Saturday, April 18, 2015

For the Record: A Drug Trial’s Frayed Promise (#markingson Seroquel)

From the New York Times:

Last fall, an article in the American Journal of Psychiatry caught the attention of specialists who treat borderline personality disorder, an intractable condition for which no approved drug treatment exists.

The article seemed to offer a glimmer of hope: The antipsychotic drug Seroquel XR reduced some of the disorder’s worst symptoms in a significant number of patients. “It was an exciting development,” recalled Mark F. Lenzenweger, a professor at Binghamton University and Weill Cornell Medical College and an expert in borderline personality disorder.

In the realm of clinical trials, however, reality is sometimes far messier than the tidy summaries in medical journals. A closer look at the Seroquel XR study shows just how complicated things can get when a clinical trial involves psychiatric disorders and has its roots in intersecting and sometimes competing interests: a drug company looking to hold onto sales of a best-selling drug, a prominent academic with strong ties to the pharmaceutical industry and a university under fire for failing to protect human study subjects.

The trial was paid for by AstraZeneca, the maker of Seroquel XR, and was conducted by Dr. S. Charles Schulz, the head of psychiatry at theUniversity of Minnesota. Two of the study participants were living in a residential treatment facility for sex offenders and may have lied about their diagnosis to qualify for the trial. One of those men slipped the drugs to unwitting treatment center residents and staff, an alarming development that nevertheless did not seem to ruffle the university oversight board that is charged with looking into such episodes.

The University of Minnesota’s clinical trial practices are now under intense scrutiny. In February, a panel of outside experts excoriated the university for failing to properly oversee clinical trials and for paying inadequate attention to the protection of vulnerable subjects. The review, commissioned by the university after years of criticism of its research practices, singled out Dr. Schulz and his department of psychiatry, describing “a culture of fear” that pervaded the department.

In March, after another critical report by Minnesota’s legislative auditor, the university announced that it would halt all drug trials being conducted by the psychiatry department until outside experts could review them. And this month, the university announced that Dr. Schulz would step down as head of the psychiatry department. The dean of the medical school, Dr. Brooks Jackson, said in a statement to reporters that Dr. Schulz’s decision “was completely his own” and that he would “remain a valued member of our faculty.”

“Medical research involving drugs like this — involving potentially vulnerable human subjects — shouldn’t be done sloppily,” said Dr. Michael Carome, director of the health research group at Public Citizen, a consumer advocacy organization. “Because when we do things sloppily, we do things where people could potentially be harmed.”

Spiked Oatmeal

One morning in May 2010, residents and staff members at Alpha Human Services, a residential treatment facility for sex offenders in Minneapolis, sat down to breakfast and noticed something strange about their oatmeal. It was pink.

Later in the day, several people reported feeling unusually tired. One employee approached the director, Gerald T. Kaplan. “There’s something going on here,” he recalled being told. “I’m a morning person, and I can’t keep my eyes open.”

After some digging, Mr. Kaplan discovered that the facility’s cook, a resident, had crushed up a large quantity of Seroquel, which hassedative effects, and mixed the pink pills into the morning oatmeal.

The director’s alarm deepened when he learned that the man, as well as another resident, had secretly enrolled in a clinical trial at the University of Minnesota. Their motivation, Mr. Kaplan said, was most likely financial: The trial promised participants up to $300 for completing the study.

Participating in a drug trial was prohibited by the rules of Alpha, which is licensed by Minnesota’s Corrections Department. Most of the people living there were fulfilling the terms of parole or probation. Prescription drug use is closely monitored, and residents are not permitted to take unapproved medications.

But even more concerning, Mr. Kaplan said, was that the men did not have a diagnosis of borderline personality disorder. Somehow, he said, they were able to bluff their way into the study.

At that point in the trial — over a year after enrollment had begun — the researchers were well behind in their recruitment goals.

Borderline personality disorder, which is estimated to affect 1 percent to 2 percent of Americans, is characterized by extreme mood swings,impulsivity and fears of abandonment. Studies have shown that the most successful treatments are specialized forms of talk therapy, but finding practitioners who are trained in these methods can be difficult. Many doctors prescribe antipsychotics and antidepressants to help with some symptoms.

Studies have examined the use of antipsychotics, including Seroquel, in patients with the disorder, but they have been small and did not measure patient progress compared with a placebo, which is considered the gold standard for clinical trials.

Dr. Schulz said he had hoped that a larger, placebo-based trial — involving about 100 patients followed over eight weeks at three study sites — would help clarify whether antipsychotics such as Seroquel could help people with the disorder, and he proposed the trial to AstraZeneca.

He already knew the company. He had served on one of AstraZeneca’s scientific advisory boards, and from 2002 to 2007 he received more than $112,000 from AstraZeneca in speaking and consulting fees and other payments, according to records collected by the Minnesota Board of Pharmacy. Dr. Schulz said that the relationship did not affect his objectivity and that, in any case, he ended his financial ties to the company after the borderline personality disorder trial got underway.

The trial was expected to take about two years, but soon after enrollment began, one of the three clinical sites, McLean Hospital in Massachusetts, essentially dropped out, citing lack of interest from patients. That left the University of Minnesota and the University of Iowa, the other site, to find more study subjects.

In April 2010, one month before the resident spiked the oatmeal at Alpha, a report from the study’s safety officer noted that enrollment was “less than half of what it is expected to be” and that it was now expected to take five years instead of two.

Dr. Schulz said that AstraZeneca was disappointed to learn of the delay. Seroquel was a top seller for the company, bringing in billions of dollars a year. But by the time Dr. Schulz proposed the borderline disorder study in 2007, the company knew that Seroquel’s blockbuster days were limited: It stood to lose its patent protection in 2012. When that happened, a flood of cheap generic alternatives would cause sales to plummet. Seroquel XR, the extended-release version and the subject of Dr. Schulz’s study, would keep its patent protection until 2017, but with generic competition for the standard version, sales were unlikely to be robust.

“I know that they wanted things to be done quicker,” he said, “but they said we could keep our grant and finish the study.”

Questions Raised

The man who drugged his fellow Alpha residents was sent back to prison, and Mr. Kaplan called the university to let them know what had happened.

“They were mortified,” he recalled, and the men were removed from the study. But no one ever followed up with a more detailed investigation, he said.

A university spokesman said in a statement that the institutional review board, which is charged with overseeing all medical studies, did not investigate because the men had already been terminated, and it was not clear the investigators could have done anything to prevent it.

But while some outside ethics experts acknowledged that the story appeared to be a bizarre fluke, they also noted that the episode revealed evidence of lax reporting practices.

The man who drugged the oatmeal, for example, had failed to return his pill bottle at his previous clinic visit, which was necessary so investigators could see if doses were missed. The claim that the two men may have faked their way into the trial should have also raised eyebrows, some said, as well their being under court supervision.

Under guidelines governing federally funded clinical trials, the men would have been considered prisoners and their participation given special scrutiny, several outside ethics experts said. Although the trial was not federally funded, many universities follow similar rules for research involving human subjects. (The university asserts the men were not prisoners.)

Other concerns about the study were raised even before the oatmeal drugging. The study’s safety officer, Dr. Scott Crow, noted in a memo that not a single patient had failed the screening process for enrollment in the study, even though outside experts said it was unlikely that everyone who applied would meet the criteria. Dr. Schulz said the failures were not recorded because the patients were formally screened only after undergoing an initial telephone interview that eliminated unlikely candidates.

“What a sloppy trial,” said Nancy Dubler, a bioethicist who served for years on the Institutional Review Board, or I.R.B., at Montefiore Medical Center in the Bronx. She is an expert on the inclusion of prisoners in clinical trials and said closer attention should have been paid to the events at Alpha. Dr. Schulz said he was disturbed and upset about what had happened at Alpha, but he remained convinced the men had the disorder but had not previously been diagnosed. “We felt we had been screening the people very well,” he said, “but we were also aware that these are patients that do have a lot of impulsive, aggressive behavior.”

After the episode, he said, he reviewed the study protocol with the trial’s project coordinator. They decided not to make changes, but to be more careful about whom they enrolled.

Others said that the event was troubling, given the recent scrutiny of research practices at the university.

“If I’m on an I.R.B. and I see problematic studies and public controversy coming up again and again,” said Carl Elliott, a bioethicist at the University of Minnesota, “I’m going to look carefully at those studies. And yet our I.R.B. seems to do the opposite.”

Mr. Elliott obtained documents relating to Dr. Schulz’s borderline personality disorder trial through a public-records request and made them available to a reporter. In January, he filed a complaint with the Food and Drug Administration about the university’s research practices in the trial.

Mr. Elliott has spent years calling on the university to overhaul the way it conducts research on patients. His activism began after the death of Dan Markingson, a psychiatric patient who committed suicide in 2004 while he was a participant in a clinical trial of Seroquel. Last year, the university commissioned an external review of its research practices, and the report that came out in February was unsparing, taking the university to task for paying inadequate attention to securing the consent of vulnerable patients.

The experts had harsh criticism for the department of psychiatry, as well as for Dr. Schulz and another researcher, whom it described as “two investigators whom faculty and staff do not trust and who fail to communicate a set of priorities that align their own research agenda with the best interests of patients and patient care.”

The outside committee recommended that Dr. Schulz and the other investigator “receive supervision, coaching in leadership, and advanced training in human subjects protections.”

Dr. Schulz’s name was not on the public copy of the report, but an unredacted version was provided to The New York Times by a member of the external review committee.

In an interview, Dr. Schulz painted much of the criticism as stemming from years of campaigning by Mr. Elliott. He said that under his leadership, the department was thriving.

When the university announced that Dr. Schulz was leaving his post as head of psychiatry after 16 years, it said he would continue to serve as the executive medical director, which “will allow him to focus his time more exclusively on patient care.”

“ I felt it was time for me to step down in order for the medical school to make a recruitment for a new chair,” Dr. Schulz said, “so the department can continue its excellence.”

Still No Treatment

In March 2013, four years after recruiting the first patient, the investigators closed the trial after enrolling almost 100 patients. A statistically significant number of participants who took a lower dose of the drug, the researchers concluded, saw their symptoms improve over eight weeks.

But even as some said the study offered a new treatment option, others questioned spending so much on a trial that was unlikely to lead to major improvements in the way the condition was treated.

Dr. Lenzenweger, the borderline personality disorder expert who cautiously praised the trial, also noted that the short time period limited its applicability. “This trial only lasted eight weeks, and personality disorders last for years,” he said.

And even during that short period, about one-third of the participants — many citing the sedating effects of the Seroquel — dropped out.

“There is something phony — wrong — about doing a study that can only run for eight to 12 weeks in what’s basically a long-term condition, and where the side effects of the drug are really the big issue,” said Dr. Ross McKinney, director of the Trent Center for Bioethics at Duke University. “Unless you have an immediate plan to take it into something long term, I’m skeptical that it’s of any value at all.”

But Dr. Donald W. Black, the investigator at the Iowa site, said short-term trials were the norm for testing drugs for psychiatric conditions.

“Ideally, these studies would last six months, one year, two years or longer, but who’s going to do it, who’s going to pay for it, and what patient is going to stay in a study that long?” he said.

The study of Seroquel XR was valuable, he said, because even with about 100 patients, it was larger than the previous trials.

“Bottom line,” he said, the drug “seems to work in borderline patients, who improve in many different ways.”

People with borderline personality disorders, meanwhile, do not appear to be any closer to getting an approved treatment for their condition. After five years and the $700,000 that AstraZeneca paid for the trial, it seems the company has no plans to market Seroquel XR for use in borderline personality patients.

Michele Meixell, a spokeswoman for the company, said that while trials like this one were once approved “in areas where the company may have had a therapeutic interest,” she added, “we do not currently have a further interest in borderline personality disorder.”

Jack Begg and Christina Capecchi contributed reporting.

A version of this article appears in print on April 19, 2015, on page BU1 of the New York edition with the headline: A Drug Trial’s Frayed Promise.

Wednesday, April 15, 2015

For the Record: Former Governor Arne Carlson: Markingson case: University of Minnesota can't regain trust under current leadership

Arne Carlson’s portrait ultimately finds a great deal of acclaim. As far as the best, Heywood says, “the honor has to go to Arne Carlson, who loved Minnesota (and the U of M in particular) that he made his portrait twice the size of anybody else’s, and lavished attention on every last detail. The picture gives over a full quarter of the frame to the old stone of the U, with Uncle Arne leaning casually, sporting his favorite U of M jacket. 
Butterflies frolic symbolically on the stone, while a yellow bird hovers behind amongst the ornamental trees. The flat paint and 'artless' composition is instantly recognizable as derivative of the (derivative themselves) Brotherhood of Ruralists, known to a generation of British schoolchildren as the illustrators of the front covers of the Arden Shakespeare.” 
Swiszcz, too, is touched by the scale and attention to detail: “I am glad I went to see this in person, or I would never have known this painting is roughly three times as large as all the others. 
Oh – guess what? Arne really loves the U! You can almost feel the little tufted surface on the “M” of his letter jacket. In case there is any doubt, the painting's frame has little maroon "M"s in each corner.    MinnPost

Arne Carlson - Governor's Portrait

“The University constructed a defense to deny liability by claiming immunity. I think that defense evolved or you might say devolved into a strategy to simply avoid any accountability or responsibility and to deny that there were any serious ethical issues. And we found that serious ethical issues and conflicts of interest just permeated this case.”
James Nobles, legislative auditor, March 20, 2015
link to original in Star-Tribune

The University of Minnesota, like many other universities, has a sizable clinical research program that tests experimental drugs for safety and efficacy. The understanding between the companies that develop these drugs and the consuming public is that such drugs are carefully tested on humans and that these clinical trials must comply with strict ethical, scientific and regulatory standards. These research protections were developed after a series of research scandals that involved abusive treatment of vulnerable populations such as economically disadvantaged communities, prisoners, children, and individuals suffering from mental illness.
Ever since the violent suicide of Dan Markingson in 2004, the administration of the University of Minnesota has received repeated calls for the release of more details about the care and protection afforded the victim. These calls have come from faculty members at the university, from local community members and from researchers from around the world. But instead of being transparent and forthright, the administration created a standard response similar to that expressed by the university’s former general counsel, Mark Rotenberg: “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 any of our faculty.”
If correct, that would be a most understandable and appropriate response. However, it falls far short of the truth. Consider this:
• State attorney general’s office: Never conducted any such investigation.
• Hennepin County District Court: In a lawsuit brought by Mary Weiss, the mother of Dan Markingson, the judge ruled that the university’s Institutional Review Board (IRB) was “statutorily immune from liability.” But immunity is a far cry from exoneration. As Matt Lamkin, an alumnus of the University of Minnesota’s graduate program in bioethics and a current member of the faculty at the University of Tulsa Law School, has noted: “to suggest that the University of Minnesota was exonerated in this lawsuit is like a diplomat who got drunk and ran over a child claiming he was ‘exonerated’ by diplomatic immunity.”
• The University of Minnesota Institutional Review Board: Richard Bianco, the university official responsible for overseeing research subject protection, stated under oath in his deposition that the university had not done any investigation into Markingson’s death.
• The Minnesota Board of Medical Practice: The legislative auditor’s report released last month describes the board’s review of Markingson’s death as “compromised” because the “independent investigator” the board hired had “numerous conflicts of interest.” (Dr. David Adson, a colleague of the psychiatrist under investigation, also received more than $585,000 from the drug industry and more than $145,000 from AstraZeneca, whose drug was being tested in the study in which Markingson committed suicide.)
• The U.S. Food and Drug AdministrationThe FDA did review the case, and its report is public. Critics have taken exception to the narrowness of scope in that the report failed to examine the conflicts of interest, enrollee mistreatment, the unresponsiveness of Markingson’s doctors to his mother’s concerns and the civil-commitment order used to pressure Markingson into enrolling in the study.
Despite the obvious falseness of the claim of numerous and exhaustive investigations, the university president, Board of Regents and various administration officials all have used this cover as a hammer against those who dissented and called for an independent investigation.
Unfortunately, this weapon worked all too well. Time and again, news stories covering the Markingson case contained a paragraph citing these numerous and thorough investigations and a finding of no fault. What was missing was an effort to fact-check that claim.
No one wants to believe any administration of higher education would engage in conduct not representative of the highest standards of truthfulness. As a society, we view politicians with a certain skepticism, but tend to have the opposite view when it comes to religious leaders, judges and educators.
But the reality is that any management system can deny wrongdoing and block calls for an independent investigation. When Eric Kaler took the reins as president of the university in 2011, he had already been sent material by Dr. Carl Elliott, a critic of the university’s handling of the Markingson case and faculty member at the Center for Bioethics. In his 2010 article for Mother Jones magazine, Elliott wrote about the issues of poor standards, conflicts of interest involving an all-too-cozy relationship with drug companies, the lack of independent oversight and the way the threat of involuntary commitment was used to coerce Markingson into the drug study.
During his first year at the university, Kaler had to make a major decision. Prudent management would have involved meeting with Elliott, learning about the specific ethical issues related to Markingson and broader concerns about psychiatric clinical research, and dealing with the growing scandal. But Kaler chose instead to perpetuate the prevailing coverup. He opposed any independent review, never responded to the charges made in the media, ignored or dismissed critics, and stood firm in his belief that it would all blow over.
In so doing, President Kaler tarnished his office and abandoned the principles of truthfulness, openness and integrity. He also frittered away the moral authority that is so essential to governance. His failure to provide ethical leadership permitted the scandal to grow. The result was more stonewalling of requests for information from faculty and media and increased attempts by administration officials to demonize critics, including referring to some scientists as “wackos.”
Perhaps most troubling is the culture of intimidation associated with the Department of Psychiatry. The university’s own external review refers to this culture as a “climate of fear.” Extending from that department to the university’s senior management team, the apparent goal was to make certain no one questioned authority.
On June 16, 2014, I met with Kaler and Board of Regents Chairman Richard Beeson, and went over all the materials covering conflicts of interest, the falseness of their claims of endless investigations, as well as the damage being done by news articles highly critical of the university’s handling of the Markingson scandal. Kaler was quiet and rarely asked a question. As a result, I focused more attention on the lack of oversight and leadership provided by the Board of Regents and its failure to examine the circumstances of Markingson’s death. Given the deeply troubled history of research in the Department of Psychiatry over the past 25 years, a history that includes six suicide deaths, untold injuries, the conviction and imprisonment of one professor, the barring of two researchers by the FDA, and a barrage of poor publicity, I was stunned by Beeson’s response that this matter “has not risen to the level of our concern.”
Last week, the university announced that Charles Schulz has decided to resign as chairman of the Department of Psychiatry. He will retain his position as executive medical director, and his faculty appointment. The news release announcing his departure made no mention of the department’s troubled record, or the research controversies in which Schulz has been personally involved. Rather than removing him as department chairman and taking additional disciplinary action, the university has provided Schulz with a soft landing.
The very administrators and regents responsible for the current debacle now promote themselves as trustworthy agents of change. We will not see meaningful reform of research on human subjects, nor the restoration of prestige at the university, so long as Kaler, Beeson and other leaders responsible for years of denials and stonewalling remain in charge.

Arne H. Carlson was governor of Minnesota from 1991-1999.

Some comments from the Star-Tribune web site
It's and shame more people aren't commenting. James and Arne are both straight shooters. Anyone doubting Arnes devotion and love of the U only need look at his picture in the Capitol. Arne bleeds maroon and gold. I'm sure like a lot of Minnesotans you hope and expect excellence, and it's difficult to criticize. But it's time for a Regime change. It starts with the Board of Regents. The Board needs a reset with members who want to roll up their sleeves and define their proper role, appoint a new President who they will hold accountable. Anything less will not do. From 1200 miles away I can see its bloated and accountable to no one.

Gov. Carson comments are on point. I applaud his efforts to hold the U accountable.
I have a U professional degree and worked there in many capacities, including as adjunct prof.
There is little or no U accountability, the Regent promulgated Code of Conduct is essentially meaningless and not at all enforced. (Yet the U and Kaler 'go after' students if they violate their 'Code.')
Regent Vice Chair Dean Johnson should be aware that the U's Office of General Counsel (OGC) and the Office of Institutional Compliance (OIC) blatantly disregard or ignore statute provisions passed during his long legislative tenure.
Regents provide inadequate oversight and the OCG ad OIC hold inordinate sway and essentially have insufficient professional ethics to hold their important U positions.
It is truly a shameful situation at U and unfortunately there is insufficient leadership at U to address situation.
I have little faith in Dayton, or MN House/Senate to adequately address U problems,

 It's not the crime, it's the cover up. No one forced Kaler to repeatedly lie in public about this and no one else needs to smear him. He's done a bang up job of that himself.

We all understand that nobody wants to own this.  In particular we've seen a complete abdication of responsibility by the Board of Regents.  The University of Minnesota has constitutionally guaranteed autonomy, the degree of which is unique among the educational institutions of this state. Our constitution thus levies a high burden of responsibility on the Regents, especially in cases like this which strike at the heart of the integrity of the University.  Unfortunately the Board of Regents appears to have become a safe haven for politically connected nonentities who haven't the slightest interest in exercising the level of authority granted to them.  It's a shame and an embarrassment to Minnesota that this case has dragged on for over a decade while the Regents have been content to allow it to fester and grow in toxicity.  That this had to be taken up by the State Auditor (with a great deal of prodding by outsiders like former Governor Carlson, and many others) represents a management disaster of the first order.  I don't believe the Regents are easy to remove.  However, they all should resign immediately to make way for competent oversight of the management of our University.  At last they could finally make an important contribution to the University's future.

The entire PR and legal counsel offices should be immediately dissolved. I know more about how to handle a situation like this from watching the TV show, Scandal, than they do. You'd think that over the past several years someone would have taken Kaler aside and said, "This looks really, really bad for the University." Instead, they kept insisting that the U was beyond reproach. This all points to an incredible level of political naivete and hubris exceeding even that shown during the Najarian debacle. Clean house and scrub the floors till there's not smell left.

I would think that at some point the University, and especially President Kaler, would get tired of seeing themselves as the lead story on Fox 9 news every night.  Nothing against Fox news, they've done an admiral job of covering this debacle at the U, but it just seems that either the U is that ignorant to think that this scandal is not going away anytime soon, or it's just that they are so arrogant that they think they can't or won't be held accountable.  My money is on Arne and his army.

Unfortunately, University of Minnesota administrations have listened more closely to the U's attorneys than to its ethicists.

Thank you, Governor Carlson, for this very important op-ed. Kaler and his very highly-paid administrators and staff need to be held accountable. The time for spin and PR gimmicks is over.

A sad spectacle of abuse of power, willful neglect, and intentional abdication of responsibilities

Tuesday, April 7, 2015

"Where is there dignity unless there is honesty?" (Markingson Case)

A Restoration of Trust?

Richard Beeson, the chair of the Board of Regents, claims that reports of clinical research misconduct at the U of M "had not risen to the level of our concern." He made this assertion during a meeting with former Governor Arne Carlson earlier this year. (President Kaler was also present at the meeting and did not dispute Beeson's claim). See p. 8 of the Open Letter of Governor Carlson.

But a February 7, 2011 letter of Clyde Allen, then chair of the Board of Regents, refers to "broader concerns you raise related to protection of subjects involved in clinical research." The letter is a response to Carl Elliott and other professors in the Center for Bioethics. See the link to the letter in section (1) of The Buck Stops? Beeson was a member of the Board of Regents at that time.

How can the administration restore trust when the chair of the Board of Regents makes statements that are contradicted by the record ?

Or as one ancient statesman and orator asked: "Ubi est autem dignitas nisi ubi veritas?" ("Where is there dignity unless there is honesty?") Cicero, Letters to Atticus.

Michael W. McNabb

University of Minnesota B.A. 1971; J.D. 1974
University of Minnesota Alumni Assocation life member

Tuesday, March 31, 2015

For The Record: Don't let foxes guard the henhouse

U of M human subjects reform: Don't let foxes guard the henhouse

By Teri L. Caraway, David Pellow, Naomi Scheman and Karen-Sue Taussig 

The Board of Regents’ record on oversight does not inspire confidence.
The University of Minnesota has recently received two external reviews of its practices concerning the protection of human subjects participating in medical research. The resulting reports identified many substantive problems both in how the university conducts and oversees human subjects research and in how administrators have responded (or more often failed to respond) to concerns about ethical breaches in medical research.  In response to these scathing reports President Eric Kaler has submitted and on Friday the Board of Regents passed a resolution that outlines “decisive action” to address these problems. 
The proposed actions are not as decisive as they need to be. We applaud the steps that the administration has taken to invest more resources in the University’s Institutional Review Board (IRB), the body charged with balancing the benefit of research with the protection of those participating in research, but it was not primarily concerns about our IRB that led faculty and the public to call for independent investigation. Rather, these calls arose because of the cloud of suspicion hanging over the U caused by the perception that our administration was sweeping research misconduct under the rug.
The legislative auditor’s report presented damning evidence that substantiated these concerns, finding that the administration “dismissed the need for further consideration of the Markingson case by making misleading statements about past reviews.” The external reports suggest that top administrators, with the complicity of the Board of Regents, have repeatedly distorted the facts. They stonewalled requests for information that would have shed light on misconduct and conflicts of interest and ignored repeated warnings by whistleblowers. Their behavior suggests that they placed a higher priority on institutional reputation than on basic ethical principles.  The irony is that in their effort to protect the university’s reputation, they tarnished it.

More of the same?

Now the administration would have us believe that it is ready to tackle these tough problems vigorously and transparently. Unfortunately, the administration’s public responses to the reviews demonstrate that we are in for more of the same. For example, in his response to the Legislative Auditor’s report, President Kaler made the astonishing claim that “our only intent has been to be factual in our responses . . . if [earlier] external reviews were flawed, we were not aware of those shortcomings.”  Yet for years it is precisely these shortcomings that critics have been persistently trying to bring to their attention, only to be dismissed or stonewalled.  In short, if they really were not aware, it was willful ignorance.
We are deeply concerned that the people leading the response to the recommendations of the external reviews are the very people who have insisted all along that there were no problems. 
Not to worry, we are assured, because if you do not trust the administration, you can trust the Board of Regents.  The board’s record, however, does not inspire confidence. In a summer 2014 meeting with President Kaler, Board of Regents Chairman Richard Beeson told former Gov. Arne Carlson that reports of research misconduct had “not risen to the level of our concern” and that the negative publicity had “not hurt our brand.” Regent Patricia Simmons, who now is designated to serve as the Regents’ liaison on this matter, dismissed the legislative auditor’s criticism of the board for never holding public hearings about the Markingson case, arguing that the board received many briefings from the administration and was sufficiently informed.
Given the findings of the external reviews, this assessment of what constitutes adequate oversight is troubling. At Friday’s board meeting, Regents showed no signs of turning over a new leaf. They praised the administration and adopted the resolution it put forward without so much as a single question or critical remark about the handling of the situation to date.

True independence needed

If we cannot trust the administration and the Board of Regents, perhaps faculty and community involvement, which the resolution calls for, will provide the needed oversight of the process. The administration’s extensive past record of dismissing critics from the faculty and community, however, do not give us much confidence that the U will meaningfully include these constituencies in the process of reform. The Board of Regents resolution helpfully calls for the task force to be “comprised primarily of faculty,” but it is crucial that the membership include people — faculty and community members — who are truly independent and capable of providing the critical perspective necessary to restore trust in the institution.
We must be vigilant to ensure that research at the U accords with the highest ethical standards. Both independent reviews singled out U leadership, starting in the Department of Psychiatry and extending all the way up, as the most serious barrier to reform. The “decisive” action the U must take is first and foremost to decisively assure the public that those in charge of implementing reforms are not the same actors who were willfully unaware of past abuses.
Teri L. CarawayDavid PellowNaomi Scheman and Karen-Sue Taussig are faculty members at the University of Minnesota. They were among the faculty senators who helped to introduce and push for the passage of the resolution calling for the external review. The views expressed in this piece are their own and do not reflect those of the university.

Monday, March 30, 2015

Part of the Solution or Part of the Problem?

University of Minnesota

Medical School Dean, President Kaler, Mr. Pfutzenreuter

Sad, but true ...

From a comment in the Star-Tribune on their editorial criticizing the University of Minnesota administration:

",,, As you know, the tragic death of Mr. Markingson has been fully reviewed by the U.S. Food and Drug Administration and has been the subject of proceedings before the Hennepin County District Court and the Minnesota Board of Medical Practice, as well as the University's Office of General Counsel.  None of these investigations or proceedings found that the University in any way contributed to the unfortunate death of Mr. Markingson.  Accordingly, I do not believe additional review is warranted and do not support your petition."
May 29, 2013, letter from Eric W. Kaler to Associate Professor Leigh Turner.

Rarely has a president of the University of Minnesota had to perform as embarrassing a U-turn as has President Kaler on this issue.  To be fair, he inherited the situation from his predecessor.  But there was an obvious lack of interest at the U in getting to the truth of Markingson's case - and at this point it can be justly said that Kaler was part of the problem, not part of the solution.

Sunday, March 29, 2015

For the Record: Leadership and transparency were lacking in research subject’s suicide.- Star-Tribune - #Markingson

Link to original.

(Emphasis added)

Trust but verify' to rebuild trust in the U

  • Article by: EDITORIAL BOARD , Star Tribune 
  • Updated: March 27, 2015 - 7:19 PM
Leadership and transparency were lacking in research subject’s suicide.

Generations of Minnesotans have entrusted their health care to physicians and researchers trained at the state’s flagship educational institution — the University of Minnesota. But two new reports rooted in the 2004 suicide of a patient in a Department of Psychiatry medical study have raised disturbing questions about the U’s transparency and leadership on the case over the past decade.
One report, by the state’s Office of the Legislative Auditor, focused on the death of the patient, Dan Markingson, who suffered from schizophrenia when he was enrolled in a study funded by the drugmaker AstraZeneca. The other report, an external review of clinical trial practices, was set in motion by the Faculty Senate because of its concerns about handling of the case.
In November 2003, Markingson, a recent college graduate, was put under the care of Dr. Stephen Olson, who is still a professor in the U’s Psychiatry Department. Markingson initially responded to a drug called Risperdal. But within days, he agreed to be enrolled in a drug study overseen by Olson. Whether he was competent to provide consent or felt pressured to do so has been at issue.
The study compared the effectiveness of three drugs. Neither Olson nor Markingson and his family knew which drug he would be on. But there was a two-out-of-three chance that it would not be Risperdal — a risk that raises serious questions about the care he received. Markingson did end up on another drug, and the alarms his mother raised about his deterioration went unheeded. He killed himself in May 2004, although it is not possible to say his enrollment in the study caused his death.
It took 11 years for all of the details to come out about Markingson’s suicide and the bungled institutional handling of it. The auditor’s report revealed an institutional failure to adequately investigate the case and concluded that U officials had made “misleading” statements about the rigor of reviews of the case, including one by the U.S. Food and Drug Administration.
Lawmakers have already made a key reform with the 2009 “Dan’s Law,” which prohibits patients facing institutional commitment, as Markingson did, from being enrolled in research studies. But further changes are needed, and the external review launched by the Faculty Senate has offered guidance for implementing these reforms. Among them: ensuring that the U’s Institutional Review Board performs rigorous reviews of research safeguards and adverse outcomes.
It is not enough to finally say that the university is committed to reforms, as U President Eric Kaler, Board of Regents representatives and the medical school’s leadership have done. The Legislative Auditor has also offered pragmatic “trust-but-verify” solutions. Lawmakers should require the U to fully implement reforms outlined by the external review. In addition, lawmakers should authorize the state’s own mental health ombudsman’s office to monitor the U’s psychiatric studies.
Other needed steps include authorizing the legislative auditor to investigate the state Board of Medical Practice, which failed to objectively investigate Markingson’s death. It’s also critical that the U have adequate whistleblower protections in place. University bioethicist Carl Elliott has been marginalized professionally after challenging handling of Markingson’s death.
On Friday, U officials said they had asked Dr. William Tremaine, head of the Mayo Clinic’s Institutional Review Board, to provide independent guidance on its reforms, and he agreed to chair a key reform committee. That’s a sign the U is taking criticism to heart. But more work is needed.
Minnesotans have been ill-served by their flagship university in this tragic affair. Yet the state owes a debt of gratitude to Elliott and others who unrelentingly pushed for truth. Among them: Markingson’s mother, Mary Weiss; his friend Mike Howard; former Gov. Arne Carlson; and state Sen. Terri Bonoff. Their persistence shouldn’t have been necessary, but if lawmakers and Kaler follow through, it will help rebuild the institutional integrity that Minnesotans expect and deserve.