Page 1 of 2 Wetmore, Kevin (NIH/OD) [C] Fro Shore, David (NIH/NIMH) [E] Sent: Saturday, May 16, 2009 3:28 PM To: Insel, Thomas (NIH/NINMH) [E} ‘Subject: Re: NIMH DSMB DECISION ON HPA TREATMENT STUDY AND BASELINE STUDY = MH050804 ‘The Stanford Pls were noe’ within minutos of re DSMB Meeting E= Detsonat 8 Aclibecatwe. IneoCmanon | _ L.__5 ittney canuize poychiatiy staff, then maybe ie Kadatfne HER seoasemet component nl 'ti be Viable, bat were done wth the mifepristone Sopoct.- David ‘Sent from my BlackBerry Wireless Handheld From: Insel, Thomas (NIH/NIMH) [E] To: Shore, David (NIH/NIMH) [E] Sent: Fri May 15 20:02:43 2009 ‘Subject: Re: NIMH DSMB DECISION ON HPA TREATMENT STUDY AND BASELINE STUDY - MHO50604 ‘Thanks for letting me know. Who will notify Stanford? From: Shore, David (NIH/NIMH) [E] To: Insel, Thomas (NIH/NIMH) [E]; Goodman, Wayne (NIH/NIMH) [E]; Zalerman, Steven (NIH/NIMH) [E]; Wang, Philip Sung-En (NIH/NIMH) [E]; Volkov, Marina (NIH/NIMH) [E] Cc: Hillefors, Mi (NIH/NIMH) [E]; Zachariah, Etlzabeth (NIH/NIMH) (E]; Shell, Pamela (NIH/NIMH) [E]; Steinberg, Jane (NIH/NIMH) [E]; Claycamp, Rebecca (NIH/NIMH) [E] Sent: Fri May 15 17:29:25 2009 Subject: NIMH DSMB DECISION ON HPA TREATMENT STUDY AND BASELINE STUDY - MHO50604 Late this afternoon NIMH DSMB-B reviewed information recently provided by the Stanford research site and unanimously decided that the mifepristone (RU-486) tral should be terminated immediately and permanently. ‘This was done for multiple reasons Including inadequate recruitment to answer study questions, changes in Stanford's COI Policy which would have halted the trial July 1, 2009 anyway, and concerns about ability of staff now working on this study to manage such difficult (psychotically depressed) participants. New recruitment into the baseline study (HPA assessment, no trial component) was also suspended (at least temporarily) until the DSMB can be reassured that adequate staff expertise will be avallable to deal with the patients to be evaluated both now and after the new CO! Policy at Stanford takes effect in July. The Stanford IRB is being informed, and OHRP will also need to be notified of this action. We wanted you to know about this ASAP. If you have any questions about the situation or rationale, please let me know. This was originally the Schatzherg study which was being run recently by Dr Kramer... David ‘achariah, Elizabeth (NIH/NIMH) [€] Sent: Friday, May 15, 2009 4:39 PM To: Zachariah, Elizabeth (NIH/NIMH) [E]; "Jennifer Keller; "bk@stanford.edu’ Cc: Hillefors, Mi (NIH/NIMH) [E}; Severe, Joanne (NIH/NIMH) [E}; ‘alembke@stanford.edu’; akshike Tennakoon’; Shell, Pamela (NIH/NIMH) [E] ‘Subject: URGENT:NIMH DSMB DECISION ON HPA TREATMENT STUDY AND BASELINE STUDY 2/24/2010Page 1 of 1 Wetmore, Kevin (NIH/OD) [C] From: Shell, Pamela (NIHINIMH) [E] Sent: Thursday, June 04, 2009 4:35 PM To: Shore, David (NIH/NIMH) [E; Insel, Thomas (NIH/NIMH) [E}; Goodman, Wayne (NIH/NIMH) [E]; Zalcman, Steven (NIH/NIMH) (EJ; Wang, Philip ‘Sung-En (NIH/NIMH) [E]; Volkov, Marina. (NIH/NIMH) [E] Ce: —_Hillefors, Mi (NIHINIMH) [E]; Steinberg, Jane (NIH/NIMH) [E]; Claycamp, Rebecca (NIH/NIMH) [E] ‘Subject: RE: NIMH DSMB DECISION TO CEASE REVIEW OF HPA. Good Afternoon Everyone ‘As you may recall on May 15, 2009 the NIMH DSMB voted unanimously to terminate the RCT component of the HPA study. At that time the DSMB also voted to direct the investigators to cease enrolling subjects into the Baseline study because of the impact that the revised Stanford University COl policy would have on the overall study. Specifically concerns were raised regarding the ability of the current investigators to continue Participating in the study. The Board asked that no other subjects be enrolled in the baseline study until such time that the investigators could demonstrate to the Board that the individuals conducting the research had the knowledge and expertise to do so. On June 1, 2009 the investigators provided a satisfactory response and the Board voted to allow the baseline component of the study to continue. Further, in that the RCT component is no longer included in the protocol and the original potential CO! in the study has been managed by Stanford University, the Board voted unanimously to cease review of the baseline study. THE Stanford IRB has been notified of this decision. Pam From: Shore, David (NIH/NIMH) [E] Sent: Friday, May 15, 2009 5:29 PM Tot Insel, Thomas (NIH/NIMH) [E]; Goodman, Wayne (NIH/NIMH) [E]; Zalcman, Steven (NIH/NIMH) [E]; Wang, Philip Sung-En (NIH/NIMH) [E]; Volkov, Marina (NIH/NIMH) [E] ilefors, Mi (NIH/NIMH) [E]; Zachariah, Elizabeth (NIH/NIMH) [E]; Shell, Pamela (NIH/NIMH) [E]; Steinberg, Jane (NIH/NIMH) [E]; Claycamp, Rebecca (NIH/NIMH) [E] ‘Subject: NIMH DSMB DECISION ON HPA TREATMENT STUDY AND BASELINE STUDY - MHO50604 Importance: High Late this afternoon NIMH DSMB-B reviewed information recently provided by the Stanford research site and unanimously decided that the mifepristone (RU-#86) tial should be terminated immediately and permanently. This was done for multiple reasons including inadequate recruitment to answer study questions, changes in ‘Stanford's COI Policy which would have halted the trial July 1, 2009 anyway, and concerns about ability of staff ow working on this study to manage such difficult (psychotically depressed) participants, New recruitment into the baseline study (HPA assessment, no trial component) was also suspended (at least temporarily) until the DSMB can be reassured that adequate staff expertise will be available to deal with the Patients to be evaluated both now and after the new COI Policy at Stanford takes effect in July. The Stanford IRB is being informed, and OHRP will also need to be notified of this action. ‘We wanted you to know about this ASAP. If you have any questions about the situation or rationale, please let me know. This was originally the Schatzberg study which wes being run recently by Dr Kramer... David 2/24/2010Re -¥ letterre FCOl involving C ae cal Page 3 of 3 ‘Sent: Wednesday, May 27, 2009 1:02 PM too ne [E]; Dean, Diane (NIH/OD) [E]; Hancock, Kathy (NIH/OD) [E]; Muroff, Julie d Ce: Steinberg, Jane (NIH/NIMH) [E}; Insel, Thomas (NIH/NIMH) [E]; Guzman, Marlene (NIH/NIMH) [E]; Claycamp, Rebecca (NIH/NIMH) [E] Subject: (4)! letter re FCO! involving 2 ye a Please see the attached draft letter to 4 310 regarding an apparent COI problem. While this situation is not explicitly addressed in the 1995 Regs, it closely resembles the ‘©. -> situation strongly criticized by Senator Grassley in which an individual with a financial interest in the study ‘outcome had supervisory authority over the clinical trial investigators. (FYI, Stanford has recently banned such arrangements in its new COI Policy, and ordered the mifepristone study halted as of July 1; our NIMH DSMB ended the trial last week.) This(C sy _* 2S application goes to our Council tomorrow, and we will carry out independent DSMB review at NIMH, but that does not address the obvious problems of Gelioetalve nPormahon Given time considerations, we would appreciate your looking at this brief attached letter as soon 8s reasonably possible, and suggest revisions or provide additional input so we can responsibly address this difficult issue. If you cannot review this in the next several days, or would like to meet |m person to discuss this, please let me know. Thank youas always for you expertise and advice... David A dm a abner rdlewhPaing yn Poomeh oe 2/24/2010