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Seroquel XR For Borderline Personality Disorder Continuing Review, University of Minnesota IRB
Seroquel XR For Borderline Personality Disorder Continuing Review, University of Minnesota IRB
Review Period:
01/10/2008-01/09/2009
-Continuing-Rev-iew-of-IRB-^Pending-
Rev; 03/01/2005
:M.e.dica,LResearch ..-=^
Funding Source(s)
AGENDA.
i^M JMSL
Funding Source:
Funding Type:
Funding Source: AstraZeneca
Investigational Drug(s)
IND Number: 45,456
IND.Holder: AstraZeneca (Sponsor)
Study Enrollment
Number of Subjects Approved for study:
50
Total
0 ~T2~
Page 2
Page 1
^_1=1\-0 ^2=^.
Is this a multi-center study?
Yes
Total national accrual to date; 2
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?
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
Other Comments
Study start has been slgnigicantly delayed by contract hold-ups.
Page 4
rP-Tr"-S-cbulz,:Sellman=^^""='O.TiiveFsity^'f-M:imeso'^
-Meeting-Date:- - - -- "-- - - - -
Full Committee ReviewContinuing 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."
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
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?
Yes
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:
Page 23
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
Page 24
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.
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:
Date: 12/17/2008
PagaZb
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
Agenda Item:i
Continuing Review-Medical
Reviewer: Johnsotf
Reviewer; Belew
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.
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
D 21CFR50.27 &45CFR46.117
D 21CFR50 & 45CFR46-Subpart D
45CFR46.408)
IRB Decision:
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^
F282/2AWest-B
2450 Riverside
Minneapolis, MN 55454
.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.
^
..
...
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
The IRB: Human Subjects Committee renewed its approval of the referenced stidy
listed below:
For grant certification purposes you will need this date and the Assurance of
Compliance number, which is FWA00000312 (Fairview Health Systems Research
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.
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
AGENDA
Funding Source(s)
Funding Source: AstraZeneca
,_^^0^
Study Enrollment
Number of Subjects Approved for study;
50
Number of subjects enrolled this review period:
]1
-E
-n
Total
Page 1
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?
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
Other Comments
Page 6
"
"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
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
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
D Quarterly
D Other interval;
I have completed a substantive and meaningful feview based on the information made available
at this time,
Version 10/27/09
Page 27
. ^
"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
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.
Recommended Stipulations:
1. Provide HIPAA form
Recommended Suggestions;
II Quarterly
[_j Other interval;
/ have completed a substantive and meaningful review based on the information made available
at this time.
Version 10/27/09
Page 30
Agenda Item;
Continuing Review-Medical
Kevie'wejft Krach
'Iteyie'wer;:i?(Dees?:
|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
S 21CFR56.111 &45CFR46.1U
(Applicable Criteria Met)
D45CFR46-SubpartB
(Research Involving Pregnant Women or Fetuses)
D 45CFR46-Subpart C
D 21CFR50.27 &45CER46.117
(Waiver of Consent Documentation)
45CFR46.408)
IRB Decision:
Approve Continuing Review with Stipulations
Additional Info: None
Vote Yes: 9
No: 0
Abstain: 0
Not Present:
12/17/2009
Selhnaim C Schulz
Psychiatry Department83 93 ^
F282/2A West-B
2450 Riverside
Minneapolis, MN 55454
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.
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-noteIn^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-
Institutional'Review Board
University of Minnesota
Mayo Mail Code 820
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."
S.^MM^l^i
S. Charles Schulz, MD
Principal investigator
Driven to Discover5
Page
UNIVERSITY OF MINNESOTA
s^Hu-i/2- -0-jo^t^.y-f^
z/,g/.,,AGEME
'//On.i^^ac^^
-Instr-uc.tJoos;-
Campus Mail;
MMC 820
MMC 820
Minneapolis Campus
Delivor to:
D-528 Mayo Memorial Building
. Minneapolis Campus
8-4:30, M-F
0709M16844
S. Charles Schulz
MD, Dept Head
Submission Date
30 DEC 2009
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.
Date
1 af2
University of Minnesota
Review Period:
09/25/2009-02/17/2011
Rev; 03/01/200.5
Funding Source(s)
Study Enrollment
Number of Subjects Approved for study:
50
[I
^4
Total
J2S[
Page 1
18 114 |0 f22 } |
Is this a multi-center study?
Yes
Total national accrual to date: 52
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
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
Other Comments
C^: 50
UNIVERSITY OF MINNESOTA ^ ^
Twin Cities Campus Depiirtmenl of Psychiatry F2S2/2A West
Memo
Minneapolis, MN 55454
Office: 612-273-9800
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
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.
Driven to Discover5
MEMORANDUM
TO: Scott Crow, M.D.
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.
"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
Are all persons listed on consent form also listed in the IRB records? Q Yes ^ No
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
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:
gguuumi
lllllliilBl.HIII
Agendaltem:1
Continuing Review-MedicaI
ReVie^yer; Pgnjanoxic
Reviewer: NoMe
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
D 21CFR50.27 &45CFR46.117
D 21CFR50 & 45CFR46-Subpart D
45CFR46.408)
Vote
Yes:
No: 0
Abstain: 0
Not Present:
Date: 02/07/2011
To: S. Charles, Schulz (scs@umn.edu)
From: irb@umn.edu
The IRB: Human Subjects Committee renewed its approval of the referenced study
listed below:
For grant certification purposes you will need this date and the Assurance of
Compliance number, which is FWA00000312 (Fairview Health Systems Research
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
Rev: 03/01/200?
Funding Source(s)
Study Enrollment
Number
of Subjects Approved for study:
50 ~' ~~~J"" ' -''------ -- -.'
|total enrolled: 34
I:
3E
14 |
Male
rr
Female
Unknown
,10
Total
: 14 ~|
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
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
Other Comments
We hope to complete enrollment for the study in 1 year^
Memo
To: S. Charles Schulz, M.D.
From: Scott Crow, M.D.
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.
"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
Are all persons listed on consent form also listed in the mB records? [^ Yes Q No
University ofMumesotaIRB
Conttnumg Review Form
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
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
Agenda Item;
Continuing Review-IVIedical
IR.evievyer^ Quick
IRevieyrer; 3None
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.
D45CFR46-SubpartB
(Research Involving Pregnant Women or Fetuses)
D 45CFR46-Subpart C
45CFR46.408)
IRB Decision:
Approve Continuing Review with Stipulations
No: 0
Abstain: 0
Not Present:
11/21/2011
Selltnann C 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,
FM/mq
CC; Scott Crow, Kathryn Cullen, Michael Miller, Richelle Moen, Ann Romine
University of Minnesota
Review Period;
10/21/2011-11/14/2012
Rev; 03/01/2005
Medical Research
Funding Source(s)
Georges-Jakob
Heller,
Monika
(Staff/Lab)
(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.
Study Enrollment
Number of Subjects Approved for study:
50
Number of subjects enrolled this reporting period:
Male Female Unknown Total
R~
^13
~J
Female
T35~
Unknown
10 C
Total
55_
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?
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
"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
Version 10/27/09
Substantive Changes: If any ofthe following are evident from the continuing review,
describe the changes for Committee discussion,
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:
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.
Version 10/27/09
Agendaltem:
Continuing Review-JVIedical
Reviewer; ^ Quick
Reviewer: None
]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.
D45CFR46-SubpartB
(Research Involving Pregnant Women or Fetuses)
D 21CFR50.23 &45CFR.116
D 45CFR46-Subpart C
D 21CFR50.27 &45CFR46.117
(Waiver of Consent Documentation)
D 21CFR50 &45CFR46-SubpartD
(Research Involving ChildrenDetail 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)
No: 0
Abstain: 0
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
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,
FM/ac
CC: Scott Crow, Kafhryu Cullen, Alaa Houri, Michael Miller, Richelle Moen, Ann. Roltiine
CIP
Office: 612-626-5001
Felicia Mroczkowski
Institutional Review Board
University of Minnesota
Mayo Mail Code 820
D528 Mayo Memorial Building
420 Delaware Street S.E.
Minneapolis, Minnesota 55455
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.
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
Rev; 10/1/09
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
Campus Mail:
MMC 820
'Minneapolis Campus
Deliver to;
D-528 Mayo Memorial Building
Minneapolis Campus
8-4:30, M-F
0709M16844
S, Charles Schulz, MD
Seroquel XR for the Management of Borderline Personality Disorder (BPD)
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:
3. Summarize the scientific progress indicating what you have learned. If there has been no substantial progress, then
provide an explanation:
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
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,
3 Of 3
UNIVERSITY OF MINNESOTA
7'iciH Citifs Cmilpus
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/
8393A
2450 Riverside Ave
Minneapolis, MN 55454
RE; "Seroquel XR for the Management of Borderline Personality Disorder: A Rafidomized Double-Blind
Comparison witii Placebo
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
Review Period;
09/07/2012-10/30/2013
Rev: 03/01/2005
Medical Research
Funding Source(s)
Personnel
Schulz, S Charles (P. I.)
Investigational Drug(s)
The University of Minnesota is an equal opportunity educator & employer. Page'
2004 by the Regents of the University of Minnesota.
Study Enrollment
Number of Subjects Approved for study:
80
Number of subjects enrolled this reporting period:
Male Female Unknown Total
3:
13 I
22
Female
y36~
Unknown
3:
Total
|58 |
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
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.
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.
University of Minnesota Mail - Fwd: IRB# 0709M16844 sfaidy closure letter lTttps://n3ail.google.com/imil/u/l/?ui=2&ik=dd3dle7c9e&view=pt&searc...
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>
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,
of
2/13/2014
10:53
AM