Twin Clues Campus

Research Sthjects Pr ltioi Programs Institutional Review Board: Human Subjects Committee (IRD) Institutional Animal Care and Use Committee f 1ACUC)

May 13, 2004

sukkels lum Official Notification: Serious Adverse Event involving a Research Subject

Mayo Mail Code 820 1)528 Mayo Memorial Building 420 Delaware Street S.E. Minneapolis, MN 55455-0392 612-626-5654 Fax: 6I2626-6061 icb@utnn.edu lacuc@umti.edu http://www.research.wnn.edu/

TO: Food and Drug Administration: Minneapolis District Office Sharon Mattson, Investigations Division FAX: 612334-4134 Office for Human Research Protections (OHBP) 301 402-0527 Assurance Officer Harold Blatt :Wm 0003 JTA )L:

FROM: Richard W. Bianco

Institutional Official for k1uxuat1 Std t Protections RE: "Efficacy and Tolerability of Olanzapine, Quetiapine and Risperidone in the Treatment of First Episode Psychosis: ARnndomized Double Blind 52-Week Comparison - The Cafe Study" Human Subjects Code Number: 0202M1 7441 Stephen C. Olson, MD, Principal Investigator The University of Minnesota is reporting an unanticipated serious adverse event in an Institutional Review Board approved research project. A subject enrolled in the referenced study committed suicide on May 8, 2004. The principal investigator has reported this event and will continue to provide us with information. The investigator has made reports to the commercial sponsor who in turn is making reports to the FDA. The study completed enrollment in March 2004 at this site, therefore, no additional subjects will be recruited. When a complete report is available, the IRB will review the incident and determine if additional safeguards are necessary for currently enrolled subjects. We will continue to keep you informed. This is a tragic event, unfortunately not uncommon in this study population. The University of Minnesota continues its commitment to protection of human subjects and will continue to assure that every precaution is in place to limit potential for such events. If there are any questions, please contact me or Moira Keane, Director of Research Subjects Protection Programs. CC: Stephen, C. Olson, Jean Kenney, S Charles Schulz, John Vuchetich

Page 24

UNIVERSITY OF MINNESOTA
Research Subjects Protection Programs Institutional Review Board: Human Subjects Committee (IRS) Institutional Animal Care and Use Committee (IACUC) Mayo Mail Code 820 D-528 Mayo Memorial Building 420 Delaware Street S.E. Minneapolis, MN 55455 612-626-5654 Fax: 612-626-6061 irb@umn.edu iacuc@umn.edu www.irb.umn.edu www.iacuc. umn,edu

Institutional Review Board: Human Subjects Committee

Minutes

Health and Biological Sciences Panel 05 Wednesday May 26, 2004 Meeting Convened at: 1:00 pm Meeting Adjourned at: 3:45 pm
Chairperson: David Adson Members in Attendance: David Adson, Matt Bower, Nancy Flenimons, Robert Haight, Kathryn Johnson, Elizabeth Kipp-Campbell, Jill Klingner, Jan McNeIly, Michael Schwartz, Scott Velders Non-Scientific Member: Carol Siegel Community Member: Elizabeth Kipp-Campbell Members Absent: none Quorum Requirement: 7 Quorum Established at: 1:00 pm Conflict of Interest Declaration Request: None Declared Minutes Ratified: April 28, 2004 The following Minutes were reviewed and approved by the chairperson in attendance at the meeting.

David Adson,

Chair

Date

Committee Meeting Minutes May 26, 2004 Page 9

Olson, Stephen C.

"Efficacy and Tolerability of Olaisznpine, Quetiapine and Rlspsidone in the Treatment of First Episode Psychosis. , A Randomized Double Blind 52-Week Comparison The Cafe Study" 0202M17441

At its meeting on May 26, 2004 the IRB: Human Subjects Committee reviewed and approved the change in protocol, for the above referenced study, described in your letter of May 10, 2004. The approved change involves a new version of the adult consent form that now includes diabetes as a risk for patients taking atypical antipeychotic agents, including CAFE study medications. The consent form dated March 24, 2004 was included in this review and has been approved. In other business, the IPJI: Human Subjects Committee reviewed and noted the unanticipated problem and adverse event report for the referenced study received on May 12, 2004, involving subject 00100013. As noted in the IRBs correspondence of May 13, 2004, this event was reported to appropriate regulatory agencies and on May 17th, the FDA acknowledged receipt of the report, The WB further notes receipt of requested follow-up information on this event from the P1. This information (P1s letter of May 17, 2004 and accompanying attachments) will be forwarded for review by the committee at its next meeting on June 23, 2004. Thank you for keeping the IRB Informed of the status of your research, As Principal Investigator for this study, you are required by federal regulations to inform the IRB of any proposed changes to your study that will affect human subjects. Changes should be reviewed and approved by the iRS before they are initiated. Unanticipated problems and adverse events should be reported to the IRB as they occur. Research projects are subject to continuing review and approval. 11/0/0

UNIVERSITY OF MINNESOTA
Research Subjects Protection Programs Institutional Review Board: Human Subjects Committee (IRE) Institutional Animal Care and Use Committee (IACIJC) Mayo Mail Code 820 D-528 Mayo Memorial Building 420 Delaware Street S.E. Minneapolis, MN 55455 612-626-5654 Fax: 612-626-6061 irb@umn.edu iacuc@umn.edu www.irb.umn.edu www.iacuc.umn.edu

Institutional Review Board: Human Subjects Committee Minutes Health and Biological Sciences Panel 05 June 23, 2004 Meeting Convened at: 1:00pm Meeting Adjourned at: 3:57pm

Chair: David Adson Members in Attendance: David Adson, JoanneBillings, Matt Bower, Nancy Flemmons, Bob Haight, Kathryn Johnson, Elizabeth Kipp-Campbell, Jill Klingner, Morry Rothstein, Michael Schwartz, Scott Velders Nonscientist Member: Carol Siegel Members Absent: Jan McNelly Community Member: Elizabeth Kipp-Campbell Quorum Requirement: 8 Quorum Established at: 1:00pm Conflict of Interest Declaration Request: None Declared Minutes Ratified: May 26, 2004 The following Minutes were reviewed and approved by the chairperson in attendance at the meeting.

fl4
David Adson, Chair Date

Committee Meeting Minutes June23, 2004 Page 10

Olson, Stephen C.

"Efficacy and Tolerability of Ohsnzapine, Quetiapirse and Riaperidone In the Treatment of First Episode Psychosis: A Randomized Double Blind 52-Week Comparison The Cafe Study" 0202M17441

The MB; Human Subjects Committee received your response to its stipulations of May 13, 2004. Since this information satisfies the requirements set by the IRB, review of the recent unanticipated problem and serious adverse event report involving Subject 00100013 is concluded. The committee reviewed and noted the additional information regarding the consent process and interim clinic visits for study Subject 00100013. For your records and for grant certification purposes, the approval date for the referenced project is January 2, 2004, and the Assurance of Compliance number is FWA000003I2 (Fairview Health Systems Research FWA00000325). Thank you for keeping the lR.B informed of the status of your research. 12/0/0