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Advisory Committee on Organ Transplantation
November 4 & 5, 2004
Doubletree Hotel and Executive Meeting Centers
Thursday, November 4, 2004
Nancy Ascher welcomed the meeting participants and noted that the three areas of concentration—valuable consideration, fair treatment, and waitlist—are reflected in the subcommittees' titles. Dr. Ascher then introduced Dr. James Burdick who spoke about the progress achieved in regard to the Advisory Committee on Organ Transplantation's (ACOT) first 28 recommendations.
Update on ACOT's Recommendations
James Burdick filled in for Thom Balbier, Executive Director of ACOT, who was unable to attend the day's meeting. Dr. Burdick asked that anyone who wished to make a public comment please speak to Sherry Whipple to arrange a time to address ACOT. He thanked Sherry Whipple for her part in planning ACOT meetings.
Dr. Burdick acknowledged Mr. Balbier's efforts to bring in Ex-officio members from four of HRSA's sister agencies. Ruth Solomon of the U.S. Food and Drug Administration (FDA), Marcia Newton of the Centers for Medicare & Medicaid Services (CMS), Nancy Bridges of the National Institutes of Health (NIH), and Matt Kuehnert of the Centers for Disease Control and Prevention (CDC) are all here in that capacity. This cross-disciplinary approach will help ACOT discern what needs to be done and make recommendations that are likely to bear fruit.
Insofar as the ACOT membership, Dr. Burdick noted that nomination packages are in the works for the new members. The incumbents will continue until the new people come in.
Dr. Burdick briefed the meeting participants on the status of ACOT's first 28 recommendations. He said that we are close to but have not yet garnered the approval of the U.S. Department of Health and Human Services (HHS) for recommendations 29 through 35. He noted that approval is likely a matter of the bureaucratic process, which requires some time. He noted that a conference call at a later date may be the best way to discuss the status of these recommendations. Below are some notes regarding the progress of certain of ACOT's recommendations 1-28:
Flora Solarz made two comments. First, the intent behind Recommendation 4 was to provide consistent information to all donors across transplant centers and to have a live staff person available who would be independent of the hospital and who could engage potential donors and their families in dialogue and deal with their questions. UNOS has made great strides in putting together information, but there has been no progress in putting a live person in place. Second, Ms. Solarz said that in regard to the database of outcomes for living donors (Recommendation 3) we need to look at the toll that living donation can take on someone who is trying to save a life. There are other important implications besides health outcomes (e.g., psychosocial, financial, implications for medical, disability, and life insurance). If we look only at survival, we are not giving appropriate attention to the spectrum of consequences faced by living donors.
Dr. Ascher responded that the NIH study will address a larger universe of data, including things brought up by Ms. Solarz. The question is: How can these issues be addressed in an affordable way? Dr. Burdick said that some aspects (e.g., insurance implications) might be easier to address than others (e.g., psychosocial consequences). Perhaps we can look at the easier aspects first. He also said that it might be difficult for the government to hire someone to serve as a donor liaison because of the costs involved and other logistical problems.
Robert Gibbons noted that Recommendation 25 netted two proposals by OPTN in regard to (1) regional sharing and (2) minimum listing criteria. These have been passed and implemented.
Kathy Turrisi observed that one problem has been the public perception that ACOT has not been moving fast enough on some agenda items. Some recommendations were made with the intent of moving recommendations and agenda items along more quickly. It seems, though, that we are still bogged down and not getting things in place although ACOT and UNOS have done a great deal of work. We should put some time points in place to show that we are moving along. Dr. Burdick responded that approximately one-third of ACOT's recommendations have had some aspects put in place. Some recommendations have taken some time but will be implemented. In its three and a half years, ACOT members can feel good about the progress achieved.
Another participant noted that Recommendation 28 contains two conflicts. CMS will work to resolve these.
Report from the OPTN Transplant Administrator's Work Group on the Request for Information (RFI) Form
Ms. Turrisi discussed clinical outcomes reporting. She noted that a standard RFI form is available, but payers often request many other items of information. How can we solve that problem? She outlined some progress that has been made in this area. For example, there will be an annually updated, Web-based version of the RFI form available. Information may then be faxed or mailed to insurance companies. Data from the Scientific Registry of Transplant Recipients (SRTR) can be downloaded.
On July 22, Ms. Turrisi represented ACOT at a meeting in Chicago with insurance administrators and UNOS. At that meeting, the participants asked insurance representatives about the types of information they need. Many payers have addendums to request information other than that on the RFI. Many companies have been asked to forward their addendums, which will be added to the 2006 RFI.
She noted that some insurers commented that SRTR data seem to be outdated. The insurers rely on transplant centers to provide the most recent information. Ms. Turrisi commented that the insurers asked about how they can get more timely data. The insurers want to know what centers are doing to fix their problems. Ms. Turrisi reported that the insurers said they want to see some kind of practice plan within transplant centers to ensure that timely data can be made available by sources other than the centers themselves.
Fritz Port commented that the criticism about outdated data appears to be invalid. Follow-up data must be based on an entire year of data collection. If the insurers just want counts, SRTR can provide up-to-the-minute data. SRTR has uniform data and captures additional follow-up from Social Security master files. Dr. Port said that SRTR's data continue to improve.
Ms. Turrisi said there is room for improvement. Questions in the RFI address other items. Some centers are not even approached by insurance companies. Such centers have taken corrective actions but they are still being punished years later. Some centers provide data that purports to be more recent than SRTR data. Again, this is a work in progress.
Alan Leichtman of SRTR said that SRTR's data are accurate and better than what had been provided by the centers. In terms of timeliness, if we are reporting 1-year follow-up, it requires closure of one year. SRTR is limited by the laws of the calendar. It important that insurers understand the framework that underpins data collection and reporting.
Roger Evans described a scenario in which a center gets in trouble, the center then recruits new staff and tells insurers that the center has improved. The data provided by centers must be considered questionable. He also made the point that insurers compete with each other through networks. There is a great deal of overlap among the networks. With all of the addendum materials, insurers are competing to get the best networks.
Ms. Turrisi reiterated that her focus has been to present the feedback about what insurers say they want. We have made progress because the insurers have indicated that they will look at the RFI addendums. The RFI will be standardized for 2006 and it will be Web-based.
Dr. Ascher asked if insurers think they will be held responsible if suboptimal outcomes occur at centers of excellence. Ms. Turrisi said that, indeed, insurers have expressed that concern.
Proposal to Amend Section 301 of the National Organ Transplant Act (NOTA)
The Valuable Consideration Subcommittee (Subcommittee A) presented recommendations related to two issues: valuable consideration and presumed consent.
Ms. Agrawal recalled discussions at the May ACOT meeting about why it would be desirable to get clarification and greater specificity in regard to the broad and somewhat confusing prohibition of valuable consideration in the context of organ donation. This subcommittee proposed that the Secretary seek some authority to define the prohibition on valuable consideration through amendment of existing regulations to provide for beneficial and ethical means to promote organ donation.
Ms. Agrawal drafted some language for a recommendation, which has been reviewed by HRSA staff:
Ms. Agrawal observed that this approach would preclude the creation of a commercial market and it cannot enrich donors. We do not want the rewards to be so great as to generate a coercive effect. We also provided a mechanism for an ethical review of the proposal prior to being put out for the notice and comment period. The effect of this recommendation is to bring the idea of clarifying valuable consideration to the fore. Ultimately, congressional action would be required.
Frank Delmonico applauded this effort because ACOT would be opposing commercial markets in organs for transplantation. Hans Sollinger commented that the recent Denver case plus the fact that some 500,000 people are on dialysis indicate that this measure may not be enough. He commented that a presentation by Janet Radcliffe-Richards in Vienna intrigued him about the idea of having a controlled system operating above the table to monitor what happens. He said that the growing demand for organs in the coming years will likely drive a black market in organs: "We must offer oversight; we cannot just say, don't do it." Dr. Ascher advocated oversight without commercialization. Ms. Agrawal said that the recommendation reflects the opinion of the subcommittee—purchase and sale of organs are not permissible. If we want to consider purchase and sale, then the subcommittee does not want to offer this recommendation.
Bill Harmon asked if this proposed amendment of NOTA would preclude the Wisconsin tax benefit. Ms. Agrawal responded that the Secretary and HHS staff would have to make that determination. In her opinion, that would not be purchase or sale of an organ. Whether it constitutes coercion or purchase/sale would be a question to address. Emily Marcus Levine observed that the Wisconsin law is permissible because it reimburses for donor expenses already allowable under NOTA.
There was some discussion about whether OPOs can help people find matching donors outside the construct of for-profit organizations. The concept of someone being monetarily enriched by donating organs is the problematic area. We need to find an ethical way to bring people together.
Dr. Sollinger said that presently some altruistic individuals are becoming living donors, but the situation is likely to move away from an altruistic approach and to move toward commercial markets in organs, such as those that exist in Pakistan and India. ACOT has heard only one side of this issue and the world does not necessarily agree with the view we are trying to support. Dr. Sollinger suggested that ACOT should invite speakers to present the other side. Several participants suggested moving forward on this recommendation because ACOT has been opposed to pure buying and selling of organs. Nevertheless, ACOT should consider hearing from presenters on the more controversial topic of commercial markets in organs. Dr. Harmon said that this recommendation would allow us to go forward. If we open the question about buying and selling organs today, we will not be able to reach an agreement soon. This step does not prohibit the next step. He noted that some nations (e.g., Kuwait) have reconsidered and eliminated their buy/sell market.
Carlton Young pointed out that we have a limited resource that we are trying to parcel out. We are trying to protect the disenfranchised while trying to implement everything we can do improve organ donation. We must improve the supply side.
Dr. Ascher then moved to insert the word "unregulated" before the word "commercial." Dr. Sollinger seconded the motion. Ms. Agrawal called for further discussion. Ms. Agrawal cautioned that such a modification of the proposal might imply the obverse of the statement's intent. Dr. Delmonico said that if we open the door for a regulated market, then we will be going back to ground zero. Dr. Ascher responded that we do not know where this field is going. Adding the word "unregulated" gives us some modicum of control. Dr. Harmon said he agreed with Dr. Delmonico, that this recommendation will be a lightning rod if accepted. Ms. Turrisi suggested taking out the word "commercial." The word "unregulated" is important. Ms. Solarz said that substituting this language is likely intended to give us flexibility down the road because it takes so much time to get a regulation through the process. Nevertheless, this is a slippery slope. Those who are disenfranchised by our health care system would be exploited. It would be anathema to allow people to sell pieces of themselves, even in a regulated situation. She said she would not back this proposed modification. It pains her to think that our system could encourage selling of organs even if regulated. We must be above that. We have an organ shortage, but we cannot have people risk themselves because they do not have what they need.
Dr. Sollinger said that it is not necessarily true that the poor and disadvantaged will bear the brunt of this (buying/selling of organs). But, that does happen every day. Think of how many of the rich and famous are serving in Iraq. He expressed concern that we are facing an eventual black market in organs. It has happened already in so-called civilized countries. We must be realistic. We have been very unilateral, but we must expand this discussion.
Amadeo Marcos stated that it is the transplant center that has the ultimate control in preventing black markets. Dr. Delmonico said that the American Society for Transplantation has discussed a commercial market in organs, but has expressed its opposition. The Congress considered it via Senator Frist's bill and rejected it. It was rejected by Senator Kennedy's staff as well. Just because a black market might be coming is no justification for creating a regulated market in organs, according to Dr. Delmonico.
Ms. Agrawal called a vote to amend the language in the proposed recommendation by inserting the word "unregulated" before the word "commercial." The vote was 4 for, 9 opposed, 2 abstentions. The motion failed.
Ms. Agrawal called a vote to adopt the recommendation as originally written (and reproduced above). The vote was 15 for, 0 opposed, 1 abstention. The motion passed, and the recommendation was adopted as written.
Ms. Agrawal recalled that Phil Berry has previously presented to ACOT on the topic of presumed consent. Moving toward a presumed consent model would have to be done at the State level because the Uniform Anatomical Gift Act (UAGA), which make provisions for consent is a State law, not a Federal law. The subcommittee proposes language for a recommendation to encourage the Secretary to support State initiatives for demonstration or pilot projects for making anatomical gifts under a presumed consent model:
Ms. Agrawal envisions that a State could come to HHS with a proposal and bring the design to the Secretary with parameters and safeguards. The Secretary and staff would review the proposal. The object would be to see if these programs might increase the supply of organs.
Dr. Berry moved to approve the recommendation. Dr. Delmonico seconded the motion. Ms. Agrawal opened the floor for further discussion.
Susan Gunderson moved to change the words "consent to an anatomical gift" in the last sentence to "authorize an anatomical gift." Dr. Berry seconded the motion. Ms. Agrawal asked for discussion. She said that under a presumed consent model it is different from an anatomical gift. The default position is non-authorization. Mr. Seely warned that the phrase "presumed consent" has been used for years now. We do not want to muddy the waters or distract from the important issue at hand. Ms. Gunderson suggested changing only the last sentence and not the title of the recommendation.
Mike Seely said that States that have registries in place might be able to see if a presumed consent model would affect donation rates. Dr. Berry mentioned that he celebrated his 18th birthday last week (18 years since his liver transplant). More than 87,000 people are on the waitlist for livers now. We must look at alternatives. It is speculated that presumed consent or presumed authorization might be better, but it is mere speculation until we do it. Any State that has the wherewithal to make it happen should be allowed to do so for several years to be an adequate test to see once and for all whether it makes a difference. If a handful of States undertake such demonstrations and show a positive change in donation rates, then we can say that presumed consent is a viable alternative to what we are doing now. Until we do the studies, we will keep talking about it. It is time to see if it will work.
Ms. Agrawal called for a vote on proposing the recommendation with the following change: In the last sentence, change the words "consent to an anatomical gift" in to "authorize an anatomical gift." The vote was 14 for, 0 opposed, 0 abstentions. The motion passed, and the recommendation was adopted as amended.
Report from HRSA's Independent Expert Panels on Statistical Methods for the Analysis of Organ Transplant Data: Analytic Methods and Simulation Modeling
Gregory Fant said that ACOT's role in increasing the public's confidence in the integrity and effectiveness of the national transplantation system requires current and reliable analytic data on which to base decisions. HRSA is committed to ensuring that the analytic results relied upon in the decision-making process are current, correct, and reliable.
To that end, HRSA is charged to enter competitive contracts to provide analytic and simulation-modeling support. The proposals are evaluated according to their technical merit. The contract is presently with SRTR. SRTR works with OPTN committees to better understand the statistical nature of the research questions of particular committees and then employs the most appropriate statistical methods to address research questions. HRSA monitors the SRTR contract, not only to verify the completion of contract deliverables, but also to assess the content of the analysis submitted by SRTR.
As part of the ongoing commitment to ensure that analytic results are current, correct, and reliable, HRSA convened two panels of independent statistical experts to review and assess the analytic methodologies and simulation modeling developed and utilized to serve OPTN and ACOT. The two independent expert panels (IEPs) were held in Chicago from September 19 through 21, 2004. Dr. Fant provided biosketches of the experts and agendas for both sessions.
Both HRSA and SRTR made presentations to the panel members. OPTN also made presentations regarding simulation modeling. The panelists listened to the presentations and asked relevant questions. As part of the process, some preliminary findings were presented to the Scientific Advisory Committee on October 12, 2004. Many of the issues and related questions were highly technical. The panels are still working on their consensus documents, but Dr. Fant presented the highlights of their recommendations. (Dr. Fant will provide the final consensus documents to Mr. Balbier when they become available.)
Insofar as analytic methods are concerned, the IEP indicated that:
The highlights from the IEP report on simulation modeling pertain to several different topics:
The IEP offered some overall impressions in regard to analytic methods. First, the panelists said that the statistical approaches used by the SRTR to analyze data are standard and state-of-the-art methods widely used by statisticians. Second, they note that other innovative, cutting-edge methods are also being developed.
The simulation modeling IEP stated that the Simulation Allocation Models (SAMs) developed by the SRTR for liver (LSAM), thoracic-heart/lung (TSAM) and kidney-pancreas (KPSAM) represent appropriate modeling approaches. They appear to be reliable and useful. All three SAMs have undergone various levels of validation and are still evolving, as is to be expected.
Dr. Fant reminded the group that the responsibility for the assurance of the quality of the analysis belongs collectively to ACOT, OPTN, HRSA, and SRTR.
Dr. Gibbons commented that convening a group of statisticians who have not done work in this area has overlooked the problem of highly competing risks. If one tried to add up the probabilities from many SRTR analyses, they total more than 1. The other thing that is so unique about this area that would be missed by the IEPs is that this is a nested problem. Centers are nested within OPOs. Centers and OPOs do things in their own ways. They exhibit different degrees of aggressiveness in transplantation and procurement. The effect of geographic variability may be small or large. Which factors predict OPO variability and center variability? It may be possible to find associations in the data that do not really exist because the variability is understated. SRTR has raised the bar in the analyses from where they started. Dr. Gibbons said that it is critical to educate the independent expert panels about the field and the process to learn what issues are important.
Dr. Fant reminded the group that he was presenting only the highlights of the IEPs' initial findings. He said that the IEPs are indeed addressing the key issues of competing risk and informative censoring. In fact, there were two presentations on these issues at the Chicago meetings. Fritz Port further noted that SRTR has a new method to deal with informative censoring.
Some Additional Topics
Dr. Burdick briefly addressed the dilemma of how to measure the impact of activities related to organ donation awareness and acceptance. This dilemma highlights the successes of the HHS Breakthrough Collaborative. Many activities are underway nationwide to improve donor education and information. Conversion rates are improving even in hospitals that are not participating in the Collaborative, perhaps because of the Spread Initiative. This is an issue that researchers must deal with: isolation of the effects of a given initiative.
On another topic, Dr. Burdick noted that one requirement in the Frist bill was for a study of the ethical impact of efforts to improve organ donation. The Institute of Medicine (IOM) is to carry out a wide-ranging and intensive study. The IOM will be asked to assess interventions so that we could begin to think to the extent about how a given process is making a difference. An example is the presumed consent model that was just voted on. We could find out if it works and then replicate it. A challenge to the IOM is to tell us the impact of what we are doing.
Roger Evans said that many of these same issues arise with quasi-experimental designs. The other problem is that continuous improvement has its own problems (e.g., whether one can sustain the gains). Attributing causality is very difficult. Dr. Evans further noted that the wide-ranging and far-reaching activities associated with the Collaborative complicate the task of making new grants because of the challenges of evaluation.
Friday, November 5, 2004
Update on the HHS Breakthrough Collaborative and the Latest Secretarial Organ Initiative
Dennis Wagner and Virginia McBride
Mr. Balbier welcomed the presenters and introduced Dennis Wagner and Virginia McBride who head up the HHS Breakthrough Collaborative, which has been a tremendous success. The Secretary has recognized their work and recently bestowed the Distinguished Service Award on them, along with Lorah Tidwell and Jade Perdue from the Division of Transplantation. The AOPO also presented Mr. Wagner and Ms. McBride with the Executive Director's Award.
Mr. Wagner explained that a collaborative is an intensive, full-court press to facilitate breakthrough transformations in the performance of organizations based on what already works. The HHS Organ Donation Breakthrough Collaborative is committed to saving or enhancing thousands of lives a year by spreading known best practices to the Nation's largest hospitals to achieve organ donation rates of 75% or higher.
The first collaborative involved 95 hospitals, and 43 OPOs. The second collaborative comprises 131 hospitals, and 50 OPOs, plus 50 or so teams participating via satellite. The participating large hospitals account for approximately 50% of the donor potential in the Nation.
Mr. Wagner then presented some typical results achieved by hospitals participating in the Collaborative. The Washington Regional Transplant Center had 14 donors in October compared to its monthly average of 8. Their record is 18. Their conversion rate is usually in the range of 30% or 40%. Since the September learning session, five of six eligible donors were converted.
In the Midwest Transplant Network, four of the five hospitals that participated in the first Collaborative achieved average conversion rates of 75% or greater. The hospitals in the network increased the number of DCD donors from three in 2003 to 24 in 2004. Hospital team members from the second Collaborative resolved to pursue DCD at the September learning session and had already accomplished two DCDs by October 10.
One of the hospitals affiliated with the University of Wisconsin OPO and T.E.A.M. improved conversion rate from 50% to 77%. The Theda Clark Medical Center improved its conversion rate from 71% to 94%. This hospital achieved the Nation's longest streak of 20 donors before nondonor and is still going. (The number of donors before a nondonor is a measure collected by the Collaborative of consecutive successful donor requests.) The number of DCD donors increased from one or two per year to a total of nine in 2003 and six in 2004. The hospital is adding staff and making some operational changes to accommodate the increased number of donors.
The University of Wisconsin-OPO is on pace to break the record number of donors per year, again. Notable with this team is the involvement of the surgeon community. This appears to contribute to their results. Dr. Sollinger said that Tony D'Alessandro, a transplant surgeon, was appointed to the OPO. He is unusually committed. Much credit goes to him, and the OPO is situated next to the clinic. The members of the OPO see the successful patients walk by every day. They are reminded daily of the good they do. He suggested that other hospitals invite the OPO staff to make rounds, visit the clinic, and so forth in order to see the fruits of their work.
Virginia McBride reviewed some Action Period 3 results and said that the Collaborative's new process measures reflect a new practice and a greater urgency to refer to OPOs timely.
The new practice is making appropriate requests; i.e., the right person, the right time, in the right way. It may be that the request involves one person or several. The requestor may be the OPO, surgeon, social workers, or others. The appropriate request rate in the Collaborative hospitals has gone from about 75% to 90%. Right now it is around 82%.
For the year prior to the Collaborative, nationwide conversion rates hovered around 50%. Since the initiation of the Collaborative, conversion rates have trended upward. In October 2004, conversion rate was 62%. There remains a need, however, to continue to widen the gap between the number of "yes" and "no" responses to the request.
Another goal of the Collaborative is to decrease medical examiner denials. During the last quarter, for the 95 teams in the Collaborative, only three such refusals have occurred. Coroners have been invited to join the Collaborative.
Ms. McBride said that another measure is for hospitals to get to a 75% conversion rate — one month at a time. For the July-September 2003 quarter, only 17% made the 75% goal, but in August 2004, 70% made the goal. For the first time, the Nation is going over 600 donors per month nationally.
She made the point that increasing organ donation is all about the "ones":
Mr. Seely commented that in his local area, one of the most remarkable things is that they are measuring things in a tangible way. That information guides the area hospitals and helps them discern where to push and where to put resources.
Dr. Higgins said that one of their administrators came back from the learning session very excited, saying that it had been an almost evangelical experience. He noted that the hospitals in the Collaborative are already committed and high performing. He said that the best practices need to be catalogued and disseminated to every hospital in the country because conversion rates in non-Collaborative hospitals need to be targeted more. That would make a real impact on nationwide conversion rates. Ms. McBride said that 60 hospitals are participating in the Spread Initiative. An ever-widening circle of hospitals is being impacted by the Collaborative. The process and outcome measures are becoming standards of practice.
Dr. Higgins asked if there is a legitimate reason not to donate. In many respects, 100% donation would be ideal, but are there any legitimate reasons why a person should not be a donor? Ms. McBride responded that the Collaborative's goal is to achieve 75%, a reflection that there are legitimate reasons not to donate. The success of the Collaborative is based not on barriers, but on successes. It is a very positive approach. Carlton Young said that these results are great, but what about the hospitals that are not be achieving the set goals? Do they get feedback? Ms. McBride responded that the Collaborative is in partnership with JCAHO and UNOS. Every hospital CEO gets an e-mail stating what the hospital's monthly conversion rate is. The CEOs can compare their performance to others'.
Mr. Seely said that they use the Collaborative's results to quickly realign by tapping into veins of information. The Collaborative provides a context and framework for change that often is not easy. Nevertheless, such changes allow us to transplant more patients and serve the public by getting us organized. Ms. McBride listed six high-leverage changes that can make big changes in conversion rates:
These changes are all necessary for a successful donation program. In successful donation programs, physician and clinical champions are known. A process is in place for conducting real-time death record reviews. The OPO presence is manifest in the hospital, often through an in-house coordinator. Focused change agenda is based on analysis of current hospital data. Team huddles are the norm, during which all the important players meet and talk about how the donation situation will be handled. Clinical triggers are in use. After-action reviews are the norm. Effective requesting is in place and in action. These pieces were all in place after the first Collaborative.
Mr. Seely said that the Collaborative is yielding results. It would be a shame if this effort lost its momentum at the end of the funding cycle. He advocated appropriate funding to keep this going. He suggested the possibility of tracking data from the first Collaborative for 5 years, not just one.
Dr. Marcos applauded the Collaborative's DCD effort. Every hospital should offer DCD as an option, although the practice is not accepted everywhere. He noted, though, that DCD must be accepted by transplant programs. Ms. McBride said that the OPOs must recognize that even if local programs do not use DCD organs, other programs do and the local programs still have an obligation.
Ms. McBride showed a video on mastering effective requesting in culturally diverse communities. It demonstrated the importance of diversity training to learn about differences in grieving processes. Trust is the key. Minority requesting works. The requestor does not necessarily have to look the same as the family does, but the requestor must be aware and sensitive. The teams receive copies of all the videos.
Dennis Wagner said that the teams have learned what works and have implemented those practices. He said that 50% of donor potential resides in 226 hospitals. There are about 6,000 hospitals in the United States. The Collaborative is seeking to increase the donor pool in the country through the Spread Initiative, which is aimed toward non-Collaborative hospitals. The OPOs and hospitals have identified 90 people to be Spread leaders for the country. They are leaders in their donor service areas (DSAs). They meet periodically. A knowledge management system (Web-based) will be used to track implementation.
Dennis Wagner said that the teams have learned what works and have implemented those practices. He said that 50% of donor potential resides in 226 hospitals. There are about 6,000 hospitals in the United States. The Collaborative is seeking to increase the donor pool in the country through the Spread Initiative, which is aimed toward non-Collaborative hospitals. The OPOs and hospitals have identified 90 people to be Spread leaders for the country. They are leaders in their donor service areas (DSAs). They meet periodically. A knowledge management system (Web-based) will be used to track implementation.
He concluded with two final sets of data. During the time period of the Collaborative, participating hospitals have achieved 19% increase in organ donation; nonparticipating hospitals achieved a 7% increase. Not all of these increases are due to the Collaborative, but it is likely that a substantial portion is.
Report on Transplantation Extramural Grant Program
Mary Ganikos (Chief of the Education Branch) invited two grantees to speak about their work. Sheldon Zink of the University of Pennsylvania and Susan Morgan of Rutgers presented. One program is geared toward increasing intent to donate, and the other is aimed at increasing consent rates in hospital. One is community-based, and the other is hospital-based.
Ms. Ganikos said that the Division of Transplantation has three grant programs:
The Division requires that grantees utilize a consortium approach. Some beautiful teamwork has developed as a result. The programs must have a scientific design and include a rigorous evaluation component. The Division identifies performance measures that each program must approach. The programs must measure impact on consent (hospital-based programs) or the impact on intent to donate with verifiable family notification (community-based programs).
Ms. Ganikos described two new 2004 projects:
Each application is reviewed by a technical review panel. The Division offers technical assistance workshops and pre-application workshops. The programs address different settings and populations. Target populations have been general and minority. Diverse topic areas have been proposed and studied. She distributed some project findings via handouts.
Ms. Ganikos reviewed some general lessons learned:
In terms of lessons learned from consent (hospital-based) programs, Ms. Ganikos pointed out that:
Public education studies, according to Ms. Ganikos, have shown that:
Lessons learned from school programs include:
The Division funds three types of programs: pilot studies, replication studies, and roll-out studies. Program results are being publicized through journal articles, grantee publications, the Breakthrough Collaborative, the North American Transplant Coordinators Organization (NATCO) annual meeting, Progress in Transplantation journal, and OPTN communications.
Dr. Ascher asked why no data were available for projects begun in 2001. Ms. Ganikos replied that the three-year projects were funded in late September 2001. They then had to go through the institutional review board process. Data will likely be available in next 4 or 5 months. Most grantees requested no-cost extensions. She did note, however, that one project begun in 2000 is behind schedule.
A Study of the Presumptive Approach to Consent for Organ Donation
Sheldon Zink spoke about the presumptive approach to consent. The premise of the research is that given the opportunity to save a life, most people would do it. Organ donation is the right thing to do. She said that their primary research objective was to examine the effectiveness of the presumptive approach to increase the probability of consent for solid organ donation.
The study was assisted by an external advisory committee, consisting of 11 experts in the field of organ procurement and transplantation, communication, psychology and donor family representatives. In collaboration with a linguistic anthropologist, the committee worked to develop appropriate language for presumptive requests. (Dr. Zink mentioned that she will make available copies of their training manual upon request.)
They worked out a flowchart depicting the consent process, highlighting the points where there are opportunities for presumptive approaches. Dr. Zink outlined the major components of the presumptive approach:
First is the intention to be presumptive. The requester should not focus on the family's possible responses. The requester should serve as the voice of the recipient and guide the family toward the goal of donation. It is important to use open-ended questions to keep the conversation going and obtain a series of "small" yeses throughout the family discussion.
Second, the presumptive introduction represents a subtle but important shift for the family. The idea is to present organ donation as a normal step for families.
Third, the presumptive transition elicits empathy for potential recipients and helps the families focus on the good that could come from their tragedy. It pairs loss with gain, death with life, tragedy with heroism. The transition helps the family move from death to a positive look forward to a hopeful future.
Fourth, the transplant coordinator's role shifts to one of an advocate for both the recipients and the donor families. This helps the family to see the decision as the right thing to do by allowing them to understand the great benefits of donation. Dr. Zink mentioned that mentioning potential recipients to donor families had been considered taboo because of possible guilt feelings that may arise if donation is denied.
Fifth, presumptive phrases serve as strong affirmations of donation and help the family be confident in their decision to donate. The requester should use phrases such as "when you donate" (instead of "if you donate").
Sixth, the presumptive ask is an affirmative movement toward donation, open-ended, and focuses on moving forward in the consent process. It also reduces the stress on the family in their time of grief. The requester uses language like "Are there any final questions you would like me to answer before we continue?" This step is a trigger to start the psychosocial paperwork.
Dr. Zink described their research approach used to gauge the effectiveness of the presumptive approach. She encouraged ACOT to develop standard definitions for such terms as "donor potential," "consent rate," and "eligible donor." She noted that data collection will end in December 2004 and then showed some of their preliminary data. Among their findings:
Dr. Zink concluded by saying that the best practices initiative is working, but the idea of solid research is critical. We need to identify best practices for the OPOs. We need to sort out the Hawthorne effect, and we need transparency of data. She noted that the Collaborative's data and AOPO data are not made available.
Public Education through Worksite Interventions
Susan Morgan said that some people feel qualified altruism; they want the recipient to be deserving of a donated organ. She is working on the public education end. Their studies are funded through the Division of Transplantation. Each project builds on the findings of the project before. Dr. Morgan mentioned studies of three worksite campaigns (quasi-experimental design):
For worksite campaigns, Dr. Morgan said that they are developing principles and procedures for constructing effective worksite campaigns, which include the following:
Dr. Morgan highlighted some findings of their studies. Theory-driven campaigns are effective in improving knowledge, attitudes, and behaviors relevant to organ donation. Nevertheless, there are previously unexamined factors that are barriers to the willingness to donate. One of the most important barriers, identified during studies of family communication about donation, is the mass media. (Several publications describing these studies and their findings have appeared in national journals and presented at conferences, garnering two Top Paper awards.) She suggested that these findings may be of interest to ACOT.
There is much published literature on donation attitudes. Dr. Morgan said that they have learned from qualitative investigations of how families communicate about organ donation that medical mistrust is a significant barrier to donation. Families often cited the source of their misinformation as the mass media. Television shows such as "ER," "Law and Order," and daytime dramas tend to be the worst offenders. People have many questions about deservedness of recipients.
Persuasion research demonstrates that people suspend their disbelief when viewing entertainment media and engage in little critical thinking. Effective national counter-campaigns tailed to the messages the public receives from mass media must be constructed.
Their studies have shown that people do not trust medical/organ allocation systems. People are questioning whether recipients are deserving of donated organs. Many people insist that a black market in organs exists. They believe that doctors kill people for their organs.
Dr. Morgan screened a brief video of a dyad family example. The people referred to the movie "Coma" and to a "Law and Order" episode. The television news media are sensationalistic. The coverage of the Jessica Santillan case emphasized that she was an illegal alien and, therefore, undeserving of an organ. ABC News did an in-depth report on brokering organs for rich people who go abroad for transplants.
She spoke about a storyline from "One Life to Live" that involved a surgeon getting organs from his patients and selling them to the highest bidders. She noted that 19 major movies made since 1970s contain myths about organ donation, which play into people's fears. The media perpetuate and exploit people's fears. We need campaigns to counter these myths.
Dr. Morgan recommended the following actions:
She concluded by saying that development and funding of theoretically grounded and targeted organ donation campaigns should be increased. Worksite campaigns have the potential to reach a large percentage of the public. Media framing of organ donation should be addressed to stem the source of misinformation.
Ms. Solarz asked if the next cycle of grants will be based on learnings from the first cycle. How can we maximize that information? Ms. Ganikos replied that one way is to publish so as to build a body of literature. Because these are three-year projects, one cycle really cannot build on the next. She said that they want to hold a program with a summit to spread the results of the grants. She also said that they are posting information on their Website to disseminate the results from these programs. When reading the applications, the reviewers look to see if the applicant is aware of other research in these areas.
Dr. Sollinger observed that the donors' doctors could have profound effects, but we have not targeted them. He said that some health care workers (especially physicians) are major villains when it comes to falling short of our potential. He asked if the Collaborative is planning to address this. Ms. McBride replied that doctors want to be part of the solution. Teams are encouraged to identify doctor champions on their hospital staffs. Representatives from the Society for Critical Care Medicine and the Critical Care Society have been champions and encourage development of other champions.
Dr. Evans said that "with continuous improvement once you get started, you don't stop. Improvement is not a destination." He expressed concern that we have to keep the momentum going. He said that because most of the activity is going on with the Collaborative at this point, that it may be time to relegate funds to the Collaborative. He said that hospital-based projects are probably futile as long as the Collaborative is going on. Community projects should continue, though.
Dr. Zink noted that with her hospital-based study was aided by the Collaborative because of more referrals, hence more subjects for her study. Some projects, however, have complained of data contamination. She attended the Collaborative's Learning Session 1 to learn if it might affect her study. She said that it is important for the Collaborative to be transparent about what they are doing so that researchers can control for it. Dr. Evans responded that if the Collaborative is accomplishing what it says it does, we have to face budget realities. Dr. Ascher suggested that this topic merits further discussion.
Subcommittee C: Waitlist
Mr. Seely thanked members of the subcommittee for its productive conference calls and discussion yesterday. The focus of this subcommittee is fourfold: (1) burden of disease; (2) heart utilization; (3) kidney waitlist; and (4) whole-body donation.
Burden of Disease
Burden of disease (BOD) has been the subject of discussion at several OPTN meetings, the last ACOT meeting, ACOT subcommittee meetings, and independent expert panels. The Waitlist Subcommittee proposed the following recommendation:
It is hoped that this recommendation captures the spirit of what was discussed yesterday and gives direction to the entities that are looking at burden of disease. Mr. Seely said that ACOT can take these elements of BOD to look at endpoints that are different from what we traditionally look at. Ms. Solarz recalled that during the breakout session, the subcommittee had a very involved discussion about pushing more toward BOD in some sort of quality of life (QOL) model. Dr. Ascher said that BOD has to include QOL endpoints plus other elements (e.g., hospitalizations, mortality). Ms. Solarz emphasized importance of incorporating patient standpoints. Mr. Seely emphasized that this is the point of this recommendation. Dr. Evans said that the transplantation community would not be served, for example, by using the standard SF36 instrument used as a QOL indicator.
Ms. Turrisi said that ACOT has previously recommended that transplant centers use some sort of QOL indicator, but there seems to be little agreement about what we need to be looking at. Many things still need to be worked out. Mr. Seely pointed out that no consensus exists yet on this point. OPTN will continue discussion on these points, but this subcommittee cannot do any more on this issue. Ms. Turrisi asked that we do not let QOL "get lost in the shuffle." Dr. Evans said that it would likely be useful if this subcommittee has continued input even as the subcommittees are reorganized and new ACOT members are brought on board. We are all concerned about QOL. He suggested that ACOT continue its involvement with QOL issues for transplant recipients. Mr. Balbier noted that HHS will develop an implementation plan for this recommendation, as it does for all ACOT recommendations.
Dr. Evans moved to approve the recommendation, seconded by Ms. Solarz. The vote was 14 for, 0 opposed, 0 abstentions. The recommendation was approved as written.
Mr. Seely recalled that Bob Higgins spoke to his peer group about heart utilization rates and organ wastage at a recent meeting of cardiac and thoracic surgeons. He noted that heart utilization rates vary from center to center, and from DSA to DSA. The question is why. Utilization rates vary according to OPO performance, surgeon preferences, and so forth. It is a complex issue.
Recently, the OPTN Thoracic Committee put out a policy for comment by the regions and public to widen the sharing area for status 1 patients. The intent is to increase utilization. Presently, 100 or more hearts per year are going unused. By widening the sharing area, immediate utilization by status 1 patients would be increased. Twenty-two percent of DSAs do not do match runs for placing hearts. It is possible that some diagnostic tests performed on the potential donor may have shown that the heart is compromised in some way. Changing the allocation strategy as modeled by SRTR would allow 112 more transplants per year and 20 more deaths. There is a net benefit. We see this change in the sharing area as a positive step in utilizing more donors. The rub is that there has been pushback from the regions regarding this policy; they have not seen this potential change in a positive light. According to Mr. Seely, the challenge at OPTN level will be to look at this proposed change and decide whether to implement it.
Ms. Turrisi emphasized the importance of balancing outcomes other than graft and patient survival. Where is the benefit of transplant if the patients are confined to a hospital for their remaining lives? Ms. Solarz concurred, saying that if we give someone an organ and the person dies 3 months later, we have not given a life-saving organ. It is a very traumatic and difficult time. The patient and family must prepare for both life and death. To give an organ and restore their hope only to have the patient die causes unspeakable pain. Yesterday, this subcommittee talked about balancing mortality and other outcomes. We must think much more critically about that.
Dr. Sollinger noted that heart utilization is suboptimal. Why do we look at wider sharing before we look at heart utilization? Common sense dictates says that we only ask for shipping if we do not have organs at home. We need to make sure we are using the hearts that are already there. Mr. Seely observed that the aggressiveness and size of programs differ widely. Heart failure treatment has changed drastically. Waitlists vary greatly. Dr. Ascher said that this discussion is moving away from the context of the discussion that occurred during the breakout. The idea was to institute local review, as well, to learn about why only half the viable hearts available in a region are being used. OPTN has to figure that out. This is a broad recommendation. The recommendation would encompass all these pieces.
Ms. Gunderson noted that organ yield will be addressed by the HHS Organ Donation Breakthrough Collaborative. That initiative will be relevant and important for heart utilization. Dr. Sollinger said that the Collaborative will have a positive impact only if the initiative is tackled in the right way. For example, if an OPO only takes the best organs from the best donors, their numbers will look great. It is important to look overall (e.g., usage of DCD and ECD). Dr. Higgins said that the other issues on the table were considerations of program performance, surgeon preference, and availability, local review of turndowns at the regional level—all mechanisms to increase heart utilization. The vehicle for this discussion is much more complex.
Mr. Seely proposed the following recommendation:
Dr. Higgins moved to approve the recommendation, which was seconded by Dr. Ascher. The vote was 14 for, 0 opposed, 0 abstentions. The recommendation was approved as written.
Mr. Seely said that the subcommittee has no specific recommendation to offer at this time. ACOT should continue monitoring the related activities being undertaken by the OPTN taskforce, the CMS panel, and SRTR. The subcommittee members requested routine reports from these bodies to ensure that issues of the kidney waitlist are being addressed. The OPTN taskforce will meet over the coming year. Its members are committed to work together for some time. Other projects (CMS) are dealing with how patients get from dialysis to transplant. Ongoing efforts of SRTR are aimed at providing information to ACOT and other OPTN committees. Much work is underway. Although there does not appear to be a need for a recommendation, the subcommittee wishes to monitor the situation and be kept informed via meeting minutes.
Mr. Seely stated that this subcommittee wants to keep the whole-body donation issue alive. The concern we have is that when an untoward event is covered by the media, there is a big impact on what we do in transplantation. It casts a shadow. This has been going on for years. We get excited and then forget about it until the next event occurs. There is a public safety issue, as well.
No single regulatory body has oversight over this area. Perhaps whole-body donation lies outside our purview, but our recommendation is for strengthened HHS oversight and greater accountability. Dr. Ruth Solomon confirmed that the FDA does not have control over human tissue for study. The FDA would become involved only if there was crossover and some tissue for study was transplanted or used for treatment. Dr. Young asked if there is regulation governing disposition of bodies. Mr. Seely responded that such regulations vary among the states. Some states have laws about transporting bodies over state lines. Dr. Burdick said that it is true that there is no clear, general oversight or potential for oversight. It would be helpful to have the Secretary advised by ACOT that this issue needs to be addressed. We have a great interest in getting this straight.
Dr. Seely proposed the following recommendation: Provide strengthened HHS oversight for whole-body donations. Ms. Turrisi suggested removing the word "strengthened" because at present there is no oversight. Emily Marcus-Levine (Office of the General Counsel) said that various provisions could be construed as giving HHS some oversight in light of public health concerns. Ms. Turrisi moved to approve this reworded recommendation:
The motion was seconded. The vote was 13 for, 0 opposed, and 0 abstentions. The recommendation was approved as rewritten.
Ms. Turrisi presented in the absence of the subcommittee chair Bill Harmon. There were seven subgroups handling the various agenda items for this subcommittee: (1) nondirected donors; (2) special needs of pediatric patients; (3) quality of life; (4) extended criteria donor (ECD) organs; (5) reasons for organ refusals; (6) minimal listing criteria; and (7) unfairly treated groups. Ms. Turrisi focused on special needs of pediatric patients, nondirected donors, ECD organs, and unfairly treated groups.
Special Needs of Pediatric Patients
Ms. Turrisi noted that children have been provided preference by OPTN deceased donor allocation policies. The incidence of end-stage organ disease in children is low and is not increasing. Children represent a minority of organ transplantation candidates. Traditionally, society has provided preference for children in its laws and customs. Therefore, this subcommittee makes the following recommendation:
Dr. Ascher said that what is going on with pediatric liver patients is different from what is happening with pediatric kidney patients. Dr. Sollinger agreed, saying that the focus of this recommendation is on kidney transplantation. Ms. Solarz observed that there have been three pediatric donations for every pediatric transplant; in other words, children have been giving more organs than they have been receiving. Dr. Ascher said that she would have a problem granting preference to an 18-year-old over a 21-year-old. She said she did not understand the rationale behind this recommendation in light of the fact that OPTN has already built in a preference for children for livers, kidneys, and hearts. Ms. Turrisi said that Dr. Harmon wants to continue the preference even if people are waffling. Ms. Marcus-Levine said that there is a provision in NOTA that requires addressing the special needs of those less than 18 years old.
Ms. Turrisi called for a vote on the recommendation. The vote was 1 for, 7 opposed, and 5 abstentions. The recommendation was not approved.
Ms. Turrisi said that individuals offering nondirected organ donation should not be subjected to any sort of coercion. Payment for organ donation is illegal in the United States. Reimbursement for medical and related expenses, including housing, travel, and lost wages is acceptable and encouraged. In fact, a grant was approved for supporting reimbursement for travel and expenses. Congress must approve this every year. Some insurance companies are not paying for donor workups.
Furthermore, this subcommittee believes that the nondirected donor should be able to choose the hospital where the donation procedure occurs. The allocation of the living, nondirected donor organ is under the stewardship of the transplant community in the same manner as deceased donor organs.
Therefore, the Fair Treatment Subcommittee made the following recommendation:
Dr. Delmonico said that donors may go either to the OPO or to a particular hospital. Allocation would depend on where he or she goes. Ms. Turrisi said that if the donor approaches the OPO, then the OPTN criteria should be followed insofar as assigning the organ to someone. Dr. Young said that in some regions, the issue of cold ischemia time would eliminate the advantage of getting a living-donor organ. Dr. Delmonico said that individual OPOs should develop policies on how to handle nondirected donors. There needs to be a standard, transparent, objective way of assigning the organ using the list. Ms. Turrisi said that the subcommittee left the recommendation's wording rather general because so many things are going on in turns of organ swaps and so forth.
The appropriate allocation unit for a nondirected donor organ should be a small geographic unit, so as to minimize cold ischemia time and maximize the benefit of using a living donor. The unit might legitimately be the transplant center or the city in which the transplant center is located. The unit of allocation should be determined prospectively by the OPTN.
Ms. Turrisi went on to propose another recommendation related to nondirected donations:
Some discussion ensued. Dr. Delmonico said that preferences are awarded to children in many aspects. It is not a discriminatory practice if someone wishes to donate to a child. We do not want to outlaw designation of a child as a recipient of a living-donor organ. We do not, however, want to endorse discrimination by gender, social status, or race/ethnicity. Ms. Solarz observed that several people during the breakout session related anecdotes about people who wanted to give to certain patients based on medical diagnosis. She suggested rewording the second sentence to read, "a group of patients with a specific medical condition." Dr. Burdick opined that the last part of the recommendation is the most important. Ms. Marcus-Levine suggested including the fact that this recommendation pertains to living donors.
Ms. Agrawal asked for some clarification. Is the overarching recommendation that the OPTN should develop criteria for the allocation of nondirected living donor organs? Ms. Turrisi responded that such is the case, plus we want to preclude nondirected living donors from stipulating to whom they want the organ to go. Ms. Solarz said that the issue for OPTN is to decide on the size of the allocation unit. We all want the criteria to be followed as for a deceased donor. Should the match run be to the hospital or to the OPO? It should be a structured process, not haphazard.
After further deliberations, the group modified the wording of the recommendation thus:
There was some subsequent discussion about offering views on what the allocation policy should be. Dr. Delmonico moved to add the following sentence to the recommendation: ACOT is to provide guidance to the Secretary on the criteria for such an allocation policy. The motion was seconded. The vote was 3 for, 9 opposed, 1 abstention. Therefore, the proposed amendment was rejected, and the recommendation was approved as originally written.
Extended Criteria Liver Donors
Ms. Turrisi said that the analysis by SRTR does not support the hypothesis that there should be specific allocation of ECD livers based solely on donor characteristics. SRTR looked at combinations of donor and recipient characteristics that led to greater rates of primary nonfunction (PNF). SRTR is requested to define recipient characteristics that might result in poor outcome of liver transplantation from ECD donors. The subcommittee discussed hospitalizations and other outcomes that might be important in addition to PNF and 1-year survival rates. Using ECD organs costs more. The subcommittee wants CMS to look at those additional in terms of reimbursement.
Dr. Delmonico said that the ECD criterion is a moving target. To make an ECD definition for allocation policy would be very difficult. Some liver donor characteristics, steatosis and age for example, are important for informed consent. Insurance factors also must be considered. Ms. Turrisi said that this is important work that needs to be done. Dr. Sollinger said that he is interested because of the cost of using ECD organs and because of donor utilization issues. Some centers shy away from ECD organs just because of their cost, which results in underutilization of organs. ECD donors cost 2 or 3 times more. Dr. Delmonico noted that New York has highest use of ECD organs, but that State has the highest retransplantation rate, as well. Dr. Sollinger said that centers using ECD organs should be rewarded. Using ECD organs does not necessarily involve higher retransplantation rates. It is much more work, however. Ms. Solarz said that the next part of the SRTR analysis involved the transplant recipients of ECD organs. We are going to continue with the analysis and try to get a better understanding. She asked that the participants send their comments and questions to the subcommittee.
Unfairly Treated Groups
Ms. Turrisi stated that Medicare-only patients who are on the waitlist are having difficulty because of the money they need for co-pays and medications. She also spoke the reluctance of some states and transplant centers to accept Medicaid-only patients because of low reimbursement rates. She also spoke about the 45 million uninsured in this country. Those who fall into this category must engage in fundraising if they need an organ transplant.
Centers also face the challenge of rising standard acquisition charges (SAC). Many OPOs pay 100% to hospitals to procure organs. These costs are passed on to the centers. We are going to out-price transplantation if we don't take some steps now. We need to think about how we are going to do business in the future. Mr. Seely observed that market forces vary across the country. We would have to be careful about how we do capitation. Many things are beyond our control. Few economic issues have prevented us from pursuing a donor. Ms. Turrisi said that it comes down to helping patients get organs and keep them.
Dr. Ascher asked for public comments. There were none. She said that some conference calls will be taking place over the next few weeks. Mr. Balbier said that the next meetings of ACOT are scheduled for May 9-10, and November 3-4, 2005.
1 This $20 million, 7-year study of the effectiveness of live donor liver transplants and optimal care for donors and recipients is called the Adult to Adult Living Donor Liver Transplant Cohort Study. It involves 10 universities and is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the Health Resources and Services Administration, and the American Society of Transplant Surgeons. The national project will track a group of approximately 1,000 patients eligible for live donor liver transplantation, enrolling about 200 a year for five years. The researchers will study factors that influence outcomes for donors and recipients and will compare the outcomes of patients with live donor liver transplantation to the outcomes of those who receive livers from cadavers. In addition to clinical issues, the researchers will investigate liver regeneration, liver cancer, and infectious hepatitis (Dougherty M. "In Vivo." 2002. New York: Columbia University Health Sciences .