SUMMARY MEETING NOTES

U.S. Department of Health and Human Services

Advisory Committee on Organ Transplantation

Hyatt Dulles

Herndon, Virginia

December 3-4, 2001

Welcome

The Honorable Tommy G. Thompson

Secretary, U.S. Department of Health and Human Services (HHS)

Elizabeth M. Duke, Ph.D.

Acting Administrator, Health Resources and Services Administration (HRSA)

After an introduction by Dr. Elizabeth Duke, the Honorable Tommy G. Thompson, Secretary of the U.S. Department of Health and Human Services (HHS), thanked the members of the Advisory Committee on Organ Transplantation (ACOT) for participating in the meeting.

Secretary Thompson emphasized that the purpose of the committee was to pursue the goal of saving lives by expanding the availability of donor organs. More than anything else, the Secretary hoped that the Committee would focus on making more organs available and encouraging states to find ways to persuade more people to commit to donating organs.

On his first day in office, Secretary Thompson vowed that organ transplantation would be a priority of HHS. On April 17, 2001, during National Organ and Tissue Donor Awareness Week, he launched the Gift of Life Donation Initiative, whose goal is to reduce the country's critical shortage of organ and tissue donors. The Secretary also called for a national forum on donor registries, which took place in November. At this forum, development of State and national registries was discussed, as a means to making donor wishes known. Under The Gift of Life Donation Initiative a model donor card was introduced and a donation curriculum is being developed that is modeled on Wisconsin's mandatory donation education for all driver's education programs in the State.

The Secretary hoped that these and many other initiatives will lead to a steadily increasing number of organs available for transplantation, so that less time is spent on the emotional and divisive issue of allocation. However, an equitable allocation system is needed, and consensus in the medical community is growing on how to assess medical necessity to ensure the fairest distribution of available organs.

Secretary Thompson then swore the members of ACOT into office, and thanked them for their service to the United States and the American people.

Overview

Nancy Ascher, M.D., Ph.D., Chair, ACOT

Dr. Ascher welcomed committee members to the meeting. She expressed the hope that during the course of the meeting, the ACOT would develop into a working group that would serve as a liaison between the Organ Procurement and Transplantation Network (OPTN) and HHS, bringing advocacy and relevance to organ and tissue transplantation issues.

Introduction of the Committee

Jack Kress, Executive Director, ACOT

Mr. Kress introduced the ACOT members and then each of the 36 members of the Committee [out of a total of 41] who were present at the meeting spoke briefly about the transplantation issues that mattered most to them.

Federal Advisory Committee Act

Jeffrey Davis, Office of the General Counsel, HHS

The Federal Advisory Committee Act (FACA), enacted by Congress in 1972, sets the ground rules for ACOT's activities. The committee's meetings must be open (except, in rare cases, for statutorily allowed reasons), and must be preceded by a notice in the Federal Register. The meeting's records, which include any documents distributed to the committee during the meeting, must be made available to the public. However, subcommittee meetings are not subject to the same requirements, as long as these groups regularly discuss their activities with the full committee at open meetings.

Conflicts of Interest and Other Ethics Concerns

Jack Kress

While they serve on this committee, ACOT members must know and fully understand that they are government employees, subject to the ethics rules of the Federal government. The government has issued a waiver to protect committee members from any allegation that members were in violation of the criminal conflict of interest statutes because, although some committee members had conflicts of interest, the government's interest in obtaining their advice outweighed those conflicts. Since the committee will review policies submitted by the OPTN, three members of ACOT resigned their positions on the OPTN board of directors before joining ACOT.

Screening of Film "No Greater Love"

Lynn Rothberg Wegman, M.P.A., Director, Division of Transplantation, HRSA

The committee viewed a 15-minute version of the hour-long film "No Greater Love," which depicts patients in need of organ transplants and their families, donor families and the donation process. The full-length version will be shown on PBS in April. The Health Resources and Services Administration (HRSA) plans to work with local PBS stations to promote the film and identify local members of the transplant community who could comment on the film on local tv/radio shows immediately after the film airs.

Discussion

The antismoking campaign that has been the most effective health campaign to date owed its success to its ubiquitous presence. The PBS audience may not be sufficiently broad to communicate the message to all communities in the country. Ms. Wegman welcomed suggestions on how to use the film to convey the message to a larger and more diverse audience.

Since the film's message will be more powerful when joined with local donation and transplantation stories, HRSA will arrange for local representatives to discuss their transplantation experiences either directly before or after it is shown, and explain how it relates to their communities. It was suggested that production of versions in Spanish and other languages might be helpful. HRSA is working on other communication tools, including a video for community health centers.

The Secretary's Gift of Life Donation Initiative

Lynn Rothberg Wegman

Workplace Partnership for Life

Secretary Thompson launched the Gift of Life Donation Initiative on April 17, 2001. On that date, 18 organizations announced plans to educate their employees on organ, tissue, marrow, and blood donation, as part of the Workplace Partnership for Life, and many more organizations have since joined the Secretary's Initiative.

National Forum on Donor Registries

The goal of the donor registry conference was to explore ways to strengthen existing registries, discuss opportunities and challenges for more states to create registries, and to address the potential role of the Federal government in registry development. Conference participants looked at the minimum set of data that all registries should collect, portals of entry to these data, funding mechanisms for registries, and how to evaluate donor registries. The forum produced guiding principles that addressed several issues, including whether registries should function as a declaration of donor intent or documentation of donation consent.

Discussion

Currently, registries only track individuals who have agreed to donate their organs, not those who have refused. To pursue consent, registries might track several options, such as "yes," "no," "undecided," and "ask my family." But most organ procurement organizations (OPOs) are reluctant to include the "no" response because this might imply that a "no" is binding and the family can no longer be approached to request a donation. OPOs prefer to have the option of tracking the "yes" responses and approaching the families of everyone else, as they currently do, to determine whether the individual had changed his or her mind. Moreover, tracking the "yes" option only is much simpler than tracking several options, and simplicity is key to making this effort successful.

If the system requires that each organ or tissue be listed on the registry, motor vehicle clerks might have the difficult task of explaining the differences between different organs for organ donor designations on driver's licenses.

Organ and Tissue Donation Education

Model Donor Card and Gift of Life Medal

HRSA Grants

Mary Ganikos, Ph.D., Division of Transplantation, HRSA

The HRSA Division of Transplantation expects to collect 15-17 organ donation curricula from across the country to help develop a multifaceted, generic education package that could be used in driver's education, high school, and other educational settings. One grantee of the division is developing an organ donor curriculum for kindergarten-12the grade and, after this is tested, it may be made available on a national basis.

The Division has drafted a design for a Gift of Life Donor medal and is working with the Department to ascertain whether this will be a congressional or departmental medal. The model donor card was designed to meet the requirements of every State and is being distributed nationally.

In the past, the Division's grant program focused primarily on small demonstration projects. The new grant program includes research and evaluation on how to increase organ and tissue donation. Under the new program, all projects must address increasing organ procurement, consent for procurement, or declaration of the intent to donate. The new grants are much larger ($100,000 to $400,000 per year) than the previous grants, which will allow investigators to include a more sophisticated evaluation component. The program has funded 35 projects since 1999, for a total of more than $26 million.

Opportunities to Expand the Donor Pool

Live Organ Donation

Francis L. Delmonico, M.D., Massachusetts General Hospital, ACOT Member

In 1990, most live donors were parents, offspring, siblings, or other relatives of the recipients, but today, more than 20 percent of live donors are unrelated to the recipients. Live kidney donations to unrelated donors are quite successful and produce better results than cadaveric donations.

Laparascopic donor nephrectomy and other advances have made recovering kidneys from living donors less cumbersome and complicated, with less morbidity. With the availability of live kidney donation, at least one potential donor can be found for 50 percent of those in need of a kidney transplant.

In spite of its safety, living donation raises ethical concerns about the protection and well-being of the donor. This prompted the transplant community to develop a consensus statement that the live organ donor must be competent, free from coercion, willing to donate, and medically and psychosocially suitable.

The current system of living organ donation is premised on the uncompensated donor's altruism. Indeed, the National Organ Transplant Act of 1984 specified that human organs cannot be acquired for valuable consideration for use in human transplantation. The altruistic basis of donation could be compatible with the following incentives, acknowledgments, and intended reciprocity systems which could enhance the live organ donation process:

• "donor exchanges: individuals who cannot donate to a family member because of incompatibility could provide an organ to another person in exchange for a compatible organ from a third individual or donate an organ to a recipient through a regional pool;
• "employee medical leave for organ donation;
• "ensuring access to organs for those who have donated previously; and
• "donor insurance to cover the medical risk of donation.

Live Liver Donors

Amadeo Marcos, M.D., University of Rochester, ACOT Member

Adult-to-adult living donor transplantations of the liver have significantly increased in number--the number of centers conducting such transplants has grown from 3 in 1998 to 42 in 2001.

More than 15,000 people are on the waiting list for a liver transplant, but fewer than 5,000 cadaveric liver transplants are performed each year. Meanwhile, 12 to 15 percent of those on the waiting list die every year. By the time individuals on the waiting list obtain an organ, they are often very sick, which means that the transplant is less likely to be successful. But with the increase of living and cadaveric transplants, waiting list mortality is dropping.

Living donor liver transplantation requires the removal of more than half of the donor's liver and is very complex. Even when the surgery is uncomplicated, most donors and their families incur economic hardship, including loss of employment in some cases. Mechanisms are needed to protect donors and their families from financial hardship.

Live donation significantly reduces waiting time for an organ and is as effective as cadaveric donation for end-stage liver disease. But donors must be carefully selected to reduce the risk of death or disability from the procedure.

To improve the system, the following are needed:

• "mechanisms to protect donors and their families from financial hardship, such as full reimbursement of medical expenses;
• "establishment and funding of a registry to follow outcomes of living donors; and
• "funding for research on living donation.

Expanded Organ Donation--Non-Heartbeating Organ Donation

Howard Nathan, Philadelphia Donor Program, ACOT Member

Hans Sollinger, M.D., Ph.D., University of Wisconsin, ACOT Member

The Nation's 59 OPOs have a population base ranging from 1 million to 17.9 million people, and a performance range of 13 to 35 donors per million people.

There are approximately 8,000 to 14,000 brain-dead potential donors in the United States each year. With 6,000 donations each year, the system is reaching 40 to 50 percent of its potential. One means of increasing the number of donations is through use of expanded donors, defined as those who:

• "are older than 60 years of age;
• "have positive serology for hepatitis B or hepatitis C;
• "have comorbid factors (such as past medical history of diabetes or hypertension); or
• "are non-heartbeating organ donors (NHBDs).

The percentage of NHBDs has increased from one percent of all donors in 1993 to two percent in 2000. The number of OPOs involved in NHBD has increased from 13 in 1993 to 29 in 2000.

Graft survival for NHBD kidneys is almost identical to the survival rate for other cadaveric kidneys. The Institute of Medicine (IOM) has therefore recommended that OPOs explore NHBD, which could result in a 10 percent increase in organ transplantation on a national basis.

Minority Donation

Robert S.D. Higgins, M.D., Medical College of Virginia, ACOT Member

Carlton Young, M.D., University of Alabama, ACOT Member

pproximately 35 percent of people waiting for a kidney transplant are African American, 20 percent of individuals on the waiting list for an organ are members of minority groups, and 11 percent of cadaveric donors are minorities. Although the proportion of African American donors is commensurate with their proportion of the overall population, the prevalence of end-stage renal disease in African Americans is several times that of the Caucasian population. Because their need is so much greater, minorities must donate a larger proportion of organs.

A recent survey on organ donation found that both African American and Caucasian populations understand the need for organ donation, and most are not concerned about the ethnicity of potential recipients of their organs. But many fewer African Americans than Caucasians trust doctors and the medical system. African American respondents are also concerned that organ donors might not receive the necessary medical attention to prolong their life to the maximum extent. This points to the need for education/sensitization of physicians in medical school to the concerns of individuals from different cultures.

A study of U.S. Latinos found that barriers to organ donation in this population consisted of concerns that; physicians would not try to save a potential donor's life; celebrities and wealthy individuals move to the top of the waiting list for organs; organs are sold through a black market; and confusion exists about brain death and coma. Culturally sensitive education is needed on organ donation and the need of members of these communities for organs should be emphasized.

In addition, more minority educators, requesters, and healthcare providers should be part of the organ procurement system.

The Minority Organ and Tissue Transplant Education Program was established in 1991 to improve minority donation. The program offers comprehensive education through community- and hospital-based programs to promote organ donation, in addition to health, diabetes, and hypertension education. The program has increased minority donation significantly.

Non-Human/Artificial Organs and Tissue Engineering

Bartley P. Griffith, M.D., University of Maryland, ACOT Member

Dr. Griffith discussed three different types of alternative organs:

• "xenotransplantation (from animals);
• "totally artificial organs, and
• "tissue engineering/repair.

New muscle can be put into diseased hearts, livers, and kidneys, and human beings can regenerate injured areas. Reparative medicine may make a clinical impact within the next 15 years. But biohybrid organs (with combined cell and bioengineered components) are not likely to be feasible alternatives in the near future.

Xenotransplantation has a mixed history. Patients have not done well with transplants from baboons. In addition, pigs need to be made more immunologically similar to humans in order to become appropriate sources of organs.

Public Comments

Dennis Heinrichs, President of the Association of Organ Procurement Organizations (OPOs), recommended that the ACOT address:

• "strengthened partnerships to increase organ donation and acceptance among diverse ethnic populations;
• "research on organ donation, recovery, transportation, and consent;
• "shared accountability for organ donation across the entire healthcare system; and
• "maintaining the public trust and advancing stewardship in a principled approach to seeking donation.

Mr. Heinrichs called for a series of HHS-sponsored regional hearings to increase the visibility of organ donation at the community level and obtain important grassroots input on such issues as alternative financial incentives to donation.

A participant suggested that national television advertisements or public service announcements by national celebrities on organ donation be produced and utilized. These advertisements could be funded by corporations and HHS.

Committee Discussion

The ACOT should explicitly examine the ethical framework of registries, as well as what happens to donors and recipients after transplantation. Specific issues include:

• "when and how families should be approached;
• "conflicts of interest providers face caring for both the potential donor and the potential recipient;
• "uncertainties involved in surrogate decision-making;
• "uncertainties faced in predicting when the patient will die,
• "whether determination about consent is truly informed and voluntary; and
• "cultural sensitivity.

An ethically sound system is needed to preserve public trust that requires that national policies and practices be clear to patients, families, and the medical community.

An independent donor advocate could convey information to the donor in an objective way. This would not place the physician in a position of conflict of interest involved in serving as an advocate for the transplant.

Committee members agreed that the ACOT should address the plight of donors, who should not have to bear the personal expenses of organ donation. To help families of cadaveric donors, many OPOs now have professional staff members whose sole job is aftercare for donor families. However, grief counseling and aftercare are not reimbursable.

In New England, transplant centers receive an incentive to conduct NHBD, resulting in a dramatic increase in the interest in NHBD in the region. However, approximately 50 percent of OPOs in the U.S. do not participate in NHBD. Perhaps the ACOT could establish guidelines to encourage NHBD. Physicians will need time to become comfortable with NHBD, and they must understand that graft survival with NHBD is similar to that of other cadaveric transplants. Family members also have difficulty understanding brain death, although many are eager to donate the organs of their loved ones once they are educated about the process.

Enhanced Methodology to Increase Organ Donation

Centers for Medicare and Medicaid Services (CMS) Efforts to Improve System Performance

Stephanie Senior, Centers for Medicare and Medicaid Services

The Centers for Medicare and Medicaid Services (CMS) have established regulatory requirements to improve the country's organ procurement system that include the establishment of OPO conditions for coverage and hospital conditions of participation in Medicare and Medicaid. This regulation requires the referral of all deaths and imminent deaths to OPOs. CMS is now developing regulations to promote quality and encourage OPOs to adopt best practices in maximizing the procurement of healthy organs for transplantation. CMS will publish its proposed rule and provide an opportunity for public comment.

Ms. Senior is one of four regional OPO coordinators at CMS, and works directly with OPOs to implement the conditions for coverage and improve quality. An effective organ procurement system is one that requires:

• "quality assessment and continuous performance improvement;
• "periodic death record reviews;
• "good communication with transplant hospitals;
• "active medical directors;
• "good relationships with tissue and eye banks; and
• "safeguards to prevent staff burnout.

Discussion

Safeguards against staff burnout might include allowing staff sufficient time off and hiring a large pool of transplant coordinators. This issue will become more critical as the nation's nursing shortage intensifies, especially since most critical care nurses are not exposed to organ procurement.

Although CMS reimburses aftercare for a few months, duration families may need to be followed for longer periods of time. If families are left alone after they donate, distrust of the medical system will only increase.

Organ donations are costly procedures. If this committee and others are successful at increasing organ donation, lives will be saved but more funding may be needed.

Optimizing the Actual Donor Pool

Kenneth Wood, M.D., University of Wisconsin

Maximizing the number of potential organ donors who become actual donors requires:

• "surveillance to identify patients with severe neurologic injury likely to progress to brain death;
• "a standardized method for brain death declaration;
• "uniform requests for consent;
• "optimal medical management of the donor;
• "continued intensity of support prior to organ recovery;
• "a shift in focus from cerebral protective strategies to optimizing donor organs for transplantation;
• "simultaneous critical care for organs of multiple potential recipients; and
• "facilitation of donor somatic survival, maintenance of organs to be procured in the best condition, and recognition that donor management affects recipient function.

Approximately 3 to 10 percent of hospital deaths involve clinical brain death, but only 25 percent of these individuals become donors. The approximately 6,000 donors each year suggests that an additional 18,000 potential donors exist. These potential donors are lost due to:

• "failure to detect potential donors;
• "failure to ask the families to donate organs;
• "failure to obtain consent for donation; and
• "medical failures.

Physicians often mistakenly assume that a patient is medically unsuitable for donation because of age, a lung infection or renal failure, or a pre-existing disease or lifestyle (such as hypertension or alcohol intake). Moreover, most health professionals, including neurologists, are not well trained in diagnosing brain death.

Constant vigilance at the bedside is critical to prevent the medical failures that lead to loss of potential organs. Physicians must recognize that they are actually managing four or five patients who will receive the individual's organs. Research also suggests that separating death notification from request for consent significantly increases the number of donors, although this is not well known by healthcare providers. Education is needed in medical and nursing schools, as well as during internship and residency.

Discussion

The weakest link in organ donation and transplantation is the healthcare professional. Many physicians resent required request laws, and families are often approached in a very distressing manner. Education in organ donation must be included in all aspects of healthcare.

The figure cited for potential organ donors (24,000) may be high. In fact, 8,000 to 14,000 potential donors may be a more realistic number. The American Academy of Neurology has neurological intensive care groups that educate intensivists in the care of potential organ donors. However, since most hospitals do not have full-time intensivists, other providers need this kind of training.

ACOT Discussion of Increasing the Donor Pool

When President Bush was governor of Texas, he signed into law an initiative that discouraged medical examiners from insisting on preserving organs for forensic examination in cases of violent death. Donation rates increased significantly once these medical examiners were required to come to the operating theater where the donor surgery was performed to explain to the surgeon why the organ would not be available.

A second problem in Texas related to individuals with brain death who had no apparent family. Under a new law, if no family is found within a certain period, the law allows the hospital to recover the organs. This could potentially be enacted at the Federal level.

When a potential donor does not donate organs, patients will often die as a result. Governments have mandated certain requirements, such as wearing seatbelts, when a clear public benefit exists. Just as wearing a seatbelt or a motorcycle helmet has become an expectation, donating organs must also become an expectation.

Presumed consent is one way to increase donation, but many of the people who are most committed to organ donation are opposed to this concept. Moreover, presumed consent would probably fail in the United States on first amendment grounds. Presumed consent, as practiced in other countries does not go into effect in the absence of an agreement from the family.

This Committee could clarify the ethical and legal status of an individual's declaration of intent to donate. Even if the efforts discussed at this meeting result in an expansion of the number of people who have agreed to donate their organs, families will still have the right to veto those wishes. This committee might make recommendations to give more weight to the wishes of the individual and not allow families to veto those wishes. This would require telling the family that the patient has agreed to donate, rather than asking the family for permission to recover the organs.

Property law states that, after death, the family owns the remains, to the extent that a property interest exists in those remains. However, property law is not entirely relevant to the transplantation area. What the law needs to address is whether the expression made by a living individual is an enforceable expression of his or her intent or of his or her disposition. This would determine whether the hospital and physician have the authority to act on the individual's expressed desire, regardless of the family's wishes, and would also impose a penalty for not doing so. In many States, hospitals, physicians, and OPOs have a right to act on an individual's expression of wishes without consulting the family, provided that the individual has clearly expressed his or her desire. However, no one wants to add to the family's grief, and one must guard against the possibility of being taken to court for going against a family's wishes.

A fiscal analysis of the costs of keeping a patient on kidney dialysis versus transplanting the patient with a transplantation found that transplantation saved money. Perhaps the money saved could be used to offer incentives for donation.

Requirements of the Amended Final Rule on the Organ Procurement and Transplantation Network (OPTN)

Lynn Rothberg Wegman

Emily Marcus Levine, J.D., Office of the General Counsel, HRSA Branch

The National Organ Transplant Act of 1984 created the Organ Procurement and Transplantation Network (OPTN), established Federal oversight of organ procurement and transplantation in the United States, set forth requirements for OPOs, authorized HHS to make grants or contracts to OPOs and nonprofit organizations to improve organ procurement and transplantation, created the Scientific Registry of Transplant Recipients (SRTR), and prohibited the sale or purchase of human organs. Under Section 1138 of the Social Security Act, OPOs and transplant hospitals are required to be members of the OPTN and abide by its policies in order to participate in Medicare and Medicaid, and consequently the Secretary of HHS must oversee OPTN policies, and other OPTN standards used to determine eligibility for such participation.

The HHS amended final rule on the OPTN was published taking into consideration, public comments, input received at meetings with representatives of the transplant community, and the July 1999 report of the Institute of Medicine (IOM), whose five recommendations were:

• "decreased emphasis on waiting time;
• "broader sharing of organs;
• "importance of Federal oversight;
• "creation of an independent scientific advisory committee (ACOT); and
• "improved data collection and dissemination.

The final rule sets performance goals to:

• "standardize minimum objective and measurable medical criteria for listing and delisting patients;
• "set priority rankings expressed, to the extent possible, through objective and measurable medical criteria, for patients who are medically suitable candidates for transplantation, to receive transplants;
• "distribute organs over as broad a geographic area as feasible and in order of decreasing medical urgency; and
• "use performance indicators to assess transplant program performance and reduce the inter-transplant program variance to as small as can reasonably be achieved in each indicator.

The OPTN is required to review OPOs and transplant programs for compliance with the rule's requirements and OPTN policies. HHS can request a further review if it has reason to believe that a breach in compliance has occurred or if a risk to the patients or to public safety is posed. Enforcement actions can include removal of a hospital's designation as a transplant program under the final rule, termination of the hospital's participation in Medicare and Medicaid, and termination of the OPO's or the hospital's reimbursement from Medicare and Medicaid.

The ACOT was established under the final rule to serve as an independent, multi-disciplinary review board to help the Secretary ensure that the transplantation system is equitable and based on sound medical and scientific evidence, advise the Secretary on allocation and other significant OPTN policies and on ways to maximize Federal efforts to increase organ donation nationally, and provide advice on other transplantation-related matters.

Discussion

The ACOT is not scheduled to meet again until late spring, but has been asked to consider a proposal for a modified liver allocation policy which is scheduled to be implemented in February. The new proposal before the Committee can be put into place as a voluntary proposal until the committee has a chance to review the proposal and make a recommendation to the Secretary. If the Committee endorses the proposal at its spring meeting and the Secretary so chooses, he can then make the policy mandatory and enforceable. In the past, the OPTN has generally taken approximately 6 months to accomplish the necessary programming changes and to otherwise implement policies after they have been approved by the OPTN Board of Directors. The ACOT could meet in between OPTN Board meetings in order that the Committee may provide recommendations to the Secretary in time for changes to policy, the Committee could authorize HHS and the Secretary to implement such changes without Committee review.

Once an allocation policy is approve and implemented, if the ACOT were to learn of a better alternative, it should be possible to alter the policy in a fairly short timeframe. Since HHS has not yet gone through the new approval process, the timeframe is not clear. In the event of a major threat to public health and safety, the Secretary can take more expeditious action.

Currently, the OPTN has no mandatory, enforceable policies. The Secretary will determine, based in part on advice from the ACOT, whether any and if any, which policies should be deemed binding and enforceable.

To help expedite the process for review once policies are submitted to HHS, Ms. Wegman suggested that the OPTN and HHS public review process could be conducted concurrently, with the understanding that the OPTN Board could still change the policies after they have undergone public review, and the policies must still be approved by the Secretary. The Secretary will base his decisions regarding a given policy on recommendations from the ACOT, public comments and HHS review and analysis of these sources of input, as well as the policies themselves.

Whenever changes are made to allocation policy and thereby to clinical practice, hospitals and physicians are in essence conducting clinical trials. The question was raised whether such changes require institutional review board (IRB) review and approval and informed consent from patients. Ms. Wegman offered to look into this issue. In addition, changes to policy may also fit into health services research, and should therefore be tracked so that the Committee can determine the impact of changes on individual patients.

Of note is the availability of the scientific registry to provide analyses when ACOT members believe that additional studies or data are needed that were not requested by the OPTN Board or committees.

Since the OPTN policy-making process takes in the input of numerous experts in the field of transplantation, the ACOT should be careful to avoid duplicating its activities, although ACOT could serve as a tie breaker when a clear difference of opinion exists. The ACOT might consider limiting itself to making broad recommendations, in order to avoid second-guessing the group that was constituted to develop these policies.

Kidney and Pancreas Allocation and Distribution System

James J. Wynn, M.D., Chair, OPTN Kidney/Pancreas Transplantation Committee

In most cases, kidneys are allocated first locally, then regionally among the 11 OPTN regions, and then nationally. Patients on the list are ranked and assigned priority on the basis of several factors, including waiting time, ABO blood type, panel reactive antibody (PRA), and based on whether they have been a living donor.

In 1987, mandatory sharing of 0 antigen mismatched kidneys was implemented due to the unique benefit to highly sensitized patients of receiving a perfectly matched kidney. These patients receive priority when an appropriate kidney becomes available, but the receiving OPO must reimburse the national pool so that no individual OPO's patients are disadvantaged disproportionately. Approximately 15 percent of transplants involve 0 antigen mismatch.

Graft survival depends on such factors as age, hypertension, kidney function, and cause of death. Three-year survival is 79.4 percent for standard donors and 68 percent for expanded donors.

The OPTN Kidney/Pancreas Transplantation Committee is trying to develop an alternative allocation system for expanded criteria kidney donors that minimizes cold ischemic time and maximizes organ use. The committee recommended that recipients of these kidneys be ranked according to waiting time alone, while continuing to follow the local/regional/national paradigm and allocating 0 antigen mismatched organs with payback provisions. This recommendation was approved by the OPTN Board in November 2001. It remains to be resolved whether waiting time should start at activation on the waiting list or at the onset of dialysis.

Some patients wait longer for a kidney than others due to medical factors (such as being ill at the time of kidney offer) and socioeconomic factors (difficulties in locating or transporting the patient). Minority patients wait almost twice as long as white patients. This may be due to the relatively high prevalence of blood type B, disproportionate incidence of renal failure, socioeconomic factors, and increased human leukocyte antigen (HLA) polymorphism in African Americans.

Pancreas allocation involves 0 antigen mismatch sharing with priority for highly sensitized patients and follows local, regional, and national allocation. Pancreas are allocated locally to kidney/pancreas, isolated pancreas, or islet/solid-organ recipients then regionally and nationally to pancreas or kidney/pancreas recipients before they are allocated for isolated islet transplantation.

Discussion

According to a Scientific Registry of Transplant Recipients (SRTR) analysis, eliminating HLA from the allocation system improves the allocation to African Americans on the waiting list by two or three percent. However, in Texas, a large OPO that does not use HLA type as a basis for allocation has equal waiting times for African Americans and Caucasians, while another large OPO that does utilize HLA type demonstrates a waiting time that is three to four times greater for African Americans than Caucasians.

The percentage of African Americans on the waiting list is greater than their proportion in the overall population. In addition to the HLA disparity between African Americans and Caucasians, African Americans are more likely to have B positive blood type Caucasians.

The payback system has always been controversial. For example, if a center receives a 59-year-old kidney, it may not want to pay back with an organ from a 22-year-old donor. However, the recipient center may choose not to accept a 59-year-old kidney and the transplant physician has the right to turn down the organ. Some would prefer that the OPO offering the kidney receive payback credit, even if the kidney offered is not accepted. Without the payback system, kidneys would flow from areas with large African American populations to areas with large Caucasian populations because 0 antigen mismatch transplants are more likely to occur between Caucasians than African Americans.

The OPTN Kidney/Pancreas Allocation Committee examined the possibility of establishing a more uniform kidney/pancreas allocation system, but determined that a nationally mandated system would not be appropriate, since local factors are important.

Donation varies widely across the country, and the allocation system is unlikely to be able to address this. With a fixed number of donor kidneys, waiting times are likely to increase everywhere.

Discussion of ACOT Role

ACOT members expressed some concern about duplicating OPTN debates, since the OPTN has extremely broad input. Committee members emphasized that the ACOT subcommittees should not replicate the OPTN's current activities but, rather, should consider broader, overall issues. The ACOT should set the bar very high before recommending the overturning of the OPTN's decisions.

Dr. Ascher proposed that the ACOT form subcommittees to review and evaluate the policies submitted by the OPTN subcommittees. Subcommittees could also be formed on the basis of the procurement issues discussed earlier in the meeting. Dr. Ascher and Mr. Kress requested that ACOT members e-mail suggestions for subcommittees.

Update on the OPTN/UNOS Heart and Lung Organ Allocation System

Frederick L. Grover, M.D., Chair, OPTN Thoracic Organ Transplantation Committee

In the past, patients waiting for heart transplants were assigned to status 1 if they had only days or hours to live and required cardiac or pulmonary assistance. In January 1999, status 1 was divided into 1A (patients with mechanical circulatory support for acute hemodynamic decompensation, mechanical circulatory support for <30 days with objective medical evidence of significant device-related complications, mechanical ventilation, and continuous infusion of inotropes, or who are believed to have a life expectancy of less than 7 days without heart transplantation) and 1B (patients with mechanical circulatory support and continuous infusion of inotropes). Status 2 patients are those who do not meet the criteria for 1A or 1B, and status 7 patients are temporarily unsuitable to receive a transplant. Since status1 was split into 1A and 1B, waiting list mortality for status 1 patients has decreased by 15 percent. Thus, this decision appears to have helped distribute more organs to the sickest patients.

This OPTN committee is trying to develop a more objective risk scoring system to replace the current medical status system for allocating hearts. These scores will be based on objective and quantifiable pretransplant, posttransplant, and donor factors.

Lung allocation is prioritized strictly according to waiting time, with no risk stratification. Waiting list and posttransplant mortality vary primarily by disease. The OPTN committee is attempting to develop a risk stratification which balances the risk of death on the waiting list against the patient's chances of survival after transplant. Waiting time will serve to break ties for patients with the same risk score. A risk-based lung allocation system would prevent many deaths on the lung waiting list each year.

OPOs vary in the number of hearts and lungs obtained per million population. To some extent, this can be explained by differences in socioeconomic status. But OPOs without lung programs produce far fewer lungs than OPOs with lung programs. This indicates that education is important.

Other strategies of the OPTN committee are to:

• "monitor variance in thoracic donor organ productivity of each OPO and educate underperforming OPOs;
• "improve baseline evaluation of donors by OPOs; and
• "evaluate reasons for organ turndowns.

Discussion

The OPTN committee is attempting to minimize deaths on the waiting list and maximize posttransplant survival, but this raises the issue of equity. Does equity differ if a 25-year-old 1A patient or a 60-year 1A patient dies on the list? Under the current strategy, they would be treated equally, but the 25-year-old has much more to lose, including expected years of life, than the 60-year-old. On the basis of equal opportunity or fairness, the younger person who will lose more without the transplant should receive the organ first.

Quality of life needs to be addressed in allocating organs, as this is a major benefit of thoracic transplants.

Dividing status 1 into 1A and 1B does not appear adequately to address the way in which assistive devices are used. It could be argued that using assistive devices merely shifts who receives an organ from someone with a device to someone without the device, and that using the devices increases the overall cost of transplantation.

Liver Allocation Policy

Richard B. Freeman, Jr., M.D., Chair, OPTN Liver/Intestine Transplantation Committee

Under the current system, status categories utilized to allocate livers consist of the following:

• "Status 1: Fulminant liver failure with a life expectancy of less than 7 days
• "Status 2A: Child-Turcotte-Pugh (CTP) score of 10 and at least one of several possible medical complications
• "Status 2B: CTP score of >10 or a CTP score of > 7 and at least one of several lpossible medical complications
• "Status 3: CTP score of >7 and in need of continuous medical care

In general, livers are allocated first to status 1 locally, then to status 1 regionallly, then to statuses 2A, 2B and 3 locally, followed by statuses 2A, 2B and 3 regionally, and finally to statuses 1, 2A, 2B and 3 nationally. Allocation is based on geography, waiting time, and medical severity, with some flexibility built into the system. Graft survival differs for organs preserved less than 6 hours compared to those preserved longer. Since even a difference of 3 hours has an impact on graft survival, the extent to which organs can travel needs to be limited.

The Institute of Medicine (IOM), in its 1999 report, recommended that organ allocation areas be created based on a minimum population of approximately nine million. According to

Dr. Freeman, the IOM predicted that this would not significantly improve transplantation rates or pretransplant mortality for status 1 patients, would not change transplantation rates but would reduce pretransplant mortality for status 2B patients, and would reduce transplantation rates but not pretransplant mortality for status 3 patients. The IOM concluded that the current allocation scheme could be improved by creating allocation areas that were large enough to shift some of the transplants from status 3 to status 1 and 2 patients.

The OPTN formed a subcommittee to evaluate different realignments of liver distribution units to broaden sharing, as the IOM suggested. Based on simulation models, the subcommittee predicted that broader sharing would slightly decrease interregional variation in numbers of transplants performed (with a few exceptions) and that some schemes would increase and others would decrease interregional variation in pre- and posttransplant deaths.

The subcommittee concluded that wide variation exists among many different factors that affect the probability of transplantation, and altering the population over which livers are distributed affects only one of these variables. Equalizing or increasing sharing areas by population would not necessarily reduce variation to a significant extent, and would not effectively shift some of the transplants from status 3 to status 1 and 2 patients. Moreover, the subcommittee found that broader sharing would not increase the total number of transplants performed, reduce total deaths, or increase total life years. The only significant effect of broader sharing that the subcommittee identified was the redistribution of organs. Therefore centers, but not patients, would be affected by broader sharing. The subcommittee also found that U.S. liver transplant waiting list deaths are primarily a function of the severity of disease, not center, geography, or waiting time variables.

The IOM report also recommended eliminating waiting time as a criterion for liver allocation for status 2B and 3 patients. The OPTN subcommittee agreed and proposed using a continuous disease severity score. In the Model for End Stage Liver Disease (MELD) and the Pediatric End Stage Liver Disease (PELD) model, liver allocation follows a continuous medical urgency score that is based on a prospectively validated mathematical model which utilizes objective criteria. The criteria assess how urgently the patient needs the liver within the next 3 months. Waiting time is used only to break ties. The MELD/PELD system would significantly reduce the number of patients removed from the list due to illness or death. This method appears to have a more direct impact and would do more to distribute organs to those most in need than changing the allocation areas.

The OPTN Liver Committee plans to develop post-liver-transplant survival models that are as predictive as MELD. Adding the MELD score for pretransplant survival to the new posttransplant score will make it possible to give highest priority to individuals who are most likely to die without a liver transplant and who would most likely survive after transplantation.

Proposed Pediatric End-Stage Liver Disease Scoring Policy

Paul Colombani, M.D., Chair, OPTN Pediatric Transplantation Committee

Pediatric patients comprised 30 to 40 percent of the waiting list 15 years ago, but now make up approximately 8 percent. Unlike adults, pediatric patients can be assigned to status 1, no matter what their liver disease diagnosis, because younger patients are at significant risk for death on the waiting list and growth failure (including neurologic growth failure). Adolescent donor organs are preferentially allocated to pediatric patients. Split liver transplants from living donors are utilized to transplant pediatric patients on a timely basis, and these young patients have a very low mortality rate on the waiting list.

The PELD model is similar to MELD, except that it adds age less than 1 year and growth retardation to the allocation criteria utilized by MELD. PELD correlates well with patient morbidity on the waiting list.

Some concern exists regarding how pediatric patients who reach the age of 18 years will fare on the list once they are assigned a smaller number of points as adults.

Discussion

The MELD system does not apply to acute failure or status 1 patients because the MELD scores for status 1 patients are consistently higher than any other MELD scores. The predictive value of the MELD score is currently being ascertained. But since status 1 patients account for only eight percent of the waiting list, not enough status 1 patients survive longer than 30 days to show whether the MELD score is predictive enough. The old status 1 criteria still work for these patients, and the MELD system is focused on status 2A, 2B, and 3 patients.

A member of the IOM committee present argued that the committee had found waiting time to be irrelevant except for status 1 and possibly status 2A patients. He declared that its recommendation for broader sharing was based on data that demonstrated the inefficiency of small OPOs which transplant many of the less sick 2B and 3 patients. If these OPOs served populations of 9 million, 300 fewer of these 2B and 3 patients would have been transplanted in 1998. That same year, 300 status 1 patients did not receive an organ. So by redrawing the districts or broadening sharing, the excess organs that would currently be transplanted in 2B and 3 patients could be given, instead, to the status 1 patients who need the organs more. The IOM committee developed the 9 million population plan because the probability of having a status 1 or 2A patient is small and the probability of having an organ is also small, so the joint probability of having both is extremely small, especially in a region with a small population.

However, others responded that broader sharing can impose more cost and increase ischemic time. In addition, many of the status 3 and 2B patients who receive transplants under MELD are sicker. The MELD score predicts mortality well and reduces waiting list mortality.

The proposed MELD/PELD policy will change over time. The ACOT might endorse this policy, while recognizing that changes will be forthcoming. Also, the Committee might choose not to review a policy every time a change is made. This Committee needs to decide which changes are major and require ACOT review and which are minor. The Committee could also endorse a policy and leave the details up to HHS.

Public Comment

The CTP scoring system uses two sets of diagnostic test results, as well as symptoms, while MELD has only three criteria, which will result in more transplantations in recipients with multiple problems, who have lower survival rates after transplantation. Recipients who have "abused" their bodies would be given the same priority as patients who have cared well for their bodies and may be more likely to adhere to the difficult posttransplant medical and physical requirements.

MELD will not address the regional variations in transplantation rates. A Gallup poll has shown that 85 percent of those who are willing to donate their organs prefer that their organs go to the sickest recipients and 32 percent say that they would be more likely to donate if they knew that the recipient would be the sickest person, regardless of location.

Data and Performance Indicator Needs

OPTN Contractor

Mary D. Ellison, Ph.D., United Network for Organ Sharing

The National Organ Transplant Act (NOTA) of 1984 provided for the creation of the OPTN and a registry that would provide the Secretary of HHS with information on the scientific and clinical status of transplantation, and collect data needed for patient matching and ranking, policy development, outcomes research, performance measurement, and public reporting. The data are provided by OPOs (donors), transplant hospitals (candidates, recipients, and follow-ups), and histocompatibility laboratories (candidates, recipients, and donors). The data are collected and analyzed, and then provided to the government and the transplant community. Based on their feedback, the OPTN institutes system and clinical practice improvements. Ultimately, the OPTN provides performance data to all stakeholders, including consumers.

The first OPTN performance indicator developed was effectiveness of care. During the 1990s, the OPTN focused on appropriate healthcare use, quality of care and medical errors, access to and consistency of care, cost of care, and satisfaction with care. Focus areas also include health services research, which fosters the growth of outcomes- and evidence-based medicine; data at all levels of complexity; performance measures and public reporting; and the demand for user-friendly information.

The amended OPTN's final rule specified that additional performance indicators that are organ specific, provide timely and accurate information, and enable assessment and minimization of variation across the system should be used. These indicators would allow measurement of the OPTN performance indicators specified in the final rule:

• "standard waiting list criteria,
• "objective and measurable criteria for allocation, and
• "the broadest sharing that is feasible.

To allow the OPTN to continue to provide the data needed, the databases require some reevaluation. A data working group is updating certain data elements in the database that are no longer useful, to make room for new ones. The OPTN is beginning to focus on data submission compliance and living donor follow-up.

Scientific Registry of Transplant Recipients (SRTR) Contractor

Philip J. Held, Ph.D., University Renal Research and Education Association (URREA)

The Scientific Registry of Transplant Recipients (SRTR):

• "conducts scientific analyses for OPTN committees, the ACOT, HRSA, and the public;
• "implements the scientific advisory committee research agenda;

• "makes available individual center and OPO outcomes every 6 months; and
• "tests and reports on data quality.

Ongoing science projects at SRTR include:

• "HLA and access, HLA and outcomes;

• "liver (MELD, PELD) and lung acuity indices;
• "organ allocation simulation models (liver, heart, lung, kidney, pancreas);
• "predictive models for the kidney waiting list and posttransplant outcomes;
• "pediatric liver transplants and metabolic disorders;
• "expanded kidney donor criteria;
• "alternative sources of death and graft ascertainment; and
• "end-stage renal disease after living donation.

The SRTR is also focusing on death ascertainment for kidney waiting list candidates and transplant recipients. Some centers do not report patients who die, and the OPTN is not commissioned to follow patients after they are removed from the waiting list. Use of Social Security data from the Centers for Medicare and Medicaid Services (CMS) to supplement the data reported by transplant centers yields higher mortality rates. In some cases, reported posttransplant mortality is off by as much as 200 percent.

• service to donor and donor families (study process, feedback, recognition, designated donors);
• legislative issues as they relate to presumed consent, national application of local laws, mandating donor identification, work in hospitals in identifying donors;
• living donors, removal of disincentives, informed consent;
• NHBD and how to legislate approaching these donors;
• kidney/pancreas allocation oversight;
• heart/lung allocation oversight;
• liver allocation oversight;
• SRTR oversight;
• how to manage data; and
• success of OPOs (this may not be needed if CMS is already looking into this issue).

Committee members again expressed concern about differentiating the ACOT's role from the role of the OPTN, and stressed the need to avoid replication of the OPTN's activities.