March 14, 2015

Catherine Parker, RN
Team Lead, Human Subject Protection Team
Good Clinical Practice Compliance Oversight Branch
Division of Clinical Compliance Evaluation
Office of Scientific Investigations, Office of Compliance
Center for Drug Evaluation and Research
Food and Drug Administration
Bldg. 51, Room 5368, 10903 New Hampshire Avenue
Silver Spring, MD 20993
Follow-up Open Letter Requesting the FDA to Investigate Institutional Protections for Human Research
Participants and Psychiatric Clinical Research at the University of Minnesota
Dear Ms. Parker:
Thank you for your response to my March 6, 2015 letter. As that letter notes, I was prompted to request an
investigation by the FDAs Office of Scientific Investigations following public release of the report, An
External Review of the Protection of Human Research Participants at the University of Minnesota with Special
Attention to Research with Adults Who May Lack Decision-Making Capacity. While the report addresses
policies and practices related to human research subject protections at the University of Minnesota, it does not
examine particular allegations of psychiatric research misconduct at the university. I want draw your attention
to this limitation of the AAHRPP-appointed reviewers findings because problems with the conduct and
oversight of human subjects research at the University of Minnesota extend far beyond the list of issues
identified in the report. Let me illustrate this point by describing a case of alleged psychiatric research
misconduct as well as the University of Minnesota Institutional Review Boards inadequate response to
complaints filed by my colleague, Professor Carl Elliott. I am bringing this case to your attention because it is
important that the FDAs Office of Scientific Investigations investigate specific allegations of psychiatric
research misconduct at the University of Manitoba as well as more systemic problems with the universitys
human research subjects protection program.
On November 17, 2013 and May 19, 2014, Minneapolis-St. Paul television station KMSP aired investigative
reports describing the experiences of Robert, a research subject in a clinical trial conducted by Dr. Stephen
Olson. According to the reports, Robert was injured while taking a non-FDA approved drug, Bifeprunox. The
study in which he was enrolled was Protocol S154.3.002A, titled, An Open Label, Flexible Dose, Long term
Safety and Efficacy Study of Bifeprunox in the Study of Schizophrenia. The statements Robert made in these
reports generate many disturbing questions about the care he received while he was a research subject at the
University of Minnesota Medical Center, Fairview.
Competency to Decide Whether to Participate in a Clinical Trial
Robert was enrolled in the study as an autonomous decision-maker deemed to be capable of providing his

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informed consent to participate in research. However, in the May 19, 2014 KMSP investigative report Robert
stated, I was incompetent and I didnt know what I was doing. This statement prompts questions about
whether Robert was competent and possessed the decision-making capacity needed to understand study-related
risks and provide his informed consent to participate in this clinical trial. As my prior letter to you notes, it
appears that there are serious problems with how the decision-making capacity of some mentally ill individuals
is assessed at the University of Minnesota Medical Center, Fairview. Roberts statement that he was
incompetent is reminiscent of longstanding concerns that Dan Markingson was not competent to enroll in the
CAF study. Allegations that incompetent individuals have been enrolled as competent research subjects in
psychiatric trials warrant urgent investigation.
Disclosure of Risks and Informed Consent
Even if Robert was competent to provide informed consent to participate in psychiatric research, his account of
the consent process prompts concerns about whether he was provided a sufficient account of all risks
associated with participating in the study. They told me the drug was safe, he said to Jeff Baillon, the
investigative reporter who conducted the interviews. Robert added, He [Dr. Olson] told me it was going to be
the next treatment for schizophrenia and everybody was going to be taking it. If Roberts account of the
consent process is accurate, he was not provided with an adequate account of the risks associated with
participating in this trial. Robert was reportedly enrolled in the Bifeprunox study on July 3, 2007. Just five
weeks later, on August 10, 2007, Solvay Pharmaceuticals, the sponsor of the study, announced that the FDA
had rejected its licensing application for Bifeprunox. According to Solvay, the companys drug application
was rejected because Bifeprunox was not as efficacious as current standard therapies for schizophrenia. In
addition, the FDA rejected Solvays drug application because it required additional information about a
research subject who had died of hepatorenal failure ten days after beginning a course of bifeprunox. Roberts
remarks suggest that risks of participating in this study were minimized. If his account is accurate, it is worth
investigating whether the informed consent process for recruiting subjects into this study complied with federal
regulations governing human subjects research.
Aggressive Recruiting of Study Subjects and Undue Inducements to Participate in Research
The interviews with Robert raise troubling questions about statements that were reportedly made to him before
he was enrolled as a research subject. According to Robert, after he was transferred to the psychiatry unit at
the University of Minnesota Medical Center, Fairview, Immediately, they were on me to do experimental
medications, non-FDA approved and I had never been on medications in my life. Robert describes the
pressure and fear he was experiencing when he was approached in a locked psychiatric ward setting. He stated,
You know, when youre locked up in a place, youre very scared and youre willing to do whatever anyone
basically suggests. Robert also claimed that specific statements were made to encourage him to participate in
research. In the May 19, 2014 KMSP report he states, They say you have a giant medical bill and if you do
the research, you wont have this giant medical bill. It is worth exploring whether research subjects in this
study were recruited in a manner that complied with federal regulations.
Reporting of Possible Side Effects as Psychosomatic
Following enrollment in the Bifeprunox study, Robert was reportedly in such pain that he had to be taken to
the emergency room three times, including once by ambulance. His symptoms of abdominal discomfort and
constipation were possible side effects of taking Bifeprunox. Three months after being enrolled in the study,
Robert was in so much pain that he began having thoughts of suicide. Robert decided to withdraw from the
study. At the time of Roberts withdrawal, Dr. Olson reportedly described his side effects as psychosomatic,
writing, He decided to quit the study due to these psychosomatic Sx. When reporting Roberts side effects
to Solvay, Dr. Olson reportedly claimed that their connection to the study drug was unlikely. Classifying

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symptoms as psychosomatic rather than as possible side effects of a study drug could have the effect of
leading to underreporting of adverse events. In Roberts case, the symptoms that led him to withdraw from the
study were reportedly not disclosed as adverse events to the University of Minnesota IRB.
Apparent Breach of Patient Privacy and Confidentiality
In a statement provided to KMSP and aired as part of the May 19 investigative report, Dr. Olson wrote of
Robert, His medical record shows extreme anxiety and paranoia, a history of head injuries and lengthy battles
with alcoholism. Given HIPAA, hospital policy, and professional standards governing privacy and
confidentiality of patients medical records and health-related information, it is of great concern to find a
clinician-investigator at the University of Minnesota publicly describing a former research subject in this
manner. One possible consequence of making such a public statement is that it could have the effect of
deterring other research subjects from coming forward with complaints about the care they received.
University of Minnesota IRBs Inexcusable Delays in Responding to Complaints
On January 2, 2014, Professor Carl Elliott filed a complaint with Dr. Susan Berry, Chair of the University of
Minnesotas IRB Executive Committee. Professor Elliott filed a more detailed complaint with Dr. Berry on
February 13, 2014. Accompanying this letter you will find copies of these complaints. Today, more than a
year after Dr. Elliotts complaints were filed, the University of Minnesota IRB has still not publicly disclosed
the results of its investigation. While an IRB Investigative Committee had reportedly completed its work by
January 27, 2015, the committees findings were not publicly disclosed. These findings have also not been
released following submission of data practices act request. Of even greater concern, it appears that despite the
passage of over a year, members of the IRBs Investigative Committee never met with Robert.
Investigate Specific Allegations of Research Misconduct & the IRBs Responses to Complaints
The report prepared by the AAHRPP-appointed reviewers identifies serious problems with the conduct and
institutional oversight of psychiatric clinical trials at the University of Minnesota. However, it does not address
specific allegations of psychiatric research misconduct. I urge the FDAs Office of Scientific Investigations to
investigate particular instances of alleged psychiatric research misconduct as well as more general problems
concerning the conduct and oversight of psychiatric clinical research at the University of Minnesota. In
conducting such an investigation, I recommend that the Office of Scientific Investigation address specific cases
such as Robert in the Bifeprunox trial and the death of Dan Markingson in the CAF study, additional
allegations of psychiatric research misconduct in publicly funded and industry funded clinical trials, and how
the University of Minnesota Human Research Protection Program has failed to investigate complaints in a
timely and transparent manner. It is possible that lengthy delays in the University of Minnesota IRBs
investigation of complaints and the subsequent failure to publicly disclose findings from investigations means
that significant problems in the conduct of psychiatric clinical research are not being identified and addressed
in a timely manner. If so, such delays could be exposing current research subjects to preventable risk of harm.
Please feel welcome to contact me if you have any questions concerning this request. I am contacting you as
an individual faculty member and not on behalf of the institution of the University of Minnesota.
Yours sincerely,

Leigh Turner, PhD

Associate Professor

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cc: Jerry Menikoff, Director, Office for Human Research Protections, DHHS
Sean Kassim, Director, Office of Scientific Investigations, FDA
Kristina Borror, Director of the Division of Compliance Oversight, OHRP
Arne H. Carlson, Former Governor of Minnesota
Terri Bonoff, Minnesota Senator, Chair of the Higher Education & Workforce Development Committee
Carl Elliott, Professor, University of Minnesota Center for Bioethics
Trudo Lemmens, Professor, Faculty of Law, University of Toronto
Michael Carome, Director, Public Citizen Health Research Group
James Nobles, Legislative Auditor for the State of Minnesota
Eric Kaler, President, University of Minnesota
Richard Beeson, Chair of the Board of Regents, University of Minnesota
Brian Herman, Vice President, University of Minnesota
Brooks Jackson, Vice President, Health Sciences & Medical School Dean, University of Minnesota
Bruce Blazar, Associate Vice President for Clinical & Translational Science, University of Minnesota
William Donohue, General Counsel, University of Minnesota
Keith Dunder, Legal Counsel, University of Minnesota Academic Health Center
Susan Berry, Chair, University of Minnesota IRB Executive Committee
Debra Dykhuis, Executive Director, University of Minnesota Human Research Protection Program
Elyse Summers, President, Association for the Accreditation of Human Research Protection Programs