{3 Cleveland Clinic ,ames B, W, M, Professor and Chairman George and Linda Kaufman Chair Division of Medicine November 7, 2007 Richard G. Cowart, Esq. Baker, Donelson Bearman, Caldwell and Berkowitz, PC Commerce Center, Suite 1000 211 Commerce Street Nashville, TN 37201 RE: REVIEW OF HEART TRANSPLANT AND MECHANICAL CIRCULATORY SUPPORT PROGRAM, ST. EPISCOPAL HOSPITAL AND TEXAS HEART INSTITUTE, Houston Texas. Dear Mr. Cowart, This report is provided to you pursuant to the terms of my engagement set forth in your letter dated April 19, 2007, and is subject to the "attorney-client" or "work product" privilege. Thank you for asking me to review the Heart Transplant and Mechanical Circulatory Support Program at St. Luke's Episcopal Health System and the Texas Heart Institute have studied documents regarding this activity and traveled to Houston, Texas for a meeting on August 27, 2007 with selected program personnel. My charge was to specifically evaluate current practices with respect to patient selection for heart transplantation and mechanical circulatory support device (MCSD) therapy and recommend steps to improve operations. Specific issues reviewed included: 1. policies, procedures and processes for selection of patients as ?bridge to transplant", ?destination therapY', or clinical research subjects for, in particular, Mechanical Circulatory Support Device (MCSD), 2. Documentation procedures for determination of transplant eligibility or ineligibility, 3. Compliance with policies, procedures, and processes dictated by the Centers for Medicare and Medicaid Services (CMS) as well as other regulatory authorities monitoring heart transplant activities, 4. policies, procedures and processes for obtaining informed consent for the selection and use of MCSD therapy, 5. SLEH patient records to determine if MCSD selection criteria resulted in appropriate patient entry into clinical trials, 6. SLEH selected patient records to determine if those receiving MCSD as an ?investigational device? appropriately qualified under approved protocol patient inclusion/exclusion criteria. in order to provide commentary I reviewed: 1. An overview of the Cardiac Transplant Program sent to the Centers for Medicare and Medicaid Services by Dr. 0. "Bud" Frazier on May 24, 2006, am lav as rec-ts Tel 216 444-2333 . Fax 216 445-8 9500 Eucild Avenue/T13 215 444/2257: 1 ldCl'IF. t' - eve an mic ou'lda lon C1evcland.0??gs?r1aa?d Privileged by St. Luke?s Episcopal Health System 2. information sent to the United Network of Organ Sharing (UNOS) and other regulatory agencies in April and July 'of 2006 documenting leadership changes in the Heart Transplant Program at 3. Documents accompanying a letter dated February 2, 2007 to UNOS Membership and Professional Standards Committee, again reviewing leadership personnel changes in the Heart Transplant Program, 4. Documents summarizing patient selection criteria for heart Transplantation at 5. Documents summarizing guidelines for MCSD ?destination therapy" in heart failure patients, ?Operations" protocols for inpatient management of MCDS patients, CMS "coverage determinations manual? sections dealing with MCSD as it is relevant to the Program, 8. The research protocol including informed consent documents for ?The Evaluation of the Heartmate ll dated August 28, 2003. Finally, i reviewed a draft report dated February 12, 2007 detailing an internal review of the programs in question. it is necessa to point out that i have general and reputational familiarity with the Hi program because of my professional relationships with key members of the program thatdeveioped during my tenure as Clinical Coordinator and Scienti?c Director of The Methodist Hospital and Baylor College of Medicine's Muiti-Organ Transplant Center, which ended in June 1995. Furthermore, i have continued to engage professionally with Dr. Frazier and other past and present members of the program through professional societies, such as the international Society for Heart and Lung Transplantation, and during clinical research projects that were multi-institutional and included the Cleveland Clinic Foundation and My comments are based on all of the information at hand as well as historic and contemporary observations made and knowledge of operations in a spectrum of programs, including the one i directed at Baylor College of Medicine (BCOM) and The Methodist Hospital, and our current program at the Cleveland Clinic Foundation. Comments regarding this program should be taken into a perspective that recognizes has been a major and longstanding contributor to the art and science of cardiac transplantation and MCSD therapy. They have been a leader in technology development and vocal advocate for these aggressive therapies in near dead and dying advanced end?stage heart failure patients. Muitiple seminal contributions to the field have emerged over the last two and a half decades with Dr. Bud Frazier being a primary force moving MCSD development, new cardiac transplant immunotherapy, and clinical and basic research in this ?eld fonNard. Dr. Frazier has been frequently as described a 2 Restricted Privileged Material Provided by St. Luke?s Episcopal Health System "pioneer" in these ?elds. Of note is the fact that Dr. Frazier has been assisted, from an organizational and research standpoint, by key people having long~standing positions as research scientists in the program. Clearly, the personality and professional stature of, Dr. Frazier in particular, have advanced the program to a highly visible level while sparking opinionated commentary about the style and culture of the program from prominent individuals nationally and internationally. indeed, there is a cultural characteristic of programs such as this one that must be recognized and understood to place commentary about organization structure into proper perspective. With this in mind, it is evident based upon my interview and examinations the program is dedicated and committed to the highest standards regarding patient care for an extraordinarily challenging group (those with end-stage and advanced heart failure who are at high risk of dying and have, for the most part, extraordinarily challenging co- morbidities). it is common knowledge confirmed by review of the data that the heart transplant and MCSD team at fights diligently to keep these patients individuals. Sometimes this has resulted in very aggressive approaches to medical and surgical management of these patients. Though practices do not appear to be clearly outside of reasonable bounds, they certainly "push the envelope? at times. Interestingly, this aggressiveness is a necessary thing in any prominent and innovative academic practice center to advance any field. innovation emerges as a regular and recurring theme when this program is evaluated. This is related to personalities directing the program, as well as the demands of the ill patients they are caring for. indeed, it is likely that the spirit of the program director contributes to some of the dif?culties observed. This attitude is necessary for any great program to thrive, progress, and maintain prominence. However, keeping the energy within the ?bounds of the playing field? is challenging in any environment and, particularly so. in this one. Of importance is the fact that during my review I found no evidence of a violation of criminal, civil or administrative law, to the extent that i am familiar with those statutes. Specifically, it does not appear that any egregious professional misconduct has occurred. i do believe, however, that lack of adequate patient care and research documentation places the program, in certain instances, at an increased level of scrutiny with respect to Joint Commission, FDA and CMS reviews which might occur. Speci?cally, documentation of protocol violations during implementation of clinical research trials raises the specter of more intense FDA scrutiny. Because there have been allegations that some individuals in the program may be practicing outside of their licensure scope, Joint Commission review could be unfavorable. Finally, there may be problems with respect to CMS reimbursement based on decisions made and documentation of patient's eligibility for "bridge to transplant" or "destination? MCSD therapy. To address this in more detail, a speci?c question was asked regarding patient selection for MCSD therapy as either "bridge to transplantation" or ?destination therapy", both clinically and in research protocols. In the program, although FDA approval for left ventricular assist device implantation may appear clear cut and concrete (as are CMS reimbursement rules), the practice is not so clear out. That is, however, the same dif?culty shared by many prominent and distinguished programs. Technically. for MCSD therapy used with a "bridge to transplant? indication the patient should have already been listed for transplantation or intend to be listed within 24 hours before device implantation. This is an acceptable principal fOr patients without co?morbidities that ordinarily would make patients unacceptable for heart transplantation such as infections, 3 Restricted Privileged Material Provided by St. Luke?s Episcopal Health System renal and hepatic failure, and questionable neurologic status. The reality is, however, clinicians in the programs with which i am familiar struggle with determining when these ?relative" contraindications become ?absolute?. indeed, patient selection is made challenging by the fact that left ventricular assist device therapy can, at times, dramatically improve the clinical status of a patient to the point where, though not transplant eligible at the time of device insertion, they become eligible after this aggressive therapy. This tactic is sometimes termed ?possible bridge to transplant? in the professional community but is not recognized as a legitimate indication by CMS or FDA. Three separate categories of patients have emerged. There are those ?likely to be eligible? for transplantation and this de?nes a patient in whom the transplant evaluation has not been completed but no contraindications are anticipated, or in whom a current contraindication is anticipated to resolve rapidly, such as a treatable infection. The "moderate likelihood" of becoming transplant eligible is similar to this but with some concerns that might overshadow definitive transplant eligibility such as worsening renal or hepatic function. The category of ?unlikely to become eligible? for transplantation refers to patients in whom major concerns have already been identi?ed. These concerns however may not have clearly been quanti?ed or evaluated and include issues such as known chronic lung disease without recent pulmonary function test measurements, or difficulties that might be reVerslbie with chronic mechanical circulatory support, such as severe renal insufficiency or pulmonary hypertension. it may be the expectation at the time of implant that the patient'will most likely have the assist device as a "permanent? therapy and this seemingly is the CMS recognized indication for "destination" therapy (which refers to an elective implantation of MCSD in a patient who is definitely not eligible for cardiac transplantation). All factors that weigh into the decision of non-transplant candidacy should be considered, as well, in these patients because co-morbidities which make the patient a suboptimal heart transplant candidate also make them poor "destination? therapy candidates. These procedures should not be done urgently in an unstable patient near death. The final general use of left ventricular assist devices today is in those patients being bridged to ?recovery? which refers to implantation of a long-term and durable device in patients experiencing acutely decompensated heart failure to effect hemodynamic stabilization such that the device can be removed and transplantation may not be necessary. It is importantto realize that these utilization categories do quite match the FDA and CMS defined indications. Programs have handled this in a variety of ways to stay within, at the least, some de?ned boundary and this is generally done by accepting the patient as a "transplant candidate? even though at the time of device insertion, if a donor offer was made, it likely would be turned down or the patient made a "status 7" which is "inactive on the UNOS waiting list?. it appears to me that this is the practice of the program with little patient selection committee oversight documentation and rather autocratic decisions being made. One could argue about the wisdom of some patient selection because of the seeming lack of more formal clinical, academic, and administrative purview which in other programs allows for constructive professional interchange regarding the dif?cult patient. The overall patient selection process seems inadequate, or, at the least, poorly documented. Again, i found a theme throughout my interviews that indicated the program was rather autocratic with a leader who is opinionated and commanding in authority, but also an incredibly skilled surgeon and driving force. This has resulted in the perception that decisions have been made to place MCSD in futile patients who have not been properly cleared for subsequent procedures such as transplantation. This needs to be taken in to context of the above description of how programs today have 4 Restricted Privileged Material Provided by St. Luke?s Episcopal Health System evolved with respect to device utilization. It appears that there has been some disdain for the regulatory issues challenging us all. Although research protocol violation that observed was relatively minor. it is not unlikely that other more signi?cant protocol violations have occurred because of the lack of attention to administrative details. suspect that the problem surrounds, again, patient selection with respect to protocol inclusion and exclusion criteria. Related to this is confusion regarding Institutional Review Board oversight by SLEH and BCOM of clinical research activities. Specifically, it was unclear which was responsible for the research activities in the heart transplantation and MCSD program. These issues seem related to an appearance of ?chaos and confusion? that emerged. Though leadership of the effort has been well meaning, with the interests of saving the lives of horribly ill patients, the program is in a vulnerable position. This adversely affects the image and credibility of The fact that there is an ill-de?ned chain of command and organizational structure, with autocratic leadership, seems to allow for both minor and more substantive transgressions to occur. Also, because of the lack of a clearly defined and organized administrative structure, there'is a mixture of talented individuals that do not appear to effectively be working as a team. Speci?cally, the interaction between "private practice? heart failure-heart transplant MCSD physicians with "staff model-full time academic" surgeons seems tense at times (particularly amongst the cardiologists) and produces disagreement, dissent, and dif?culties. believe that this has led to less than stellar outcomes after heart transplantation (as reported in publicly available quality assessment databases). This may be the result of doing these procedures in futile patients. The command and organizational structure present could, in my opinion, be improved by implementing, more of a true ?team effort" for the enterprise with meaningful cardiology and surgical leadership that was completely academic and full time based. This approach might address the rather substantive issue of the carping and competition which goes on in the cardiology support team. This can be a destructive element in any program. Cardiologists will ?shop? for an opinion from a heart transplant expert when they do not like one which has been initially proffered. The fact that no true structured patient review system is in place that credibly works, allows this to occur. During my visit I had the opportunity to review a limited number of patient medical records that were randomly selected and had been reviewed previously during the internal investigation of this program. The three records detailed care of extraordinarily ill individuals and, though one could argue that documentation could be substantially improved. there were only relatively minor issues noted such as one patient falling out of an age exclusion window for a clinical trial (though just barely) and another patient record having incomplete documentation of informed consent, despite reporting requirements to FDA. The medical record review did suggest that there had been incomplete consideration of heart failure co-morbidities during patient selection for MCSO and heart transplant. have an extraordinary opportunity to restructure this program along a better organized "product oriented line" that will preserve and enhance the innovative spirit as well has improVe clinical and academic outcomes, but several things need to be done; 1. Determine the commitment and overarching view of the relationship between and SLEH with respect to this program. 5 Restricted Privileged Material Provided by St. Luke?s Episcopal Health System 2. Address seriously the issues regarding regulatory purview and develop a mechanism to ensure compliance. 3. Determine how the surgical and medical leadership will optimally work together with everyone "playing by the rules" (this requires clearly de?ned and empowered medical and surgical leadership that, in appropriate ways, jointly manage the program). 4. improve patient selection by more rigorously applying existing guidelines to patient review and selection for heart transplantation and MCSD activities. Important is the maintenance of explicit documentation regarding these activities. 5. Establish a peer review process that enhances compliance with FDA and CMS regulations and procedures. 6. Establish formal patient/procedure "quality? and ?outcomes" reviews and hold program personnel responsible for meeting appropriate targets. 7. Empower a true Medical Director to create a bona ?de clinical and academic Heart Failure Program with adequate administrative support that will eliminate the current destructive competition that is apparent between ?fulltime academic? and ?private practice" staff. 8. Support a bona ?de and committed cardiology expert to achieve point Dr. Roberta Bogaev may be an appropriate individual to be charged formally with this responsibility. Though this has seemingly been done, in reality, it is not the case as she appears to be undermined by the existing autocratic program structure and current cardiology support services. 9. Form a true "Committee" based structure that documents patient selection and management discussions that will keep process and outcomes properly in perspective. 10. Reconcile the issue of institutional ?guidelines" versus external "rules and regulations" with regard to indications for the various devices, reasonableness of patient inclusion in research protocols, FDA oversight of clinical research projects, and CMS reimbursement. It is my opinion that change is necessary for the program to survive and capitalize on a unique clinical opportunity. SLEHNHI must have the courage to change and develop a long range vision for the future. Mn 9 ?19 James [-71 Young, MD. \0 Chairmcq I, Division of Me lne Clevelanu Clir ic Foundation 9500 Euct'd 'enue, T13 Cleveland, io 44195 6 Restricted Privileged Material Provided by St. Luke?s Episcopal Health System