015

For the Record: FAQ: U drug trials, patient safety and the death of Dan Markingson

Dan Markingson and his mother, Mary Weiss. 
Weiss was concerned that her son wasn't getting better during his six months in a U of M study. Courtesy Markingson family

Alex Friedrich writes for MPR

More than a decade after the suicide of a patient in a University of Minnesota drug trial, the incident is prompting the university to make some changes to the way it conducts such trials.

The changes are coming about now through the persistence of critics who demanded further investigation into the death of Dan Markingson. After years of little action, the case has generated a flurry of activity in just the last few months — new reports, proposed reforms, staff changes. Here are some of the key points to emerge:

What has all of this been about?

Critics believe some University of Minnesota researchers have coerced vulnerable patients into participating in studies, and then neglected their welfare during the research. Much of the focus has been on a few researchers in the Department of Psychiatry, which often conducts clinical drug trials sponsored by drug companies. Critics say university officials have ignored years of requests to look into the matter.

What prompted it?

It all started with the suicide of a mentally ill man named Dan Markingson over a decade ago. He'd seen Dr. Stephen Olson, a university psychiatrist, who enrolled Markingson in a corporate-sponsored drug trial for an anti-psychotic drug. Markingson's mother, Mary Weiss, believes Olson coerced her son into participating and kept him in the study despite her repeated warnings that he might hurt himself. Markingson's suicide in 2004 prompted her to sue the university in 2007.

A series of articles in 2008 by the St. Paul Pioneer Press brought the case to light.

A court ruled the university was immune to litigation. Weiss later settled with Olson for $75,000.

Was any wrongdoing proven?

The federal and state investigations that Markingson's death sparked have been a subject of contention for years. They included reviews by the university's research oversight panel, the U.S. Food and Drug Administration and the Minnesota Board of Medical Practice.

University officials long said the results exonerated the U.

But the Pioneer Press stories raised the suspicion of U of M bioethicist Carl Elliott. He looked into the case, and began a campaign of articles and letters pointing out what he saw as flaws and inadequacies in the investigations. He pushed the U's top officials to launch another investigation of the case, and their refusal led Elliott to accuse them of a cover-up.

Why did the case make news this year?

The work by Elliott, who was later joined by U of M colleague Leigh Turner, caught the attention of some university faculty, alumni and scholars from around the world, who began pressuring university officials to reopen the case.

Former Gov. Arne Carlson also wrote letters to both regents and lawmakers criticizing the university's actions and asking for another investigation.

After mounting pressure from faculty, President Eric Kaler in December 2013 agreed to launch an outside review of the U's clinical research practices. And in 2014, two leading legislators asked the state legislative auditor to look into the Markingson case specifically.

The results of both cases came out earlier this year, and sparked reaction from both lawmakers and the university.

What did the investigations find?

In February, the external panel hired by the university said the university had weak oversight of research. The reviewers noted that personnel didn't feel the U's leaders were committed to protecting test subjects, and they expressed special concern over a "culture of fear" in the psychiatry department they said kept people from raising safety concerns. It suggested dozens of reforms.

In March, Minnesota Legislative Auditor Jim Nobles criticized the U for its handling of the Markingson case.
Nobles said it was impossible to link Markingson's death to the drug study, but said he found "serious ethical issues and numerous conflicts of interest." He said the conditions under which researchers recruited Markingson were potentially coercive, and that researchers ignored repeated warnings about Markingson's deteriorating condition.

The report noted multiple potential conflicts of interest among the researchers and subsequent investigators. Nobles said the FDA investigation had been "limited," and that the U's own investigation had been "superficial." He said university leaders had repeatedly made misleading statements about the thoroughness of past reviews, and that they'd damaged the university's reputation by rejecting calls for further investigation.

Since those reports, more information about university researchers has surfaced.
This month, an internal review found some Fairview Health Services personnel held a "profound" distrust of some U of M psychiatric researchers working there, and it blamed leadership at Fairview and the U for ignoring it.
In a separate case this month, the university wrote a letter of apology to a former test subject, saying researchers had failed to follow several safety procedures during a 2007 university drug trial he participated in. The U issued the letter after an outside consulting firm said Olson and his staff had made the mistakes, calling two of them "serious."

However, the report rejected the patient's claims that Olson and his staff had coerced him into participating.

How has the U reacted to all of this?

Although Kaler said he didn't agree with all of the findings in March's legislative audit, he accepted it, as well as the findings of February's external review.

Kaler said he thought the medical school was doing better than it was in protecting test subjects, and called it "worrisome that we have such a distance to go to reach the very highest standards."

He apologized to Markingson's family "for his death under our care." He also apologized for the university's prior misleading statements on the matter, saying they were not meant to mislead and that he'd relied on investigations he thought were credible.

Kaler suspended patient enrollment in 17 active and pending drug studies until they're reviewed by an outside firm, and ordered an action plan to carry out the reforms.

What's changing?

According to the draft plan the university released Monday, it will add personnel, boost training and increase oversight in an attempt to make sure a case like Markingson's doesn't happen again.

Many of the changes focus on strengthening oversight panels so the U can make sure researchers in all departments are conducting their experiments appropriately. It's instituting a tougher patient consent process, and is giving researchers more training so they can better judge whether patients are mentally capable of consenting to a study. The U will also work to curb conflicts of interest among researchers and drug companies.

Campus leaders say they're trying to change the research culture by injecting more checks and balances into the power structure, and enable those who are not physicians to have more say in the research process. And the U will be offering physicians more education and training in ethics and the new standards.

Has anyone been disciplined as a result of all this?

Not publicly, at least.

However, last month Dr. Charles Schulz, who was a co-researcher with Olson in the Markingson study and led the psychiatry department at the time, resigned his leadership of the department. Recently, he said he'd also agreed to step down as executive medical director of behavioral health services at the university hospital.

What happens now?

The public has through June 1 to comment on the reform plan, which regents are expected to vote on next month. Medical School Dean Brooks Jackson said he hopes to see most reforms in place within nine months. Legislative auditor Nobles says he'll return late this fall to see check on the U's progress, and wants to follow up several times in the next few years.

Nobles called the reform plan "very encouraging," and university leaders say elements go far beyond what other institutions do. Some critics say it does have the potential to improve things, but remain skeptical that it will bring about significant change.

Meanwhile, Nobles hopes to release in the next few weeks the results of his review of the past decade of university drug trials. He's trying to determine whether the university's files contain more cases such as Markingson's or other major mishaps.

How has all of this affected the U?

Its reputation has taken a beating, and multiple colleges in the U.S and abroad use the Markingson case as a study in how not to conduct research and handle criticism.

Meanwhile, drug studies remain suspended as an outside consultant reviews them.

The reforms will cost the university lots of paperwork and millions of dollars to carry out — all during a time when it's trying to boost its national ranking as a major medical research institution.

Jackson said in an email, however, that higher rankings and protecting subjects "are not mutually exclusive." He acknowledges that some reforms could increase red tape, but said others could actually make some studies get started more quickly.

"Expansion of research should in no way come at the expense of patient safety," he said, "so we don't anticipate these reforms impeding us as we look to grow our research portfolio."

For the Record: How others see us. Recent comments in NYT about #umn

Carl Elliot has recently written a piece in the New York Times. (link)

Here are some comments on the piece:
(not #umn proud ...)

Thank you Dr. Elliott for blowing the whistle loudly and clearly. This mistreatment of the participants in these drug studies is appalling, if not criminal. As a person who conducts research with human subjects, I consider the treatment of each individual to be sacrosanct and if there are researchers who are mistreating their subjects they should be banned from conducting research. 

It's sad that at the same time the university officials were hiding the internal investigation, they were piously preaching the principles of academic honesty to their undergraduates and threatening them with expulsion. What a sham! 

Dr. Elliot appears to be calling for greater power for IRBs to regulate, or a greater role within the institution, but I fear his concerns may be applicable only to the University of Minnesota, which by his description, is seriously flawed. Any researcher (Principal Investigator or Co-I) who broke IRB rules where I've worked was fined, placed on administrative leave, or fired. My experience is that IRBs exist less to protect subjects and more to protect the institutions with which researchers are affiliated. Maybe the issue isn't the lack of power within the IRB, but the lack of will at Univ. of Minn to confront the culture within the department of Psychiatry within the college of Medicine. Its easy to blame a body with oversight duties for the failings of a research culture that reside within the college of medicine.

As taxpayer contribution to biomedical research dwindle (NIH budget adjusted for inflation keeps coming down year after year) universities and medical schools are depending more and more from pharmaceuticals and biotech companies to keep research going. There is an obvious conflict of interest between reporting unbiased scientific facts and a company need to hype their products. Thus, an increase in cases of unethical or questionable research is to be expected. At the end you get what you pay for and the companies that fund research certainly want something in return.

IRBs have the right to monitor research and the consent process. They have the right to impose restrictions and suspend research protocols. The fact that the UM IRB did not perform its duties is not a reason to do away with the IRB system; it is a call for the UM IRB to function as it is supposed to function. Unfortunately, institutional support is essential to the proper functioning of an IRB. Clearly that institutional support was completely missing here.

It is quite possible to have adequate review and protection using the IRB model, IF the university's administration is willing to support the IRB's efforts, administratively and financially. At the institution where I chaired the IRB we had a major scandal, not unlike what occurred at Minnesota. It did serve as a wake-up call for the school. The President and the deans provided facilities and funds for an infrastructure that not only enhanced initial review but follow-up reviews and announced and unannounced audits of the studies.

This is a remarkable article. Those of us who have been medical practitioners know how rare it is and how risky for a reputable clinician to come forward, stating that scandalous behavior by physicians both persists and is minimized by a University administration. "Go along to get along" has been an expectation among physicians. Consider that there are students within the University of Minnesota Department of Psychiatry, residents fellows. Their training there may now raise some eyebrows, to be sure, but what about their attitudes and values, learned from the behavior of their mentors?

Wow, I bet the author is about as welcome as a case of hives around the Center for Bioethics these days. I adore people who can and will speak courageously and with little regard for their own security.

Several questions come to mind: Have there been, or will there be, any criminal charges filed against any of the "researchers," particularly in the case of the young man's death? And how will the University punish you, Dr. Elliott, for your unusual honesty? Never mind the ethics code; you have broken the code of silence.

I am ashamed of my specialty of psychiatry. All too often, our leaders prostitute themselves to Big Pharma. Even our diagnostic manual (the "DSM") is influenced by the pharmaceutical industry, which promotes the lie that psychiatric illnesses are purely "brain diseases," along with downplaying the important psychological dimensions of these illnesses.
Clinical Professor of Psychiatry, Georgetown University School of Medicine

I applaud the bravery of Dr. Elliot for writing this piece. Ethics in research is becoming a scarce commodity. Simultaneously, more and more professionals of every stripe are parroting the phrase "evidence-based," which is truly meaningless in the way it is being used. It will take more people like Dr. Elliot, willing to stand up and speak the truth, because we can no longer rely on self-regulation.

It is important is to find better ways to distinguish the risk level of different studies. I have submitted studies at my current and other R1 universities. IRBs vary, but I have found an extraordinary amount of scrutiny for voluntary survey research on healthy, non-incarcerated adults (e.g. low risk). Every line of a recruitment email is scrutinized and it can take months for a very simple study to be approved. If similar rigor is applied to high risk studies (e.g. where a substance is ingested, or medical procedure, or a high risk population), it is shocking to me that the studies described here were approved.

At the U, there have been other whistle-blowers, including a dear friend whose career was all but destroyed because she chose to speak up. While Carl Elliot's remarks are most welcome and so necessary, they are too long in coming.

Thank you very much Dr. Elliot. Some things seem never to change. More than 40 years ago I was placed in the U of M hospital after complaining about depression. As part of an experimental program, I was given a powerful anti-psychotic medication (though there were no signs of psychosis) with almost nothing in the way of explanation. Long story short, I was extremely lucky to have survived and did so only by leaving the facility against the will of the doctor conducting the study who threatened me with "commitment" for leaving the program against his wishes. It appears that someone has finally summoned the courage to stand up to the Department of Psychiatry at the University of Minnesota.

This article is a textbook example of the importance of tenure. Dr. Elliott has made a valuable contribution to cleaning up the mess of scientific research. No doubt he will pay a price for it, but if he has tenure, his job won't be at stake. And he is an example of the importance of professional ethics, and the need to teach every emerging professional about ethical professional behavior.

"A great grey mediocrity" it was call by Dean of the Institute of Technology Athelstan Spilhaus, The university has alway been a mess. I have little interest in going back there as an alum. There was much to be said for the quality of the staff and the overall experience, yet it was dumbed down by bureaucracy. Evidently not much has changed.

This is not a new problem for the department of psychiatry at Minnesota. Nearly 20 years ago as a graduate student, I reported several very serious instances of fraud and misconduct by a principal researcher, to the chair of the department. Despite the fact that I had concrete evidence (from a paper trail) all that every came of it was a severe lecture to me about the immorality of going behind said researcher's back. I was never allowed to conduct research at that department again. 

Congratulations to Dr. Elliott for his years of work in shining light on these abuses, and much more difficult, actually moving the institution to action. In the past few weeks the New England Journal of Medicine published a series of articles defending financial compensation of academic physicians by drug companies. The author asked for instances of harm stemming from such relationships. The U of Minn provides plenty, and I supplied more in a blog last week:

If you talk to doctors in the Twin Cities, you sense they believe the Minnesota medical school is in a state of decline.

Tenure protects Professor Elliott from reprisal from his institution. Another reason to reinforce that safeguard for critics. There are too few who feel safe enough to speak truth to money.

The morning I arrived for an academic urology job at the Minneapolis V.A. in the low '90's, the Chairman of Urology resigned under pressure from the student newspaper. They had found questionable accounting in the Dept. of Urology. At the same time, the Chairman of Surgery was under indictment by the FDA for selling a drug across interstate lines without FDA approval. He was acquitted. The board of trustees had approved the business plan and there was a resignation there. So, the problems at U. Minn. Dept. of Psychiatry are not new.

Aren't the University of Minnesota hospitals owned by a Corporation, Fairview Health Services? Does Fairview have a direct say in the acceptance and oversight of research studies? Do its attorneys determine how to respond to potential scandal? If yes, are Fairview attorney responses similar to that of similar non- profit Medical Centers?

The instances--especially the horrific death of Mr. Markingson--of failures in his department at the U of M are shocking to me because of the violations of trust between patients and researchers. His anger and strong language about the violations of the I.R.B.s and its "honor code" while apparently not new to others doing research are not able to rouse me to action since the control is totally within the research community and not sensitive to public pressure. If I agree to be a participant in any future studies, I will certainly ask more questions, but that seems to be all I can do.

The instances--especially the horrific death of Mr. Markingson--of failures in his department at the U of M are shocking to me because of the violations of trust between patients and researchers. His anger and strong language about the violations of the I.R.B.s and its "honor code" while apparently not new to others doing research are not able to rouse me to action since the control is totally within the research community and not sensitive to public pressure. If I agree to be a participant in any future studies, I will certainly ask more questions, but that seems to be all I can do.

Both for his book and this column, Dr. Elliot should be lauded most vigorously. His concerns are completely relevant to this situation in which Big Pharma will do most anything to get positive research-study outcomes for its new products. Starting with Vioxx, there are numerous examples of the failure of this model to account for the complexity of human physiology, where side-effects are the rule rather than the exception.

The author fails to cite the fact that the University of Minnesota was placed on the NIH "exceptional institutions" list in 1997 (not a good thing) for their failures to monitor Dr. John Najarian"s research and clinical trials on organ transplant drugs for immunosuppression. The University supposedly recruited a senior official to oversee clinical research. We can see how successful these efforts were.

as an alum of U of M, and someone who knows the byzantine waysmof university cultures, I would suggest that the only hope for change comes not from the top ranks who have denied, lied and hidden, but from the bottom up -- faculty, students, alumni and DONORS -- unified and individually demanding that the governing Boatd and the governor mandate change. Those who spent years hiding are not the ones who will now suddenly see the light and change their ways. U of M's destruction of its reputation affects all of us at the grass roots, and the taxpayers of Minnesota as well. The masses must speak.

For the Record: Carl Elliot in NYT: University of Minnesota’s Medical Research Mess

From the New York Times

MINNEAPOLIS — IF you want to see just how long an academic institution can tolerate a string of slow, festering research scandals, let me invite you to the University of Minnesota, where I teach medical ethics.

Over the past 25 years, our department of psychiatry has been party to the following disgraces: a felony conviction and a Food and Drug Administration research disqualification for a psychiatrist guilty of fraud in a drug study; the F.D.A. disqualification of another psychiatrist, for enrolling illiterate Hmong refugees in a drug study without their consent; the suspended license of yet another psychiatrist, who was charged with “reckless, if not willful, disregard” for dozens of patients; and, in 2004, the discovery, in a halfway house bathroom, of the near-decapitated corpse of Dan Markingson, a seriously mentally ill young man under an involuntary commitment order who committed suicide after enrolling, over the objections of his mother, in an industry-funded antipsychotic study run by members of the department.

And those, unfortunately, are just the highlights.

The problem extends well beyond the department of psychiatry and into the university administration. Rather than dealing forthrightly with these ethical breaches, university officials have seemed more interested in covering up wrongdoing with a variety of underhanded tactics. Reporting in The Star Tribune discovered, for example, that in the felony case, university officials hid an internal investigation of the fraud from federal investigators for nearly four years.

I hope that the situation at the University of Minnesota is exceptional. But I know that at least one underlying cause of our problems is not limited to us: namely, the antiquated bureaucratic apparatus of institutional review boards, or I.R.B.s, which are supposed to protect subjects of medical experimentation. Indeed, whether other institutions have seen the kinds of abuses that have emerged at the University of Minnesota is difficult to know, precisely because the current research oversight system is inadequate to detect them.

The current I.R.B. system of research protection arose in the 1970s. At the time, many reformers believed the main threat to research subjects came from overambitious government and university researchers who might be tempted to overlook the welfare of research subjects.

As a result, the scheme put in place for protecting subjects was not a formal regulatory system but essentially an honor code. Under the I.R.B. system, medical research studies are evaluated — on paper — by a panel of academic volunteers. I.R.B.s do not usually monitor research as it is taking place. They rarely see a research subject or even a researcher face to face. Instead, they simply trust researchers to tell the truth, report mishaps honestly and conduct their studies in the way that they claim to be conducting them.

These days, of course, medical research is not just a scholarly affair. It is also a global, multibillion-dollar business enterprise, powered by the pharmaceutical and medical-device industries. The ethical problem today is not merely that these corporations have plenty of money to grease the wheels of university research. It’s also that researchers themselves are often given powerful financial incentives to do unethical things: pressure vulnerable subjects to enroll in studies, fudge diagnoses to recruit otherwise ineligible subjects and keep subjects in studies even when they are doing poorly.

In what other potentially dangerous industry do we rely on an honor code to keep people safe? Imagine if inspectors never actually set foot in meatpacking plants or coal mines, but gave approvals based entirely on paperwork filled out by the owners.

With so much money at stake in drug research, research subjects need a full-blown regulatory system. I.R.B.s should be replaced with oversight bodies that are fully independent — both financially and institutionally — of the research they are overseeing. These bodies must have the staffing and the authority to monitor research on the ground. And they must have the power to punish researchers who break the rules and institutions that cover up wrongdoing.

Here at the University of Minnesota, we have reached a critical point. Two months ago, after two blistering external investigations, university officials finally agreed to suspend recruitment for psychiatric drug studies. Yet they still refuse to admit any serious wrongdoing.

An honor code is a fragile thing. All the parts have to be in place: pride in the integrity of an institution, vigilant self-policing, a collective sense of shame when the code is violated and a willingness to punish those who break it. At the University of Minnesota, we have very few of those things. And so without sustained, relentless pressure from the outside, I am afraid we are doomed to more of the same.

Carl Elliott, a professor at the Center for Bioethics at the University of Minnesota, is the author of “White Coat, Black Hat: Adventures on the Dark Side of Medicine.”

Sunday, May 17, 2015

For the Record: Former U of Minnesota Doc: What Did They Do To My U?

Former Minnesota Medical School cardiologist: What did they do to my U?

Under poor management, the school has turned into the equivalent of a junior-varsity team. Unfortunately, it produces the bulk of the state’s doctors.

From the Star-Tribune:

(Emphasis added.)

When I joined the faculty of the University of Minnesota Medical School as a junior cardiologist in 1986, it was vibrant and highly ranked nationally. Now it is ranked in the second tier of schools for research. Its main hospital, the University of Minnesota Medical Center, was then among the top in the country. Now it is ranked by U.S. News and World Report as third in the metro area, behind Abbott Northwestern in Minneapolis and Mercy Hospital in Coon Rapids.

How could this happen? And why hasn’t it been a subject of alarm for our Board of Regents or for university administration?

Over the last two decades, the Medical School has been rocked by successive ethical scandals. Poor financial management led the Board of Regents in 1996 to sell the university hospital to Fairview, a community hospital chain with an average reputation in health care. Since then, review after review has found a lackluster record of achievement; a loss of important faculty members, and inept, bloated administrative functions.

All of this prompted the dean of the University of Michigan Medical School (who is a University of Minnesota graduate) to tell the Michigan Daily about his once-great alma mater: “They have disassembled the whole enterprise … and they’ll never recover from it.”

When I recently talked to a few regents about how this could happen, I got a similar story. They did not feel capable of managing a health care enterprise, so they relied on the university administration to keep them informed and take care of business. That apparently did not happen. Few of them were informed about the fall in rankings. Most claimed to be surprised by each scandal.

In the Navy, they say, “When there is trouble on the deck, look to the bridge.” In this case, the bridge was asleep.

Why should this matter to Minnesota? After all, we have the Mayo Clinic. It could be Minnesota’s varsity health care organization, and the U could be a nice JV team.

The problem is that the U produces the vast majority of the doctors for this state. If you want a JV doctor in 10 years, then that is a good approach. If you want the best for our state, the U matters.

In addition, JV teams do not generate economic activity. The U Medical School is responsible for a great deal of the medical-device industry in Minnesota. We would not likely have a medical-device industry without the medical school that we created in the 1950s and ’60s. Imagine Minnesota without Medtronic and St. Jude Medical (not to mention more than 100 other businesses that sprang from the Medical School).

Gov. Mark Dayton recently got the message and created a blue-ribbon commission to study the problem. The commission’s decision was to throw money at the school. That is a good start, but it does not address the root cause of the problem. Compared with other public medical schools, the U med school has been relatively well-funded (not great, but in line).
The U med school, however, has lacked vision and leadership. Its goal is to be top decile in clinical care. What is that? Top 10 percent of all hospitals — one of the top 500? Wow.

As discussed by former Gov. Arne Carlson (“U can’t regain trust under its current leadership,” April 12), the administration is plagued by cronyism and conflicts of interest. There are legitimate questions about the transparency and truthfulness of its leaders. Poor leadership is how we got to where we are, not lack of money.
In addition to the leadership issues, there is an elephant in the room: Fairview. To its credit, Fairview restored the financial performance of the university hospital; the U accounts for half of the net margin of the entire Fairview chain. But Fairview has taken its toll. The hospital it manages, and the one where most of Minnesota’s doctors are trained and where research is done, has become a B-level facility. Fairview’s contribution of profits to the Medical School is meager compared with other university hospitals in the country.

There is no way to have a great medical school without a great hospital. Unless the Fairview problem is solved, we are destined to have a B-level medical school and a JV team.

After 27 years, I left my position at the U at the end of 2013 because, like the dean of the Michigan Medical School, I just did not see any hope that the U med school would turn around. I’m seeing a glimmer of hope with former Gov. Carlson’s commentary several weeks ago. The light shown on the lackluster administrative culture by the Dan Markingson case external review and legislative auditor’s report validate the problems. Gov. Dayton seems engaged. The regents may be waking up. Sunshine may be the best antiseptic.

Let’s hope that the Medical School responds with new, clean growth instead of withering in the light.

Robert F. Wilson is former chief of clinical cardiology at the University of Minnesota.

Tuesday, May 12, 2015

For the Record: Final IRB Investigation Into Fairview Concerns Regarding Psychiatry Research Studies at the University of Minnesota

For the Record: The University of Minnesota Regents Get Marching Orders: "See no evil, hear no evil, speak no evil." (#Markingson)

University of Minnesota Board of Regents

Get Marching Orders

The University of Minnesota Regents are told to keep quiet and  present a unified front with the president.

For whom does the president work?  Who is responsible for this order?

"If you are contacted about this case, please refrain from responding or otherwise weighing in. Regent Allen's letter is the only statement the Board has made on the Markingson Case and it is important that the Board Chair and President present a single unified voice on this topic." (see document below)

Monday, May 11, 2015

For the Record: Fear and Loathing at Fairview over U Psychiatry Research #Markingson

How does one "trust but verify" when there is
an admitted  culture of  "profound distrust?"

From MPR news:

Report: Deep distrust at Fairview over U psychiatry research

Alex Friedrich ·
An internal investigation at the University of Minnesota found that some Fairview Health Services personnel have a "profound" distrust of some U of M psychiatric researchers working there.

The report is the third this year to reveal dysfunctions in the university's psychiatry department. Critics suspect many of those problems were linked to the death of a mentally ill research subject during a drug trial in 2004.

The report, released late last week, adds context to findings in an external review from February that said the university's psychiatry department suffers from a "culture of fear" that hindered efforts to improve the protection of vulnerable research patients.

• Earlier: Legislative auditor blasts U over ethics, conflicts in drug trial patient's suicide

Although the internal report found no evidence that researchers had violated university policies regarding the protection of research subjects, it said some Fairview employees felt that policies ensuring proper consent and recruitment of patients were weak.

Conflicting attitudes about how to treat patients has created significant tension between Fairview and U of M personnel, the report said, and leaders of both organizations have done nothing to stop it.

"UMN and Fairview leadership appears insensitive to the cultural tensions and the causes of it," the report said. Management "appears to be exacerbating the tension by not understanding and/or addressing the issues at hand, real or perceived."

Epidemiology professor Michael Oakes, chairman of the panel that oversees research at the university, acknowledged the culture is dysfunctional, and that some people are afraid to speak out.

"There is clearly a cultural rift there — with distrust," he said. "It's not universal ... but it's there, and it makes people anxious."

Dr. Brooks Jackson, dean of the university's medical school, said he is "pleased" that the inquiry found no regulatory violations, but acknowledged that the culture must change.

Leaders of the university and Fairview "are both concerned," he said. "We are all working daily to come up with an action plan ... to address this issue."

Jackson said he is working on several measures to improve trust, including more education, a thorough assessment of the work climate and an oversight committee.

"When people work together on a project," he said, "that starts to break down the mistrust."

Oakes and a team of investigators were charged with looking into concerns over potentially serious or ongoing violations of on schizophrenia and bipolar disorder. The names of the studies and the researchers involved were redacted in the report.

The team interviewed more than 40 physicians, nurses, social workers and other employees of the University of Minnesota and Fairview. It found no violations, and concluded that patients "were not at undue risk."

But it said Fairview staff and some university researchers worried about a handful of their fellow researchers and some of their staff. They said they did not trust those colleagues to properly obtain the consent of patients, and that those colleagues "did not fully appreciate the vulnerable state of many patients."

The report said some researchers also did not consult enough with hospital caregivers, who the report said are in a good position to judge the ability of a patient or family member to give informed consent.

"Several interviewees expressed concern about the lack of transparency, consultation and scientific motivation for psychiatric studies run by some [researchers]," the report said.
Legislative Auditor Jim Nobles called the report "disturbing."

Fairview personnel "are the people who are there [in the hospital] day in and day out observing what's going on in the care of these vulnerable people. And they're expressing this kind of concern," he said.

Fairview spokesperson Jennifer Amundson said in a written statement, "A lack of trust in the workplace is unacceptable, and we are taking action based on the findings that were just released. Our plans will include specific actions to establish an environment of inclusion, shared values, trust, transparency and integrity for psychiatric clinical care and research."
In April, Nobles said the university had failed to adequately protect Dan Markingson, a patient enrolled in a psychiatric drug trial, and that U of M leaders had ignored "serious ethical issues" in the case. It found real and potential conflicts of interest in the case, and said Markingson enrolled in the trial under potentially coercive conditions.

• Related: U's handling of drug study suicide earns an 'F' among peers

University leaders are expected to roll out a plan by May 15 to carry out dozens of reforms suggested in February's external review, which was conducted by the Association for the Accreditation of Human Research Protection Programs.

For the Record: U. of Minnesota Acknowledges Errors in a Second Psychiatric-Research Case

From the Chronicle of Higher Education:


The University of Minnesota has issued a written apology to a man who said he had been coerced into a joining a psychiatric-drug trial, the Star-Tribune reports.
Robert Huber, now 44, was admitted to the university’s medical center in 2007 with symptoms of schizophrenia; while confined there, he said, he was pushed to enroll in a safety test of the drug bifeprunox. Mr. Huber said he had participated in the study because he felt he would not be permitted to leave the hospital otherwise.
The patient’s accusation led the university to commission a yearlong review of the case. The review concluded that Mr. Huber had not been coerced, but that he had been prepared for the study prematurely and had been denied access to information about the safety of the drug.
The case has reignited concerns about the university’s troubled psychiatric department. In 2004 another patient, Dan Markingson, committed suicide while enrolled in a drug trial at the medical center. The university defended Mr. Markingson’s care, but since then, scathing reviews of its research using human subjects prompted the chairman of the psychiatry department to resign.
In the cases of both Mr. Huber and Mr. Markingson, one associate professor in the psychiatry department, Stephen Olson, was accused of coercive recruiting.

Friday, May 8, 2015

For the Record: My three minutes at the Regent's Public Forum #Markingson

Presentation to the Board of Regents, May 7, 2015

Members of the Board of Regents:

I am a retired medical school faculty member, Bill Gleason. Since 2009, I have made about 100 blog posts on the Markingson tragedy.

From the call for this meeting:

The public forum is an opportunity to provide input to the Board. The Board will not engage in a discussion or a question/answer session.”

Such opportunities are sadly rare. Apparently this is a way for the public to vent, the Regents nominally having done their duty to obtain public input. We are at this meeting today because previously you have NOT paid attention to the community in the Markingson scandal. You have ignored them. Many times. Your lack of action is very disappointing to me as an alumnus. Perhaps you have depended too much on the advice of the stonewalling General Counsel's Office?

For example:

In 2010 you dismissed the request of eight U of M bioethicists who asked for an outside review of the Markingson tragedy. As I wrote five years ago in MinnPost:

I am deeply disappointed in this head in the sand behavior. It is not going to do our reputation any good. Major changes are needed in the Department of Psychiatry - and elsewhere in the med school - to restore our good name.

A tiny fraction of people are involved in this unethical behavior. The great majority of U of M docs are wonderful people - it is sad to see them pilloried for the gutless behavior of a few, and now the Regents.”

Another example shows how out of touch the Regents appear to be:

Former Gov Carlson wrote a letter to the legislature and noted that he had brought his concerns about research misconduct to the Board Chairman:

"Beeson’s response was that it 'has not risen to the level of our concern.' When pressed on the negative publicity, he could only offer that 'it has not hurt our brand.'”

To the contrary, our brand has obviously been badly hurt.

These examples cause me to ask:

Is no one on the Board of Regents going to take any responsibility for this situation?

Is anyone going to apologize for multiple mistakes and say that they are sorry?

Finally, I point out something obvious. You don't put the fox in charge of the hen house. People responsible for the Markingson fiasco are now being put in charge of fixing it. And we are being asked to trust them? This situation is ethically the same as putting Dr Furcht on the panel to draw up conflict of interest rules. This was done at our university.

And how did that work out?

Three minutes is not much time. I guess that is the point.

Thursday, May 7, 2015

For the Record: "Power concedes nothing without a demand" #Markingson

From Carl Elliott's blog, Fear and Loathing in Bioethics

Wednesday, May 6, 2015

Power concedes nothing without a demand

One year ago, I stood with a committed crowd of activists at a vigil for Dan Markingson on the tenth anniversary of his death. Shortly afterwards, we interrupted a meeting of the Board of Regents and presented funeral flowers to President Eric Kaler and Board Chair Richard Beeson.

Tomorrow the Board of Regents will sponsor a forum on human subjects research. I will be there, and I hope many others will be there as well. Below are the comments I made at the vigil last year.

I grew up in the 1960s and 70s in the South. If you look back at the research scandals of that time, there’s a common thread that unites all of them. And that common thread is exploitation. With the Tuskegee syphilis studies, it was exploitation of poor black men in Alabama. With Willowbrook, it was disabled children. With Holmesburg, it was prisoners. In every case, what you had was people with power taking advantage of people with no power. It’s a simple formula. That’s what exploitation is all about. Using the powerless for your own purposes.

There are a lot of ways to exploit a person with a mental illness. You can lock them up. You can medicate them against their will. You can threaten them with involuntary commitment. You can tell them that the way to avoid all this trouble is to sign up for your research study. That’s what happened to Dan Markingson. A psychotic young man who thought demons were torturing him was signed up for a drug industry study over the explicit objections of his mother. And that study killed him.

To the University of Minnesota, Dan was not a patient. He was a commodity. To be exact: he was a commodity valued at $15, 637, payable from AstraZeneca.

You might say: look, this death was a mistake. Sometimes doctors make mistakes. I don’t think that’s what happened here. And what is indisputably not a mistake is the way that Mary Weiss has been bullied and intimidated by University of Minnesota attorneys during the ten years since her son died. What kind of university would file a legal action against a mother whose son had killed himself in a university drug study? What kind of university would demand $57,000 from a mother whose son had been victimized by its own researchers? I’ll tell you what kind of university: ours. This is what has been done by the attorneys in this building, in our name. And it’s a disgrace.

Back in the early 90s, I worked in South Africa. I worked at a medical school in Durban for African and Indian medical students. And if you lived in South Africa back then you knew that the government was ruthless and repressive. But on the surface, it looked like a democratic society. It had courts; it had laws; it had elections. Of course, it was just an elaborate stage set. If you weren’t white, you didn’t stand a chance, because the entire system was designed to keep the boot on your neck. And yet somehow, the apartheid government needed to pretend that it was a functioning democracy. The props and the costumes had to look real.

That's what this university feels like to me. On the outside, it looks like a functioning university. We have all the offices and committees and procedures that you’d expect a university to have. These things are supposed to be protecting patients. But it’s just a façade. Instead, they exist to protect the university. You ask for records; they say, “We lost those records.” You say, “There’s ethical abuse here;” they say, “We’re not the ethics police.” You file a complaint; they turn around and file a complaint against you. I’ve been trying to get research death and injury records from the General Counsel’s office for nearly seven months now, and they have still not budged. You want to know how research oversight at this university works? This is how it works. When the nearly decapitated corpse of Dan Markingson was found in a bloody bathroom in the middle of the night ten years ago, this university didn’t even think it was worth investigating.

In the documentary Eyes on the Prize, there’s an interview with Reverend Fred Shuttlesworth about the civil rights movement in Alabama. Shuttlesworth said, We thought we could just shame America. We thought we could just say, look at all your broken promises and the way that you’re treating black folks, and say, you ought to be ashamed of yourself. But that strategy doesn’t work, he said. You can’t shame segregationists. Rattlesnakes don't commit suicide. Ball teams don't strike themselves out. You gotta put 'em out.

And when I heard that, I said, Amen. But the fact is, you can shame segregationists. Believe me, I’m a white guy from South Carolina. I know. And we can shame the people sitting in that board room upstairs. They don’t want to know we’re here. They don’t want to know about Dan Markingson. They don’t want to know whether there have been other Dan Markingsons. They don’t want to know whether there are others who have been coerced and threatened and who have died. What we have to do it make sure that they can’t keep looking away. Separately, we can’t do that. But together, we can.

Posted by Carl at 10:16 AM

For the record: Public Grills Health Officials Over Research Practices #Markingson

Mike Howard, a friend of Dan Markingson's mother, holds the ashes of Markingson, who committed suicide in 2004 while enrolled in a University antipsychotic drug trial. Howard was addressing University Medical School administrators at a meeting on May 4, 2015, at the Mayo Memorial Auditorium.

From the Minnesota Daily:

Public grills health officials over research practices

U leaders were criticized for how they have protected human research subjects.


    Charlie Bartlett 
May 05, 2015

About 100 faculty members, students and local residents gathered to share their concerns about the University of Minnesota’s human subject protection program.

In the wake of two external reports earlier this year that heavily scrutinized the University’s human subject research programs, Vice President for Health Sciences and Medical School Dean Brooks Jackson and the Academic Health Center hosted a town hall public forum at the Mayo Building to discuss the program.

Several audience members feverishly demanded accountability from Brooks and other University leaders.

Decade-long criticism of how the University handled the death of Dan Markingson, who killed himself in 2004 while enrolled in a University antipsychotic drug trial, sparked recent investigation into the program.

A March report released by the Office of the Legislative Auditor criticized the University’s response to his death. Following this report and a University-hired external review managed by the Association for the Accreditation of Human Research Protection Programs — which found ethical flaws in the program — the University halted enrollment in psychiatric drug trials until an independent review board lifts the suspension.

Department of Psychiatry head Charles Schulz also stepped down from his position last month amid the controversy. Schulz was head of the department at the time of Markingson’s death.

Jackson opened meeting by addressing the criticism directed toward University leaders and discussing the steps they are taking to reform the program.

“I don’t think there was a cover-up,” he said at the forum. “But what we failed to do was listen to the critics.”

Jackson told the forum that an implementation team — which includes himself, Vice President for Research Brian Herman, professors and health professionals — charged with making recommendations for the program will deliver a proposal to University leaders by May 15. 

Some of the recommendations will include timelier program reviews, ramped-up ethics training and the establishment of a culture of trust surrounding human subject protection, he said.

Jackson, along with Herman, opened the floor for comments and questions. Some of those in attendance expressed passionate opinions, including some harsh criticism for the leaders and disappointment in how criticism has been handled.

Associate bioethics professor and longtime critic Leigh Turner questioned why the leaders under fire are part of the implementation team making recommendations to reform the program.

He said those leaders need to accept blame and allow an outside body to take charge of making recommendations. Herman urged Turner to read the implementation team’s proposal before questioning its decisions.

Mike Howard, a friend of Markingson’s mother, Mary Weiss, told the forum he wants to hold Jackson and the other leaders accountable for the University’s response to Markingson’s death and the concerns outlined in the reports.

Howard said he and Weiss both hope that from now on the University leaders change their practices, both in the research itself and in responding to controversial situations like Markingson’s.

“There’s no more litigation,” Howard told the leaders. “Just get the truth out.”