briefings to university of minnesota board of regents on markingson case

8/9/2019 Briefings to University of Minnesota Board of Regents on Markingson Case

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University of Minnesota Mail - Several Media Items https://mail .google.com/mail/u/0/?ui=2 ik=28 lfa64bb4 view..

V

Brian Steeves

Several Media Items

BranSteeves Wed Nov14 2012at 301PM

To: Linda Cohen David Larson

Cc: Eric Kaler Amy Phenix mark rotenberg

Bcc: Clyde Alien David McMillan Dean J ohnson

J ohn Frobenius Laura Brod Maureen

Ramirez Patricia Simmons Richard Beeson

Tom Devine Venora Hung Angela Menzel

Ken Savary Mary Swords Pamela Hudson

Sarah Dirksen

T O : A L L RE GE N T S

I am writing to provide a heads up on several items that have or may generate media attention.

Defibrillator Research

Professor Frank Bates, head of Chemical Engineering, published a study yesterday in the journal

Macromolecules that highlights significant issues with St. J ude defibrillators. The study includes clear

language that identifies Bates as a paid consultant to Medtronic, and it is my understanding that the research

was funded by Medtronic. Like all published research, this study was peer-reviewed. The study has already

received some attention in Business Week (http://www.businessweek.com/ap/2012-11-13/analyst-study-

shows-new-st-dot-jude-wire-problems) and may also generate local attention since both companies are

located in Minnesota.

Social Worker Sanctioned

Several media outlets (including the Star Tribune: http://www.startribune.com/local/179042061.htm?refer=y)

have reported on a Corrective Action agreement between former D of M social worker J ean Kenney and the


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University of Minnesota Mail - Several Media Items https://mail .google.com/mail/u/0/?ui=2 ik=281fa64bb4 vievv..

Two years ago, the University of Minnesota Medical School launched the Preparation for Residency Program

(PRP) to train immgrant physicians and get them on a track to practice medicine in the United States. After

some initial success, the landscape and prospects for the program have changed. Therefore, the Medical

School has suspended the PRP program as it looks for new ways to leverage the talents of these physicians.

A fact sheet on the evolution of this program is attached.

Please let me know if you have any questions on these items.

Brian R. Steeves

Executive Director & Corporate Secretary

Board of Regents

University of Minnesota

612-625-6300

[email protected]

PRP Fact Sheet.pdf

8 K


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University qf Minnesota Mail - Updates https://mail.google.com/mail/u/0/?ui=2 ik=281fa64bb4 view..

A

Brian Steeves

Updates

BranSteeves Tue Dec3 2013at 239PM

To: Richard Beeson Dean J ohnson

Cc: Eric Kaler Amy Phenix

Bcc: Abdul Omari Clyde Alien David Larson

David McMillan J ohn Frobenius Laura Brad

Linda Cohen Patricia Simmons Peggy Lucas

Tom Devine Ken Savary Mary Swords

Pamela Hudson Sarah Dirksen Stephanie

Austin

TO: ALL REGEN TS

K ALER INV ITED TO WH I TE H OUSE

President Kaler has been invited to the White House next Wednesday for a day-long summit dedicated to

launching a plan of action for increasing college access and success for low-income and disadvantaged

students. The event is being jointly coordinated by the National Economic Council, the Domestic Policy

Council, and the Department of Education.

SENATE HEAR ING ON CAMPU S SAFETY

The Senate Higher Education & Workforce Development Committee will hold a hearing on metro campus

safety on Tuesday, 12/10. VP Wheelock and UMPD Chief Hestness are scheduled to appear. (Details can be

found here: https://www.senate.mn/schedule/schedule.php?ls=&type=upcoming&cmte_id=3072&

cmte_type=standing).

U N I V E R SI T Y S E N A T E T O D E B A T E H U M A N S U B J E C T S RE S E A RC H R E SO L U T I O N

Several faculty members have continued to express concern about the circumstances surrounding the 2004


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Unnjeteity gf Minnesota Mail - Updates https://mail.google.com/mail/u/0/?ui=2 ik=281fa64bb4 vievv..

Brian R. Steeves


Board of Regents


612-625-6300

[email protected]

BOR resp to Elliott et al re Markingson.pdf

638K


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University of Minnesota Mail - Markingson Case https://mail.google.com/mail/u/0/?ui=2&ik=281fa64bb4&vievv..

A

Brian Steeves

Markingson Case

BranSteeves Tue Apr 29 2014at 511PM


Cc: Eric Kaler Amy Phenix William Donohue


David McMillan J ohn Frobenius Laura Brod


Tom Devine J ason Langworthy Mary

Swords Pamela Hudson Sarah Dirksen

Stephanie Austin

T O : A L L R E G E N T S

As you know, a small number of individuals continue to express concern about the circumstances surrounding

the 2004 suicide of Dan Markingson while he was enrolled in a clinical drug trial at the University of

Minnesota. Several independent investigations and reviews have been conducted (see attached summary)

and in February 2011 then-Chair Clyde Alien sent a letter on behalf of the Board stating we do not believe

further University resources should be expended re-reviewing a matter such as this, which has already

received such exhaustive analysis by independent authoritative bodies. (See complete copy of Alien letter

attached.)

On 12/5/13 the University Senate passed a resolution seeking an external review of the University's human

subjects research policies, practices and oversight. An RFP for that review has been issued.

Recently, individuals from inside and outside the University have attempted to escalate this matter by

contacting prominent community leaders and University donors. We have also been informed that a peaceful

protest/vigil is being planned outside McNamara Alumni Center in conjunction with the upcomng Board of


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University of Minnesota Mail - Markingson Case https://mail.google.com/mail/u/0/?ui=2&ik=281fa64bb4&vievv..

Dan Markingson Investigations and Reports Updated 4-22.pdf

56K

BOR resp to Elliott et al re Markingson-3-pdf

1638K


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Dan Markingson Case

Reviews, J udgments and Investigations

In the ten years since the death of Daniel Markingson (DRM), there have been multiple

investigations and rulings about the case, the care that he received, and the University's

policies for the protection of human subjects in clinical research.

None of the investigations found evidence of misconduct by the University of

Minnesota,

The investigations and reports include:

May 26, 2004:

• J une 17, 2005:

J uly 22,2005:

The University of Minnesota Institutional Review Board

performed a routine, full-board review of the death ofDRM

The State of Minnesota's Office of the Ombudsman for Mental

Health and Mental Retardation closes its case re: allegations of

misconduct or neglect by the group home charged with

monitoring DRM

Report found no predictors of DRM's suicide and no failure by the

facility to recognize any predictors of suicide. Allegations of neglect

are found to be false.

The Food and Drug Administration concludes investigation into

complaints of misconduct related to the care ofDRM and their

clinical inspection of Dr. Stephen Olson and his role in the Cafe

Study


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Feb.11,2009:

The Minnesota Board of Medical Practice responds to complaints

against Charles Schulz, M.D., by Mary Weiss

After a review by a Board Medical Coordinator and a review by the

Board's Complaint Review Commttee, the Board found that the facts

of the case did not provide a sufficient basis for the Board to take

disciplinary or corrective action against the Respondent physician's

license.

J uly 15, 2010:

The Minnesota Board of Medical Practice responds to complaints

against Stephen Olson, M.D., by Mary Weiss

After a review by a Board Medical Coordinator and a review by the

Board's Complaint Review Commttee, the Board found that the facts

of the case did not provide a sufficient basis for the Board to take

disciplinary or corrective action against the Respondent physician's

license.

Sept. 23, 2010: The Council on Accreditation of the Association for the

Accreditation of Human Research Protection Programs, Inc.

(AAHRPP) awards the University of Minnesota full re-

accreditation for another five years

We congratulate you on this important achievement, which reflects

your organization's commitment to protecting the rights and welfare

of research participants.

Oct. 26, 2012

Board of Social Work - State of Minnesota reviews allegations


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U N I V E R S I T Y OF M I N N E S OT A

The Honorable Clyde E. A lien, J r. 600 McNamara Ahimni Center

Chair, Board of Regents 200.0ak.s',reel Ê^

M inneapolis M N 55455-2020

Office: 612-625-6300

Fax: 612-624-3318

February 7,2011

Carl Elliott, Professor

Dianne Bartels, Assistant Professor

J oan Liaschenko, Professor

Mary Faith Marshall, Professor

J ohn Song, Associate Professor

Leigh Turner, Associate Professor

Susan Craddock, Associate Professor

J oan Tronto, Professor

Center for Bioethics

N504 Boynton

410 Church S treet SE

Minneapolis, MN 55455-0346

Dear Professors Elliott, Bartels, Liaschenko, Marshall, Song, Turner, Craddock, and

Tronto:

Thank you for your correspondence of November 29,2010, in which you raise

significant questions related to the suicide of Dan Markingson, who was enrolled in

a psychiatric research study at the University of Minnesota in 2003-04. On behalf of

the entire Board, I take this opportunity to express again the University


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Page Two

February 7, 2011

I have asked our General Counsel to provide you with a more detailed response to

the allegations you raised in your letter. At this time, however, we do not believe

further University resources should be expended re-reviewing a matter such as this,

which has already received such exhaustive analysis by independent authoritative

bodies.

More generally, we note that the University maintains a human subjects protection

program that is fully accredited by the Association for the Accreditation of Human

Research Protection Programs (AAHRPP), the gold standard, to ensure the

protection of subjects participating in University research.

We do not intend to suggest that the broader concerns you raise related to

protection of subjects involved in clinical research are unimportant. To the

contrary, we encourage the University community to engage in further discussion

about these wider issues. In an era when public funding of our University and its

research is limted, we must recognize that critically important medical and health

research requires substantial private investment, both from donors and from

corporate sponsors. Those funding sources provide great opportunities - and pose

significant challenges -- for the University. We believe our faculty is ideally suited to

engage in a rigorous, open, and honest exploration of these opportunities and

challenges, and the impact they may have for the integrity of our research mssion.

We ask the administration to work with interested faculty to create an appropriate

forum where these issues can be fully examined.

Thank you again for sharing these important and serious concerns with the Board.


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University of Minnesota Mail - Possible Protests & Additional... https://mail.google.com/mail/u/0/?ui=2&ik=281fa64bb4&vievv.,

L

Brian Steeves

Possible Protests & Additional Meeting Details

BranSteeves Wed May7 2014at 857PM








Stephanie Austin Dave McMillan (MP) Brian Steeves

T O A L L RE G E N T S

POSSIBL E PROTESTS

Whose Diversity?

We have received reports that an organization calling itself Whose Diversity? may stage protests during this

week's Board or committee meetings. You recently received an e-mail from this group outlining a series of

demands. Whose Diversity? has taken a very confrontational tone and recently organized a disruptive protest

during an event at Coffman Memorial Union (see coverage here: http://www.startribune.com/local/minneapolis

,257602471 .html). VP Katrice Albert is spearheading a response to the demands, which I will forward once it

has been finalized.

Markingson Vigil

The Board Office has also been informed that a vigil in honor of Dan Markingson is being organized for 12:00

noon on Friday, 5/9 outside McNamara Alumni Center. This is intended to place pressure on the University to

reopen investigations into the Markingson case. Additional details are available on Professor Carl Elliott's


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University of Minnesota Mail - Beeson Response to Gov. Carlso... https://mail.google.com/mail/u/0/?ui=2 ik=281fa64bb4 view...

A

Brian Steeves

Beeson Response to Gov. Carlson re: Markingson Case

BranSteeves Fri May9 2014at 439PM


Cc: Eric Kaler Amy Phenix William Donohue

Bcc: Abdul Oman Clyde Alien David Larson





Stephanie Austin smith, tracy Keith Dunder


Attached is Chair Beeson's response to a recent letter from former Gov. Arne Carlson regarding the

Markingson case (Gov. Carlson's letter is also attached).

Please let me know if you have any questions.

Brian R. Steeves


Board of Regents


612-625-6300

[email protected]


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U N I V E R S I T Y OF M I N N E SO T A

The Honorable Richard B. Seeson 600 McNamara Alumni Center

Chair. Board of Regents 200 Oak Street S.E.

M inneapolis AM 55455

651-523-7830

Fax: 612-624-331S

fTebsile: www.regenls.fimn.edu

May 9,2014

The Honorable Arne H. Carlson

145 H olly L ane N orth

Plymouth MN 55447

Dear Mr. Carlson:

I write in response to your April 29, 2014, letter regarding the suicide death of Dan

Markingson. As this month marks ten years since his death, the University continues to express

its heartfelt sympathy to Mr. Markingson's famly and friends.

I understand you have declined our offer to meet with President Eric Kaler and me.

Again, we are happy to meet with you. At this point, however, we are responding to you in

writing.

Your letter makes assertions based on the writings of Professor Carl Elliott that have


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Hon. Ame Carlson

May 9,2014

P age 2

and practices to ensure best practices in all of our research involving human subjects. All of us

at the University are commtted to maintaining the highest integrity in our research mssion.

Sincerely,

^

Richard B. Beeson, Chair

Board of Regents

c; Members of the Board of Regents

Eric W. Kaler, President

William P. Donohue, General Counsel


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University of Minnesota Mail - Markingson Case Statement & ... https://mail.google.com/mail/u/0/?ui=2&ik=281fa64bb4&vie\ v..

A

Brian Steeves

Markingson Case Statement & Supporting Materials

BranSteeves Fr, May16 2014at 1049PM








Stephanie Austin


The attached statement and supporting materials regarding the Markingson case have been assembled in

response to the recent uptick in letters, phone calls, and in-person questions being posed to the University.

I am sharing this information with anyone who contacts the Board on this matter. It concisely states the

University's position, provides a chronology of events, and includes a number of supporting documents.

The document is also available in the Resource Library >Key Messages & Background >Markingson Case

folder, linked here:

Statement & Supporting Materials re Markingson case May 2014

Please let me know if you have any questions.


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M ay 16, 2014

Academic Health Center Communications


Statement in response to calls for further inQuiry into the Dan Markineson case

The suicide death of Dan Markingson in 2004 was a tragic reminder of the devastation of mental

illness. It was not, and is not, a scandal.

Calls on the University of Minnesota to further investigate this case through public hearings or

by conducting an "independent investigation" fail to recognize some of the basic facts of the

case. Those who continue to raise the issue assert:

1. The University has refused to allow an independent professional inquiry on the matter

2. The University did not review or inform itself about the matter

In fact, this tragic event and the research study in which Mr. Markingson was a participant were

extensively reviewed by external independent agencies and the courts, as well as by the

University. As explained below, the University is also currently engaging an outside

professional to review all of its policies and procedures governing human subjects research.

Background

Dan Markingson was transferred from Regions Hospital to the Fairview University Medical

Center in November 2003 as a result of an acute episode of mental illness and was hospitalized.

Mr. Markingson was evaluated for possible commitment by the Dakota County District Court.

He was evaluated by a neuropsychologist and a psychologist prior to the hearing on his stay of

commitment on November 20, 2003, in the Dakota County District Court. Those examiners


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drugs for schizophrenia. Mr. Markingson committed suicide at Theodore House on May 8,

2004. None of his many trained caregivers observed indicators of suicide risk in the months or

weeks prior to his death.

External and Internal Reviews

This matter has been thoroughly reviewed, both internally and externally. Of particular note are

investigations by the Food and Drug Administration, the independent federal agency with

oversight for research in drug trials, and also by the state Board of Medical Practice and the

district court. There has never been any finding that Mr. Markingson's death was as a

result of his participation in the research study.

Investigation by the FDA. Upon Mr. Markingson's death, the University's Institutional Review

Board ("1KB") promptly notified the federal Food and Drug Administration ("PDA"), the

independent government agency with jurisdiction over deaths in drug trials in the United States.

The PDA conducted a full audit of the research study, interviewing witnesses and gathering and

reviewing related documents.

On J uly 22, 2005, the PDA issued its 21-page Inspection Report concluding, "No evidence of

misconduct or significant violation of protocol or regulations was found in this inspection." The

report specifically investigated, and made findings rejecting, claims of research misconduct and

lack of competent informed consent. The FDA's report is public and is included in this packet of

information. The FDA did not find wrongdoing by the University of Minnesota or the

Department of Psychiatry, or any causal connection between Mr. Markingson's death and his

participation in the study.

Assertions that the University did not notify public officials with oversight responsibility about

Mr. Markingson's death are incorrect. The principal public body responsible for oversight of

research and adverse events in research is the FDA. The FDA, both in Minnesota and in their

national office, was notified of Mr. Markingson's death by letter dated May 13, 2004, just a few


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Hennepin County District Court. In 2006, a lawsuit was commenced against the University,

the principal investigators on the study, and AstraZeneca, the sponsor of the study. After a

thorough litigation process, production and review of all records, and the depositions of dozens

of witnesses, the Hennepin County District Court dismissed the case against the University,

AstraZeneca, and one of the principal investigators, while the other principal investigator entered

into a nominal settlement to dismiss the few remaining claims.

Importantly, while the court dismissed the case against the University on the basis of

governmental immunity, the court specifically found that Mr. Markingson appropriately

consented to enter the study and dismssed all claims against all parties that Mr. Markingson did

not, or could not, validly consent to participate in the study. Thus, the Minnesota district court

reviewed the issue of Mr. Markingson's consent, which has been a central allegation of

wrongdoing by those who are calling for additional investigations, and the court supported his

ability and right to exercise his consent. In Minnesota, and elsewhere, questions of consent are

ultimately decided by the courts, and a fully informed court decided the issue.

University Review. In addition to the independent external investigations and reviews described

above, and as observed by the FDA in its report, the University's Institutional Review Board

performed a routine, full-board review following the adverse event report of Mr. Markingson's

death and found no irregularities. The FDA also found, in its independent investigation, that the

death was appropriately reported to the IRB, the internal University body with oversight over

human subjects research. The University also reviewed and responded in detail to complaints

and questions raised by Ms. Weiss, Professor Elliott, and others. The letters from the University

are included in this packet of information. You will see that, contrary to assertions by critics, the

University treated Ms. Weiss respectfully and appropriately.

Critics in this case also suggest that the Regents have not been informed of this matter. That

assertion, too, is incorrect. Included here you will find a copy of a letter from Clyde Alien,

former Chair of the Board, responding to issues asserted by Professor Elliot.


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protection of human subjects in research. AAHRPP has re-accredited the U ofMN twice since

Markingson's death, in 2007 and 2010. Another re-accreditation review is scheduled for next

year.

Both federal law and University policy require the reporting of adverse events in clinical

research. Serious adverse events sometimes do occur when people participate in clinical trials,

and they are reported to the IRB and to the study sponsor as required by PDA regulations.

The reporting of an adverse event, in and of itself, does not mean or even imply that the drug,

device, or procedure under study caused the event. It simply means that the adverse event

occurred while the person was enrolled in the study. Serious adverse event reports submitted to

the IRB are evaluated by the IRB to ensure protection of the rights and welfare of research

participants.

Recently, critics of the University's research function have asked for an accounting of how many

research subjects have died or been "seriously injured" in psychiatric research studies over the

history of the University, and to account for "the circumstances surrounding those deaths and

injuries." At any given time, the University of Minnesota is engaged in more than 2,000 active

biomedical research studies involving human subjects. The Psychiatry Department alone is

currently associated with 262 active projects. While the IRB maintains comprehensive files on

every IRB-approved research study, including adverse event reports filed in connection with the

study, the 1KB does not maintain a tabulation of adverse event reports by department, type of

research, or nature of the adverse event. Nor, in our experience, do IRBs at comparable research

institutions. Nor are such running counts required by the accrediting standards governing IRBs.

To provide an answer based on data would require gathering and reviewing literally hundreds

and hundreds ofIRB study files to determine whether a serious adverse event report was filed for

a study. Even if department leaders have no knowledge of deaths in psychiatric studies other

than Mr. Markingson's, we would not state with certainty that no death was reported in any

research study without actually reviewing 1KB files for all such studies, and such a project would


20/288

A request for proposals has been sent, and it is our expectation that the review will be completed

in the next several months. These actions are fully responsive to the Faculty Senate resolution.

Summary

This tragic case has already been extensively reviewed in a number of forums, and in none of the

reviews was the drug study in which Mr. Markingson participated found to have caused or

contributed to his death. It cannot reasonably be argued that the University has refused to allow

an independent professional inquiry or that the agencies and courts that performed such inquiries

were not wholly independent of the University of Minnesota.

The University is committed to carrying out the Faculty Senate's request for an independent

review of our policies and practices, to ensure best practices in all of our research involving

human subjects. This review and its results will be transparent to all.

Biomedical research is a key component of the University's mission and an important

contributor to the health ofMinnesotans and the economy of Minnesota. The University will

continue to perform this important research while also maintaining a rigorous oversight system

for the protection of research participants.

Enclosures

• FDA Report (J uly 22, 2005)

• Faculty Senate Resolution (Dec. 5,2013)

• Letter from former Chair Clyde Alien (Feb. 7, 2011)

• Other letters from University Office of General Counsel


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U N I VER S I TY OF M I N N E SOTA

The Honorable Clyde E. Alien, J r. 600 McHamwa Ahimm Center

Char, Boardo Regens 2woakstne.5.Ei.

Miiwmpolis, Mff 55455-2020

Offi ce: 6L 2-625-63QO

Fax: 612-624-331S

February 7,2011






Lejgh Turner, Associate Professor




N504 Boynton

410 Chur ch Street SE


Dear Professors Elliott, Bartels, Liaschenko, Marshall, Song, Turner, Craddock, and

Tronto:

Thank you for your correspondence of November 29,2010, in which you raise

significant questions related to the suicide of Dan Markingson, who was enrolled in

a psychiatric research study at the University of Minnesota in 2003-04. On behalf of

the entire Board, I take this opportunity to express again the University


22/288

P age T wo

February 7,2011

I have asked our General Counsel to provide you with a more detailed response to

the allegations you raised in your letter. At this time, however, we do not believe

further University resources should be expended re-reviewing a matter such as this,

which has already received such exhaustive analysis by independent authoritative

bodies.

More generally, we note that the University maintains a human subjects protection

program that is fully accredited by the Association for the Accreditation of Human

Research Protection Programs (AAHRPP), the gold standard, to ensure the

protection of subjects participating in University research.

We do not intend to suggest that the broader concerns you raise related to

protection of subjects involved in clinical research are unimportant. To the

contrary, we encourage the University community to engage in further discussion

about these wider issues. In an era when public funding of our University and its

research is limited, we must recognize that critically important medical and health

research requires substantial private investment, both from donors and from

corporate sponsors. Those funding sources provide great opportunities -- and pose

significant challenges - for the University. We believe our faculty is ideally suited to

engage in a rigorous, open, and honest exploration of these opportunities and

challenges, and the impact they may have for the integrity of our research mission.

We ask the administration to work with interested faculty to create an appropriate

forum where these issues can be fully examined.

Thank you again for sharing these important and serious concerns with the Board.


23/288

v ,...:,

?, I

D E P A RT ME N T O F H E A L T H A N D H U MA N S E R V I C E S

F ood arxTD rugi Administration'

Minneapois District Office

Central Region

212 Third Avenue South

Mi nneapolis, MN S6401

Tesphone;(S12)33-(-4100

PAX: (812) 3K-41M

J uly 22, 2005

Stephen C. Olson, M.D.

Clinical Investigato.r

2450 jyverside Avenue

P282.2A'Weat-B

Minneapolis, Mtonesdta 55454

Dear Dr. Olson;

We enclose a copy of the Establishment I nspection Report (EIR) for the mspect-ion

conducted at your premises at Minneapolis,,MN, on J anuary 3-6, 1 1, 19, 21 and

26, 2005, by Investigator Sharon L, Matson of the Food and Drug Administiation

(FDA). This procedure is applicable to EI Rs for inspections completed.on or after

April 1, 1997. Per-those inspections completed prior to the above date a copy of

the BIR may still be made available through the Freedom of Information Act (FOIA),

The Agency is working to make its

transparent to regulated industry..

The copy being provided to you c<

may reflect rcdactions made by th|

CFR Part 20, This, however, does

obtammg additional information

egulatoiy process and activities more

ieleasing the EIR to you Is part of this effort,

iprises the narrative portion of the report; it

I'Agency ui accordance -with the POIA and 21

>ot preclude you from requesting and possibly

deFOA ••

I f there is any question about the released information, feel free to contact me at


24/288

Establishment Inspection Report

Stephen Qlson, MD

Minneapolis, MN 55454

F B I ;

El Start;

El E nd:

3004927371

01/03/2005

01/26/2005

TA B L3 E O F C O N TE N TS .

SUMMARYOFF̂ oNGS............,.................;.,..........;...............,...........,...,,,..,...........,,,....,..̂

ADMNSTRATFVEDATA,............,...,,„......,........,,....,,....,..,...,,.,.,...,,.,..,,...,,,.,........,............,, 1

raSTORYOFBUSNESS........;.......,....,..,...,.,.,;.,.,.......,,,.,..,,.,...,..,,.,:.......,........,.....-..;..,...,.......2

PERSONS INTERVIEWED and rNDP/IDUALRBSPONSIBILITY..,.,....,,..,,.......,..,,........,,,..,3

DS Compan 1006,...,,,.,...,.,.....,....................;..........,,.......,.....,...,,.,......,;...,...,,......,;.,,.....,....,,5

~NSFECTON...........................,,..,.,,,,,...,,,,......,.-...,».̂ ...,....,..,.,...,,,..,..,o....,...̂

DATAAUDT.,,,.....,....,..,.,....,..,.,,,..,.......,.,..,...̂ ..,..,...,.....,..,.......,....,,.,.,...,..,.,.......,..,..,,.......,.l5

DSCUSSONWTHMANAGEMENT....................................................................................ie

ATrACĤfiNTS...........................................................u,.................,..,,;.....,....,....,.,,....,...̂

EX̂TS...........................................................................................................̂

S U M M A R Y Q T V W W N GS

I conducted this clinical investigator inspection and data audit per a For Cause assignment-from the

Center for Dmg Evaluation and Research (CDER/HPD-46), dated 12/14/04 to follow-up on Division

of Scientific Investigations Complaint #1 ̂ 06 (Attachment #1 and 2).

This is the first FDA inspection of this cjmcal uivpstigator,

•s

The study assigned for audit is titled "Efficacy and Tolerability ofOlaazapuie, Quctiapine and

Risjperidone in the Treatroent of First Episode Psychosis: A Randomzed Double Blind 52-Week


25/288

EstabJ ishmeat Inspection Report

Stephen Olsor), MD •

MinneapoliSi M M. 55454

F B I ;

El Start:

El End:

3004927371

01/03/2005

01/26/2005

F282-2A West-B


Phone; 612/273-9763

FAX.; 6.12/273-9779

.Maing address: (samea5 above ' ;

B-mai-1: [email protected]

Dates of inspection: 1/3/2005, 1/4/2005, 1/5/2005, 1/6/2005,1/11/2005,1/19/2005,

1/21/2005,1/26/2005

Days in the facility; 8

Participants; .SharonL, Matson, Investigator

jH ISTORYOF.BTCjlStNESS

Stephen C. Olson, MD started at the University of Minnesota (UMN) in December 2000 as an

Assoqi'afe Professor of Psychiatry. He has been involved in clinical research as a principal and co-

investigator since about 1986 and those studies are listed in his CV, attached as .Exhibit til .

Besides teacliing and research. Dr. Olson's responsibilities include; . '

• Director, Schizophrenia Program within the UMN Academc Health Center

• - Attending Psychiatrist on Station 12, FUMC'R (farthei described below)

• pacUitatwg some group therapy ses'sions at the FUMC-R. Day Treatment (")

•, arid, providing private outpatient practice services.


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Esfabishtnen InspectionReport FBI: 3004927371

Sephen0(son MDE Sart: 01032005

MnneapoJis, MN55454El End; 01/26/2005

Dr. Olson is compensated through both University of MN Physicians (UMP) as an independent

licensed physician, and through UMN research funds.

PE R SON S I N T E R V I E W E D and I N D I V T D U A I / J R .E SPO N SFB I L I T Y

This inspection was uneunnou.noed. I showed up at the referenced address, showed credentials, and

. issued a FD 482 Notice of Inspection to Stephen C. OIson, MD, Qjnical ]av


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SephenOson MDE Sart: 01032005

Mnneapos, MN5545< E End; 01262005

Admnistratively, as UMN psychiatry staff Dr. Olson reports to Dr. Schulz who reports to Deborah

Poweil, MD, Dean, Medical School, UMN ->Frank Cerra, MD, Senior VP, Academc Heallh

Center, UMN ->Robert Brumnks, President, UMN, 100 Church St., Rm 202 Moml Hall,

Minneapolis, MM 55108.

J ean Kenney became the study coordinator in 6/Q2 ajfter the original coordinator - Rvtl i T liomson,

left. Ms. Kenney's responsibilities for this study include evaluating patienls ability to consent;

explaining the study to prospective subjects'and obtaining nrfohned consent; seeing subjects at eactf

visit; performing evaluation.s; receipt, dispensing, and accounting fortest articles; entering data

collected into electronic case report forms; participating in monthly study coordbator telephone

conferences; and, overseeing other staff fhat perform some of the above. Ms.Kenney is 40% paid

fhrough UMP as an independent licensed social worker at FUMC-R, outpatient. She is 60% paid

through UMN researc} funds. She reports to Dr. Olsan, Her CV is attached as Exbjbit#4,

A number of study staff besides Ms, Kenney were trained and Certified to'perform evaluation scales

such as the Structured Clinical Interview for DSM -TV Ax^s I Disorders (SCID)| Positive aod

Negative Symptom Scale (PANSS), and Clinical Global Impressions (COT) per review of records;

Elizabeth Lemke, Julie Pcarson, Tanya Adelman, Angda Guimaraes, and Christa Surerus-J ohnson,

TAcy al;o were involve.d in explaining the study to subjects and oblflim'ag and/or witnessing signed

consent. Ther CVs are attached as Bxlp'bj't #5 - 9. ' .

I spoke to several other persons by phone iri the course of this inspection and complaint follow-up;

Bill Andersen, Eagan Counseling Clinic (a memo of telecon is atteched, A_ttachn]en1 #4J

Adrienne Baranauskas, Director of Research, FUMC-R ••


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Internal medicine consult" TSH normal, hypsrlipidema, elevated total bilirubin;

othenvise normal.

11/14/03 Psychosis NOS, DSM code: 298

Examiner's Statement in Support of Petition for Commitment by Dr. Olson states '

psychosis N03: paranoid schizophrenic vs. psychotic rnaniiivs. psychasis dw to

meidica.1 conciir ioa per examination 11/13/03.

11/15/03 Psychosis NOS

ll'/n/03 Attending Note stales MRJ and -thyroid studies normal, Diagnosis: Psychosis N03

Pre-Petition Screening Program Report recommends Qommitaient due to "mentally

ill", diagnosed Psydiosis NOS, Mood Disorder'N03; R/0 Bipolar, R/0

Schizophrehia '•:

11/18/03 . Psychosls NOS - schizophrenia vs. mania •

Neuropsychologfcal evaluation - normal fimctioni'ng

111903PsychossNOS. ••

112003PsychossNOS• • . .


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Stephen Olson, M E )


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11/25/03 PsychosisNOS

11/28/03 Psyohosis N.OS


12/1/04 Psychosis NOS, probable paraaoid schizoplirenla

12/2/04 Psychbsis NOS-


12/4/04 Psychosis N03

12/5/(M Psychoss's'N~OS,..probable paranoid schizophninio ••--

Baseline visit with Ms, Kenney, DRM to begin test articls that evening

12/8/04 • Discharge Diagnoses, Axis I;

PsychosisNOS

Probable schizophrenia '•

.Questionable history of alcohol abuse versus dependence

As noted, DRM met criteria for schi'zophrenia on 11 ,24/03 per Struclured Clinical Interview for

• DSM-IV Axis I Disorders (SCID) -Exhibit #16. He r&tams the diagnosis ofschizophrenJ a

throughout outpatient study visits - records attached as Exhibit #17.

In evaluating a new, psychotic patient Dr. Olson described the first things they lo'ok at to rule out are

a medicai condition, drugs, and then mood disorder, When asked how bipolar psychosis was ruled

out Dr. Olson described thsri they took a detailed history fsom tbe mother; Neillier mom nor DRM

could identify anyone that could provide, first hand accounts of his behavior while living iu

Califoraia [for about 3 years] other tlian brief visits by the molher on 2 occasions, DRM.did not

report any manic episodes - question A16, SCID (Exhibit #16). Dr. OIson described that ultimately


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Esfabb'shment I nspection Report

Stephen 0]son, MD

M'iimeapolis, MN 55454

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2) DRM was court ordered to get medical treatment and instead was put in a study,

Court and coiirt-related documents are attached as Exhibit 1̂9, A petition for commitment was filed

forDRM 11/17/03, A stay oF coTnroitment was court ordered 11/20/03 for 6 months under agreed

upon terms and conditions tha.t included (Exhibit tfl 9 paw 13);

•• remain hospitalized and cooperate with trea.toient until medically discharged;. ,

» enter, participate, and complete an inpatienVoutpatient treatment program and aftercare

rs'comm&ndations as determined by social worker;

« cooperate and follow rules at n̂y living-facility arranged by social worker;

" take dmgs or medica-tions only as prescribed; and, •

o • cooperate with social v/orker'as determined,

The terms of the stay of commitment and conditions ofdisch'arge are rorived at by a patient's

treatment team that includes a- psychiatrist and county Case Manager, in this cnse David Pettit. I was

not able to meel/talk/review records with Mr, Petti't as noted above but a 12/11/03 progress note

stales that he was supportive ofDRM being in fte CAPS Study . ExhLbJ t #17 pagelZ..

Before discharge from Station 12, arrangements for after care are discussed and made. The choices

'for DRM included participating in a study or receiving standard luedical care. Wjhen asked what

"stendard care" is Dr. OIson described that most patients would tie prescribed medication and asked

to return within a couple weeks of discharge and on some regular basis after tbal. He said the wait

for & new patient to gel in with a psychiatrist -is about 4-6 weeks. Standard care was described

simlarly by several others (telecons noted above)" patients see a psycliiatrist for medication

tolersLnce checks atiout each 3 nionths for 5-10 minutes. Dr. Olson and Ms. Kemiey described that

at least one significant advantage of a clinical study is tliat a patient is seen more -frequently, for

longer visits, and can therefore be more closely monitored. They des&ribed Vast medication

compliance is very important and with'more frequent monitQring, compliance is better, He said

there is a 5x greater rate ofre-bospitalization for patients who do not take tlieir Btiti-psycliotics,


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Stephen 01 son, MD

MiruaeapoHs, MN 55454

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3} DRM was no( in a state to have been able to give voluntary, iuformed conssnt.

As noted, DRM was admitted to FUMC-R on. 11/12/03 upon transfer j&ocri Regions Hospital where

he had been brought in by police in handcuffs and placed on a 72-howhold, By 11/13/03 he started

• taking Risperdal voluntarily while i.npatieirt on Station 12. A pelition for commitment was prepared

and filed in. court 1 1/17/03. On. 11/20/03 the court issued a stay of commtment. The terms ofths

stay and conditions of discharge were arrived at by DRMs treatment team. At no time was DRM

under aJam Oder, .' •

On 11/21/03 DKM was evaluated as able to give consent by Ms. Keoney and witnessed by Ms. •

Lemke. He subsequently signed tho study consent fonn with Ms, Kenncy and Dr, Olsoii, Both the

evaluation and consent documents are attached as E5{bibit_#14andl5, Note that the evaluation of

sulj ects abili ty to consent is an addi-ti onal step perfbnned at tliis study site - it Is neither Teqwr ed

nor mentioned in the study protocol.

By the time DRM consented on 11/21/03 he had undergone an internal medicine'evaluation

(11/13/03), had an MRI and thyroid studies (11/17/03), a neuropsychological ev&l wtiou (11/18/03),

a chemical dependency evaluation (1 1/21/03), and had been observed on a daily basis by n'u.merous

medical and'mental health care staff oa S-tation ,12. There was nothing different about this subject

than. others enrolled to indicate he couldn't provide voluntary, informed consent per review of his

medical records or the approved study pyotocol which allows foreiu'ollineot ofinpatient subjects,

4) DRM was kept on s.tudy despite deterioration.

DRM consented to Un's study 11/21/03 and began taking study medication 12/5/03, The symptom he

• consistently scored on the PANSS a.s mild to moderately severe is'G12, "Lack ofiudsroent.gnd

jnsight; Impaired a-wareness or understanding of one's own psychiatric oondition and life


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Est.abh'shmendjispecdoti Report

Stephen OI son, MD .

J vlinneapoli 's, NW 55454

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""'Abbreviated PAWS at screening

*rater up to Visit S9 was J ean Kenney, V10 and VI 1 ralerwas J ulie Psarson

The SAE report for DRMs death CExhibit#12) states in pan "Over the last few months, DRMs

ADLs have detwiorafcd, often with a dish'eveled appearance and wearing the same dothes &s

previous visits." I asked Ms. Kenney about "ADLs" and she described that it is terminology, not an

actual list or scale that is do.cumentsd and tracked. There is also a reference to dwli'ning ADLs in a

pTOgress note (Exhibit #] 7.page 18). Otbeiwise, leview ofDRMs records - attached and described

further b


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Stephen Olsbn. MD


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4/28/04 Visit #) ], Calgary Depression Rating Scale is performed looking at 9 items and DRM

is raled 1 - Absent for each indicator of depression,

-PANSS comments; "DRM presents disheveled today, .hair vnkempl, wearingj&cket

onho day •

Besides tlus study, DRM was participating and being obsen'ed in'hls group bome - Theodore I; the

Day Treatment program at FUMC-R three llnies per week; mdividuaJ therapy at Ihe Eagau .

Counseling Clinic; and regularly meeting with his Dakota County Case Manager who is (he

responsible liaison between the court and physician for a committed person. No deterioTa.tion

' appears to havebeennotedinthesearenas. . ' ' . •

When DRM was discharged Irom tlw FUMC-R on 12/8/03 he went directly to TJ ieodore I, a "Rule

36" residential facility for adults with mental illness. Dr. Olson described that DRM would have

been discharged sooner but they were waiting far bed to become available at Theodore I,

"Medication exchange records" were earned by DRM between Theodore I with steff notes on one

side and MD/Dr. CUson notes 'on the other. No problsms were noted in exchange records except on

3/30/04. That note states home staff began more rigorous medication check with DRM - liaving him

observed during and after dosing>to assure, he was swallowing meds- [It was suspected that he

mght be palmng medication because of one occasion when it was thought he brought his hand

down from his mouth too quickly - see Memo of Tekcon with Eric Anderson, Attachment #8] . No

other concerns were suggested 'by the notes which are attached asExhjbiL ffl 7 page 20 - 27,

DRM was admtted to the FUMC-R outpatient Day Treatment Program on 1/14/04. In this

program he received 2 boui-s of group therapy and 1 hour of occupational therapy 3 times per-.week,


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person interviewed as a very good, involved, experienced case manager. There was no indication in

records, discussion, or interviews during this inspection of disagreement with DRMs enrolling or

con-tiniting in this study.

' Overdll, there is no evidence of suggestion or request lo clmge DRMs treauxisnt plan, change

medications, or re-bospitaUze him from.any of the 4 non-study arenas noted.

At the same time. Dr. Olson described that no one was in favor of dropping DRMs commitment.

when his 6-monfh slay was neanng expiralion. He said DRM cii'd not object tQ tbis. He said their-.

inlention was to keep. him in the area, to stabilize and continue treatment whether on or off study .

instea'd of rushing on his ultimate goal which was to return to California, Dr. Olson's :

recommendation to extend his stay of commtment is attached as Exhibit #]g pâ e ,1̂ .

. Both Dr. Olson and Ms. Kermay said DRMs main presentali'ori was not fully graRplng, having insight

into the severity ofhi's disease. He did not present any depression, syicidal thoughts, satanic or •

religious thoughts [as had been present at admt]. He appeared to be compliant with medications.

He was thought to have improved somewhat in. the Day Treatment program such that close to

discharge from that program he was looking for an apartment with his case manager, and bad started

at a drop mcenler/coromuiuty program. They were aware that DRMs mother did no


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Stephen Olson, MD

MinncapoHs>MN 55454 •

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5) The Cis are guilty of miscouduct and the University ofMN is possibly shieldiug tb.eir

staff,

I did not find any evidence of msconduct, significant violation of the protocol or regulations

go-verrung clinical investigators or LRJ 3s in tTiis inspection, data audit, or interviews.

Other J nvestis;atlons of DJ RjMsJ cathj. (1) The UMN ?.8 perfonned a routine, full-board review of

• DRMs dwtb/SAE. No in-egularities were noted or further follow-up performed per recoTds (EsMbit

#12̂ &ge-3s) and per contact with the LRB (memo oftelecotr'withMoiraKeane, Attsclimeni #7),

(2) A post-mortem/morbidity and mortality conference on the DRM case was conductsd'on 1/5/05.

No reports, sununaries, notes, pr formal recommeDdations were or are roads reportedly. I t is a

' hospital-driven internal peer-review used for improvement and teacliing per Keith Dunder, XJ MN

artomey (reference memo oftelecom, ̂ ttacfcment#5),

(3) The MN Department of Human Services perfonned an investigation in response to a Complaint

' that staff at the Theodore I group home neglected DRM, a "vulnerable adult" prior to his death at .

that facility. No indication of maltreatmeiri/neglectof supervision was found and no further follow-

up recommended. The report was provided througli MN DH3 and is attached to a memo oftelecom

with Investigator Norm Isaacson - Attachment #6, . . -

(4) DRJ Mts death is also being investigated by the MN Office of the Ombudsman for Mental Health

8t Mental Retardation. That investigation is still in-process. Results will be available publicly.' See

memo oftelecom with J o Zillhardt of that ofiioe.- AttechmontfflO,

Dr. Olson said [and records show] that in addition to the above he and Ms. Keimey have been


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Stephen Olson, MD


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INSPECTION • •

Pro(ocol: The protocol sent with this assignment - ASfifI lElSUt ̂]s the saiae as that on she and so

no additional copy was collected, Deviations from the protocol were documented and a log is

attached for reference as Exhibit #22, No un-reported deviations wore founci In tliis inspection.

Sub fee ts ̂ r ec o rd s; Subject records consist of a din ical cbarf/binder containing signed conssnt

forms, lab reports, shidy visit note's, etc,; and, a binder of source data forms for mainly the various

evalualion scales, e.g, SCID, PANS S, CGL These are maintained in a locked room in the ARC,

Subjects additionally have an inpatieut medical chart if hospitalized and ovtpatleaf medical chart

ifs/he participated in for example the Day Treatment program, which are maintained ui themedical

records department at FUMC-R, Subject records are adequate to account for all subj'Bcts through

their stated participation in.lhis study. There are examples of subject records for DRM attadied as

Exhibit #17, 2L13, and ,20, respectively.

.GoxiscnJ ' of human ŝubi'ects:, A consent form is on file for each subject, signed prior to screening,

per review of subject Source records. Additionally, an Evaluation to Sign Consent Fonn was

performed, witnessed, and documented for subjects prior to obtaining informsd consent. This •

CivaJuation to sign consent form was initiated liy this site, i.e, it was.ncrt required or suggested by the-

protocol or sponsor. Ah example signed consent fomi and evaluation are attached for reference as

Exhibit #14 and 15. The consent form vras revjsed on 5/2/02,7/1/02» 10/23/02, 3/25/03, and 3/24/04

• and approved by the IRB.


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Stephen Olson, MD

Mimeapoli's, MN 55454

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To date, reports and change requests appear to have been appropriate and submitted timely with one

exception- see verbal observation #2 under Discussion with M'anagemenf regarding a consent

form update on risks ofdiabeies and hyperglycema. Also, the original application to the IRB stated

this study wasn't associated with an I ND- verbal observation # 1. .

Adverse even (s:. Adverse events to date appear to have been appropriately captured and. reported per

review of subject records. Two serious AEs occurred and were reported'to Ihe sponsor and IRB;

» Subject ifl3/DRMdeath73uic)de on 5/8/04-ExhibiV ,̂ •

« Subject #20/CLW pregnancy/fetal raisearriage on 5/6/04 - exhibit #24.

Sponsor/moBi'tor:. Quintiles is the contract monitor on this study. A Senior Clinical Research •

•Associate from CJ ncuatti; OH was assigned to this site first fQllowed by another senior CRA. located

in Waulcosha, WT. The first monitor visit-was on 1/7/0.3 and additicmal visits liave lieen made about

quarterly including during this inspection, the week of 1/10/05. A copy of the Site Visit Log and

post-visit letters/r.eports are attached for reference as Exhibit K25, . •

Test article accountability: Test articles were ordered for mdividuid subjects via an Interactive

Voice Response System (IVRS) phone system operated by QuintiJ es CTriangle Park, NC). Test

articles were delivered to the attention. of-Ms, Kenney at the ARC, Subject compliance was checked

at each visit. No deficiencies were noted in accounting for test articles received, dispensed, .or

returned. Records appear adequate to track all TAs received and dispensed.

iilectfoni'c records and signatures: Data was eriteTed into an e]ectronic,system from source

documents such as data forms provided by the sponsor/monitor, lab reports, etc. versus direct entry.

None of the electronic case report forms are copied or kept here and I did not request any for review,


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EstabIisbmentTnspectioaReport FEf; 3004927371

SephenOson MDE Sart; 01032005•

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Record ŝ -evjewed in this inspection and data audit that gre not elsewhere noted include;

» ail correspondence with the sponsor, monitor, and JRB

» 1572's" copies are aUached as Exliibit #26

i- ]2 sets of subject records in depth, mcIu(iingsubject#3/DRM . .

» , all subject records regarding consent, eligibility, adverse events, concomitant medica.tions,

current status, etc.

e financial disclosure information .

h)bitf23̂ ESge-5J . Eventuiilly thj's-was resolved, Dr. Olson said he didn't know an IND

. was involved initially. I stated this is important information to provide to an IRB, why, and that any

•trale he signs a 1 572 that's an indicator that he's working on an &QD study. He said he is more

aware of this now and will be attentive to it.

2. Study site's wê apprised of new risks of diabetes aud hyperglycema by the sponsor on S/15/0'1.

This site added new risk language to the consent forms on 3/24/04 bnt did not submt these changes


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Estflbtishroent Inspection Report

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Minneapolis, MN 5S454

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ATTACHMENTS

1. Assignment from CDER/HFD-46, dated 12/14/04

2. Complaint, and log of communications since the complaint

3. Protowl, dated 3/1/03

Memos ofTeecons:

4, Bill Andersen, PhD, LP, Eagan Counseling Clinic, Eagan, MN

5. Keith Dundcr, Attorney, Office of the G ênera.1 Counsel, AHC, UMN mcluding-copies of

ie.tters he's sent to DRMs mother and requested to'fo'i-ward bare


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EstaMishmeatIuspection Report

j , - StephenOson MD


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13. DKM inpatient medical records;

•AdmssonNoe 111203

»Interna mdcneconsut, 111303(pg3) ::

• Discharge Summary, 12/8/03 Cpg 4)

» Regions Hospital Emergency Center records (admit prior to transfer here) j

o72HouHod 111203 (pg7 ••' ̂

o Crisis Program Psychiatric Assessment, 11 /12/03

o Emergency Physician's Record

oEmrgencyNursngRecod —

Progress notes,1112-] 2803(pg] 2 incudng Atendng Notes on • • ;

o111303pg15 • . . ^̂

o111703pg25•

o111903pg29 •

o 11/21/03 (pg 35)

o112503pg40

o12103pg46•

o 12203pg48•

o12303pg51•

o12503(p36• . . . .

o12803pg58 . •

Odeso treaenen pg60}. . . .

MedcaonAAanstratoi Recods (pg71 ' • ' • :

Neuropsychological Evaluation, 11/18/03 (pg 78)

Chemcal Dependency .Evaluation, 11/21/03 (pg 82)

Adut CDAssessmn, 112803(pg83) • '

Treatment Plan Review on 11/21/03, 12/1/03, mid 12/8/03 (pg 84) ' .

Adut Sr Assessment ofSucdeRiskforDsoharge 12803(pg 87 i


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EstabJ ishme.n ̂Inspection Report

Stephen Olson, MD


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19, DRM court and court related records:

» Petition for J udicial Commtment, I V] 4/03 filed. 1 1/17/03

• Examner's Statement in Support of Petition for Commtment, 1 1/14/03 (pg 3)

» Pre-Petition Screening Program Report, 11/17/03 (pg 5)

» Order to Confine, to Transport for Examination, Hearing; Appointment qf Attorney,

Examner and Noce 111703(pg9) ' . . • •.

o Order to Release Medical Records, ] I/] 7/03 (pg '11)

• ' Court Medication S.ummary, 11/20/03 (pg 12) .

*. Findings of Fact, Condusions ofLawand Order for Stayed Commtment, 11/20/03 (pg 13)

» Court Medication Summary, 1 1/26/03 (pg 17) •

• Letter la Dakota County Social Services from Dr. Olson, 4/27/04 re; recommendation to

extend stay of commitment to disallow leaving the state, (pg ] 8)

• Addendum to 4/27/04 letter from J ean Kenney, 5/3/04 re; diagnosis info. - 295.30

Schizophrenia, paranoid type,(pg 20)

20. DRM outpatient chart records:

» Discharge Summary, 5/5/04,

• • Adult Day Treatment Progress Notes, 1/14 - 5/5/04 (pg.4)

* Intake assessment, 1/J 4/04 (pg 39)

• PhoneContacts log(pg45 . . • .

• Miscellaneous correspondence

21. Source Document data forms, portions ofFANSS aiid CGI with any score of 3 or higher,

sereenng to Vst #11• •

22 Prooco DevaonLog•. •

23. BR.B records;

• Portionof appicationfor IRB revew, 21102. • •

* Response to IRB from Dr. Otson, 4/3/02, including re; ,'itatus of test articles (pg 5)

. • Progress report to IRB, 12/24/03 (pg 7) ' •


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•• >' •«


Stephen OIson, MD


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26. -1572s, dated:

4/2/02

6/13/02

11/25/02

10/21/03

12/22/03

1/7/04

7/9/04

--.»• 12/17/04

ĈVA ,̂ ( , /̂ .

Sharon L, Matson, Investigator

Issues Arising from the CAFE Study and the Suicide of Dan Markingson hllp://wwwl.umn.edu/usenate/resolutions/131205panelres.html


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Approved Faculty Senate - December 5,2013

by the: Administration - Faculty 2014*

Board of Regents - no action required

*The Admnistration recognizes the Faculty Senate resolution requesting an external

review of clinical research on human subjects at the University of Minnesota and is

moving forward with this review. The review will be managed by an independent,

external firm who is expected to call upon national experts in the field of clinical research

on human subjects research and who are widely recognized for their expertise, knowledge

and achievement in this field. This review will include a review of relevant standard

operating procedures and an assessment of University compliance with regulations and

applicable law. It will result in a detailed report outlining strengths and weaknesses of

current policies, practices, and oversight and any recommendations for any deficiencies

identified. This process will include consultation with faculty and the final report will be

public.

Issues Arising from the CAFE Study and the Suicide of Dan Markingson

PREAMBLE:

In May 2004, Dan Markingson, while enrolled in a clinical trial of an antipsychotic drug (the CAFE

study) at the University of Minnesota, committed suicide. Since then individuals and groups within

and outside the University have raised questions about the study, how Markingson was recruited into

it, his treatment during the study, and the circumstances of his suicide.

On October 21, 2013, a letter co-authored by six bioethicists from outside the University, with 175

co-signatories, was addressed to President Eric Kaler and Professor Eva van Dassow, as chair and

vice-chair (respectively) of the Faculty Senate, and to members of the University of Minnesota Senate.

The letter asked the Senate to endorse and request an independent investigation of the issues arising

from the Markingson case and the CAFE study. That letter is available at: http://wwwl .umn.edu

Issues Arising from the CAFE Study and the Suicide of Dan Markingson http://wwwl.umn.edu/usenate/resolutions/131205panelres.html


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specifically had been investigated several times from different perspectives, and that those

investigations did not address the broader question of whether the University's current policies,

procedures and practices, some of them changed since the Markingson case, reflect both best practices

in clinical research on human subjects and the faculty's high ambitions for ethical behavior. Members

of the FCC also recognize that external evaluations can have the advantage of fresh perspectives not

biased by familiarity with current practice, and are a way for the public to have the utmost confidence

in the integrity of the research conducted at the University of Minnesota.

For this reason, the FCC feels that the way forward is to recommend that an independent and

transparent examination be undertaken to evaluate the University's procedures, practices, and policies

governing clinical research on human subjects, and in particular clinical research involving adult

participants with diminished functional abilities. While the specific charge for such an examination

requires further work, FCC believes issues to address may Include investigator conflict of interest,

institutional conflict of interest, consent policies and procedures, case management of enrolled

participants, mechanisms for overseeing such research and mechanisms for addressing adverse events.

Therefore, the FCC suggests to the Faculty Senate the following resolution:

Resolution on the matter of the Markingson case

WHEREAS the faculty of the University of Minnesota are committed to upholding high ethical

standards in the conduct of research;

WHEREAS questions continue to be raised about the policies and procedures followed in the case of

Dan Markingson, a 26-year-old participant in a clinical trial who committed suicide in 2004;

WHEREAS the University has suffered reputational harm in consequence of this tragic case and its

aftermath;

WHEREAS the faculty seek to ensure through independent evaluation that the University's ethical

standards for clinical research on human subjects meet or surpass the norm,


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U N I V E R SI T Y O F M I N N E SO TA

Office nfllie Gcnerul Counse 360 McNwncnv Alumni Center

200 Oak Slreel S.E.

M inneapolis. M N 5545 S

Office: 612-624-4100

/YU-; 612-626-9624

J une 7, 2011

V I A E - M A I L

Professor Carl Elliott

Bioethics

N-302 BoynHS

1171

410 Church Street SE

Minneapolis, Minnesota 55455

Dear Professor Elliott:

This responds to your request for background information related to the

letters you received from the Board of Regents' Chair Clyde Alien and myself

dated February?, 2011 regarding the Markingson matter.

You indicated that you have reviewed "the litigation." If so, you have long

had available to you the reviews by external psychiatrists and other experts

contained in the court files, as well as the decision of the Hennepin County

District Court. Nevertheless, for your convenience I have attached electronic

copies of the decision of the court dated February 11, 2008, and summaries of


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Professor Carl Elliott

J une 7,2011

Page 2

University is unable to provide documents to you detailing the conclusions

reached by these governmental units m this matter. However, as you have

indicated publicly that you are in communication with Mary Weiss, who made the

complaints to the Board of Medical Practice, you may ask her for copies of her

complaints and also obtain from her, as the compiainant, the Board's conclusions

regarding her complaints.

Sirycerey, /\

/

l


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U N I V E R S I T Y O F M I N N E SO TA

Office of the Generuf Counsel 360 McNmnara Alumni Center

200 Oak Str eet S.E .

M inneapolis, MN 55455

Office: 612-624-4100

Fax: 612-626-9624

April 22,2011

M ike H oward

9876 H amlet L ane South

Cottage Grove, M N 55016

Dear Mr. Howard:

I am writing in response to your letter of April 6,2011, in regard to the "signed Caf6-HIPAA"

release. You inquire as to where that document was found.

I am advised that the document was located among the voluminous records in the lawsuit

relating to Dan Markinson's death.

Sincerely,

^̂ U4̂ h ^

J


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U N I V E R S I T Y O F M I N N E SO TA

Office ofllie General Counsel 360 McNamara Aiumni Center

200 Oak Street S.E.

M iimeapotls, AW 55455

Office: 612-624-4100

Fax.- 612-626-9624

March 16,2011

Mr. Mike Howard

9876 H amlet Lane South

Cottage Grove, MN 55016

Re: Complaint of Misconduct against Stephen C. Olson, M.D.

Dear Mr. Howard:

The Board of Regents has asked me to respond to various allegations you raised in a complaint

submitted to the Board in April 2010 against Dr. Stephen OIson, Associate Professor in the

Department ofPsychiaby in our Medical School.

The University identified seven allegations in your lengthy complaint materials. After careful

examination of each allegation, we have found no University policy violations or other improper

conduct by Dr. Olson warranting University action against him. Each allegation is outlined

below, followed by a summary of the University's findings.

Allegation 1. Dr. Olson shared protected health mfonnation in regard to Dan Markingson with

members of his research team without obtaining a HIPAA release from Mr. M'arkingson.

University Finding. Attached is a copy of the HIPAA authorization executed by Dan

Markingson on November 24, 2003.

Allegation 2. Dr. Olson did not understand how or when HIPAA regulations applied to


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Mr. Mike Howard

March 16,2011

P age 2

Markmgson could participate in the study. The interval behveen the date the consent was signed

and the randomization date is th:e "screening period" during which there were no changes in his

treatment. I f the case manager had determined that the study was not an appropriate form of

ti-eafmeht, he would, have been dropped before giving him study medication. Mr. Markingson

began receiving study medication on December 5,2003.

Allegation 4. Dr. OISon testified in a deposition that he had no knowledge of certain regulatory

Statutes requil-ed for conducting clinical trials and the protection ofhdman subjects.

- University li'iiidiug; A GOm'plete reVi'e'w of Di-. Olson's depogition transcript, consisting of

hmdreds of pagieis,, Simply does Hot $uppoft this allegation.

AU'egafion 5. Dr. Olsort allegedly delegated the dispensing of very powerful aflti-psychotic

drags to a study cooi-diriator not licensed to dispense drugs, who had received no prior training

flof education regarding how these drugs are taken.

UAiversity Finding. Dr. Olson was assisted in the CAFE Sfudy by a research coordinator who

had a bachelor's degree in psychology and a master's degree in social work. As the study

coordmator, ftds person worked under the close supervision of Dr. Olson as the principal

investigator.

Throughout the study, Dr. OlSon was responsible for "dispensing" the medication in his capacity

as principal investigator. .Under Dr. Olson's supervision, the study coordinatbr merely gave the

pre-packaged and marked bottles of pills to Mr. Markingson. Mr. Markingson, upcinretummg to

Theo House, the half-way house where he resided, would then give the bottle of medication to

the Theo House staff Wlio oversaw the delivery of the medication to him on a daily basis, and

helped assure that he wa's taking the right doses at the right time.


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Mr. Mike Howard

M arch 16, 2011

Page3

interest, and must conduct themselves accordingly. Dr. Olson did not violate any University

policy.

Allegation 7. Dr. Olson acknowledged having received numerous mentally ill patients in the

psychiatric unit at the University into his own study.

University Finding. I t is true that Dr. Olson, and many other researchers, have enrolled

mentally ill patients into studies. Academic clinical research into mental illness, and the

potential to cure mental ilbiess, requires research involving those who suffer from mental ilkiess.

The issue is not whether such mdividuals may participate in such research, but whether

appropriate protections are in place to protect those research subjects, All clinical research at the

University involving a mentally ill patient is reviewed by the RB to assure that the study

protocol is appropriately constructed, and that subjects give informed consent for their

participation.

The University appreciates your patience in awaiting the completion of this thorough review of

the allegations you raised.

Sincerely,

M A T K I t o U ^ k y ^^

MarkB.Rotenberg ̂

General Counsel

MBR: mwl

Attachment


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UN IVERS ITY OF M IN NES OTA

Office of the Generul Counsel 360 McNamara Ahmmi Center

200 Oak Street S.E.

M inneapolis, MN 55455

Office: 612-624-4100

Fax: 612.626-9624

February 11,2011

Mr. Mike Howard

9876 Hamlet Lane S.

Cottage Grove, Minnesota 55016

Re: Complaint of Misconduct against S. Charles Schulz, M.D.

Dear Mr. Howard:

The Board of Regents has asked me to respond to various allegations you raised

in a complaint submitted to the Board in December 2009 against Dr. S. Charles Schulz,

Head of the Department of Psychiatry in our Medical School. This letter summarizes the

University's extensive review process and our findings.

Your allegations against Dr. Schulz were evaluated under the following

University policies and procedures: Academic Misconduct, Individual Conflicts of

Interest, Disclosing Individual Health Information for Activities Preparatory to

Research, and Code of Conduct. Because the Code of Conduct is intended to reflect other

University policies and "does not create any different or additional rights or duties"


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55/288

Mr. Mike Howard

F ebruary 11, 2011

Page 3

Allegation 5. Dr. Schulz allegedly committed wrongdoing because he was

untruthful in a 2008 deposition in a civil lawsuit when he failed to mention his earlier

study on akathisia.

University Finding. There is no University policy violation by Dr. Schnlz based

on this deposition response, and there is no factual basis to find his response was

un truthful. In his deposition, he was asked what the term akathisia means; he responded

with a straightforward explanation. He was not asked whether he had published any

papers on akathisia or what were the finding of his papers. The 1992 paper described

akathisia as a "syndrome of motor restlessness" (Compr Psychiatry: 33(4) at 233), which

is similar to the description provided by Dr. Schulz in his deposition.

Allegation 6. Dr. Schulz allegedly violated the rights of patients because he stated

in a 2008 deposition in a civil lawsuit that he does not always inform patients of his

relationships with industry.

University Finding. There is no University policy violation by Dr. Schulz based

on this deposition response. The relevant exchange in the deposition asked about Dr.

Schulz's opinion, not his personal practices, regarding disclosure to patients. The

University's review of Dr. Schulz's compliance with his conflict management plan of

2007 shows that he made the required disclosures of his Scientific Advisory Board role at

AstraZeneca to the research subjects in an Astra Zeneca funded trial.

Allegation 7. Dr. Schulz allegedly breached the confidentiality rights of patients


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Mr. Mike Howard

February 11,2011

Page 4

University Finding. There is no University policy violation or other improper

conduct by Dr. Schulz in connection with his CME presentations. When Dr. Schulz gave

CME presentations about antipsychotic drugs, his focus was not limited to a particular

drug, consistent with CME guidelines that require balanced presentations. His

presentations were directed primarily at other mental health professionals, not primary

care providers, and he has not recommended Seroquel for uses other than very serious

psychiatric conditions.

Allegation 9. Dr. Schulz allegedly committed wrongdoing by conducting clinical

trials that force subjects to go off established drugs and potentially receive a placebo in

order to promote a drug.

University Finding. There is no University policy violation or other improper

conduct by Dr. Schulz based on his participation in placebo controlled drug studies.

Dr. Schulz did not participate in Study 41 because no subjects were enrolled at the

University. He served as a co-author but not investigator for Study 132 which was

conducted internationally. The use of a placebo controlled study is a widely recognized

and approved scientific standard for studies evaluating extended release forms of

approved drugs for approved indications of the drug. There is no evidence that Study 132

violated applicable scientific or regulatory standards related to use ofplacebos.

2007 Conflict Management Plan. In addition to investigating the allegations in

your complaint, the University also examined Dr. Schulz' compliance with his 2007


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U N I V E R SI T Y O F M I N N E SO TA

Offiw of the General Counse 360 McNamwa Alumni Center

200 Oak Street S.E.

Minneapolis, MN S54S5

Office: 612-62-1-4100

February7 2011̂ 6?.-626-9624






Leigh Turner, Associate Professor




N 504 B oynton

410 Church Street SE


Dear Professors Elliott, Bartels, L iaschenko, Marshall, Song, Turner, Craddock, and Tronto:

I have been asked by the Chair of the Board of Regents to supplement the response he provided

today to your letter of November 29,2010, At the Board's request, my office has reviewed the facts

and circumstances surrounding the CAFE research study and the suicide of Dan Markingson to

which you refer in your letter. Based on the examinations of this case already conducted by the

U.S. Food and Drug Administration (PDA), the Hennepin County District Court, and the Minnesota

Board of Medical Practice, assisted by the Minnesota Attorney General's office, the Board of

Regents determined that further University resources should not be expended re-reviewing this

matter.


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February 7, 2011

Page 2 of 3

Your letter to the Board of Regents suggests that this case may illustrate "an alarming series of

ethical violations and lapses." Our response to the allegations in your letter are as follows:

1. "Recruiting a mentally ill, possibly incompetent subject into a research study, while he

was under an involuntary order."

The allegation that Mr. Markingson was improperly admitted into the CAFE study was reviewed by

the PDA, the District Court, and the Board of Medical Practice, and found to be completely without

merit. It must be understood that Mr. Marldngson was determined to be competent to consent to

treatment at the time he consented to participate in the study in the judgment of two courts and

independent evaluators. The District Court judge that ordered Mr. Maridngson's stay of

commitment and participation in the treatment plan specifically found that "the rights of

Respondent [Markingson] have been protected throughout these proceedings," and that "the Dakota

County Social Services Department has developed a plan for services to treat the Respondent's

mental illness which is agreeable to the Respondent." During that court proceeding, Mr.

Markingson appeared in person, was represented by counsel, and, as noted by the court, a Dakota

County case manager recommended and endorsed Mr. Markingson's treatment program, In a

second, and separate, judicial proceeding, the Hemiepin County District Court specifically

addressed the allegation that Mr. Markingson had not provided his informed consent to participate

in the CAFE study, and dismissed that allegation "based on several undisputable facts."

2. "Large financial conflict of interest on the part of University researchers conducting the

study.

Both Dr. Olson. and Dr. Schulz received consulting fees from Astra Zeneca. Those amounts were

properly reported in the University's REPA system, and all University regulations were followed.

The University's examination of this allegation reveals no violation of existing conflict of interest


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February 7, 2011

P age 3 of 3

5. "The failure of University researchers to address the legitimate concerns of Mr.

Markingson's mother, Mary Weiss."

Ms. Weiss did express heartfelt concern for the welfare of her son. Her concerns not only were

heard at the tirrte, they were carefully reported in the record. However, the record also shows that

all of the mental health professionals involved in Mr. Markingson's treatment felt that he was

improving. His death was a tragic shock to his caregivers, including his social services case

manager and others not associated with the University. Notwithstanding Ms. Weiss' belief, there

simply is no evidence that Mr. Markingson's death was causally connected to his participation in

the CA F E study.

6. "The apparent development of a s

briefings to university of minnesota board of regents on markingson case

Documents