9 TEXAS HEART INSTITUTE Ill] i all?? ST, Episcopal Hospital July 9, 2008 Kristina Borror, Director Division of Compliance Oversight Office for Human Research Protections Department of Health and Human Services The Tower Building 1101 Wootton Parkway, Suite 200 Rockville, Maryland 20852 RE: Human Subject Protections under Federalwide Assurance FWA-00002312 St. Luke?s Episcopal Hospital Research Projects: The HeartMate II LVAS Pivotal Study (IRB Study Number 2416) Clinical Evaluation of the Jarvik 2000 Heart Assist System (IRB Study Number 2019) Principal Investigator: 0. Howard Frazier, MD. Institution - Research: Texas Heart Institute Institution? Patient Care: St. Luke?s Episc0pal Hospital Dear Dr. Borror: Thank you for taking my call today. As we discussed, through our corporate compliance program, St. Luke?s Episcopal Hospital (?St Luke? the Texas Heart Institute and St. Luke?s Institutional Review Boards have identified instances of ongoing research noncompliance in connection with the protocols referenced above. In compliance with our obligation to report such noncompliance pursuant to Office for Human Research Protections regulations at 45 CPR. 46.103, we offer this notification of the identified noncompliance and the corrective actions undertaken to address these activities and prevent their recurrence. As you know, regulations provide that each operating under a Federalwide Assurance must follow written procedures for ensuring prompt reporting to the IRB of proposed changes in a research activity, and for ensuring that such changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval except when necessary to eliminate apparent immediate' hazards to the subject.1 In compliance with this requirement, the St. Luke?s require, as a condition of research approval, that investigators must submit any change in research activity to an IRB and obtain approval prior to initiation of such change unless such change is necessary to eliminate an apparent immediate hazard to the research subject. In cooperation with our compliance department and the Texas Heart Institute St. Luke?s conducted a review of records associated with the above referenced protocols spanning a period of years and identified several instances in which subjects were enrolled without the necessary prior approval of an IRB, although the subject did not meet one or more of the entry criteria for inclusion in these protocols. Although some of these deviations qualified under emergency use exceptions, this was not the case for all of the changes in research activity. Additionally, an IRB was not always notified of the noncompliance with the protocols? entry criteria. In order to address these identified instances of noncompliance occurring over a period of years, St. Luke?s and THI have agreed to implement a corrective action plan, including the following elements: 1. The Board of Directors of St. Luke?s Episcopal Hospital/Health System and the Trustees of the Texas Heart Institute will establish a Standing Joint Committee on Clinical Research (?Joint Committee?) of not less than two outside directors each to meet for the purpose of monitoring clinical research activities of THI at St. Luke?s. The Joint Committee shall report its findings and recommendations to the St. Luke? 3 Board of Directors and the THI Trustees on a quarterly basis as a standing agenda item allowing sufficient time for questions by board members. 2. Using an independent third party, within 90 days, THI will audit all current studies involving an investigational device and report any unapproved protocol deviations and previously unreported adverse events to the providing oversight for the particular study involved, the study sponsor, the Joint Committee and St. Luke?s. Device- related studies performed on non- living or non?human subjects are excepted. 3. Using an independent third party, within 120 days, THI will conduct an audit of all current studies in which 0. H. Frazier, is the principal investigator and report any unapproved protocol deviations and previously unreported adverse events to the IRB providing oversight for the particular study involved, the study sponsor, the Joint Committee and St. Luke?s. 4. Following completion of the audits undertaken in fulfillment of 2 and 3 above, THI will use an independent third party to routinely audit not less than one current clinical research study per quarter and report any unapproved protocol deviations and previously unreported adverse events to the IRB providing oversight for the particular study involved, the study sponsor, the Joint Committee and St. Luke?s. Studies selected for audit shall be based on greatest potential for risk to human subjects as determined by the joint decision of the President-Elect/President of THI, the Medical Director of Clinical Research for THI, and an IRB representative. 145 can. 46.108. 5. Any continuing pattern of noncompliance with investigational device research" protocols, untimely reporting of adverse events, lack of preapproval of protocol deviations (in the absence of a well?documented medical emergency in which case concurrent documentation by a heart failure/mechanical device cardiologist confirming the emergency and reporting of same within 5 business days) or other continued noncompliance may result in suspension of the study by the providing oversight for the particular study involved or St. Luke?s. In addition to the above corrective action steps, St. Luke?s and THI have agreed to the selection of BRANY as an outside IRB. As soon as possible (estimated to be 4-6 weeks), St. Luke?s plans for all new studies that involve more than ?minimal risk?2 to be directed to BRANY. St. Luke?s is committed to ensuring that all research conducted under its Federalwide Assurance is conducted in compliance with the currently effective protocol, IRB conditions of approval, Good Clinical Practices, and applicable regulatory requirements. If you have any questions about this report or the proposed corrective action, please feel free to contact David C. Pate, M.D., .D., Chief Executive Officer and Institutional Official, St. Luke?s Episc0pal Hospital by phone at 832?355?2300 or by email at dpate@sleh.com. Sincerely, Frank Redmond, M.D., David C. Pate, M.D., JD. Chairman Chief Executive Officer St. Luke?s Institutional Review Board St. Luke?s Episcopal Hospital es T. Willerson, MD. dical Director and President?Elect exas Heart Institute 2 As that term is defuied at 45 CFR 46.303.