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University of Minnesota

Review Period:

01/10/2008-01/09/2009

-Continuing-Rev-iew-of-IRB-^Pending-

Rev; 03/01/2005

:M.e.dica,LResearch ..—-=^

-Study" Number:-0709M168-44- --- - -..----.-

Principal Investigator: Sellmann C Schulz
Title(s): Seroquel XR for the Management of Borderline Personality Disorder:
A Randomized Double-Blind Comparison with Placebo !
Study Status
Active (Enrolling Subjects)

Funding Source(s)

AGENDA.

i^M JMSL

Funding Source:
Funding Type:
Funding Source: AstraZeneca

Funding Type: OTHER
Personnel

Schulz, Selimann (P. I.)
Crow, Scott (Co-lnvestigator)
Milev, Peter (Co-lnvestigator)
Miller, Michael (Co-lnvestigator)
Moen, Richelle (Co-lnvestigator)
Romine, Ann (Correspondent)

Investigational Drug(s)
IND Number: 45,456
IND.Holder: AstraZeneca (Sponsor)

IDS Number: 3462

Study Enrollment
Number of Subjects Approved for study:

50

Number of subjects enrolled this review period:
Male Female Unknown

T

T

Total

0 ~T2~

The University of Minnesota is an equal opportunity educator & employer.
© 2004 by the Regents of the University of Minnesota,

Page 2

Page 1

Number of subjects enrolled to date:
-Male- —- —-Female- ~~~" "Unkn'own •

^_1=1———\-0 —^2=^.
Is this a multi-center study?
Yes
Total national accrual to date; 2

Unanticipated Problem Reporting
Since the most recent IRB continuing review approval, have any participants withdrawn from the
research?

No
Since the most recent IRB continuing review approval, have any participants complained about the
research?

No
Have any serious and unexpected adverse events been reported to the IRB?
No

Study Suimmary
Summarize preliminary information about any results and/or trends:
In beginning phases of enrollment with 2 subjects enrolled.

Have there been any changes in protocol approved by the IRB since last continuing review?
No
Since the most recent IRB continuing review approval, have there been any progress reports on the
research?

No
Since the most recent IRB continuing review approval, have there been any multi-c.enter trial reports?

No
Since the most recent IRB continuing review approval, have there been any other information
relevant to this research discovered, especially information about the risks and benefits associated
with the research?

The University of Minnesota is an equal opportunity educator & amployer. Page 2
© 2004 by the Regents of the University of Minnesota.

PageS

No
Since the most recent IRB continuing review approval, have subjects experienced any benefits?
Yes
2 acti.ve subjects report receiving benefit frpm.stydy.participatjon {.hys_far,

External Findings
Is there anything in the relevant recent literature that the IRB should know about concerning this
research?

No

Consent/Assent Forms
Have there been any changes to the consent and/or assent form(s) since the last IRB approval?
No
Have. translated consent short forms been used in conjunction with an interpreter to obtain consent

for this study?
No

Other Comments
Study start has been slgnigicantly delayed by contract hold-ups.

The University of Minnesota is an equal opportunity educator & employer. Page 3
© 2004 by the Regents of the UnlvsrsityofMlnnssota.

Page 4

rP-Tr"—-—S-cbulz,:Sellman=^—•^""—=—'O.TiiveFsity^'f-M:imeso'^

HSC#; 0709M16844 Research Subject's Protections Programs
Reviewer: • Institutional Review Board

-Meeting-Date:- -—— • — — - -- "—-———- - —- — - —• — •-—
Full Committee Review—Continuing Review of Approved Research
If you choose to submit this form eleytt-onically, please send to u-b(%umn.edu.
"/in IRS shall conduct 'continuing review of research covered by this policy ut inte.n'als appropriate to the
degree ofmk, but not less than once per year, andfsha/i have the aulhorUy to ohaen'e or have a third party
ohseri'e the consent process and the research."

21CFRS6.109 and 45CFR46.109
"Continuing, review ofresuurch must be siibslcuiiive and meamngfiil."
OffRP Guidance on Continumg Review 1-15-07

Study status: [X] Enrolling subjects
Following subjects

D On hold

Closed to enrollment
Study Enrollment: Note any issues. Is enrollment as expected, has PI overenroHed, is
there a lack of subjects or are they nearing approved totals? Is the PI requesting more
subjects OR should PI request more subjects?

2 of 50
Funding; Any changes in the last year? Q Yes • D No

Federally funded? . D Yes D No
Study personnel; Any personnel changes in the last year? Q Yes Q No
Are personnel lists in agreement with recent Con Ren form and consent forms?

D Yes D No
List discrepancies: Nathalie Vizueta, MA. listed on consent - not listed on con rev form
Conflict of Interest: Have there been any change in COI in the last year?

Yes Q No
Investigation al Drugs or Devices: Have there been any changes or additions in the

last

year?

Q

Yes

Q

No

UPTRTSOS (unanticipated problems or serious adverse events): Since the most recent
IRB continuing review approval have there been any UPIRTSOS to report?

D Yes D No
List issues or concerns: none given

Page 22

Study Summary: Is the summary descriptive enough to assess ongoing risk and
benefit -in relation to the length and complexity of the study?
l-.Y-es-"" Q-No-

Comments: study just started enrollment - two patients receiving medication have reported benefit
External Findings (such as interim analysis or DSMB reports, etc.): Tins report
should reflect how long the study as been open.

Yes Q No
Comments: none to report
Consent and Assent Forms: Are forms current for 1KB practice and/or standards?

D Yes D No
If the risks and/or benefits are not described accurately the committee should discuss and
make a determination. (Please edit forms and hand in edited, forms to IRB staff.)
Comments:

Inclusion of Children in Research:
If children are included in this research confirm that they should still be included m this

research. Q Yes D No [X] NA
(According to Subpart D and tlie requirements for pennisyion by parents or guardians and
for assent by children, 45CFE46.408, see yellow sheets).
If children are included this inclusion must meet one of the following criteria for
risk/beuefit assessment according to federal regulation (21CFR56 and 45CFR46 Subpart
D, see yellow sheets),

[_] (404) Minimal risk
Ij (405) Greater Ami minimal risk; but holds prospect of direct benefits to subjects.
(406) Greater than minimal risk; no prospect of direct benefit to subjects, but likely to
yield generalizable knowledge about the subject's disorder or condition.

Page 23

Criteria for IKB_AKProva]:

Confirm that the criteria for IRB approval are still met.
(21CFR56.111 and45CJ?R46.ni)
II Risks to subjects arc minimi/.ed
[_] Risks to subjects are reasonable in relation to anticipated benefit, If any, to subjects,
and the importance of the knowledge that may be expected to result
Q Selection of subjects is equitable
II Informed consent will be sought from each prospective subject or the subject's legally
authorized representative, in accordance with 21CFR50 and/or 454CFR46.116
Q Informed consent will be appropriately documented, in accordance with 21CFR50.27

and/or45CTR46.U7
Where appropriate, research plans make adequate provisions for monitoring the data
collected to ensure the safety of subjects, QYes |[ NA
Where appropriate, there arc adequate provisions to protect the privacy of subjects and to
maintain confidentiality of data. • QYes D NA
Where appropriate, vzilncrable populations have adequate protection; risk and benefit
analysis confirms their inclusion in the research. [_JYes Q NA

General questions:
**m' questions 1-4 are YES please address and document in the comments and
discussion section.

1. Does the ongoing continuing review information indicate any alteration in the risk and
benefit balance or ratio from previous reviews? Q Yes Q No
2. Does the consent or assent form(s) require revision or updating? Q Yes ' || No
3. Does the ongoing continuing review information prompt notification ofstudy subjects

already enrolled? Q Yes Q No
4. Should the committee request or seek verification of information from other sources,
such as DSMB, fonder, sponsor, or literature search? [_] Yes D No
If question 5 is NO please address and document in the con-iments and discussion section.

5. If vulnerable populations previously were subjects should they continue to be included

in this research? Q Yes • Q No DNA

Page 24

-I.s-lh v-i'-vy-i tiW—iutciLv.d 1-s ti ll-ap.p r-o.pEiii.te-toi—this^s.tu.dy-i

For continuing review approval federal regulations state that studies need to be reviewed
no-iess-that yearly-but the-committcc may-set continuing-feview-at-a-morefi'equentinterval.

Check the review interval appropriate for tllis study:
Annually
D Every 6 months

Q Quarterly
Other interval (state specific renewal interval and provide justification)

Committee Determination:
Cannot make "suggestions " due to automatic email, suggestions must be listed as

stipulations
Q Approved as Submitted: no change required in ongoing approval
Approved with Stipulations: as noted
Response to original reviewer
Q Response can be reviewed by expedited review (by senior staff)
Approval Deferred: additional information required. This is a serious decision as
deferral halls all research processes. Committee should 'consider subject status and

funding issues. Response will go back to the continuing review committee for review
Common stipulations:

Update Contacts and Questions section information on the consent forms;
i.e. "University of Minnesota Medical Center Fairview"

D Add HIPAA reference on the consent form.
D Add the human subject code numbcr/page numbers/version date to all pages of the
consent forms,

The 1RB should observe the consent process or the research,
n Reapply as required every 5 years,
I have completed a substantive and meamngfyl review based ou.the information
made available at this time.
Print name of reviewer: KG Johnson

Signed name of reviewer;

Date: 12/17/2008

PagaZb

-D o Gum ent-items-fo i^eommittee-iidis cus sioti^-b elo w:-

Document "comments, changes, and stipulations" below:
(write out stipulations clearly)

Nathalie Vizueta, MA. listed on consent and not listed on con rev form
Correct address for out-of study contact Information - remove room number, and correct street
number

Page 26

Committee Meeting Minutes
December 17, 2008

Agenda Item:i
Continuing Review-Medical

PI: Schulz, Sellmann

Reviewer: Johnsotf
Reviewer; Belew

Agenda Item: None
Agenda Item: None

Protocol Title arid HSC#:"Seroquel^^^^fo^
ARandomiZed^ouble^UudG^mparuoni?^Placebo^
Item Description:
None;.l"?;

(Discussion of Controverted Issues Summary:
There were no controverted issues.

iRevisiftnSt<31anlications.ibr'StipuIatwns^yW^
• Correct the following standard language in the Contacts and Questions section of the consent form: If you
have any questions or concerns regarding the study and would like to talk to someone other than the researcher(s),
you are encouraged to contact the Fairview Research Helpline at telephone number 612-672-7692 or toll free at 866508-6961. You may also contact this office in writing or in person at University of Minnesota Medical Center,
Fairview Riverside Campus, 2200 Riverside Avenue, Minneapolis, MN 55454.

]Ghange in Risk/Benefit Balance:
None

Committee Must Address:

B 21CFR56.111 &45CFR46.111
(Applicable Criteria Met)

D45CFR46-SubpartB
(Research Involving Pregnant Women or Fetuses)

D 21CFR50.23 &45CFR.116

D 45CFR46-Subpart C

(Waiver or Alteration of Consent Process)

(Research Involving Prisoners—Indicate Level of Risk, e.g. Minimal or
Greater Than Minimal)

D 21CFR50.27 &45CFR46.117
D 21CFR50 & 45CFR46-Subpart D

(Waiver of Consent Documentation)

(Research Involving Children—Detail Inclusion or Exclusion Justification
and Indicate Level of Risk, e.g. Minimal or Greater Than Minimal,
Describe Consent Requirements as Specified in 21CFR50.55 and

45CFR46.408)

Determinations and Justifications Required by Regulations and Guidelines;
None

IRB Decision:

Length of Approval: One Year

Approve Continuing Review with Stipulations
Additional Info: None

Vote Yes: 6

No: 0

Abstain: 0

Members Not Present for Vote Due to Conflict of Interest: Dr. Scott Crow

Not Present:

12/19/2008
...S.e;llmann.C.S.chulz._

.

,

\..^-

:fM^

Psychiatry Department \ \^'^
'

F282/2AWest-B

.

^

2450 Riverside
Minneapolis, MN 55454

RE; "Seroquel XR for the Management of Borderline Personality Disorder: A Randomized
Double-Blind Comparison with Placebo"

IRB Code Number: 0709M16844
Dear Dr. Schulz,

.At the meeting on December 17, 2008, the IRB; Human Subjects Committee reviewed the
referenced study. The following stipulations must be resolved, mid written approval should be
received, before renewed approval is confirmed,
The following changes to the consent form are stipulated;
• Correct the following standard language in the Contacts and Questions section of the
0 consent form: If you have any questions or concerns regarding the study and would like to
talk to someone other than the researcher(s), you are encouraged to contact the Fairview
Research Helpline at telephone number 612-672-7692 or toll free at 866-508-6961, You
may also contact this office in writing or in person at University of Minnesota Medical
Center, Fairview Riverside Campus, 2200 Riverside Avenue, Minneapolis, MN 55454.
^

..

.

,

...

.•

Please provide a copy of the revised consent form for review.

We cannot confirm the renewal of the referenced study until these conditions are met, If your
response is not received within ninety days, the study will be filed inactive.
Please send your response to RSPP (Mayo Mail Code 820; D-528 Mayo Memorial Building; 420
Delaware St, SE; Mmncapolis, MN 55455) The entire application does not need to be resubmitted;
your, response should address the sections requiring change. The signature of the Principal
Investigator is the only signature required with the response. Only one copy of the response is
necessary,

If you have any questions, please contact the IRB office at 612-626-5654.
Sincerely,

Andrew Alien
Research Compliance Supervisor

AA/mq
CC: Scott Crow, Peter Milev, Michael Miller, Richelle Mocn, Ann Romine, Nathalie Vizueta

Page 1

Date: 01/06/2009
To: S. Charles, Schulz (scs@umn.edu)
From: irb@umn.edu

Subject: #STUDYNBR# - PI #PILASTNAME# - IRB - APVD Continuing Review
Message: TO : crowx002@umn.edu, scs@umn.edu, romi0004@umn.edu, nvizueta@umn.edu,
moenx008@umn.edu, mjmiller@umn.edu, milev002@umn.edu,

The IRB: Human Subjects Committee renewed its approval of the referenced stidy
listed below:

Study Number: 0709M16844
Principal Investigator: Sellmann Schulz

Expiration Date: 12/16/2009
Approval Date: 12/17/2008
Title(s):
Seroquel XR for the Management of Borderline Personality Disorder: A Randomized
Double-Blind Comparison with Placebo
This e-mail confirmation is your official University of Minnesota RSPP notification of
continuing review approval. You will not receive a hard copy or letter.

This secure electronic notification between password protected authentications has
been deemed by the University of Minnesota to constitute a legal signature.
You may go to the View Completed section of http://eresearch.umn.edu/ to view or
print your continuing review submission.

For grant certification purposes you will need this date and the Assurance of
Compliance number, which is FWA00000312 (Fairview Health Systems Research

FWA00000325, Gillette Childrens Specialty Healthcare FWA00004003). Approval
will expire one year from that date. You will receive a report form two months before
the expiration date.

In the event that you submitted a consent document with the continuing review form, it
has also been reviewed and approved. If you provided a summary of subjects'
experience to include non-UPBRTSO events, these are hereby acknowledged.

As Principal Investigator of this project, you are required by federal regulations to
inform the IRB of any proposed changes in your research that will affect human
subjects. Changes should not be initiated until written IRB approval is received.
Unanticipated problems and adverse events should be reported to the IRB as they
occur. Research projects are subject to continuing review.

If you have any questions, please call the IRB office at (612) 626-5654. The IRB
wishes you continuing success with your research.

University of MinneAQta.

KUVIBW Pertofl'

10/29/2008-12/16/2009

GontinuingReview-of-lRB-- Pending

Rev: 03/01/2005

Medical Research

Study Number: 0709M16844
Principal Investigator: Sellmann C Schulz
Title(s): Seroquel XR for the Management of Borderline Personality Disorder:
A Randomized Double-Blind Comparison with Placebo
Study Status
Active (Enrolling Subjects)

AGENDA

Funding Source(s)
Funding Source: AstraZeneca

,_£^^0^

Funding Type: OTHER
PersonneS
Schulz, Sellmann (P. I.)
Crow, Scott (Co-lnvestigator)
Milev, Peter (Co-lnvestigator)

Miller, Michael (Co-lnvestigator)
Moen, Richelle (Co-Investigator)
Romine, Ann (Correspondent)
Thompson, Marian (Co-lnvestigator)

Study Enrollment
Number of Subjects Approved for study;
50
Number of subjects enrolled this review period:

Male Female Unknown Total

K

]1

-E

Number of subjects enrolled to date:
Male Female Unknown
10^

-n

Total

Is this a multi-center study?
Yes
The University of Minnesota Is an equal opportunity educator & employer,
© 2004 by the Regents of the University of Minnesota.

Page 1

Total national accrual to date: 14

Unanticipated Problem Reporting
Since the.most recent IRB conlinuing review approval, have any participants withdrawn from the
research?
Yes-

2 subjects have withdrawn due to intolerability of study medication. 1 subject withdrew at visit 10 for reasons
unknown,

Since the most recent IRB continuing review approval, have any participants complained about the
research?

No
Have any serious and unanticipated problems been reported to the IRB?

No

Study Summary
Summarize preliminary information about any results and/or trends;
Majority of subjects enrolled have completed study or are currently active In study. Many have reported and
presented reduction in symptoms of BPD. Medication intolerabllity reported by at least 2 subjects in the form of
sedation.

Have there been any changes in protocol approved by the IRB since last continuing review?
Yes
We are developing protocol amendment #2 and will submit in paper copy with this form.

Since the most recent IRB continuing review approval, have there been any progress reports on the
research?

No
Since the most recent IRB continuing review approval, have there been any multi-center trial reports?

No
Since the most recent IRB continuing review approval, have there been any other information
relevant to this research discovered, especially information about the risks and benefits associated
with the research?
No
Since the most recent IRB continuing review approval, have subjects experienced any benefits?

The University of Minnesota is an equal opportunity educator & employer. Page 2

©2004 by tha Regents of the UnivgrsllyofMlnnBsota.

Page 4

Yes
-Many~subJe'cts-h'aVB-re'po'rted-aTTd presenteclTecluctlomn symptoms of'BPD7

External Findings
Is there anything in the relevant recent literature that the IRB should know about concerning this
research?
No

Consent/Assent Forms
Have there been any changes to the consent and/or assent form(s) since the last IRB approval?
Yes
We are submitting a revised consent uploaded with this form, dated 30 SEP 2009. The revision is on p. 9,
highlighted in yellow, change form Signature of Investigator to Signature of Person Obtaining Consent.

Have translated consenl short forms been used in conjunction with an interpreter to obtain consent

for this study?
No

Other Comments

The Unlvarsity of Minnesota is an equal opportunity educator & employer. Page 3

© 2004 by tha Regents of (he Univeralty of Minnesota,

Page 6

I

PI: Schulz University of Minnesota

HSC #: 0709M 16844 Human Research Protection Program
Reviewer: Dees Institutional Review Board
-Meetmg-Date; 1-ZT6/2009 —

Full Committee Review—Conitmiuiing Review of Approved Research
••»••!

"An IRB shall conduct mntinuing revie\v of research covered by this policy at intervals appropriate fo the degree of
mk, but not less than once per year, and shall have the authority to observe or have a third party obsewe the
consent process and the research. " 2!CFR56.J09 and45C.FR46.109
"Contmnlng review of research must be substantive and meaningfid," OIIRP Guidance 1-15-07

Short Title: To determine the safety and efficacy of Seroquel XR for treatment of Borderline
Personality Disorder
Enrollment: ^ Open Q Closed Q On hold
Treatment: ^ Continues Q Complete [_| Not a treatment study
Follow-up: [3 Continues d Complete D No follow-up required
Funding; Q Federal [X] Sponsored Q Foundation Q Departmental
Enrollmient Numbers: Approved: 50 Enrolled: 6 Years active: 2

UPIRTSOs (Unanticipated Problem Involving Risk to Subjects or Others):
Have any UPIRTSOs been reported in the last year? Q Yes ^ No
Are there concerns to be discussed by the Committee? |_| Yes DO No

Study Summary: Q Adequate D Deficient
None - too early Q None - data analysis elsewhere

External Findings: D DSMB letter D Progress report Q Action letter
Consent and Assent Forms: ^ Submitted Q Missing Q Waived or not applicable
HIPAA Forms; 0 Submitted ^ Missing Q Waived or not applicable
Closed to enrollment - forms are no longer pertinent
Are all persons listed on consent form also listed on the 1RB roster? Q Yes Q No

Inclusion of Children in Research;
If children are included in this research confirm that they should still be included,

Yes D No [X] NA - children excluded
If children are included this inclusion must meet one of the following criteria for risk/bcnefit
assessment according to federal regulation (21CFR56 and 45CFR46 Subpart D),

(404) Minimal risk
.D.(4P5).<Jreaterthanmlmmal nsk; buthplds prospect of direct benefits to subjects.
Q (406) Greater than minimal risk; no prospect of direct benefit to subjects, but likely to
yield generalizable knowledge about the subject's disorder or condition,

University ol'Minnesotn JRB
Continuing Review Form

Version 10/27/09
Page 26

Substantive Changes: If any of the following are evident from the continuing review,
describe the changes for Committee discussion,

D Change in funding
Q Change in conflict of interest

D Change in risk or benefit
Q Change in subject population

Change in data management

Minor changes in consent form
II Major changes in consent form

Items for Committee Discussion:
1. Staff-Note that second consent form that appears on the flash drive and displaying IRB Approval; 30
Sep 2009 in footer is the most recent version
2. Was Appendix A completed and submitted with the original appl,? It is not in the circulation copy on the

flash drive," ' ' "^\\\^\^^t.

2. Consent form-ls there a reason why the standard research related injury wording was previously
approved rather the the language for a sponsored study?
Recommended Stipulations:
1. Submit copy of current HIPAA form
2.^CooseftHorm7R151<s7D!scomfoiS-and Incovgntences secttCTnTp, 5, 6th paragraph
_Eroyide_aD-fixpteftatien-of lliu lytin''yxtrapyrafflidaP-er-substitute a wer4^Mvordstclay language

Recommended Suggestions:
1, Consent form, Alternative Treatment section, p, 7

Delete the '0" that appears between the first and second sentences
Recommended Action:
Click to Show
Criteri.a for
Approval

Approve as Submitted
Approve with Suggestions
Approve with Stipulations as noted
D Response to original reviewer
Response can be reviewed by IRB staff
Approval Deferred - additional information required

Continuing Review Interval: ^ Annually
Every 6 months

D Quarterly
D Other interval;
I have completed a substantive and meaningful feview based on the information made available
at this time,

Print name of reviewer Alfred Dees Date: 12/16/2009

Signed name of reviewer:
If you choose to submit this form electronically, please send to irb(%umn.edu.
Forms submitted from a umn.edu account do not need a hard-copy signature,

University of Minnesota IRB
Continuing Review Form

Version 10/27/09
Page 27

•. ^

PI; Schulz University of Minnesota
HSC#: 0709M16844 , Human Research Protection Program
Reviewer: Kracn Institutional Review Jjoard

"MeefmifDaie:—T2/T6?2009Full Committee Review—Continumg Review of Approved Research
•••••••

"An 1RB shall conduct continumg, review of research covorsdby {his policy at intervals appropriate to the degree of
rink, hut no! less than once. per year, and shall have the.authwily to observe or have a third party ohsei've the
cement process and the research. " 2JCFR56. f Off and 45CFR46.109
"Continuing review of research nmst be substantive and meaningful." OIIRP Guidance 1-15-07

••« un • i

Short Title: Seroquel XR for the management of borderline personality disorder: RCT

Enrollment: [^ Open Q Closed [_] On hold
Treatment: [x] Continues Q Complete [_] Not a treatment study
Follow-up; ^ Continues D Complete Q No follow-up required
Funding; Q Federal ^ Sponsored Q Foundation Q Departmental
EmrommentNmmbers: Approved: 50 Enrolled: 6 Years active: 2

UPIRTSOs (Unanticipated Problem Involving Risk to Subjects or Olhers):
Have any UPIRTSOs been reported in the last year? Q Yes [El No
Are there concerns to be discussed by the Committee? Q Yes |^ No

Study Summary: 13 Adequate D Deficient
None - too early [_] None - data analysis elsewhere

External Findings; Q DSMB letter Q Progress report Q Action letter
Consent and Assent Forms: [^ Submitted Q Missing Q Waived or not applicable

HIPAA Forms: Q Submitted |E1 Missing Q Waived or not applicable
Q Closed to enrollment - forms are no longer pertinent
Are all persons listed on consent form also listed on the IRB roster? [^ Yes D No

Inclusion of Children in Research:
If children are included in this research confirm that they should still be included.

Yes I I No DO NA - children excluded
If children are included this inclusion must meet one of the following criteria for risk/benefit

assessment according to federal regulation (21CFR56 and 45CFR46 Subpart D).
(404) Minimal risk
D (405) Greater than minimal risk; but holds prospect of direct benefits to subjects.
(406) Greater than minimal risk; no prospect of direct benefit to subjects, but likely to
yield generalizable knowledge about the subject's disorder or condition,

University of Minnesota IRB
Continuing Review Form

Version 10/27/09
Page 29

Siabstamtive Changes: If any of the following are evident from the continuing review,
describe the changes for Committee discussion.

Q Change m risk or benefit [~} Change in funding
II Change in subject population D Change in conflict of interest
II Minor changes in consent form D Change in data management
II Major changes in consent form

Items for Committee Discussion:
1, Three subjects have withdrawn-2 did not tolerate drug (sedatlon), one reason unknown,
2. Protocol Amendment 2 being developed, Not along with this form,
3, Minor change to consent form-sig nature of person obtaining consent rather than Pi

Recommended Stipulations:
1. Provide HIPAA form
Recommended Suggestions;

Reconn mended Action: Q Approve as Submitted
Approve with Suggestions
c"ck.tosh-ow ! IS! Approve with Stipulations as noted
Criteria for I '"' "l'Ilr—i '^ •— - -r -—^-^-—^ — -

VA'pP'rovaT | U Response to original reviewer
Response can be reviewed by TRB staff
Q Approval Deferred " additional information required

Continuing Review Interval: [X] Annually
Every 6 months

II Quarterly
[_j Other interval;
/ have completed a substantive and meaningful review based on the information made available
at this time.

Print name of reviewer; Lidna E, Krach, MD Date: 12/16/2009

Signed name of reviewer:
If you choose to submit this form electronically, please send to irb(Sl,umn.edu.
Forms submitted from a umn.cdu account do not need a hard-copy signature,

University of Minnesota IRB
Continuing Review Form

Version 10/27/09
Page 30

Committee Meeting Minutes
December 16,2009

Agenda Item;
Continuing Review-Medical

Pt; Schub, Sellmann

Kevie'wejft Krach
'Iteyie'wer;:i?(Dees?:

Agenda If eni:; None
Agenda Item; None

Protocol Title and MSC?#:''Sei^q^
AR^domizedDouble^luidCompansonmtKP 1^^:,^ Kii?l^^:®'l{:-,:l-|::i
Item Description: X - .,1,"::1;;- ^~,'::x^

M revises consent form with a m^
^Discussion of Gontrovertea Issues Summai-y;
There were no controverted issues.

|Reyisions,>CIaril^atipiMorStipuIatiQns::^^<IT1^^^^^^^^
• Please submit the most current version of your HIPAA Authorization Form for review. This form is now
required at the time of continuing review. The IRB has initiated this new requirement to help maintain substantive
and meaningful review of all continuing review submissions.
The following changes to the consent form are stipulated:
• As this study is funded by a corporate sponsor, the following standard 'sponsor-funded' injury compensation
language should be used in the consent form:
'In the event that this research activity results in an injury, treatment will be available, including first aid, emergency
treatment, and follow-up care as needed. Care for such injuries will be billed in the ordinary manner, to you or your
insurance company. The sponsor of the study has some funds available to pay for care for injuries resulting directly
from being in this study. If you think that you have suffered a research related injury and that you may be eligible for
reimbursement of some medical care costs, let the study physicians know right away.'
-If the research contract makes an exception for the corporate sponsor not to be liable for research related injury
payment, then please provide documentation (pertinent section of the contract) to support this.

|C?hahge;i&Risk/BenefiiBatancei
None

Committee Must Address;

S 21CFR56.111 &45CFR46.1U
(Applicable Criteria Met)

D45CFR46-SubpartB
(Research Involving Pregnant Women or Fetuses)

D 21CFR50.23 & 45CFR.116

D 45CFR46-Subpart C

(Waiver or Alteration of Consent Process)

(Research Involving Prisoners—Indicate Level of Risk, e.g. Minimal or
Greater Than Minimal)

D 21CFR50.27 &45CER46.117
(Waiver of Consent Documentation)

D 21CFR50 & 45CPR46-SubpartD
(Research Involving Children—Detail Inclusion or Exclusion Justification
and Indicate Level of Risk, e.g. Minimal or Greater Than Minimal,
Describe Consent Requirements as Specified in 21CFR50.55 and

45CFR46.408)

Committee Meeting Minutes
December 16, 2009
Determinations and Justifications Required by Regulations and Guidelines:
None

Length of Approval: One Year

IRB Decision:
Approve Continuing Review with Stipulations
Additional Info: None

Vote Yes: 9

No: 0

Abstain: 0

Members Not Present for Vote Due to Conflict of Interest: None

Not Present:

12/17/2009
Selhnaim C Schulz

Psychiatry Department83 93 ^
F282/2A West-B
2450 Riverside
Minneapolis, MN 55454

RE: "Seroquel XR for the Management of Borderline Personality Disorder: A Randomized
Double-Blind Comparison with Placebo"

IRB Code Number: 07(»9M16844

Dear Dr. Schulz,

At the meeting on December 16,2009, the Institutional Review Board (TRB) reviewed the
referenced study, Tlie following stipulations must be resolved, and written approval should be
received before renewed approval is confirmed.
• Please submit the most current version of your HIPAA Authorization Form for review.
This form is now required at the time of continuing review, The IRB has initiated this
new requirement to help maintain substantive and meaningful review of all continuing
review submissions.

The following changes to the consent form are stipulated:
• As this study is funded by a corporate sponsor, the following standard 'sponsor-funded'
injury compensation language should be used in the consent form:
'In the event that this research activity results hi an injury, treatment will be
available, including first aid, emergency treatment, and follow-up care as needed,
Care for such injuries will be billed in the ordinary manner, to you or your insurance
company. The sponsor of the study has some funds available to pay for care for
injuries resulting directly from being in this study. If you think that you have
suffered a research related injury and that you may be eligible for reimbursement of
some medical care costs, let the study physicians know right away.' j
I

—If the research contract makes an exception for the corporate sponsor not to be

liable for research related injury payment, then please provide documentation
(pertinent section of the contract) to support this. |
Please provide a copy of the revised consent form for review.

Page

I!

-P-kase-note—In^he-Gontwumg-r-eview-for-m^it-stated^hat-an-ame'ndment-^-wouU^^

for review. The IRS has yet to receive this. Please submit (he amendment -when it is ready for
review.

The enrollment of new subjects may continue using previously approved consent document(s),
We cannot confirm the renewal of the referenced study until these conditions arc met, If your
response is not received within ninety days, the study will be filed inactive,

Please send your response to I-IRPP (Mayo Mail Code 820; D-528 Mayo Memorial Building;
420 Delaware St. SE; Minneapolis, MN 55455), The signature of the Principal Investigator is
the only signature required with the response, Only one copy of the response is necessary.
If you have any questions, please contact the IRB office at 612-626-5654.
Sincerely,

Movolny, CIP
trch Compliance Supervisor

)/mq
CC: Scott Crow, Peter Milev, Michael Miller, Richelle Moen, Arm Romine, Marian Thompson

Page 2

,^2-

SC.R-UI^Z-

UNIVERSITY OF MINNESOTA °^Ml b^4 [^ ^1%%^^ b^
uu—-~11

Twin Cities Campus Ambututory Research Center Riverside Prdfessiwol Swid'mg
~6(16'2'4lh~Ave>we Smith —~~
Department of PsychiatnDecember 30,2009 MS/'.s-cAoo/"'"""""'" Smm.W2
lw'mc"'>wwi" MiimMimli-i, AW 55454

Christina Dobrovolny osw: 6I2-627-48W

Institutional'Review Board
University of Minnesota
Mayo Mail Code 820

D528 Mayo Memorial Building KLl'U JAN 0 6 2010
420 Delaware Street S.E.

Minneapolis, Minnesota 55455
RE: "Seroquet XR for the management of Borderline Personality Disorder (BPD)"

HSC#0709IV116844

Dear Christina:
Thank you for your Continuing Review of the referenced study. We are responding to
IRB stipulations as stated in your letter dated 17 DEC 2009, as well as submitting
Protocoi Amendment #2 dated 30 DEC 2009.
Stipulations:
1. Enclosed is the current approved version HI PAA form, version date 24 FEB 2009
& IRB approved on 19 JUN 2009.
2. The research-related injury language has been revised on p. 8 of the revised
consent form dated 30 DEC 2009.
3, In addition, we have changed the signature line on p, 9 of the revised consent
form to read "Signature of Person Obtaining Consent" rather than "Signature of
Investigator."

Protocol Amendment #2, version date 30 DEC 2009
The amendment items are listed & notated in the Protocol Amendment Summary
document dated 30 DEC 2009, The amended protocol includes changes highlighted in
yellow. Please note the green highlights were from protocol Am #1, IRB approved on 02
JUN 2008..
We have enclosed the following documents for your review:
1) Protocol Am #2 version date 30 DEC 2009
2) Protocol Am-#2 Summary 30 DEC 2009
3) Revised consent form version date 30 DEC 2009
4} Current approved version HIPAA form, version date 24 FEB 2009 & IRB
approved on 19 JUN 2009
Thank you and please contact Ann Romine, study coordinator, with any questions at
612.627-4843,
Sincerely,f

S.^MM^l^i
S. Charles Schulz, MD

Principal investigator

Driven to Discover5
Page £

UNIVERSITY OF MINNESOTA

RCT .AN 13 2010

Change In Protocol Request

s^Hu-i/2- -0-jo^t^.y-f^

z/,g/.,,AGEME

'//On.i^^ac^^

-Instr-uc.tJoos;-

^

Usa this form when submitting change requests on 1KB protocols.
t. Submit this form to the Human Research Protection Program:

Campus Mail;

U.S, Mail Address:
Human Research Protection Program

Human Research Protection Program

MMC 820

MMC 820

Minneapolis Campus

420 Delaware St. SE
Minneapolis, MN 55455-0392

Delivor to:
D-528 Mayo Memorial Building
. Minneapolis Campus
8-4:30, M-F

IRB Protocol Information
I RBSludy Number:

0709M16844

Currenl Principal Investigator:
l-'rbnary Title:

S. Charles Schulz
MD, Dept Head

Submission Date

30 DEC 2009

Indn'.ale the type of change/addition and attach all applicable documents:

IZIProlocol Amendment; Version^, Dated 30 UEC 2009
[_J Revised Jnvcstigator Brochure; Ver.siun , Unted
QR.ccruitinentChanges/Advertisemenl.s
DNotice of Closure to Accrual
QChangei's') tn Study Procedures
dOl'her:
1. l^rict'ly summarize (lie uhungc(s). Kor prol.oco! amendments, do not say "See summary of changes provided will)
amendment," Rather, summarize t)u> nature of the significant revisions.
Clarification of procedures including visit windows, study mediuatiun compliance, frequency of 2 side effect
assessments, early discontinuatjon, ynd siratif'ication by genduT.

2, Describe the rationale lor the cttange(s);
To clarify procedures Co ensure consistency of study methods across a)) 3study sites.

3. In your opinion as principal investigator, how will tliese changes affect the ovt'rall risk to subjects in this sfiidy?
These changes will not increase risk to subjects.

4. Do the changes to the study prnmpl changes to the consent form(s)?
<o. D Yes.
H'yes, attach a copy of the revised consent fonn(s) with changes tracked or highlighted as well as a clean copy. Use this space
to t'nrtlu'r describe consent form cliangcs if necessary:

J. PM^^ ^^ &/^ \\^\\f)

Principal Investigator's Signature

Date

The Univcrsily of Minnesota is an equal opportunity cduc'iilor & cmployur.
© 2008 by the Regents of the University of Minnusolii.
Rage 68

1 af2

University of Minnesota

Review Period:

09/25/2009-02/17/2011

Continuing Review of IRB - Pending
Medical Research

Rev; 03/01/200.5

Study Number: 0709IVI16844
Principal Investigator: Sellmann C Schulz
Title(s): Seroquel XR for the Management of Borderline Personality Disorder:
A Randomized Double-Blind Comparison with Placebo
Study Status

Active (Enrolling Subjects)

Funding Source(s)

Funding SourGe: ASTRAZENECA INTL
Funding Type;
Personnel
Schulz, Sellmann (P. I.)
Crow, Scott (Co-lnvestigator)
Cullen, Kathryn (Co-'lnvestigator)
Man, Georges-Jakofci (Staff/Lab)

Heller, Monika (Staff/Lab)
Houri, Alaa (Staff/Lab)
Miller, Michael (Co-lnv^stjgator)
Moen, Richelle (Co-lnvestigator)
Rom ine, Ann (Correspondent)
Vuchetich, John (Co-lnvestigator)

Study Enrollment
Number of Subjects Approved for study:
50

Number of subjects enrolled this review' period:
Male Female Unknown

[I

^4

Total

J2S[

Numtser of subjects enrolled to date:
The University of Minnesota is an equal opportunity educator & employer.
© 2004 by the Regents of the University of Mtnnesota.

Page 1

Male Female Unknown Jot^l E

18 114 |0 f22 } |
Is this a multi-center study?
Yes
Total national accrual to date: 52

Unanticipated Problem Reporting
Since the most recent IRB continuing review approval, have any partJGipants withdrawn from the
research?

Yes
8 early withdrawals and 1 lost to follow-up, 4 early withdrawals were due to adverse events, primarily sedaitlon. 4
due to subject personal circumstances.

Since the most recent IRB continuing review approval, have any partioipants complained about the
research?
No
Have any serious and unantiGipated problems been reported to the IRB?

No

Study Summary
Summarize preliminary information about any results and/or trends:
At our site 22 subjects have been enrolled and have taken at least 1 dose, of study medication. 13 subects have
completed all 11 visits of the study. 9 subjects have not completed the study. The majority of subjects who
completed study to date show a decrease in symptoms from baseline as measured by the assessment scale
scores. 2 other sites are participating jn this trial. Each site has an enrollmentgoalof33subJBetstoobtain a totalof
99 subjects enrolled. Enrollment numbers to date are as follows; University of Iowa: 27 subjects McLean Hospital,

Han/ard University: 3 subjects Enrollment goals may:need to be adjusted per site as we get closer to our enrollment
total.

Have there been any changes in protocol approved by the IRB since last continuing review?
Yes
Achartge in protocol, Amendment #3, dated July 20,2010, was approved perlRB letterdatec) Novembers, 2010.
This amendment adds an optional brain imaging (fMRt) addendum to the main study. The Gonsentform and Brain
Imaging Addendum dated October 20,2010 was also approved. To date no subjects have been enolledthe brain
imaging study,

Since the most recent IRB continuing review approval, have there been any progress reports on the
research?

No

The University of Minnesota is an equal opportunity educator & employer. Page 2
© 2004 by the Regents of the University of Minnesota.

Since the most recent IRB continuing review approval, have there be@n any multi-center trial reports?
No
Since the most nScent 1RB continuing review approval, have there been any other information
relevant to this research discovered, especially information about the risks and benefits associated
with the research?

No
Since the most recent IRB continuing review approval, have subjects experienced any benefits?
Yes
The majority of subjecte who completed study to date show a decrease in symptoms from baseline as measured by
the assessment scale scores.

External Findings
Is there anything in the relevant recent literature that the IRB should know about concerning this
research?

No

Consent/Assent Forms
Have there been any changes to the consent and/or assent form (s) since the last IRB approval?

No
!Have translated consent short forms been used in conjunGtjon'with an interpreter to obtain .consent

for this study?
No

Other Comments

The'University of Minnesota is an equal opportunity educator &'employer- Pages
©2004 by the Regents of the University of Minnesota.

C^: 50
UNIVERSITY OF MINNESOTA ^ ^
Twin Cities Campus Depiirtmenl of Psychiatry F2S2/2A West

Memo

1450 Riverside Avenue

Minneapolis, MN 55454
Office: 612-273-9800

To: S. Charles Schulz, M.D.
From:Scott Crow, M.D.

CC: Kathy Mischke and Kyle Rudser, Ph.D.

Date: April 7, 2010
Re: Seroquel XR BPD Study and Safety Meeting

We met for safety monitoring on March 3, 2010 and interviewed progress to date.
The following study issues were reviewed and discussed;

1. There is not sufficient information available on the Harvard site; they have
incomplete information on only one patient and it is unclear whether they are
recruiting or not,
2. No screen failures have been reported. Is this correct? If there are screen

failures that is not problematic, but it would help in evaluating the rate of
recruitment.
3. Retention appears to be really excellent. However, clarification is warranted
in regard to discontinuation of drug and discontinuation of study (i.e,, from
evaluation). In order to allow for an intent to treat analysis at the end of the

study, patients should be continued to be evaluated to the degree they allow
in the event it is decided to discontinue treatment regimen.

4. There appear to be preexisting symptoms at study entry that are being
captured as AE's, These should not be included as adverse events unless
they increase in severity or frequency.
5. If possible, severity ratings for the AE's experienced by the Harvard site
enrollees should be provided.

6. If subjects do not return pill bottles for count it appears that that should be
listed as a protocol deviation.

Last, it was noted that recruitment from across the sites is lagging behind that initially
proposed with current enrollment at less than half of what it is expected to be. If
enrollment stays at the current rate, the study is expected to finish in 5 years rather
than the planned 2 years.

1

Driven to Discover5

Seroquel XR BPD Study
Data and Safety Monitoring Meeting 8/26/09
Attendance: Scott Crow, M.D,, Safety Officer

Kathy Mlschke, Clinical Trial Monitor
Kyle Rudser, Biostatistician
Data regarding study recruitment, progress, and protocol adherence (all with blinded treatment
assignment) were reviewed, for the first 10 patients enrolled in :the study. Several issues for

further clarificatton/reiteration were identified:
1, There should b6 clarification ,in the protocol as to whether 50 mg dose is given for the
first two days or the entire first week.
2. If an individual is discontinued from the study or withdraws from the study, there is some
ambiguity in the protocol as to what happens for follow-up. A 14 day follow-up is
conducted for subjects who complete a regular end of study termination visit and this
should be the same for early termination/discontinuation subjects if possible, including
monitoring for adverse events.
3. All adverse events, serious or not, and expected or not should be reported.
4. There has been some delay in entering of CRF data into the database. The delay
appears to be gradually diminishing over the period of patient follow-up visits but there is
an overall concern. While there is no specification of expected time to data entry, within
two weeks of "visit 10" would seem appropriate for effective safety monitoring. Adverse
events, however, are still to be reported within timelines specified in the protocol.
5. Clarification is needed regarding study rules for visitwindows and classification of
missed visit/scheduling of subsequent visits.
6, Protocol deviations are not being reported. These include missed visits, missed doses,
missing safety endpoints, and general occurrences that deviate from the protocol.
7, There is concern over the lack of data on identified safety endpojnts, Specifically;
prolactin, glucose, cholesterol, triglycerides, and BMI (weight and height), which all need
to be assessed at both baseline and end of study for all patients.

MEMORANDUM
TO: Scott Crow, M.D.

CC: Ann Romine
FROM: Dr. S. Charles Schulz, Head, Department of Psychiatry

RE: Seroquel XR BPD Study - Data and Safety Monitoring Meeting
DATE: October 28, 2009
I am writing this memorandum to initiate a discussion regarding the Data and Safety Monitoring
Meeting of August 2009. Dr. Crow you are the safety officer and I appreciate your having discussed
the meeting with me and look forward to hearing your thoughts about my response to the meeting.

I will go through each of the point below:
1. I agree there should be clarification as to how long the 50 mg dose is given. I know that we
changed the original protocol after the feedback ffom the Titration and Taper McLean IRB.
Attached is the Dosing amendment,
2. I believe it is a good idea to clarify how subjects are managed if they are discontinued or
withdraw from the study. I am not sure it is clear to the Data and Safety Monitoring
Committee that the design of the two week follow up is to be able to transfer people from the
study to the next phase of their care. Also, people with borderline personality disorder have
difficulties with abandonment and we have always designed our studies to not have the last
rating period be the person's last appointment with us. Therefore, the idea of clarifying tha-t
people who are withdrawing from the program or are discontinued should have the follow up
is a good idea. We will request an amendment to clarify the follow-up for those subjects
(P.21).
3. The idea of reporting all adverse effects events is of course appropriate. I need more specific
information about how our sites have been doing on this issue and suggestions for how to
comply with this statement.
4. I can understand concern regarding entering data from the CRF into the database. I am not
sure whether this is related to the suspension of entering subjects or some other reason. I
have discussed with Ann having a teleconference of all sites so we can address this issue.
5. I can understand that it is important to clarify the "windows" and "classification of .missed
visit." We have designed a definition statement and will submit as an amendment.
6, Regarding theissue of protocol "deviation" I would like Dr. Crow's opinion of protocol
deviation and then work to make sure that they are appropriately recorded.

7. I have a question regarding the statement of lack of data on identified safely end-points. I
have seen all of the laboratory studies at each point and am not quite sure what the'DSMB is
requesting. In the meantime I will review laboratory data to examine for any missing values.
I look forward to discussing this with you both sooa so that I can make any needed changes to the
protocol.

PI: Schulz University of Minnesota
HSG#: 0709M16844 Human Research Protection Program
Reviewer: Ognjanovic Institutional Review Board

Meeting Date: 01/26/2011
Full Committee Review—Continuing Review of Approved Research
I

"An 1KB shall conduct cwtiniiing revbw of research covered by this policy at intervals appropriate to the degree of
risk, but not less than once per year, and shall have the authority to obsen'e of have a third party obsen'e the

consent process aiidlhe research." 21CFR56.109 and45CFR46.109
"Continuing review of research must be substantive and meaningful." OHRP Guidaiice 1-15-0.7

Short Title: Seroquel XR for the Management of Borderline Personality Disorder:
A Randomized Double-Blind Comparison with Placebo

Enrollment: ^ Open D Closed D On hold
Treatment: [X] Continues Q Complete [_] 'Not a treatment study
Follow-up: ^Continues D Complete D No follow-up required
Funding: D Federal [X] Industry Sponsored Q Foundation
Departmental Q None

Enrollment Numbers: Approved: 50 Enrolled: 22 Years active: 5
UPIRTSOs (Unanticipated Problem InvQlvlag Risk to Subjects or Others):
Have any UPIRTSOs been reported !m the last year? Q Yes ^ No

Are there concerns to be discussed by the Committee? Q Yes 1^ No
Study Summary: ^Adequate D Deficient
[_] None - too early Q None - data analysis elsewhere

External Findings: ^ DSMB letter D Progress report D Action letter
Consent and Assent Forms; ^ Submitted D Missing d' Waived or not applicable

HIPAA Form$; D Submitted d Missing D Waived or not applicable
Q Closed to enrollment - forms are no longer pertinent

Are all persons listed on consent form also listed in the IRB records? Q Yes ^ No

Inclusion of Children in Research:
If children are included in this research confirm that they should still be included,

D Yes D No ^i NA - children excluded
If children are included, is there new information which affects the regulatory classification

(45CFR46 Subpart D) indicate the change,

(404) Minimal risk
D (405) Greater than minimal risk; but holds pfospeGt of direct benefits IQ subjects.
Q (406) Greater than minimal risk; no prospect of direct benefit to subjects, but likely to
yield generalizable knowledge about the subjects disorder or condition.

University ofMimiesotaIRB
Continuing ReviewFonn
Version October 2010

Substantive Changes: If any of the following are evident from the continuing review report,
describe the changes for Committee discussion,

Q Change in funding
Q Change in conflict of interest

Change hi risk or benefit

D Change in subject population

Change in data management

Minor changes in consent form
D Major changes in consent form

Dr. Crow is reviewing subjects' adverse events

for all three sites to monitor subjects' safety,

Items for Committee Discussion:
this lias been approved by the IRB previously and
- Scott Crow was a member of DSMB and a co-investigator?
is included in 4.4 of protocol.
-Dr Shultz is a member of the Scientific Advisory Board of Astra Zeneca (the sponsor), where they discuss

other uses of the medication Seroquel, and Dr Shultz is the Pl of this study that is trying to investigate if
Seroquel can be used for other purposes than thus far approved. Conflict of interest?

Recommended Stipulations:
- Scott Crow is mentioned in the consent, but is not an investigator on the IRB application,

Recommended Suggestions:

Dr. Crow is a cuiTent Co-PI on the study. He was added after
original review oftlie project,

Recommended Action; Q Approve as Submitted
a Approve with Suggestions
Approve with Stipulations as noted

gguuumi
lllllliilBl.HIII

Response to original reviewer
Response can be reviewed by IRB staff
a Approval Deferred - additional information required

Continuing Review Interval: [X] Annually
[_] Every 6 months
Quarterly
Q Other interval:
I have completed a substantive and meaningful review based on the mformation made available
at this lime.

Print name of reviewer; Simona Ognjanovic Date; 1/26/2011

Signed name of reviewer:
If you choose to submit this form electronically, please send to irb(%umn.edu.
Forms submitted from a utnn.edu account do not need a hard-copy signature.

University of Minnesota IRB
Continuing ReviewFonn
Version October 2010

Committee IVIeeting Minutes
January 26, 2011

Agendaltem:1
Continuing Review-MedicaI

pl: Schulz, Sellmann

ReVie^yer; Pgnjanoxic
Reviewer: NoMe

Agenda Item:; None
Agenda Item: None

Protocol Title and HSC^:''Seroquel XR for ^
ARandomizedDouble^lmdConip^i^spni^WPIac^
Item Description:
-N6ne""'.l'-l,\:-^%

|Distussioalof:e(mtroYerted:Issues, Summary:^, f^,;:';;,; :;V;-; ,;^
The IRB committee notes that the Pl's conflict of interest management plan has been reviewed previously by the IRB
Committee. The committee acknowledges current, IRB approved language in the consent form that references the
Pl's role on the Scientific Advisory Board.
The committee also notes that Dr. Scott Crow is a co-investigator and he is monitoring adverse events from all three
participating sites. This does not create a conflict of interest as researchers are required to monitor adverse events.

iRevisions, Clarifications or jStipulatidns:
None

Change iii Risk/Benefit Balance;
None

Committee Must Address:

El 21CFR56.111 &45CFR46.111
(Applicable Criteria Met)

D 45CFR46-Subpart B
(Research Involving Pregnant Women or Fetuses)

D 21CFR50.23 &45CFR.116

D 45CFR46-Subpart C

(Waiver or Alteration of Consent Process)

(Research Involving Prisoners—Indicate Level of Risk, e.g. Minimal or
Greater Than Minimal)

D 21CFR50.27 &45CFR46.117
D 21CFR50 & 45CFR46-Subpart D

(Waiver of Consent Documentation)

(Research Involving Children—Detail Inclusion or Exclusion Justification
and Indicate Level of Risk, e.g. Minimal or Greater Than Minimal,
Describe Consent Requirements as Specified in 21CFR50.55 and

45CFR46.408)

Determinations and Justifications Required by Regulations and Guidelines;
None

IRB Decision: Approve Continuing Renewal

Length of Approval: One Year

Additional Info: None

Vote

Yes:

No: 0

Abstain: 0

Not Present:

Date: 02/07/2011
To: S. Charles, Schulz (scs@umn.edu)
From: irb@umn.edu

Subject: #STUDYNBR# - PI #PILASTNAME# - IRB - APVD Continuing Review
Message: TO : crowx002@umn.edu, scs@umn.edu, vuche002@umn.edu, romi0004@umn.edu,
moenx008@umn.edu, rega0026@umn.edu, mjmiller@umn.edu,

The IRB: Human Subjects Committee renewed its approval of the referenced study
listed below:

Study Number: 0709M16844
Principal Investigator: Sellmann Schulz

Expiration Date: 01/25/2012
Approval Date: 01/26/2011
Title(s): Seroquel XR for the Management of Borderline Personality Disorder: A
Randomized Double-Blind Comparison with Placebo
This e-mail confirmation is your official University of Minnesota HRPP notification of
continuing review approval. You will not receive a hard copy or letter. This secure

electronic notification between password protected authentications has been deemed by
the University of Minnesota to constitute a legal signature.
You may go to the View Completed section of http://eresearch.umn.edu/ to view or
print your continuing review submission.

For grant certification purposes you will need this date and the Assurance of
Compliance number, which is FWA00000312 (Fairview Health Systems Research

FWA00000325, Gillette Childrens Specialty Healthcare FWA00004003). Approval
will expire one year from that date. You will receive a report form two months before

the expiration date.
In the event that you submitted a consent document with the continuing review form, it
has also been reviewed and approved. If you provided a summary of subjects'
experience to include non-UPIRTSO events, these are hereby acknowledged.

As Principal Investigator of this project, you are required by federal regulations to
inform the IRB of any proposed changes in your research that will affect human
subjects. Changes should not be initiated until written IRB approval is received.
Unanticipated problems and adverse events should be reported to the IRB as they
occur. Results of inspections by any external regulatory agency (i.e. PDA) must be
reported immediately to the IRB. Research projects are subject to continuing review.

If you have any questions, please call the IRB office at (612) 626-5654. The IRB
wishes you continuing success with your research.

University of Minnesota

Review Period:

12/03/2010-01/25/2012

Continuing Review of IRB - Pending
Medical Research

Rev: 03/01/200?

Study Number: 0709M16844
Principal Investigator: Sellmann C Schulz
Title(s): Seroquel XR for the Management of Borderline Personality Disorder:
A Randomized Double-Blind Comparison with Placebo
Study Status

Active (Enrolling Subjects)

Funding Source(s)

Funding Source: ASTRAZENECA INTL
Funding Type;
Personnel
Schulz, Sellmann (P. I.)
Crow, Scott (Co-lnvestigator)
Cullen, Kathryn (Co-lnvestigator)
Man, Georges-Jakob (Staff/Lab)

Hourj, Alaa (Staff/Lab)
Miller, Michael (Co-lnvestigator)
Moen, Richelle (Co-lnvestigator)
Romine, Ann (Correspondent)

Roots, Monika (Staff/Lab)

Study Enrollment
Number
of Subjects Approved for study:
50 ~' ~~~J"" ' -''-•----- -- -—.'•

|total enrolled: 34

Number of subjects enrolled this review period:
Male Female Unknown Total

E

I:

3E

14 |

Number of subjects enrolled to date;

Male

rr

Female

K

Unknown
,10

Total

: 14 ~|

The University of Minnesota Is.an equal opportunityaducatorS, employer. ' Page 1
© 2004 by the Regents ofthe University of Minnesota.

Is this a multi-center study?
Yes
Total national accmal to date; 60

Unanticipated Problem Reporting
Since the most recent IRB continuing review apppoval, have g>ny participants withdrawn from the
research?

Yes
There have been 4 early withdrawals, all due to adverse event: sedation,

Since the most recent IRB continuing review approval, have any participants complained about the
research?
No
Have any serious and unanticipated problems been reported to the IRB?

No

Study Summary
Summarize preliminary iriformatlon about any results ancl/or trends;
One of 3 participating sites withdrew from the study early in 2011, McLean Hospital at Harvard University, pl Mary
Zanarinl, The site withdrew due to inability to enroll subjects. The 2 remaining sites,D of MN & D of Iowa, will be
completing the enrollment goal of 99 total subjects.

Have there been any changes in protocol approved by the IRBsince last continuing review?
No
Sincethe most recent IRB continuing review approval, have there been anyi progress reports on the
research?
No
Since the most recent IRB continuing review approval, have there been any multi-center trial reports?
No
Since the most recent IRB continuing review approval, have there been any other information
relevant to this research dificovered, especially information about the risks and benefits associated
with the research?
No

The University of Minnesota is an equal opportunity educator& employer. Page 2
©2004 by the Regents of (he University of Minnesota.

Since the most recent IRB confinuing review approval, have subjects experienced any benefits?
Yes
Some subjects have reported reduction In their symptoms of Borderline Personality Disorder,

External Findings
Is there anything in the relevant recent I itergfure that the IRB should know about concerning'this
research?
No

Consent/Assent/HIPAA Forms
Have there been any changes to the consent and/or assent form (s) since the .last IRB approval?
No
Have translated consent short forms been usecl in conjunction with an interpreter to obtain consent

for this study?
No

Other Comments
We hope to complete enrollment for the study in 1 year^

The'University of Minnesota is:an equal opportunity educator & employer- Page 3
© 2004 by the Regents of the University of Minnesota.

Memo
To: S. Charles Schulz, M.D.
From: Scott Crow, M.D.

CC; Kyle Rudser Ph.D., and Kathy Mischke

Date: 11/8/2011
Re: Seroquel XR BPD Study Safety Monitoring Minutes

Safety monitoring and enrollment dgta were reviewed to date and the following were
noted.

1. Tjme to data entry has dJminjshedi substantially, particularly at the Minnesota
site with the median now approaching 10 days. This is extremely useful for
adequate and timely safety monitoring.
2. It was noted previously that one subject at the Iowa site had weight gain rated
at mild but recorded as an SAE; it had been requested that this be clarified
and likely corrected. This has not yet been done but needs to be done.
3, Baseline safety data are now present for all newly enrolled subjects which also
represents gn important improvement,
4. A substantial number of AEs have a severity rating: of "unknown". In order to
facilitate safety monitoring, severity ratings need to be clarified and gssigned
to these AEs.
5. As noted previously, it appears that screen fails are being tracked and entered
info the data base at the Iowa site but they are not be entered at the
Minnesota site (unless in fgct there are truly no screen fails which seems

unlikely). Ultimately it is of greatest important simply that these be tracked
and entered somewhere as they will undoubtedly be needed for reporting trial
results ultimately. On the other hand they are being entered at the Iowa site
and it would be best to handle this consistently across sites, by the
mechanism of entering them for the Minnesota site as well.

PI: Schulz University of Minnesota
HSC#: 0709M16844 Human Research Protection Program
Reviewer: QuicH Institutional Review Board

Meeting Date: 11/16/2011
Full Committee Review—Continuing Review of Approved Research
I 'I

"An 1KB shall conduct coi-itiiitiiiig review of research mvet'ed by this policy at intervals appropriate to the- degree of
risk, but not less than once per year, and shall have the authority to observe or have a third party obsen'e the
consent process and the research," 21CFR56.109 and 45CFR46,109
"Cantiming review of research must be substantive and meatsingfiil." OHRP Guidance 1-15-07

I • ••

Short Title: Seroquel XR for the Management of Borderline Personality Disorder
Enrollment: [X] Open d Closed Q On hold
Treatment: [X] Continues Q! Complete Q "Not a treatment study
Follow-up: [3 Continues 0 Complete Q No follow-up required
Funding: D Federal |^1 Industry Sponsored d Foundation
m Departmental Q Noile
Enrollment Numbers: Approved: 50 Enrolled: 34 Years active: 4
UPIRTSOs (Unanticipated Problem Involving Risk to Subjects or Others);
Have any UPIRTSOs been reported In the last year? Q Yes CX] No
Are there concerns to be discussed by the Committee? Q Yes [^ No
Study Summary; :[X] Adequate D Deficient
Q TSIone - too early Q None - data analysis elsewhere

External Findings: ^ DgMB letter Q Progress report D Action letter
Consent and Assent Forms: [X]; Submitted D Missing Q Waived or not applicable
HIPAA Forms: ^ Submitted D Missing Q Waived or not applicable,
D Closed to enrollment - forms are w longer pertinent

Are all persons listed on consent form also listed in the mB records? [^ Yes Q No

Inclusion of Child fen in Research:
If children are included in this research confirm that they should still be included.

D Yes D No IEI NA - children excluded
If children are Included, is there new inforrnation which affects the regulatory classification

(45CFR46 Subpart D) indicate the cihange.

D (404) Minimal risk
D (405) Greater than minimal risk; but holds prospect of direct benefits to subjects,
D (406) Greater than minimal risk; no prospect of direct benefit to subjects, but likely to
yield generaUzable kncnyledge about the subject's disorder QI' conditioti,

University ofMumesotaIRB
Conttnumg Review Form

Version October 2010

Substantive Changes: If any of the following are evident from the eontinuing review report,
describe the changes for Committee diseussioti.
0 Change iti risk or benefit

Change in funding

0 Change In subject population

Change in coiiflict of interest
Change in data management

Q Min6r changes in consent form
Major changes in consent form

Items for Committee Discussion:
Pl reports that the Harvard site dropped out, leaving only UofM and l&wa,

Recommended Stipulations:
1. For continuing review, it i$ reported that 34 subjects have been enrolled, but the D8MB report notes that
screen failures have not been registered in the study database. Confirm whether the sum of 34 enroliees
includes screen failures.
2. Update the out-of-study contact address.

Recommended Suggestions:
1. Considering that D of M has enrolled 57% of subjects, the national goal is 99 subjects, and the local
allowance is 50 subjects, it may be necessary to increase the local allowance,
2. On page 2 of the consent form, update the number of study sites from "3" to "2".
Recommended Action: Q Approve as Submitted
Approve with Suggestions

Approve with Stipulations as noted
1 Response to original reviewer

^Response can be reviewed by IRE staff
Q Approval Deferred - additional information required

Continuing Review Interval: Kl Annually
D Every 6 months
Quarterly
a Other interval:
/ have completed a substarnive and mecinmgful review based on the information made. availcible
at this time.

Print name of reviewer: Donald C, QilicH Date: 11/16/2011

Signed name of reviewer:
If you choose to submit this form eleptronically, please send to irhfTOtim.edu.
Forms submitted from a unin.edu account do n&t need a hard-copy signature.

University of Minnesota IRB
Gontiliumg Review Form

Version October 2010

Committee Meeting Minutes
November 16, 2011

Agenda Item;
Continuing Review-IVIedical

Kt: Schulz, Sellmann

IR.evievyer^ Quick
IRevieyrer; 3None

Agenda Itemi None
Agenda Item ^ None

Protocol Title and^HSC^S^'Seroi^
A^Randomized;Double-Blma'Gomp:ayis^
Item Description:
Wone^11.-71®

Discussion of Cohtrovertedlssues Summary;
There were no controverted issues.

tRevisions^:Clarifl(^tibris:o)c^Stipulations;;:;^;j;^:';l:":^^^^^^^^ ':;l'll:'^?/''?'^:li^'^"'':lll:;l':^

It appears as though this study has enrolled a total of 34 subjects. Is this correct? The DSMB report notes
that screen failures have not been registered in the study database. Confirm whether the sum of 34 enrollees includes
screen failures.

[Change in Risk/Bemefit Balance;
None

Committee Must Address:

El 21CFR56.111 & 45CFR46.111
(Applicable Criteria Met)

D45CFR46-SubpartB
(Research Involving Pregnant Women or Fetuses)

D 21CFR50.23 & 45CFR.U6

D 45CFR46-Subpart C

(Waiver or Alteration of Consent Process)

(Research Involving Prisoners—Indicate Level of Risk, e.g. Minimal or
Greater Than Minimal)

D 21CFR50.27 & 45CFR46.117
D 21CFR50 & 45CFR46-Subpart D

(Waiver of Consent Documentation)

(Research Involving Children—Detail Inclusion or Exclusion Justification
and Indicate Level of Risk, e.g. Minimal or Greater Thau Minimal,
Describe Consent Requirements as Specified in 21CFRS0.55 and

45CFR46.408)

Determinations and Justifications Required by Regulations and Guidelines:
None

IRB Decision:
Approve Continuing Review with Stipulations

Length of Approval: One Year

Additional Info: None
Vote Yes: B

No: 0

Abstain: 0

Members Not Present for Vote Due to Conflict of Interest: Crow

Not Present:

11/21/2011
Selltnann C Schulz

Psychi&try, Dept of8393A
F282/2AWest-B
2450 Riverside Ave
Minneapolis, MN 55454

RE: "S^roquel XR for the Management of Borderline Personality Disorder: A Randomized
Double-Blind Comparison with Plaeebo"

IRB Code Number: 0709M16844

Dear Dr. Schulz,

At the meeting on November 1$, 2011, the Institutional Review Board (IRB) reviewed and
renewed approval for the referenced study. The IRB stipulated the following:
• K appears as though this study has enrolled a total' of 34 subjects. Is this correct? The
DSMB report notes that screen failures have not been registered in the study database.
Confirm whetlier the sum of 34 enrollees includes screen failures.
Please provide a response for IRB review.
If your response is not received within ninety days, the study will be filed inactive.

Please send your response to HRPP (Mayo Mail Code 820; D-528 Mayo Memorial Bmlding;
420 Delaware St. SE; Minneapolis, MN 55455), The signature of the Principal Investigator is
the only signature required with the response, Only one copy of the response is necessary.
If you have any questions, please contact the IRB office at 612-626-5654.
Sincerely,

Felicia. Mroczkowski, CIP
Research Compliance Supemsor

FM/mq
CC; Scott Crow, Kathryn Cullen, Michael Miller, Richelle Moen, Ann Romine

University of Minnesota

Review Period;

Continuing Review of IRB - Pending

10/21/2011-11/14/2012
Rev; 03/01/2005

Medical Research

Study Number: 0709M16844
Principal Investigator: S Charles Schulz
Title(s): Seroquel XR for the Management of Borderline Personality Disorder:
A Randomized Double-Blind Comparison with Placebo
Study Status

Active (Enrolling Subjects)

Funding Source(s)

Funding Source: ASTRAZENECA INTL
Funding Type:
Personnel
Schulz, S Charles (P. I.)

Carlson, William (Staff/Lab)
Crow, Scott (Co-lnvestigator)
Cullen, Kathryn (Co-lnvestigator)
Davis, Aubrey (Staff/Lab)

Fryza. Brandon (Staff/Lab)
Han,

Georges-Jakob

Heller,

Monika

(Staff/Lab)

(Staff/Lab)

Houri, Alaa (Correspondent)
Miller, Michael (Co-lnvestigator)
Moen, Richelle (Co-lnvestigator)
Romine, Ann (Correspondent)

Stepka, Megan (Staff/Lab)
Watroba, Lexa (Staff/Lab)

Investigational Drug(s)
The University of Minnesota is an equal opportunity educators employer- page 1
© 2004 by the Regents of the University of Minnesota.

|

|

IND Number: 45,456
IND Holder: AstraZeneca Pharmaceuticals LP (Sponsor)

Study Enrollment
Number of Subjects Approved for study:
50
Number of subjects enrolled this reporting period:
Male Female Unknown Total
R~
^13
~J£

K

Number of subjects enrolled to date:
Male
f20-

Female
T35~

Unknown

10 C

Total
55_

]

\

I

Is this a multi-center study?
Yes
Total national accrual to date: 85

Unanticipated Problem Reporting
Since the most recent IRB continuing review approval, have any participants withdrawn from the
research?

Yes
4 early withdrawals since last continuing review. 2 were due to adverse events, 1 was due to inefficacy, and 1 was
due to subject moving away. 3 screen failures since last Gontinuing review.

Since the most recent IRB continuing review approvali have any participants complained about the
research?
No
Have any serious and unanticipated problems been reported to the IRB?
Yes
13 JUL 2012 - UPIRTSO report date 06 AUG 2012- Submission acknowledged by IRB No changes to consent
form or study were needed.

Study Summary
Summarize preliminary infonnation about any results and/or trends:
We are nearing the end of ow enrollment for this study. Our total enrollment for both all 3 sites will be
approximately 90 subjects (this total does not include screen failures). All subjects will have completed study by the
end of 2012 or early 2013.

Have there been any changes in protocol approved by the IRB since last continuing review?

The University of Minnesota is an equal opportunity educator & employer- Page 2
© 2004 by the Regents of the University of Minnesota.

Yes
MRI addendum and MRI healthy controls were added to the main study. Consents documents will be uploaded
here.

Since the most recent IRB continuing review approval, have there been any progress reports on the
research?

No
Since the most recent IRB continuing review approval, have there been any multi-center trial reports?
No
Since the most recent IRB continuing review approval, have there been any other information
relevant to this research discovered, especially information about the risks and benefits associated
with the research?
No
Since the most recent IRB continuing review approval, have subjects experienced any benefits?
Yes
Some subjects have reported a decrease in their symptoms of Borderline Personality Disorder.

External Findings
Is there anything in the relevant recent literature that the IRB should know about conGerning this
research?

No

Consent/Assent/HIPAA Forms
Have there been any changes to the consent and/or assent form(s) since the last IRB approval?
Yes
The main study consent was updated and approved by the IRB on Aug 9,2012.

Have translated consent short forms been used in conjunction with an interpreter to obtain consent
for this study?
No

Other Comments

The University of Minnesota is an equal opportunity educator & employer- page 3
© 2004 by the Regents of the University of Minnesota.

PI: Schulz University of Minnesota
HSC#: 0709M16844 Humaa Research Protection Program
Reviewer: Quick Institutional Review Board

Meeting Date: 10/31/12

Full Committee Review—Continuing Review of Approved Research
I

"An 1KB shall conduct continuing review of research covered by this policy at Intervals cippropriateto the degree of
risk, but not less than once per year, and shall have the authority to observe or have a third party observe the
consmt process and the research." 21CFR56.109and45CFR46.109
"Coittinuing review of research must be substantive and meaningful." OHRF Guidance 1-15-07

Short Title: Seroquel XR for the Management of Borderline Personality Disorder

Enrollment; [X] Open Q Closed D On hold
Treatment: ^ Continues Q Complete Q Not a treatment study
Follow-up: 13 Continues Q; Complete Q No follow-up required
Funding: C] Federal ^|: Sponsored Q Foundation D Departmental
Enrollment Numbers: Approved; 50 Enrolled; 55 Years active; 6
UPIRTSOs (Unanticipated Problem Involving Risk to Subjects or Others):
Have any UPIRTSOs been reported in the last year? ^ Yes D No
Are there concerns to be discussed by the Committee? |_| Yes D>3 No

Study Summary: Q Adequate d Deficient
[X] None - too early Q Notte - data analysis elsewhere
t

External Findings; QDSMB letter D Progress report D Action letter
Consent and Assent Forms: ^ Submitted Q Missing Q'Waived or not applicable
HIPAA FOrmS: D Submitted ^ Missing D Waived or not applicable
0 Closed to enrollment - forms are no longer pertinent
Are all persons listed on consent form also listed on the IRB roster? [^ Yes D No

Inclusion of Children in Research:
If children are included in this research confirm that they should still be included.
Yes D No |EI NA - children excluded
If children are included this iiiGlusion must meet one of the following criteria for risk/benefit
assessment according to federal regulation (2ICFR56 and 45CFR46 Subp^rt D),

(404) Minimal risk
(405) Greater than minimal risk; but holds prospect of direct benefits to subjects,
Q (406) Greater than minimal risk; no prospect of direct benefit to subjects, but likely to
yield generalizable knowledge about the subject's disorder or condition,

University of Minnesota IRB
Continuing Review Form

Version 10/27/09

Substantive Changes: If any ofthe following are evident from the continuing review,
describe the changes for Committee discussion,

Change inrisk or benefit Q Change in funding
Change in. subject population |_j Change in conflict of interest
D Minor changes in consent form Q Change In data management
Major changes in consent form

Items for Committee Discussion:
MRI was added in the last year. Cfintrol subjects were added in the last year.

Recommended Stipulations:
1. Our records indicate that 50 subjects were approved for the study but 55 have been enrolled. Explain
how over-enrollrnent occurred and measures taKen to prevent recurrence, inform the IRB how many
subjects are required and provide justification,
2. Submit a 5-yr renewal.

3. Update the out-of-study contact address in the.main consent form for patients.
4. Submit a current HIPAA form.
Recommended Suggestions:

Recommended Action: Q Approve as Submitted
Q Approve with Suggestions
Approve with Stipulations as noted
Response to original reviewer

[><] Response can be reviewed by IRB staff
Q Approval Deferred - additional information required

Continuing Review Interval: ^ Annually
Q Every 6 months
D: Quarterly
0 Other interval;
I have cowpleied a substantive and meaningful review based on the mforwation made gvailable
at this time.

Print name of reviewer; Donald 0. Quick Date; 10/31/2012

Signed name of reviewer:'

If you choose to; sub mit fhis fonn electroniGally, please send to ^rj^utrtntedu.
Forms submitted from a umn.edu account do not need a hard-copy signature.

University of Minnesota IRB
Continuing Review Form

Version 10/27/09

Committee Meeting Minutes
October 31,2012

Agendaltem:
Continuing Review-JVIedical

PI: Schulz, S Charles

Reviewer; ^ Quick
Reviewer: None

Agenda Item: None
A^encla^tem: None

Protocol Title and HSC^:"Seroqu^^
ARandpmizedDduIlle^utdComparteonwithPlhacebo''^
Item Description:
Time for 5 year renewal.

iDiscussidn of Contt-overted Issues Sumimary:
There were no controverted issues.

]RevisionS).Clarifl<:ations:or;StipuIationsi:-'ll.,.;:;,/l::.\^ ;'';:-'y:'l:;AT^':1^

:?')

• The Fairview Research Helpline office moved off-campus as of May 7, 2011. The telephone number is
unchanged; however, please correct the address in the Contacts and Questions section of all consent forms. This
section should read: "If you have any questions or concerns regarding the study and would like to talk to someone
other than the researcher(s), you are encouraged to contact the Fairview Research Helpline at telephone number 612672-7692 or toll free at 866-508-6961. You may also contact this office in writing or in person at Fairview Research
Administration, 2433 Energy Park Drive, St. Paul, MN 55108."
• In response to evolving federal guidelines and increased scrutiny by regulators, the IRB must in some cases
reconsider studies originally reviewed over 5 years ago. To ensure that the IRB has accurate information,
investigators are required to provide a five year renewal form for these studies. Since the original application of this
study dates from September 2007, you are asked to complete a five year renewal form. The most current form can be
downloaded from our web site at: http://www.research.umn.edu/irb/forms.html. Provide the five year renewal form

within 90 days.
• Please submit a current HIPAA form.

I Change in RisK/BeneGt Balance;
None

Committee Must Address:

13 21CFR56.111 & 45CPR46.111
(Applicable Criteria Met)

D45CFR46-SubpartB
(Research Involving Pregnant Women or Fetuses)

D 21CFR50.23 &45CFR.116

D 45CFR46-Subpart C

(Waiver or Alteration of Consent Process)

(Research Involving Prisoners—Indicate Level of Risk, e.g. Minimal or
Greater Than Minimal)

D 21CFR50.27 &45CFR46.117
(Waiver of Consent Documentation)

D 21CFR50 &45CFR46-SubpartD
(Research Involving Children—Detail Inclusion or Exclusion Justification
and Indicate Level of Risk, e.g. Minimal or Greater Than Minimal,
Describe Consent Requirements as Specified in 21CFR50.55 and

45CFR46.408)

Determinations and Justifications Required by Regulations and Guidelines:
None.

Committee Meeting Minutes
October 31,2012
IRB Decision:

Length of Approval: One Year

Approve Continuing Review with Stipulations
Additional Info: None
Vote Yes: |

No: 0

Abstain: 0

Members Not Present for Vote Due to Conflict of Interest: None

Not Present:

November 5,2012

S Charles Schulz
Psychiatry, Dept of

F282/2AWest-B

8393A
2450 Riverside Ave
Minneapolis, MN 55454
RE: "Seroquel XRfor tile Management of Borderline Personality Disotder; A Raiidomized
Double^Blind Comparison with Placebo"
IRB Code Number: 0709M16844
Dear Dr. Schulz,

At the meeting on October 31,2012 the Institutional Review Board (IRB) reviewed and renewed
approval for the referenced study. The'IRB stipulated the following;
• Tile Fairview Research Helpline office moved off-campus as of May 7,2011. The telephone
number is unchanged; however, please correct the address in tile Contacts and Questions section
of all consent forms, This section should read; "If5?ou have any questions or concerns regarding

the study and Would like to talk to someone other than the researcher(s), you are encouraged to
contact the Fairview Research Helpline at telephone nuinber 612-672-7692 or toll free at866508-6961. You may also contact fliis office in writing or m person at Fain'iew Research

AdmMstmiion, 243 3 Energy Park Drive, St. Paid, MN 55108"
• In response to evolving federal guidelines and increased scrutiny by regulators, the IRB must in
some cages reconsider studies originally reviewed over 5 years ago. To ensure that the IRB has
accurate information, investigators are required to provide a five year renewal •fonn for these
studies. Since the original application of this study dEites from September 20,07, you ate asked to
complete a- five year renewal form. The most cuft'ent form catt be downloaded firotti our web site
at; http://www.research.umn.edu/irb/fom-is.htm]. Provide the five year renewal form within 90
days.
• Please submit a current HIPAA form.
Please provide a response and revised consent form for IRB review.

If your response is not received within ninety days, the study will be filed inactive.
Please send your electronic response to HRPP (irb@umn.edu). The signature of the Principal
Investigator is the only signature required with the response. Only one copy of the response is necessary.
If you have any questions, please contact the IRB office at 612-626-5654.
Sincerely,

^6f^

Felicia

Mroczkowski,

Research Compliance Supervisor

FM/ac
CC: Scott Crow, Kafhryu Cullen, Alaa Houri, Michael Miller, Richelle Moen, Ann. Roltiine

CIP

|

UNIVERSITY OF MINNESOTA RECD NOV 2 Q 2012
Twin Cities Campus Ambulatory Re&ewch Center F2S2/2A West
Department of PsycMM,y wowvw^e^wte^
Mhmeapolis, MN 55454
Medical School

Office: 612-626-5001

November 20, 2012

Felicia Mroczkowski
Institutional Review Board
University of Minnesota
Mayo Mail Code 820
D528 Mayo Memorial Building
420 Delaware Street S.E.
Minneapolis, Minnesota 55455

RE: "Seroquel XR for the management of Borderline Personality Disorder (BPD)"

HSC#0709M16844

Dear Felicia;
Thank you for your Continuing Review of the referenced study. We are responding to
IRB stipulations as stated in your letter dated November 5, 2012.
1) The consent form has been updated to include the correct address in, the GontQOts
and Questions section on page 9.

2) We have completed the IRB Five Year Renewal Form,
3) We are submitting the current HtPAA form, version date 24 FEB 2009. No changes
have been made to the HIPAA form,
The following documents are enclosed;
1. Consent form version date 20 NOV 2012
2. IRB Five Year Renewal Form

3. HIPAA form version date 24 FEB 2009

Thank you and please contact Ann Romine, study coordinator, with any questions at
612-626-6812.
Sincerely,

i^UMA^
S. Charles Schulz, MD

principal Investigator

UNIVERSITY OF MINNESOTA

Route this form to;

Five Year Renewal

Rev; 10/1/09

See instructions below.

Instructions:
Use this form whensubmftting for five-year renewal on IRB profocpls,
), Submit this form to the Research Subjects' Proteaions Programs Office:
U.S. Mail Address:
Human Research Protection Program

MMC 820

420 Delaware St. SE
Minneapolis, MN 554S5-0392

Campus Mail:

Human R6seareh Protection Program

MMC 820

'Minneapolis Campus

Deliver to;
D-528 Mayo Memorial Building
Minneapolis Campus
8-4:30, M-F

IRB Protocol Information
IRB Study Number:
Current Principal Investigator;
Primary Title:

0709M16844
S, Charles Schulz, MD
Seroquel XR for the Management of Borderline Personality Disorder (BPD)

1. State the original hypothesis or research question in a few short sentences:

The hypothesis of this proposal is that Seroquel XR will be statistically superior to placebo in
this controlled teial. A double-blind, placebo-controlled randomized trial is proposed to test

the efficacy and safety of Seroquel XR, A fixed dose strategy will be employed - 150 mg/d
and 300 mg/d.
2. Summarize any major changes to this study in the past five years. For instance, describe any new findings, any significant
changes in the protocol or project design, indicate any changes in study personnel;

1) The Brain Imaging Addendum was approved by the IRB on November 5,3010.
2) MeLewi Hospital withdrew participation in the study as of March 201 1, Their reason for
withdrawal was inability to meet enrollment goal. As the original enrollment goal was 33 per
site for a total of 99 subjects, the 2 remaining sites (University of Minnesota and University
of Iowa) incorporated McLean's enrollment to aim for a goal of 49 and 50 subjects per each
site,

3) The Brain Imaging Healthy Control Addendum was approved by the IRB on August 9,
2012,

2a. State if any of these changes increased risk to the subject population in your opinion:

These changes have not increased risk to the subject population,

3. Summarize the scientific progress indicating what you have learned. If there has been no substantial progress, then
provide an explanation:

Some subjects have reported a .reduction in their symptoms of Borderline Personality
Disorder.

4. List the publications developed With this research:

None yet as we are finishing up subject visits.

The University of Minnesota is an equal opportunity educator & empjoyer.
© 2008 by thfc Regents of the University of Minnesota.

1 of 3

5. If children are included in this study, is there a plan in place to re-consent minor subjects as they reach the age of

majority?

Qi Yes D No KlNA
6, Has the funding source for this research changed? If yes, then how?

D Yes E3 No D'NA

The University of Minnesota is an equal opportunity educator & employer.
i§> 200S|by the Regents of the University of Minnesota.

2 of 3

7. If there are multiple study title associated with this work, state if there are any that are no longer active:

N/A
8, How many subjects have you enrolled to date?

We have enrolled 52 subjects at our site. This includes 3 screen failures for a total of 49
randomized subjects.
9, Are you requesting additional subjects at this time?

No
10. If you are currently enrolling subjects, or plan to enroll in the future, then please provide a copy bf(he consent forms
with all informqtion up to date.

We have completed enrollment as of November 2012 and are seeing the final subjects in the
study,

Th? University of Minnesota is an equgl opportunity educator & employer,
• © 20p8 by the Regents of the University of Minnesota.

3 Of 3

UNIVERSITY OF MINNESOTA
7'iciH Citifs Cmilpus

Hunitin Kesiwrcll I'rnteetwn t'rngram
Office iiftlit.' Viye I'lvshlmiljnr Reseuivh

D52fi Mnyi) Menmrhll tiulMinf;
420 Oelawan Snvrt S.E.

MMC 820

MiiiMtiiwlis, MH 5545S
Office: ht2-6U-5654
/•at- ftl!-fi36-6061
E-nmil; irh@unm.filn or ihv^umn.t'iln
Weluiiu': htlii://wseurch.wmu'tlit/.wh)ccl!i/

November 29, 2012
S Charles Schulz
Psychiatry, Dept of
F282/2AWest-B

8393A
2450 Riverside Ave
Minneapolis, MN 55454
RE; "Seroquel XR for the Management of Borderline Personality Disorder: A Rafidomized Double-Blind
Comparison witii Placebo

IRB Code Number: 0709M16844
Dear Dr. Schulz,

The Institutional Review Board (IRB) received your response to its stipulations for renewal. Since this
information satisfies the conditions set by the IRB, approval for the recent renewal is confirmed in our files.
The consent form dated November 20, 2012 is also approved.
For youi" records and for grant certification purposes, the approval date for the referenced project is October
31, 2012 and the Assurance of Compliance number is FWA00000312 (Fairview Health Systems Research

FWA00000325, Gillette Children's Specialty Healthcare FWA00004003). Approval for the project will
expire one year from that date. You will receive a report form two months before the expiration date.
As Principal Investigator of this project, you are required by federal regulations to inform the IRB of any
proposed changes in yoyr research that will affect human subjects. Changes should not be initiated until
written IRB approval is received. Unanticipated problems and adverse events should be reported to the IRB
as they occur. Results of inspections by any external regulatory agency (i.e. PDA) must be reported
immediately to the 1KB. Research projects are subject to continuing review,
If you have any questions, please call the EU3 office at 612-626-5654.
The IRB wishes you continued success with your research.
Sincerely,

FeliciaMroczkowski, CIP
Research Compliance Supervisor

FM7ac
CC; Kathiyri Cullen, AlaaHouri, Michael Miller, Riclielle Moen, Ann Ronune

Driven to Discover5

University of Minnesota

Continuing Review of IRB - Pending

Review Period;
09/07/2012-10/30/2013
Rev: 03/01/2005

Medical Research

Study Number: 0709IVI16844
Principal Investigator: S Charles Schulz
Title(s): Seroquel XR for the Management of Borderline Personality Disorder:
A Randomized Double-Blind Comparison with Placebo
Study Status
Complete

Funding Source(s)

Funding Source: ASTRAZENECA INTL
Funding Type:

Personnel
Schulz, S Charles (P. I.)

Carlson, William (Staff/Lab)
Cullen, Kathryn (Co-lnvestigator)
Davis, Aubrey (Staff/Lab)
Fryza, Brandon (Staff/Lab)
Han, Georges-Jakob (Staff/Lab)
Heller, Monika (Staff/Lab)
Houri, Alaa (Correspondent)

LaRiviere, Lori (Staff/Lab)
Miller, Michael (Co-lnvestigator)
Moen, Richelle (Co-lnvestigator)
Romine, Ann (Correspondent)

Stepka, Megan (Staff/Lab)
Watroba, Lexa (Staff/Lab)

Investigational Drug(s)
The University of Minnesota is an equal opportunity educator & employer. Page'
©2004 by the Regents of the University of Minnesota.

IND Number: 45,456
IND Holder: AstraZeneca Phannaceuticals LP (Sponsor)

Study Enrollment
Number of Subjects Approved for study:
80
Number of subjects enrolled this reporting period:
Male Female Unknown Total

T

n

3°:

13 I

Number of subjects enrolled to date:
Male

22

Female
y36~

Unknown

3°:

Total

|58 |

Is this a multi-center study?
Yes
Total national accrual to date: 95

Unanticipated Problem Reporting
Since the most recent IRB continuing review approval, have any participants withdrawn from the
research?
Yes
One subject withdrew early due to leaving the country.

Since the most recent IRB continuing review approval, have any participants complained about the
research?

No
Have any serious and unanticipated problems been reported to the IRB?
No

Study Summary
Summarize information about any results and/or trends:
A total of 79% of the subjects receiving quetiapine XR were rated as ???responders??? compared to 62% of those
who received placebo. Treatment-emergent adverse events included sedation, change In appetite, and dry mouth.
The overall completion rate for the 8-week double-blind treatment phase was 63% (55% for quetiapine XR 150 mg,
58% forquetiapine XR 300 mg, and 79% for placebo).

Have there been any changes in protocol approved by the IRB since last continuing review?
No

The University of Minnesota is an equal opportunity educator & employer. Page 2
©2004 by the Regents of the University of Minnesota.

Describe any new information (i.e, lessons learned, things to do differently) discovered during the
course of this research study pertinent to protecting subjects:
Nothing to report.

On what date was this study completed or discontinued?

03/12/2013

External Findings
Is there anything in the relevant recent literature that the IRB should know about concerning this
research?

No

Consent/Assent/HIPAA Forms
Have there been any changes to the consent and/or assent form(s) since the last IRB approval?
No
Have translated consent short forms been used in conjunction with an interpreter to obtain consent
for this study?
No

Other Comments
The last subject completed at University of Minnesota on Feb 6, 2013. The last subject completed at University of
Iowa on March 11 , 2013. Data analysis has been completed at the University of Iowa. The manuscript draft has
been completed by Dr. Black in August 2013. Clinicaltrials.gov has been updated with results in August 2013.

The University of Minnesota is an equal opportunity educator & employer. Page 3
© 2004 by the Regents of the University of Minnesota.

University of Minnesota Mail - Fwd: IRB# 0709M16844 sfaidy closure letter lTttps://n3ail.google.com/imil/u/l/?ui=2&ik=dd3dle7c9e&view=pt&searc...

A

Almarie Coleman <colem258@umn.edu>

Fwd: IRB# 0709M16844 study closure letter

1 message
Andrew Alien <alle0302@umn.edu> Wed, Feb 12, 2014 at 4:30 PM
To: Almarie Coleman <colem258@umn.edu>, Felicia Mroczkowski <kensl001@umn.edu>
Hey Almarie,
This sponsor needs an actual letter for study close out to receive payment. Can you write one for them? I am not

sure how you and Felicia handle this when the Pl closes the study during CONREN in the past, but I thought you two
may be the best to handle this request.
Andrew
Forwarded message
From: <romi0004@umn.edu>

Date: Wed, Feb 12, 2014 at 4:27 PM
Subject: IRB# 0709M 16844 study closure letter
To: Andrew R Alien <alle0302@umn.edu>
Cc: Harvey Gross <gross042@umn.edu>

Hi Andrew,
Harvey is unable to receive our final study payment from AstrZeneca as they are awaiting the IRB study closure
letter for study IRB# 0709M16844. The IRB acknowledged study closure in response to our final continuing review,
but AZ said this was not sufficient for their records.
Could we have a study closure letter sent to us? Electronic version is fine.

Thx!
ann

Ann Romine,RN
Study Coordinator

Psychiatry
ph612.626.6812
fax612.626.5103

Mailing Address:
University of Minnesota

Department of Psychiatry
2450 Riverside Ave S
F212/2AWest
Minneapolis, MN 55454

Sincerely,

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