Advisory Committee on Organ Transplantation

Fifteenth ACOT Meeting

Rockville, MD
May 5-6, 2008

May 5, 2008

Welcome & Introductions

Ms. Agrawal welcomed the group and introduced the newest member, Dr. Robert Ettenger. She also announced that she would be able to continue to chair the ACOT.

Pediatric Transplantation: Overview, Problems in Non-adherence, Transitioning from Pediatric-Adolescent Care to Adult Care -- Dr. Robert Ettenger, Chief of Medical Staff, Department of Pediatrics, UCLA Medical Center

Dr. Ettenger recognized the group members have wide-ranging expertise and apologized for any information that was not new to the members. He began by noting that pediatric transplantation will always be the “flea on the hair of the tail of the dog” – there are only small numbers of transplants, but the numbers are constant. Most transplants are either kidney or liver. (Kidney patients tend to live longer, so the prevalence rates of pediatric kidney transplants are greater.)

Pediatric transplantation has improved. Twenty years ago, graft survival was a miserable 50 percent, but the current 2-year survival rate is over 90 percent. This improvement has provided a lot of hope, but many challenges remain. Transplantation confers more remaining lifetime years than dialysis, which is particularly true for children. However, looking at the general population, lifetime survival rates are still lower, even for pediatric patients.

New rules have placed pediatric patients at the top of the lists for transplantation, and the recipients’ increases are mainly among adolescents (for kidneys). The majority of pediatric transplant patients are, or will become, adolescents: two-thirds of non-adult recipients are 11-17 years of age. Dr. Ettenger joked that the two words that define adolescence are “me” and “now” – it is a time of emerging autonomy and multiple crises, many of which may be undetected. This affects compliance and patients’ ability and willingness to take care of themselves.

This is an issue because, in looking at graft survival by recipient age, adolescents have best outcomes at year 1. However, at 5 years, except for the very old recipients, adolescents have the worst outcomes. As they move into adolescence, they do worse. This is a problem with the population in terms of long-term graft outcome. Looking at kidney survival in pediatric recipients: among youngest patients (age 0-5), there is a declination point in graft outcome that they emerge from after 7-8 years, which is when they are around 13. They start falling off of the projected half-life. The 6-12 year olds have a similar declination, but it’s after 2-3 years – when they are the same age as those described above. There is not much declination seen in 13-18 years because they age out of adolescence. It is important to remember that patients are growing and changing over time.

This may not all be about non-compliance, however. A new National Institute of Allergy and Infectious Diseases-funded Clinical Trials in Organ Transplantation in Children indicates that adolescents may have heightened immune responsiveness. Antiviral responses may increase global immune response to alloantigens, and this may differ from patient to patient depending upon viral exposure (children have more exposure as they age and become adolescents). Differences exist in patients’ immunobiological reactivity as well. Therefore, the survival rates may result from an unfortuitous intersection of immune maturation with the developmental variability of the adolescent. It’s a bad conjunction in terms of non-adherence, however.

Non-adherence is an issue for this population. In a study of physicians’ reports about patient non-compliance, 54 percent of patients who were declared “noncompliant” were adolescents. If you combine those aged 11-15 and 16-20, the rates are well over 50 percent.

Patient characteristics that correlate to non-adherence in pediatric End Stage Renal Disease (ESRD) include: adolescence, female, family instability, insufficient social or emotional support, depression and anxiety, single-parent family, low SES, low self-esteem, poor interfamily communication, deficient acceptance of ESRD diagnosis, and poor communication and socialization skills. In fact, the situation of having ESRD is so stressful that it gives patients Post-Traumatic Stress Disorder.

Dr. Ettenger provided some definitions. Compliance is when the patient follows the medical team’s dictated orders without necessarily buying into the reasons for these orders. Adherence is when the patient understands the reasons for the medical team’s orders and participates in their execution by following these orders. Lastly, concordance is when the patient’s desires and incentives are aligned with those of the medical teams (the patient wants to do those things that will benefit him/her). The goal is establish concordance for each patient.

Dr. Ettenger noted that variability in operational definitions of non-adherence hinders the ability to compare study results. Definitions of non-adherence include: (1) when the patient misses, forgets, alters, or delays a dose at least once per month; (2) when the patient misses at least 10% of doses (6 doses per month); or (3) when the patient misses at least 20% of doses (12 doses per month). Dr. Ettenger said that he was attempting to popularize the term “chronic renal allograft pathology” (CRAP) because it describes where a lot of the research is. The field does not do a good job of tracking long-term co-morbidities (diabetes, hypertension). In fact, more needs to be learned about these issues.

Regardless of how it is measured it, however, non-adherence affects graft outcome and is expensive. A recent meta-analysis of 10 cohort studies found a 36% graft loss associated with non-adherence (a rate seven-fold higher than in adherent recipients) and a $15-$100 million annual impact -- just in solid organs.

In 2008, a consensus conference was held in Tampa with a range of organizations invested in non-adherence. Individual topics were addressed in six workgroup focusing on (1) pre-transplant assessment; (2) pre-transplant interventions; (3) post-transplant non-adherence monitoring and interventions to decrease non-adherence and increase adherence; (4) transitions from pediatric to adult health care provider; (5) issues in assessment and treatment of non-adherence in the elderly transplant patient; and (6) NIH support and initiatives for adherence/non-adherence research in adolescent and elderly transplant recipients.

There are seven multidisciplinary areas where non-adherence may be influenced:

1. Pre-transplant Prediction and/or Recognition
2. Pre-transplant – Optimize Support, Provide Adequate Information and Modify Behavior
3. Post-Transplant – Prevention/Treatment
4. Post-Transplant – Medication Modifications
5. Post-Transplant – Recognition / Assessment
6. Transition
7. Research Initiatives

For pre-transplant assessment, validated tools are needed in all areas: identification of pre-transplant adherence problems; identification of pre-transplant skill deficits (e.g., pill swallowing problems, memory/organizational difficulties); identification of pre-transplant emotional, behavioral or learning problems (e.g., depression, PTSD, anxiety, substance abuse); assessment methods for identification of provider factors that could hinder adherence; identification of potential post-transplant social/emotional support; and identification of medical team characteristics that may contribute to non-adherence.

In addition, validated “Toolboxes” are necessary for effective pre-transplant interventions, including: educational intervention methods to instruct adolescent and their caregiver(s) about post-transplant medical regimen and importance of consistent, long-term adherence; interventions to remediate skill deficits (e.g., organizational strategies, public transportation use, thermometer reading, lab value interpretations); treatment of identified emotional and/or behavioral problems; interventions to improve provider/patient relationship and communication; and interventions to increase/optimize social/emotional support for adolescent. The risk factors of non-adherence include being an adolescent; however, there are other issues, too, many which interact, including poor physician communication.

Dr. Ettenger stated that “care” does not mean transplanting the patient and turning him or her out into life unsupported. We have to modify what we do to coach and work with the kids to ensure that they stay healthy. Pre-transplant interventions are woefully inadequate. For pre-transplant interventions, we need to provide information using several different educators. This information should specifically address issues of medication knowledge, side-effects, and timing. It is important to try to emphasize reconciling health beliefs between patients and their parents, and health providers, and to stress that medications are life-long. The goal is to address non-adherence “patterns” in the educational activities.

For post-transplant non-adherence monitoring and interventions to improve adherence, Dr. Ettenger noted that we need to improve how we measure adherence; identify barriers to adherence; assess post-transplant emotional and behavioral adjustments; decrease the patient’s non-adherence potential; improve provider/patient communication; and develop patients’ abilities to problem-solve, self-monitor, and reinforce adherence. We need better interventions to increase adherence and may also benefit from exploring parenteral medications.

It is necessary to address any psychological and emotional problems that arise; and patients have to be seen frequently to succeed on this. The field does not do well at finding patients when they fail to come in. Dr. Ettenger noted that improved diagnoses of PTSD can significantly decrease non-adherence in transplant patients. Parents and patients are both susceptible to PTSD; however, parents have better compliance records.

There are ways to modify medications that would help deal with non-adherence, including simplifying medications and/or using drugs that have long half-lives and can be taken less often. There is a need to develop drugs that will last for a week or a year (like Norplant does). Pill counts and pharmacy monitoring only work if the patient is using a pharmacy associated with the program. This is difficult when many insurance companies restrict which pharmacy their beneficiaries can use in order to still be covered.

This is particularly an issue for patients who are in transition. At the time of transition, one-third of patients blew their creatinine levels up in 12-15 months. A new GAO report looked at patients (pediatric, transitioning, adults) and found that the percentage of recipients where the treatment failed was always higher in transitional patients – they do worse than both pediatrics and adults. In addition, they cost CMS a lot of money. The largest increase in the number of transitional patients who lost their grafts was among those 1-3 years post-transplant. As they transition, something happens to these patients; and this issue must be explored. Transition should be based on developmental guidelines rather than arbitrarily on age.

The issue of adolescents is critical, Dr. Ettenger stated, to whom we are and what kind of society we have. He would like to direct the ACOT’s attention to some of the underserved issues. The goal is to make these patients functional members of society who live life according to a game plan that integrates them into society.

Discussion

Ms. Suzanne Conrad said she would play the devils’ advocate and asked if the field should be preferentially directing kidneys to this group, since they are just going to lose them. Dr. Ettenger responded that some have actually recommended not transplanting kids between the ages of 12 and 19 for this very reason. But it’s not all or nothing, he added. The expectation is that the patient is ready for transplantation when he or she is put on the list. Our task is to help and nurture them; and, he added, problems that come from being on dialysis are also overwhelming. There is a need to get caregivers up to speed and to find better ways to address this problem. The answer is not to deny the transplant, but to proceed in a sound and intelligent way.

Dr. Lewis Low said this was timely for him. He has a 20-year old patient who is on her third transplant. She is emotionally about 15, and her parents treated her as if she were that age. It was clear that her parents thought of her as a child, and the entire family’s emotional growth was stunted. Dr. Low concluded that there is a need to train families, too. Dr. Ettenger said that this situation occurs frequently. In his opinion, these patients are psycho-socially 3-7 years younger than their chronological age. Tools that can help include therapy, working with the schools, bringing them up to speed; and it’s essential not to transplant the person until he or she is ready. The problems occur because there are no tools to measure readiness. Dr. Ettenger’s UCLA program can assess this just from experience; but many centers lack this experience, have no plan for addressing non-adherence, and do not educate parents and kids. He noted that if a child fails the first transplant, it’s essential that the donor look at that case very closely.

Dr. Russell Wiesner asked if it was even possible to change adolescent behavior, and the response was that it is possible to teach appropriate behavior. In restricted situations, the goal is for adolescents to be able to handle themselves. The provider is not, however, there to run their life. Dr. Wiesner asked about the role of the nurse coordinator, adding that, at Mayo, the relationship with the pediatric nurse coordinator remained throughout the patient’s transition and into adulthood. For liver, at least, this seems to be very important for the patients. Dr. Ettenger stated the pediatric nurse coordinators are indispensable. Children see them like parents. The coordinators may be, in fact, the only parental figure in the kids’ lives. They are critical to a functional program.

Dr. Mildred Solomon thinks the goal is less to change adolescence, and more to help these patients transition. She described her involvement in social marketing campaigns targeted at different age groups, and the finding that teens require an uncomfortable level of fear in their messages. In terms of message design, she asked if teens needed more graphic information. The response was that there are at least three phases of adolescence, and each phase has a different need in term of messages that will work. For those with PTSD, however, fear-based messages are difficult. A one-size-fits-all program will not be effective.

Dr. Susie Leffell commented that this is very important because when kids lose their graft, they become highly sensitized, which affects both costs and treatment plans. She asked if the data on graft loss took into account the age of the allograft and where it was in the natural allograft life span. Dr. Ettenger said this was a good point, but one that is hard to study. The GAO study involved large, raw numbers; and the study suffered as a result. It did not adjust the multivariate analysis to really see those operant issues. Dr. David Vega asked if graft loss was related to lack of insurance, since experience at Emory indicates that graft loss is related to lack of coverage. Dr. Ettenger said that the patients in the GAO study were insured, but he concurred that California also sees this problem. He added another problem that pediatric patients’ public insurance ends when they are one day over 21. The insurance problems are catastrophic; and when patients approach 21, it’s a death sentence. It’s hard to get these patients onto Medicaid, too.

Ms. Agrawal noted that ACOT has limited authority. However, the group can make recommendations to the Secretary. She asked members to consider what ACOT could suggest to address these sorts of issue.

Update on Kidney Disease Outcome Quality Initiative/Early Kidney Transplantation Conference -- Dr. Steven Bartlett, Conference Co-Chair, University of Maryland Medical Center

Dr. Bartlett reported on the Kidney Foundation’s March 2007 conference on early transplantation. ESRD cases have been rising (although they have been leveling off in the last year or so). This conference was held to address several questions about early transplantation: is it desirable; are there benefits of preemptive transplantation that make it the preferred approach to renal replacement therapy; what barriers prevent early or preemptive transplantation; can these barriers be surmounted; and, if so, what interventions are necessary to do so. Dr. Bartlett shared the results from the conference workgroups.

Work Group 1 addressed transplantation and the Chronic Kidney Disease (CKD) paradigm and asked how we can incorporate transplant education, referral, and identification of living donors into the evolving paradigm of CKD management, given that rates vary at which different races learn about transplant before beginning dialysis and are referred for evaluation.

Work Group 2 addressed training and education for early kidney transplantation, looking at how to address the educational needs of all involved in the process, as well as what can be learned from the pediatric model.

Work Group 3 explored the financial implications and removal of disincentives, examining why the finances of early renal replacement therapy are easier to navigate on the dialysis side of the equation.

As background to these work groups, Dr. Bartlett noted that ESRD consumes about seven percent of the Medicare budget and CKD consumes sixteen percent of the Medicare budget. Thus, ESRD and “recognized CKD” appear to consume close to 25 percent of the Medicare budget, which has considerable health care implications. Moreover, ESRD incidence rates are down except among younger, African American individuals with DM, yet death rates in the first year of HD have not changed in 11 years. The utilization of dialysis catheters, known for their complication rates, is very high. There are major issues related to the transition from CKD to ESRD, which may contribute to the high early mortality, yet there is currently no program to address the preparation of individuals for ESRD.

Prevention of ESRD is emerging as an important public health policy issue. The high death rate in the first year of HD needs to be addressed through an education program that increases awareness of the modalities to treat ESRD; better dialysis access planning before ESRD; appropriate assessment of vessels and processes to promote effective fistula maturation; increased utilization of early transplantation, thereby avoiding the use of a dialysis catheter; and reduction of disincentives to early transplantation.

As part of the work to address factors associated with this situation, 4,000 nephrologists were surveyed and the following conclusions were reached: nephrologists need guidance to refer patients for preemptive transplantation; post-transplant care training; there is a financial impact of preemptive transplantation on dialysis centers; they should report patient referral and education issues; and they should have a positive attitude toward preemptive transplantation. In terms of listing, there is a fairly slow trickle of referrals from nephrologists; but once the patient gets onto the list, they move more quickly.

Among all patients starting ESRD therapy from 1996-2005, 6 percent were waitlisted before, or without, starting dialysis; and 2.5 percent received a preemptive living donor or deceased donor kidney transplant. About two-thirds of all preemptive transplants are from living donors and one-third are from deceased donors. Among patients with ESRD, wait-listing and transplantation rates, both overall and preemptive, are lower among older patients; patients with diabetes or hypertension; African Americans, Hispanics, Asians and Native Americans; and those relying solely or principally on public insurance. There is also marked geographic variation in overall and preemptive wait-listing and transplantation rates.

The question is, however, “what happens if a patient went right to transplant without getting dialysis”? Peer-reviewed information suggests that these patients have higher employment rates, lower unemployment rates, and a reduced family care giving burden. Follow-up questions include whether preemptive transplant has specific quality-of-life benefits; whether ESRD-related quality-of-life problems are preventable with preemptive transplant; and whether ESRD patients must first undergo dialysis in order to “appreciate” a transplant recipient’s quality-of-life and follow a transplant regimen.

Dr. Bartlett reported that early transplant can prevent losses associated with long-term dialysis. The short-term benefits of a scheduled transplant include the ability to plan work absences, recovery support, and dependent care. There is also reduced anxiety that can be associated with transplant timing unpredictability. There are better outcomes after preemptive transplants, including lower delayed graft function rates, lower acute rejection rates, and higher graft survival rates.

There are economic benefits as well, since the monthly cost of maintenance dialysis is greater than that of maintaining a transplant. The savings accrue for time periods when a functioning transplant allows the patient to avoid dialysis. Also, preemptive transplantation avoids the high costs of maintenance dialysis during the onset of ESRD. The cost spike during the transition from CKD to dialysis is avoided by preemptive transplantation. Economic benefits also include reductions in transplant complications arising from lower rates of delayed graft function, acute rejections, or graft failure. Dr. Bartlett described the per-person/month expenditures for ESRD patients on Medicare.

The risks of preemptive kidney transplantation are that the process may waste native kidney function by hastening the transition to renal replacement therapy, and the cost of care shifts from a CKD rate to a higher ESRD rate. Preemptive transplantation may increase the chance that a patient with renal function recovery (RFR) will have an unnecessary transplant. There are financial losses associated with the costs of such a transplant. Dr. Bartlett concluded that policies to perform preemptive transplant may result in cost savings by reducing costs associated with the transition through dialysis, and reducing the rate of costly post-operative complications.

Returning to the conference work groups, Dr. Bartlett summarized their recommendations
below.

Work group 1 (Transplant and the CKD paradigm) established several goals:

• Increase access to preemptive transplants for all patients by limiting pre-wait-listing dialysis exposure;
• Reduce disparity in access to transplantation based on age, ethnicity, geography, and SES and increase providers’ cultural competence and patient educational materials (e.g., language);
• Promote early referral of patients with CKD such as by co-management by primary M.D. and nephrologists of patients in Stage III, and evaluation by transplant centers at entry to Stage IV (prior to or at the time of vascular access referral);
• Provide comprehensive education for CKD patients at the time of nephrology referral (Stage III) that emphasizes the potential for transplantation;
• Conduct timely evaluation by transplant centers (with a target of 6 weeks from referral to initial visit; expeditious completion of work-up of candidates; and early identification, screening, and evaluation of potential donors);
• Increase the percent of living donation performed preemptively from the current rate 26% to a goal of 50%; and
• Raise awareness of the benefit of preemptive transplant among the public, patients, physicians, nephrologists, dialysis providers, transplant centers, and the payer community.

Work Group 1 recommended referral to a nephrologist by early Stage III CKD by a patient’s primary care doctor; referral and evaluation at the transplant center by early Stage IV, and that patients be waitlisted at a GFR = 20 or when they become clinically symptomatic.

Work Group 2 addressed training and education for early kidney transplantation. Goals included the following. Through education, increase transplant rates, increase preemptive transplant rates, and increase early transplant. Target audiences for education were described as practicing community nephrologists, dialysis unit medical directors, nephrology fellowship training directors, nephrology fellows, primary care physicians, and financial stakeholders (commercial and government payers). These audiences need information on who to refer for early transplantation, when to when to transplant, and why preemptive transplantation is recommended.

As part of this work, the Metropolitan Nephrology Associates opened their books and let the work group explore its revenue sources. It was found that about 25 percent of its revenue stemmed from medical directors; 27 percent from hospital-based consultations; and 32 percent from in-center patients. It appeared that doctors may be unwilling to spend a lot of time with post-transplant patients, as this is a complicated process. In addition, the organization only gained 12 percent of its income from seeing these patients. The reimbursement is low for this type of work. Reimbursement codes need to be improved so that nephrologists can view those cases as being on a par with dialysis patients. If nephrologists could see a post-transplant patient as having the same income effect as a dialysis patient, it would help. It would be necessary to change transplant reimbursement, however.

The work group concluded that there is a need to increase awareness of the benefits of preemptive/early transplant by nephrology, primary care physician, physician extenders, and organizations delivering CKD and dialysis care. Barriers to early transplantation and post-transplantation care include both financial and practice patterns concerns. As living donors will likely be the means through which preemptive transplant will occur, there must be support for the United Network for Organ Sharing (UNOS) living donor activities and living donor follow-up. There needs to be a living donor registry to provide long-term data about donor safety. This would encourage more donors, protect the field, and deter risky subgroups from donating.

Work Group 3 explored the financial implications and removal of disincentives, examining why the finances of early renal replacement therapy are easier to navigate on the dialysis side of the equation. For hospitals, the incentive is that preemptive transplant is less costly (with higher margins), there are decreased operational and administrative costs, and outcomes are better. The disincentives are around increased administrative burden and potential risk, as well as the fact that the procedure is only viable with a Medicaid population. For transplant physicians, the incentive is EGHP (lower percentage discount than Medicare/Medicaid), but the disincentive is that if the patient does not sign up for Part B there is no doctor reimbursement for the donor nephrectomy procedure. There are no incentives for a non-transplant nephrologist (i.e., one who is not part of the transplant team) and many disincentives, including lost revenue, poor reimbursement, complex cases, and a lack of education benefit for transplant education of the CKD patient.

For a recipient, preemptive transplant is less disruptive to his or her earning potential, and enables the patient to maintain EGHP. It also has less impact on lifetime maximums, as the patient is not accruing costs from dialysis. Disincentives are that this applies only to Medicare beneficiaries unless the patient can meet the out-of-pocket requirements; and it may entail lost wages, travel, and other costs. Patients may also not perceive the urgency of the timing of their transplant.

For EGHP, preemptive transplants avoid dialysis’ costs and complications. It has lower costs and fulfills the companies’ obligations and social responsibilities, as well as affirming an interest in patient care. It saves other types of insurance claims (disability and reinsurance). The disincentives include the myth of 2-year payer turnover (e.g., member churn), which reduces the company’s savings opportunity and the fear of transplanting prematurely given member churn.

Work group 3 made several recommendations:

• Provide a White Paper that articulates the financial incentives for payers for preemptive transplant;
• Accelerate the processing time for Medicare enrollment;
• Create uniform minimum coverage requirements for Medicaid programs to include reimbursement for organ acquisition and adequate medication coverage including immunosuppressants;
• Support Part B premium reimbursement by third-party payers (similar to dialysis and COBRA payments);
• Create a reimbursement structure that recognizes the complexity of post-transplant care (this will enhance long-term outcomes);
• Support legislation that provides funding for CKD education/modality selection (pending legislation);
• Support appropriation of funds to the Organ Donation Recovery and Improvement Act (3-year period);
• Support pending legislation that provides extended entitlement for immunosuppressive medication coverage from 36 months to lifetime of the graft;
• Support legislation to extend existing state laws and introduce a national program to allow for a Federal tax credit to cover living donor expenses (consistent with current NOTA language); and
• Modify Medicare eligibility criteria to include patients who have reached Stage 5 CKD.

Dr. Bartlett reviewed next steps, which are to publish the findings of the Consensus Conference (upcoming in Clin J Am Soc Neph) and to begin the process of changing Medicare payer policy through analysis and action with ACOT, Congress, and the National Kidney Foundation Board. It will be necessary to balance the political power of large dialysis organizations, which seek to maintain the status quo.

Discussion

Dr. Wiesner asked if the new Life Years from Transplant (LYFT) calculation system was considering pre-transplantation. The response was that it did give the patient some points because of the benefits in life years. Dr. Robert Wolfe with the SRTR added that the status of being preemptive or on dialysis generates some benefits, with the results surprising and worth discussion. Preemptive transplantation leads to better post-transplant outcomes (compared to those who were transplanted after dialysis had started). However, the question remained whether, for someone who hasn’t started dialysis, if it was better to get a transplant or not. He noted that the answer seemed to be that a person who has not yet started dialysis has a higher death rate with a transplant than without one. This is time-dependent, in the first year as well as in years 3 and 4. So, it seems as if the patient who has not had dialysis does better without it. There is a bias, however, because the ones who do not do either (transplant or dialysis) are the healthy ones. A related study shows that starting dialysis is a marker for having problems and getting sicker. Dr. Wolfe added that it was not known how to fix this bias. The LYFT calculation showed that the person who has yet to start dialysis does better to wait than to get the transplant.

Dr. Ettenger responded that a person with CKD 3 or 4 was going to progress and get worse. It was not as if they would not get sicker if they did not have the procedure. Dr. Wolfe agreed that it was unclear how to interpret the data when just looking at the evidence. Dr. Wiesner asked if the impact on graft survival of the time a person spent on dialysis had been adjusted and the response was that it had been, by time and age. Dr. Wiesner commented that the entire argument was based on the fact that the allocation system should be changed, and so the data have to be adjusted to know that it is not just part of the spectrum. Dr. Wolfe concurred that there is no biological reason why this should be, yet it seemed to be.

Dr. Marc Lorber agreed with Dr. Ettenger that it was important to stratify by CKD stage to see when a person might clearly benefit from transplantation. Dr. Wolfe said there were some longitudinal studies that looked at this. He had GFR at the time of listing, but did not think that this was available serially. Dr. Lorber suggested this be collected to assess whether preemptive transplant had the best benefit after dialysis had begun, or before it started.

Mr. Samuel Holtzman added that early transplant appears to be more disadvantageous for African Americans. The field has started trying to look at this and the education modalities needed to get this population into transplant, better identify living donors, and overcome disparities. He stated that the population de-selected out and assumed they would not get the transplant. There is a need for more education on this issue. Dr. Solomon added that there have been studies to look at this, which specifically held patient preferences steady, to see if African Americans de-selected or if they had different cultural beliefs about transplantation. In fact, the research showed that, even among those who wanted to have a transplant, African Americans were not referred at the same rates as Whites were. The study found major referral discrepancies.

Dr. Velma Scantlebury added that more work needs to be done. As an African American, she knows there is a lack of awareness about preemptive transplantation among people of color. There is also a bias in terms of getting patients from dialysis to transplantation. Having dialysis is better than not having dialysis, and preemptive transplantation is better than spending more time on dialysis. She applauded Dr. Bartlett’s efforts and stressed that the field needed to make headway in this area.

Dr. Solomon added that the financial incentives are perverse: non-transplant nephrologists seem to have a preference for dialysis. Dr. Bartlett suggested that increasing reimbursement for post-transplant care was a good idea. However, if the code were reimbursed at a high enough level, the cost savings could be lost. Dr. Bartlett clarified that there are other cost savings in terms of life benefits, reductions in dialysis, and increased work function. Preemptive transplantation had the opportunity to mitigate a health care disparity, he concluded.

Dr. Ettenger spoke on behalf of nephrologists and addressed the misperception that they were not ready to refer or care for transplant patients. He expressed the belief that these providers are willing and ready, since their job is to care for patients. He noted that he was struck by Dr. Wolfe’s comments about the survival and CKD data. He believed the variables which have to be included in order to make an assessment about this have not been included. There needs to be better reimbursement for nephrologists and more data, he concluded. Dr. Wiesner added that the issues raised also apply to other fields. He has had difficulty getting gastroenterologists to focus on his patients because these practitioners have other things they would rather do. Reimbursement is inadequate for liver patients, too.

Recovery/Allocation/Transplantation Practices Outside the U.S. -- Dr. Nicholas Tilney, President, The Transplant Society

Dr. Tilney described the worldwide need for, and availability of, organs, particularly kidneys. He described countries with notable practices around transplantation. For example, in Spain, both Madrid and Barcelona have very good ambulance services trained in donation after cardiac death (DCD). If someone falls dead on the street, the ambulance crews start infusing the patient right away to increase viability for DCD. Belgium and Austria both have required request laws specifying that, if a person has not opted out, he or she is a potential donor. The United States does quite well, and is in the top rank of countries. Most European countries do well and keep up with their demand. The systems are good in most of these countries.

The World Health Organization (WHO) has stated that about 10 percent of all organs in the world are bought. Dr. Tilney showed a slide of the host countries, which include China, India, and Columbia.

Dr. Tilney described the Transplantation Society, which began in 1966. One of its Guiding Principles (#5) is that: “Organ, tissue and cells should only be donated freely and without monetary reward. The sale of organs, tissues and cells for transplantation by living persons, or by the next of kin for deceased persons, should be banned. The prohibition of sale or purchase of cells, tissue and organs does not affect reimbursing for reasonable expenses incurred by the donor, including loss of income, or the payment of other expenses relating to the costs of recovering, processing, preserving and supplying human cells, tissues or organs for transplantation.”

The Transplant Society just completed a summit in Istanbul on transplant commercialism, transplant tourism, and organ trafficking, terms which he defined for the ACOT members. Over 160 representatives from 71 countries came together at this event to produce guidelines that will be widely promulgated. In addition, the Transplantation Society, International Society of Nephrology, and WHO have initiatives that work with health authorities for accountability and oversight of transplantation practices.

Dr. Tilney described transplant tourism in China, noting that, in 2005, 11,000 kidneys and 8,000 livers were transplanted in that country. He said that people “come from far and wide to get these organs,” which were fresh, and originated with executed prisoners. There was no free will involved in the donation. The prisoners were shot in a field, and a field ambulance collected the organs and took them to military hospitals. A patient could get a good organ the day after arriving in China, as the executions were scheduled to fit the patient’s needs. Dr. Delmonico has been working with the Chinese government on this issue and has had some success, due to the courage of one minister, in particular. In 2007, the number of kidneys transplanted declined to 5,000. International pressure on the Chinese government seems to be helping but it is unclear what will happen after the Olympics.

The Middle East is also problematic. Renal failure is a big issue in the region, due to the heat, but brain death is not a widely accepted concept. There are a small number of living, related donors. In Egypt, the situation is hugely problematic. Since there is no central databank or organization, the information is very piecemeal. There is a large market in the sale of liver lobes from living donors. Many Israelis go abroad for transplantation (mainly to Turkey). The Israeli government may soon create new laws in Israel to address this situation, such as defining brain death.

Dr. Tilney showed a map of trafficking patterns, describing a patient from the United States who received a kidney from a donor in Brazil, in an operation performed in South Africa, and coordinated out of Israel. Pakistan is also very problematic. There are instances of bonded servants “donating” a kidney; this is exploitation. There is a new law that has reduced the organ trade, although it continues. Not much is known about the situation in India. Dr. Tilney described the situation in the Philippines, where efforts to legalize organ sales garnered Vatican opposition that seems to have succeeded. Recently, the Philippine Department of Health rescinded the approval and banned kidney transplants in foreigners. The government had been pushing legalization because it was making so much money, and Dr. Tilney described this ban as an amazing accomplishment. As the volume decreased in the Philippines, however, Columbia is increasing its volume. A lot of organs are available there due to traffic accidents and the drug wars.

The American Society of Transplant Surgeons (ASTS) opposes payments for living and deceased organs. Payment exploits the most vulnerable members of our society and arbitrarily assigns a market value to body parts (conceivably differentiated by gender, ethnicity, and the social status of the vendor). ASTS objects to payment for donor organs as against the very core of a democratic society that considers all to be created equal. Yet, wherever money speaks and there is a need, this activity will continue.

Dr. Tilney concluded by stating that it is necessary to speak out against these practices. Organ trafficking is unethical and illegal because it does not involve any choice or accountability for the donor, and has a high potential for transmitted disease.

Discussion

Mrs. Rhonda Boone expressed her view that donors in the United States are also exploited given the lack of funding for long-term follow up. Dr. Jim Burdick, Director of the Division of Transplantation, agreed there is no money currently designated for long-term follow up but that the Division is working with NIH and within the Division to address this issue.

Dr. Ettenger stated that he was impressed with what Dr. Tilney and Dr. Delmonico have done. It was alarming to him that transplant tourism was addressed in one place only to pop up elsewhere. Dr. Tilney responded that regulation and compensation issues are complicated wherever there is a need and money to be made. There is a need to be creative in addressing it, and the way to proceed is unclear. Dr. Ettenger stated that Dr. Delmonico had raised the idea of implementing passport controls for those who travel for transplantation.

Dr. Low noted that ACOT had heard presentations on the dangers of transplant tourism before and asked what the ACOT could do, beyond getting an update. Dr. Wiesner added that the last presentation on this subject had included information about U.S. surgeons going overseas to train and practice. He wondered, however, how one could justify selling women’s eggs as any different from selling cells. The response was that there is no additional information about U.S. surgeons leaving the country for this purpose. The American Society of Transplantation has never discussed the egg issue but, according to Dr. Tilney, cells were different from eggs.

Dr. Scantlebury asked about regulations in place for patients who leave the United States for an organ but return home for care. The response was that it was illegal to buy or sell organs in the United States, but it is not illegal to leave the country in order to do so. Dr. Solomon added that the issue of covering patients who return home had been debated by many insurers. The insurer on whose ethics board she serves stated that it will care for their beneficiaries. The group noted that issues of young adults losing their Medicare coverage when they turn 21 may be more significant than those arising from the occasional patient getting a kidney in Pakistan.

Dr. Lorber concluded by suggesting that the group focus on how ACOT could address this problem in a recommendation to the U.S. Secretary of Health and Human Services.

Public Comment

Dr. Mark Uknis stated that he is a transplant surgeon by training and currently the medical director of ViroPharma. As a member of ASTS, he is aware there is continued controversy over reimbursement of donors; and this affected organ trafficking. He said that people can bury their heads and say that it’s wrong, but everyone has to realize that trafficking is occurring. He recently had a patient who went to Pakistan and paid $40,000 for a kidney and then came home with an infection. This patient was self-pay at the emergency room and ended up receiving 3 months of care. Dr. Uknis said he was trained at the University of Minnesota and had been opposed to paying donors until he looked at the implications. Payment does not necessarily mean monetary compensation, he argued. It goes back to NOTA, which was designed to prevent brokerage. Organ donation can, and should, be regulated so that brokering was prevented, but in a way that donors get compensation such as guaranteed lifetime health coverage. Every day, the number of people waiting for organs increases, and this issue had to be addressed.

Dr. Uknis’ second point concerned infectious diseases. He asked the ACOT to form a panel on the impact of infectious disease. Cytomegalovirus (CMV) Disease, while rarely fatal, has clear indirect effects on survival. There is a huge drop-off of graft survival if the patient gets CMV, as much as 50 percent mortality, over 5 years, from infectious diseases. Addressing infectious diseases would also limit the number of patients needing multiple transplants, which would improve waiting time by making more organs available for transplant.

Dr. Uknis’ third point was that CMS functions on a zero-sum game. Increasing payment for one code takes funds from somewhere else. There is little chance to increase reimbursement in one place without decreasing it elsewhere. Money can be saved if a proper organ donor reimbursement process was created. He thanked ACOT for the presentations and for having the public at the meeting.

Kimberly Tracy stated that she was both a living donor and a registered nurse. On the subject of pre-emptive transplant, the living donor advocacy group had seen many donors with financial problems. The Social Security Act stated that living donors would receive Part A and Part B from Medicare, but CMS has said that this is comparative. Often, a donor submitted his or her insurance information to the transplant center to coordinate the recipient’s and donor’s insurance. It was not the fault of the transplant center, but many donors did receive bills from their insurance companies. She described a particular transplant case (in which the donor should never have been allowed to donate) where the donor eventually had a breakdown. She now had no therapy and faced very real emotional issues. She closed by stating that there was a need for better informed consent procedures.

ACOT Next Steps

Ms. Agrawal noted that Dr. Mark Schnitzler was unable to attend the meeting to make his presentation on the economic impact of transplantation. The allotted time would be used to discuss ACOT’s future direction. Members were provided copies of the ACOT charter. Ms. Agrawal reviewed the charter and led a discussion about issues of concern and plans for the future.

The ACOT was initially created pursuant to statute, and its first members were named by Secretary Shalala, who sought an Advisory Committee to help her with issues surrounding OPTN issues. Before the first meeting was held, however, a change in administration occurred and the new Secretary, Tommy Thompson, was more interested in increasing organ donations. Thus, ACOT looked at education programs, informed consent, and changes to the Uniform Anatomical Gift Act. Since the current Secretary is less focused on organ procurement and transplantation, the Committee lacks clear directives on what to focus on.

However, Ms. Agrawal noted, ACOT has a broad, regulatory charge. She asked the members what they saw as the most significant issues facing the field on which the members could reasonably and profitably focus ACOT’s attention, in light of the power of the Secretary and the kinds of authority and actions he can take or facilitate. ACOT has an advisory capacity and should focus on matters of important policy, around which it can advise the Secretary in an informed way. Ms. Agrawal did not recommend that ACOT focus on reimbursement for codes, or reforming private health care, however.

Mrs. Boone suggested a recommendation to the Secretary to appropriate funds for a living donor registry and address insurance issues that have surfaced. Ms. Agrawal summarized by stating that one function of ACOT was to look at issues that arise in the context of living donors (e.g., registry, informed consent). There was consensus among the group to examine ACOT’s previous recommendations around living donors, and to identify gaps and assess what it could do next in that area.

Dr. Ettenger suggested addressing economic and financial issues (aging out of insurance, selling organs, living donors needing insurance). Ms. Agrawal said that ACOT might want to think about having speakers address the group on coverage issues affecting CMS, State plans, and private carriers.

Ms. Mary Kelleher added that ACOT could explore variations in access to care that are based on economics, race, educational level, and/or geography. Ms. Agrawal summarized that ACOT could explore those sorts of barriers and make recommendations to the Secretary about what he can do to address them. Dr. Lorber echoed the suggestion, adding that ACOT would be remiss if it did not, at some point, address the access issue. Equitable distribution has been on the table since the Organ Procurement and Transplantation Network (OPTN) was formed, he continued, and remains a key problem that has yet to be solved. Ms. Agrawal agreed that ensuring equitable distribution was part of the Secretary’s function; thus, it was within ACOT’s scope. She suggested that the OPTN provide information on this matter at a future meeting.

Mr. Mark McGinnis, J.D., HHS Office of the General Counsel, stressed Ms. Agrawal’s use of the word “profitably” in directing ACOT’s actions. The “bully pulpit” function of an Advisory Committee can be useful, he said, but ACOT can really only make legislative recommendations and then sit back and see what happens. There are some things that the Secretary can do, in terms of regulation, although they take time and are quite involved. He encouraged the ACOT to work within its parameters. ACOT can advocate for grants or contracts, such as programs to support nurse coordinator positions, for example, or for funding for a donor registry – both are non-legislative changes. ACOT cannot, however, do much about Blue Cross coverage in the States. With respect to Medicaid, ACOT can have a voice. However, it may not turn that voice into a fiat. Interesting and controversial issues may not be within the ACOT charter, including preventing people from engaging in transplant tourism.

Dr. Yiliang Zhu stated that the impact of medical tourism is self-evident. He believes there is a need for ACOT members to gain an understanding of global issues, and he suggested that the ACOT continue to look at this issue. The complexity of the issue makes it difficult, yet it is an important issue. Dr. Ettenger commented that all of the issues come back to donors and that ACOT needed to stay current and aware of global issues that impact donor numbers.

Mr. Holtzman said that the Organ Donation and Transplantation Breakthrough Collaborative has had a remarkable impact but there was more to be done, such as preventing medical examiners from blocking donations, ensuring that Level 1 and Level II trauma centers have active organ recovery programs, the issue of DCD donors. He felt that ACOT should also explore split livers in pediatric cases, since splitting livers had the potential to eliminate deaths on the pediatric waiting list and was something ACOT should encourage.

Ms. Agrawal thanked the group for their recommendations and said that she had asked staff to also provide their thoughts. Dr. Fant’s list for the ACOT to consider included:

1. Efforts to increase donation and living donors safeguards
2. DCD: declaration of death vs. retrieval
3. Patient safety issues
4. NIH projects: recommending and following up on items for study
5. Access to transplantation (including geography, minorities)
6. Composite, vascularized transplants

Dr. Vega added that, in terms of safety, there was a burden on centers to comply with regulations that did not really protect anyone. Dr. Solomon suggested the addition of research on ways to maximize donation and transplantation, increase adherence, and assess DCD. Dr. Wiesner agreed that research was particularly essential for the DCD area.

Organ Allocation: Geographic Boundaries -- Dr. Robert Wolfe, Project Director, Scientific Registry for Transplant Recipients

Dr. Wolfe presented an overview of geographic issues in transplantation. He cautioned that there was a lot of information that takes time to grasp, including the policy implications. He began by describing the type of metrics SRTR developed to describe access to transplantation. The focus was not just on access, however. Processes that occur at varying centers lead to differences in access, including factors such as the rate of accepting or rejecting organs.

The country can be divided geographically into units in many ways, including by region (OPTN, CMS); DSA or OPO; state, county, ZIP code; transplant center or hospital; distance or travel time; exposure levels; and number of organ failure treatment providers. Likewise, differences can be measured in varying ways, including the providers’ perspective of outcomes and/or
process or the candidate’s perspective of access (e.g., access to the list, to transplant after listing, average MELD score, donor characteristics, transplant characteristics).

Dr. Wolfe showed a table on kidney transplantation that illustrated the impact of insurance, race, and geography, in which characteristics with larger Chi-square contain more variance. The larger the number, the greater the impact by that characteristic. In the end, geography matters; it had a bigger impact than either race or insurance status. This was the same in liver and heart transplantation. Once a patient was on the list, geography had a larger impact than anything else.

Dr. Wolfe showed a chart about acute liver failure that compared getting on the waiting list versus dying of markers that could be associated with liver failure. It seemed that the regions vary in terms of whether it was easier or harder for a patient to get on the list if he or she had experienced organ failure. While it was not extremely accurate, this suggested that there were differences in being listed if a person had organ failure, depending on where he or she lived.

Looking at the relative mortality rates of transplantation vs. waiting list by Model End-stage Liver Disease (MELD), in the first 2 years of follow-up, those who had a MELD greater than 15 had death rates less than those who did not get a transplant. With a MELD of over 15, there was more benefit than those with a MELD below 15. An analysis of changing allocation due to this finding indicated that almost all OPOs would see an increase in the number of organs going to patients with high medical necessity.

For heart failure, an analysis of the rate of getting onto the list vs. the rate of dying of causes associated with heart failure indicated that there may be geographic differences in getting onto the wait list. SRTR explored what would happen if individuals with Status 1a and Status 1b were moved ahead of the local Status 2 candidates. While some regions had more transplants, and some had fewer, every region benefited in terms of mortality. This change was subsequently implemented.

For kidney, there are several different metrics. Substantial variations exist, depending on the patient’s OPO, in the rate of getting a donation. Dr. Wolfe showed a map that illustrated the overall rate of getting a transplant among all of those with ESRD (not just those who were wait-listed). The map showed that OPOs differed in the number of eligible deaths they saw; some also find more eligible deaths than others do. The more waiting list candidates an OPO has per potential donor, the less access there was, because the candidates outnumbered the donors. Some OPOs had four times as many candidates as donors.

SRTR calculated how long it took for 25 percent of candidates to get a transplant within a DSA. Among 59 OPOs, the worst took 5 years for 25 percent of the patients to be transplanted. There are OPO differences in recruiting living donors with the fraction of those with living donors ranging from 30-80 percent. There are also differences in the rates of related vs. unrelated living donors – OPOs range from 15-45 percent.

In terms of what kind of organ the patient received, one OPO showed 20 percent better outcomes than another one. Access to transplantation was an issue, as was access to the type of organ transplanted and both vary. Another factor was the odds of discard for non-ECD kidneys. This discard rate ranged among OPOs by about a four-fold rate.

Dr. Wolfe summarized by stating that for every single metric examined, there were two- to six-fold differences, depending on where the patient lived. When exploring the issue of race, African Americans had a kidney transplant rate that was 60 percent compared to Whites; Hispanics were at 61 percent; Asians were at 60 percent, and Native Americans were also at 60 percent. Part of the African American deficit stemmed from age and gender, i.e., factors other than geography.

Dr. Wolfe concluded by stating that there were differences in access to wait listing and to transplantation. Many, but not all, of these differences could be measured and characterized with existing SRTR metrics. Some differences were highly dependent on existing geographic boundaries, and others on practice patterns.

Discussion

Ms. Conrad commented that on the issue of kidney discards and the Extended Criteria Donor (ECD), ECD did not explain why one might have to discard a kidney. This was an instance in which size does matter. It might not be possible to place little kidneys or, when the donor was opened up, cysts or some other problem could be identified. ECD only accounted for issues such as hypertension or age, so it was not a good descriptor to explain organ functions. Dr. Wolfe thanked her for the comment.

Dr. Wiesner asked if the data on reallocations showed improved survival or decreased deaths on the waiting list. The response was that definitive and clear data did not exist for MELD. Listing practices had changed and there were fewer low-MELD patients, so the denominator had changed. Dr. Wiesner said that, if this saved lives, it had implications for generalized sharing. Dr. Vega is the current chair of the OPTN Thoracic Committee; and he stated the change in allocation occurred in July 2006. There had been good early data since then which indicated a 60 percent reduction in wait list mortality for 1a and 1b patients, without an increase in mortality for 2a patients. It had not been long enough to assess survival after transplantation, however.

Dr. Solomon referenced the map of geographic variations and the fact that, over 5 years, the rates had worsened quite badly. It made her consider ACOT’s focus and the need to address the epidemic of huge predictors of ESRD that increased demand. The larger context for this was the change in public health status related to obesity and other preventable issues. Without scope creep, she asked if it was possible for ACOT to address this issue. Dr. Wolfe concurred that much of the increase was from type II diabetes. Mr. McGinnis commented that obesity prevention spanned the whole country and included multiple departments at HHS. It would be difficult, in his opinion, for ACOT to have an impact in this area. Dr. Lorber disagreed, noting that HHS focused on disease control and prevention and, thus, this was an appropriate issue for ACOT to consider.

Dr. Ettenger asked if ACOT could do something constructive in terms of discussing UNOS regions. Dr. Wolfe agreed that this was an area where policies had a big impact on candidates. Dr. Ettenger commented that location matters to a large extent and that geographic issues may have changed since the regions were originally created. The group discussed the fact that the OPTN Final Rule stated that geography should not make a difference and neither the OPTN Final Rule nor other regulations decreed that allocation be based on DSA. Ms. Conrad said that the V.A. had many Centers of Excellence and moved patients all over the country for treatment and transplantation. Her Iowa facility transplanted people who were not from Iowa, for example. Ms. Kelleher suggested that this reflected internal transplant tourism and indicated that people moved around, when they had the resources to do so, to be listed in a place with shorter waiting times.

Reports from Workgroups/Discussion/Recommendations

Ms. Agrawal -- Accreditation of Establishments Required to be Registered with the FDA

Ms. Agrawal led the reports from the workgroups. After the last meeting, there was a consensus that there should be a more formalized process with respect to entities involved in tissue. She and Ms. Emily Marcus Levine, J.D., HHS Office of the General Counsel, drafted the following recommendation:

The ACOT recommends that the Secretary take action to require accreditation of all establishments required to be registered with the FDA as manufacturers of human cells, tissues, and cellular- and tissue-based products.

Ms. Conrad asked how this would affect those who do not recover. Dr. Keith Wonnacutt of the FDA responded that the ACOT recommendation would capture organizations that manufacture as well as those that recover. Tissue rules described in detail what entities had to register. This definition simply stated that, if an entity had to register, it was party to this. Ms. Agrawal said that was also her understanding of the language. ACOT knows these entities are registered with the FDA, and it was ACOT’s opinion that registration is insufficient and that accreditation was desirable. ACOT did not state which entity should be the accrediting agency, however. The Secretary would decide if he was going to act on this and which entity would accredit.

Dr. Leffell asked what standards would be used to measure accreditation, and the response was that there was no single set of standards. The requirement for accreditation included the Secretary specifying the accreditor, as well as the accreditation basis that entity would use.

Ms. Agrawal called the question; the motion was moved and seconded, and the vote was unanimous.

Dr. Wiesner – Funding Sources for Additional Data Collection

Dr. Wiesner reported that the workgroup held a conference call on this issue and that members expressed concern about both the accuracy of data and the need for oversight. Many entities used the data but did not pay for the data. Data collection requirements presented a huge burden for transplant centers, and more data were needed in order to keep making evidence-based decisions. Yet, OPTN representatives indicated that the organization looked at MELD and not at the rest of the data. The work group members talked about the sorts of data needed (including levels of insulin required during transplant).

The group was interested in exploring funding to underwrite some of the data collected. Suggestions included adding a fee to list registration for data collection, or charging insurance and pharmaceutical companies for use of the data. Mr. McGinnis added that this subject came up at the April 28-29 Advisory Council on Blood Stem Cell Transplantation (ACBSCT) meeting. (The recently re-enacted statute required many data on blood and stem cell transplantations.) Everyone was thinking about it, but no perfect model had yet been created or suggested. The Secretary can set the fee schedule, but this could be problematic. Ms. Agrawal said that it might be interesting to have someone talk to ACOT about what the statute and the final Rule specify in terms of data collection about organ transplantation and procurement, so they could be compared with requirements for blood and stem cell.

Dr. Low suggested that the work group craft a recommendation around funding for data collection describing the entity’s use and payment of data. The ACOT did not need to solve the problem, merely to highlight it and to note that there are potential external sources of funding. Mr. McGinnis added that the OPTN Final Rule specified that the data must be provided, but it would be acceptable to charge at a reasonable rate to use the data. Ms. Agrawal suggested that the work group might need to get information from HRSA about the OPTN Final Rule’s specifications on data collection and availability. It would be good, she commented, if the work group could suggest the data needed.

Dr. Fant added that there is a process in place within OPTN to determine the committees’ data needs to support policy developments, and to collect and use these data, once identified. The issue was how ACOT could support the OPTN’s efforts to better identify data needs. Some members commented that there was nothing in the OPTN Final Rule limiting the type of data required to be submitted. It was whatever the Secretary felt was needed. The issue of how to pay for the data remained, however. Dr. Wiesner stated that the data provision burden overwhelmed transplant centers, and the OPTN Final Rule did not provide for a fee or reimbursement process for these programs. The group discussed the fact that data were no longer being collected on some long-term survival indicators (e.g., immunosuppression data). Dr. Fant clarified that, while the data reduction process eliminated data on tumors and cancers post-transplant, some questions were retained about post-transplant cancers. Thus, those questions were only asked when it was appropriate.

Ms. Agrawal summarized by stating that there were three issues. The first was, “what data should be collected?” The second (and related) question was, “what does the OPTN require in the way of data and why – and should ACOT have some oversight over this?” (It was part of ACOT’s original charge.) The third question was about reimbursement. The ACOT could recommend that reimbursement was insufficient and suggest that, if people were asked to provide more data, they should be paid for this process. ACOT cannot, however, set a fee schedule. Mr. McGinnis added that the ACBSCT made a recommendation at the April meeting that the data collection efforts be fully funded. ACOT could recommend that full funding be available for data collection sources, or that NIH award grants in this area.

The work group will continue to consider this issue.

Dr. Leffell – Xenotransplantation

Dr. Leffell reported that part of the work group’s report would be presented by Dr. Wonnacott. The work group was charged with considering issues around xenotransplantion. The members had a few conference calls and reviewed materials to examine the scope of ACOT’s interest and whether there was any need for ACOT to pursue this issue further.

As part of this work, Dr. Fant conversed with the former Executive Secretary from the Secretary’s Advisory Committee on Xenotransplantation (SACX). The work group also reviewed a lot of work that they had not known had occurred, or was occurring. In the end, the work group determined that there was no current, pressing need for ACOT to pursue xenotransplantation issues. The work group did discuss several ethical issues, some of which were also raised in the morning session of this meeting.

Thus, the work group’s recommendation was that, with on-going oversight, there was no need for duplication of efforts. ACOT’s role should be simply to monitor progress in xenotransplantation.

Dr. Wonnacott updated the group on ongoing activities in this area. He stated that he was the Branch Chief for cell therapy, which oversees regulation of xenotransplantation. The FDA definition did not include non-living tissues. As such, all studies that used xenotransplantation products had to be performed under Investigational New Drug application (IND) process and were subject to premarket approval requirements prior to distribution for sale.

Guidelines on xenotransplantation include: the 2001 PHS Guideline on Infectious Disease Issues in Xenotransplantation; the 2003 FDA Guidance for Industry: Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of Xenotransplantation Products in Humans; the