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ACCOUNTABILITY IN RESEARCH
http://dx.doi.org/10.1080/08989621.2016.1246969
KEYWORDS
In the spring of 2015, after years of withering public criticism, officials at the
University of Minnesota suspended recruitment of subjects into drug trials in its
Department of Psychiatry (Perry 2015). It was not a willing concession. University
officials agreed to act only after the Minnesota Office of the Legislative Auditor
released a scathing investigation into the violent suicide of Dan Markingson, a
research subject in an industry-sponsored drug study at the university. The
Legislative Auditors report presented damning evidence of coerced recruitment,
inadequate clinical care, superficial research oversight, a web of serious, disturbing
conflicts of interest, and a pattern of misleading public statements by university
officials aimed at deflecting scrutiny (OLA 2015).
This powerful indictment came only three weeks after another blistering review
of research oversight at the university. That review was commissioned at the
request of the universitys Faculty Senate in response to a letter organized by
Trudo Lemmens at the University of Toronto and signed by 175 scholars in
bioethics and related disciplines. It found a broad range of unsettling problems
with the universitys human research protection program, including shoddy
scientific review and little attention to the risks of studies, as well as a culture of
fear in the Department of Psychiatry (AAHRPP 2015).
Almost as alarming as Markingsons suicide was the fact that it took nearly
11 years for the university to respond in any meaningful way. University officials
refused to undertake a legitimate investigation of Markingsons deathor even
CONTACT Carl Elliott
ellio023@tc.umn.edu
Center for Bioethics, University of Minnesota, N504 Boynton,
410 Church St SE, Minneapolis, MN 55455-0346, USA.
2017 Taylor & Francis
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This narrative is taken from Elliott (2010) and Office of the Legislative Auditor 2015.
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Institutional responses
Markingsons death first came to public attention in May 2008, when The
St. Paul Pioneer Press published an investigative report by Paul Tosto and
Jeremy Olson 7 (Tosto and Olson 2008). Although subsequent investigations
would reveal a number of troubling issues, the most fundamental problem was
identifiable from the start. Markingson was an extraordinarily vulnerable
patient: floridly psychotic, hospitalized on a locked unit, recruited over the
strenuous objections of his mother, and subject to a civil commitment order
that legally compelled him to comply with the recommendations of his
psychiatrist.
The Institutional Review Board (IRB) was notified of Markingsons death,
but it did not conduct any investigation apart from a routine continuing
review. In 2005, the FDA investigated at the request of Mary Weiss and
issued an Establishment Inspection Report (a comprehensive record of the
investigation), but Sharon Matson, the inspector, dismissed any suggestion
that Markingsons decision-making capacity was impaired. She noted
Markingsons civil commitment order only in passing and failed to mention
the influence that the threat of involuntary confinement might have had on
his consent. Matson concluded, There was nothing different about this
subject than the others enrolled to indicate that he couldnt provide voluntary informed consent (Matson 2005).
Mary Weiss eventually filed a lawsuit. Yet a Hennepin County judge
dismissed her suit against the university, ruling that the University of
Minnesota, as a state body, was statutorily immune from lawsuit. This ruling
meant that no matter what the merits of the case, the university could not be
sued. The judge did allow a malpractice suit against Olson, which was settled
out of court for $75,000 (OLA 2015).
University officials took no action when the Pioneer Press report appeared,
and they did not comment a year later when the state legislature passed a bill
(Dans Law) placing serious restrictions on the recruitment of patients under
civil commitment orders into psychiatric drug studies (Laws of Minnesota 2009;
Olson 2009a). By 2009, however, another troubling issue had emerged.
AstraZeneca was facing federal litigation for fraudulent marketing of quetiapine
(Seroquel). As documents from the litigation were unsealed, it was becoming
evident not only that AstraZeneca had manipulated and buried research studies
in order to promote Seroquel, but also that Charles Schulzan AstraZeneca
consultant and a co-investigator on the CAF studyhad been involved. Schulz
had promoted suspect Seroquel studies in company press releases, even as
internal AstraZeneca emails referred to a smoke and mirrors job to hide
Seroquels serious metabolic side-effects (Moore and Lerner 2009; Mannix
2011). In 2010, AstraZeneca paid $520 million to settle federal fraud charges.
Later that year I wrote about the links between the Seroquel fraud and the
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dealing with industry disasters and safety issues. Participants included leaders
from the aviation, meat production and nuclear power industries, as well as a
representative from the judiciary and two communications specialists in crisis
management. A report on the workshop in Academic Medicine stressed several
points relevant to the Markingson case (Yarborough et al. 2009).
First, participants agreed that in most fields, adverse events are typically the
result of system-wide institutional failures. They are often preceded by a series of
cascade effects, some of which may seem trivial until they result in serious
problems. Second, participants agreed that compliance with laws and regulations
should be seen as a bare minimum and not as a substitute for an institutional
culture of honesty and ethics. (As one participant said, You can follow all the
rules and still not get it right.) Third, when adverse events occur, restoring public
trust depends on genuine humility and willingness to look at mistakes, rather than
mere public relations messages. Fourth, participants agreed that it is crucially
important not only to restore public trust, but to develop trust and good relationships within the institution itself. As one participant pointed out, More than 90%
of infractions reported are reported from within.
At the University of Minnesota, evidence of system-wide institutional failure
had become apparent years before Markingsons suicide. In 2000, the FDA
disqualified James Halikas, a faculty member in the Department of Psychiatry,
for recruiting illiterate Hmong opium addicts into a risky study of GHB, a CNS
depressant, without their consent (Sherman 2000, Rigert and Lerner 1993b). Just
three years before the Halikas episode, the FDA had disqualified his colleague,
Barry Garfinkel, the Head of Child Psychiatry, for research fraud (HHS 1997).
Garfinkel was sent to federal prison (Rigert and Lerner 1993a). In 1998, the
Minnesota Board of Medical Practice sanctioned Dr. Faruk Abuzzahab, a clinical
faculty member (and former full-time member) of the Department of
Psychiatry, for the deaths of five patients under his care and the injuries of fortyone others. Seventeen of these patients had been research subjects in clinical
trials Abuzzahab had conducted.
Most notoriously, the university was hit with sanctions by the National
Institutes of Health and the U.S. Department of Justice in the 1990s for the
illegal sales of an experimental immunosuppresent drug. According to the
Department of Justice, the University of Minnesota illegally profited by
selling an unlicensed drug (ALG), failed to report to the National Institutes
of Health (NIH) income from selling the drug, improperly tested the drug on
patients without their informed consent, and inflated billings on 29 federal
grants (U.S. Department of Justice, 1998).
University of Minnesota officials did not treat these episodes as signals
of institutional dysfunction. In fact, when the Garfinkel fraud case was
being investigated, according to the Star Tribune, university officials hid
the results of a university investigation from federal investigators for
nearly four years (Rigert and Lerner 1993a). As the controversy over the
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this event did not seem to ruffle the university oversight board that is
charged with looking into such episodes. Questions were also raised about
the eligibility of the subjects for the study and the status of the sex offender
facility as a recruitment site. Schulz was not sanctioned.
Two months later, Kenneth Winters, a senior faculty member in the
Department of Psychiatry, admitted to forging a federal Certificate of
Confidentiality for adolescents in a study sponsored by the National
Institute for Drug Abuse. According to news reports, the university declined
to sanction him for forging the document and instead offered him the
opportunity to retire (Baillon 2015a).
In February 2016, eight months after the reform plan was announced, the
results of yet another investigation of the Department of Psychiatry were
released (Clinical Research and Compliance Consulting 2015). That investigation found over forty critical violations of research and safety guidelines, as well
as admissions by staff members that they altered study documents when they
prepared for audits. We go behind the scenes and fix things up, one interviewee said. The consultant who conducted the investigation reported being
intimidated and verbally abused by department faculty members. Even more
alarming, university officials attempted to suppress the report while it was still in
progress, telling the consultant not to put any of her findings in writing. When
the report was leaked to the press, university officials disputed the findings and
dismissed its significance (Lamkin and Elliott 2016; Olson 2016).
University leaders have attempted to portray the universitys research
scandals as an issue of faulty policies and rules. But as repeated external
reviews have made clear, the problems at the University of Minnesota go well
beyond its policies. For decades, the universitys Academic Health Center has
had leaders who look the other way when rules are broken, who fail to
sanction those who break the rules, and who take harsh action against
those who dissent. The result is an institutional culture in which misconduct
is tolerated and opposition is widely seen as futile.
To change that culture, university leaders must convince patients, faculty,
staff, and students that they are truly committed to protecting the rights and
welfare of research subjects. This will require public apologies to victims of
research misconduct and sincere efforts to compensate them for their suffering. It will also require sanctions for those who violated the rights and
welfare of research subjects, as well as for the university officials who made
false and misleading statements or otherwise tried to cover up misconduct.
The leaders of any institution in which serious wrongdoing is revealed will
naturally try to minimize the reputational damage to the institution. Often
they are tempted to hide information, vilify critics, and protect guilty parties
who are seen as valuable to the institution. This strategy is tempting because
it so often works. The list of institutions that have confronted their own
medical research scandals honestly and openly is very short. Most
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