March 2011 Meeting Notes

ADVISORY COMMITTEE ON ORGAN TRANSPLANTATION

U.S. Department of Health and Human Services
Conference Call Meeting
March 8, 2011
12:00-4:00 pm EST

ACOT Member Participants: Mark L. Barr, M.D.; Janice Beaverson, M.D.; Raymond Benza, M.D.; Bernice Coleman, Ph.D.; Danielle Cornell, R.N., B.S.N., CPTC; Robert B. Ettenger, M.D.; Jan Finn, MSN, CPTC, CCRN; John Fung, M.D., Ph.D.; David A. Gerber, M.D.; Alexandra K. Glazier, J.D., M.P.H.; Reg Green; Eduardo Lara; Velma P. Scantlebury, M.D. (Chairperson); Russell H. Wiesner, M.D. Ex officio members: Diane Corning, CMS; Matthew Kuehnert, M.D., CDC; CAPT Ernestine Murray; AHRQ; Laura St. Martin, M.D., FDA.

Welcome

Ms. Patricia Stroup, Executive Secretary, welcomed ACOT members and others to the call and noted that the call is being held in lieu of the face-to-face meeting that was cancelled due to budget issues. Ms. Stroup said she appreciated people joining the call and noted that replays of the call will be available one hour after the end of the call and remain available for 30 days (866-415-2343). The meeting/call summary notes will be posted on www.organdonor.gov. The next meeting of the ACOT will occur in late June or in August 2011. Ms. Stroup commented that Dr. Scantlebury is in the OR and that Dr. Barr will chair the meeting until she is available.

Kidney Policy Update — Brian Shepard, United Network for Organ Sharing (UNOS), Director of Policy

Mr. Shepard provided an update to the talk Dr. Kenneth Andreoni presented at the ACOT meeting in August 2010.

The Organ Procurement and Transplantation Network (OPTN) has a very bottom-up policy development process. As ideas are generated by the community, OPTN committees discuss them and determine if policy changes are warranted. The process is data-driven and OPTN is able to provide a lot of data on these issues and model the potential impact of any changes. The OPTN committees identify necessary improvements in allocation policy and conduct a thorough analysis of the characteristics of candidates on the list, a review of historical data, and modeling of the potential impact of any changes. Public forums are held to discuss approaches and concepts. Any formal policy proposal is also offered for public comment and then the committee makes a proposal to the OPTN/UNOS Board of Directors. When approved, the policy is programmed and implemented.

The Kidney Transplantation Committee has added a few extra steps to this process to ensure it gains sufficient public input: it held two public forums (2007 and 2009) that resulted in changes to its work. For example, age-matching came out of one of these forums. At this stage, the Committee has developed a few concepts on which it is seeking public input and has circulated these ideas in a document that will remain open for public input until April 1, 2011. Mr. Shepard noted that these are supplemental steps which do not replace the Committee’s responsibility for gathering formal public comment once a formal proposal to the Board has been created.

The Kidney Committee is requesting feedback on proposals to meet the following goals:

• Better match of graft longevity and recipient longevity within biological reason and acceptable levels of accessibility;
• Decrease candidate’s return to the wait list;
• Minimize loss of potential graft function;
• Improve the system’s efficiency and address differences in organ utilization and accessibility;
• Make comprehensive data better available to patients and transplant programs; and
• Address differences in accessibility for populations described in the National Organ Transplant Act.

The kidney donor profile index (KPDI) would be a new measure for determining the projected quality of a donor kidney, as opposed to the current Expanded Criteria Donor/Standard Criteria Donor (ECD/SCD) system. The Committee’s proposal would meet the goals described above by allocating the majority (80%) of organs by age-matching that prioritizes candidates within +/- 15 years of the donor (e.g., 15 years older and younger); and by allocating the remaining kidneys (20%) by KPDI and estimated recipient post-transplant survival.

Mr. Shepard reviewed the KDPI’s three steps: Step 1. The longevity of the kidney is estimated and the KDPI generated; the KDPI is calculated only from donor characteristics, including age, race/ethnicity, hypertension, diabetes, serum cretinine, cause of death (COD), cerebral vascular accident (CVA), height and weight, donors after cardiac death (DCD), and hepatitis-C virus (HCV). Step 2 is to prioritize offers for best-matched candidates. Step 3 is to rank-order candidates within each group. (Step 3 has not yet been finalized by the Committee; it will occur in the future. When the Committee makes its final proposal, it will include the rank-order process.) The Committee is seeking input on these broad concepts right now.

The allocation process starts with the estimated potential function of the kidney that is available for allocation, first determining if the kidney is one of the 20% with the longest potential functioning (e.g., the KDPI is greater or less than 20%). If the KDPI is 0-20% (longest estimated time to function), the kidney is allocated by survival matching; if it is 20-100% (shorter estimated time to function), the kidney is allocated by age-matching and is first offered to candidates whose age is +/- 15 years of the donor’s (and only after that to the rest of the list). Mr. Shepard walked the group through several examples and reminded participants that the pathway is based on the donor’s characteristics as measured by the KDPI.

The span of 15 years was chosen after the Committee considered spans of 10, 15, and 20 years. A span of +/- 10 years resulted in fewer donors available to the youngest candidates, while a span of +/- 20 years resulted in fewer donors available to older candidates. The 15-year span creates a compromise that resulted in a fairer system and a more even number of donors available to all candidates. Using this system, donors of a very wide variety of ages have the possibility to provide a kidney that is at, or above, average post-transplant survival.

The path forward is to collect feedback on concepts; there has been a mix of reactions among the public and in the transplant community. The Committee will consider all of this input and determine whether it will advance a formal proposal that would itself include another round of public comment. The earliest this proposal would be offered for public comment is in the September/October 2011 timeframe, for consideration by the Board no earlier than June 2012. If approved, the community would be notified and the plan implemented, likely no earlier than 2013. This is the most aggressive timeframe. (The concept document is available on the OPTN website, and ACOT members are invited to submit written comments to kidneypolicy@UNOS.org. Mr. Shepard said he is also happy to take comments back to the Committee for consideration.)

Discussion

Dr. Fung asked whether the outputs that relate to specific demographics (i.e., age, race, re-transplant) are part of the modeling and available for analysis. Mr. Shepard said that they are: the appendices connected to the concept document posted on the web site contain this information and it can be downloaded and examined. Dr. Fung asked if cost savings was one of the metrics and the reply was that it was not.

Dr. Ettenger noted that, in the past, children have been given preferential access, and asked what this new potential policy would do to the guiding policy on allocation among children. He asked whether “post-transplant survival” referred to life years or life-of-the-kidney years. The answer was that there are no plans to change the pediatric priority; the change would only be for adults. Second, the KDPI is an estimate of the length of graft survival; the “estimated post-transplant survival” is an estimate of recipient’s likely survival if he or she receives a transplant.

Dr. Benza asked whether survival was calculated from the time of listing or from the time of transplant. The response was that it was from the time of transplant, not listing.

Dr. Barr asked if Mr. Shepard and the Kidney Committee had specific questions that ACOT could address or answer. The response was that any feedback on the technical approach and the merits of the concept would be appreciated. The Kidney Committee got great feedback at ACOT’s August 2010 meeting; now that the concept is out formally and the Kidney Committee is getting feedback from a variety of sources, a written response from ACOT would be very beneficial to the Kidney Committee as it moves ahead.

Dr. Coleman asked if survival was stratified for patients who are highly sensitized or whether this was all lumped together. Mr. Shepard responded that there are detailed tables about sensitization in the model.

Dr. Wiesner asked if there were any concerns that this new system would reduce living donor transplantation, which are more prominent in the younger group and, if so, what efforts would be made to prevent that. Mr. Shepard said that the Committee has looked at this. The concern stems from the pediatric experience, when the waiting list and living donations both dropped, but the Committee does not expect to see as dramatic an effect. Everyone will still have to wait. However, even the top 20% will still have waits relatively similar to what they are today, so there may not be much of an impact. The Committee has not determined what degree of drop would lead to an intervention but it is aware of this issue and plans to design a trigger. This is being discussed at the March 2011 meeting.

Dr. Barr noted that declines in living donation might be a good thing in that they ameliorate concerns about people who may feel forced to make a living donation. Reducing living donations is a controversial issue that divides the community. The numbers of living donors for any particular organ (e.g., lung vs. kidney) have an impact.

Dr. Ettenger added that, in pediatrics, the total number of kidney transplants has gone up. The total number of living donors has fluctuated around a half; in the last one or two Scientific Registry for Transplant Recipients (SRTR), the gap between living and deceased donor has closed. This might not be due to living donors pulling back, though, but due to how transplant physicians represent things to the donor. The “pediatric experience” of changes needs to be looked at more granularly than just the raw numbers, to see what is going on. The impact cannot be judged without having more years of data to review. Dr. Barr concurred that the Committee and everyone at UNOS are aware of this and will track this and look for trends and impacts.

Disease Transmission and Informed Consent — Scott Halpern, M.D., Ph.D., Assistant Professor of Medicine and Epidemiology, Division of Pulmonary and Critical Care Medicine, University of Pennsylvania School of Medicine

Dr. Halpern discussed how and when informed consent (IC) should be obtained from recipients so they can best consider the risks for donor-derived transmittable disease. Ideally, guidelines for obtaining IC are grounded in the best available evidence of probabilities of transplantation risk; the best evidence on how transplant recipients make decisions about risks and benefits of accepting certain organs; and sound ethical reasoning that advances the goals of organ transplantation and recipients’ interests.

Dr. Halpern presented a framework for this discussion, noting that mortality from a lack of donors remains high, and that:

• Transplantation will always carry some risk of donor-derived disease transmission (i.e., standard criteria donors will never be risk-free);
• Scarcity drives the use of donors who harbor non-standard risk profiles; and
• Choices must be made that pit the interests of individual recipients against the interests of all potential recipients.

The goal of organ allocation is to maximize the number of lives saved and the number of (quality-adjusted) life-years gained, while avoiding inequities (differences in access based on morally irrelevant patient characteristics). Organ safety per seis a relevant component of ethics of organ allocation — because the lack of safety threatens quality of life years that might be gained through transplantation — but safety does not have special moral relevance in this arena.

For example, which policy is preferable: one that uses only “standard” organs, saves 7,000 lives annually, and adds 70,000 quality-adjusted life-years to waitlisted patients, versus one that uses organs of low but variable risk, saves 10,000 lives annually, and adds 85,000 quality-adjusted life-years to waitlisted patients. It is clear that the second policy must be preferred, even though it causes risk for those at the top of list. This conclusion is troubling, however, because organs are scarce public goods, rather than goods that are either plentiful or privately owned, and because individuals have no innate right to choose among them for their own personal benefit. The goal of allocating a scarce public good is to maximize public health benefits rather than a specific individual’s benefits.

There is a need for IC standardization because there is undue variability in practices, which creates inequities in recipients’ odds of receiving standard vs. increased-risk organs. Few standards exist for communicating donor-derived risk factors (i.e., Hep C, infections, risks associated with ECD). Where UNOS policies do exist (e.g., designating if the patient would accept an ECD organ), there is wide variability among the DSAs. For example, among the 58 Donation Service Areas (DSAs), the proportions of kidney transplant candidates who agreed at the time of listing to accept ECD kidneys ranged from 2% to 95%. It is hard to imagine this wide variability is a result of patient’s preferences rather than how these decisions are presented to the patient.

Dr. Halpern presented three IC options: 1.Organ-specific consent at time of offer (status quo); 2. Myriad specific categories that one opts into or out of at the time of listing (which could be used with or without option 1); or 3. A few discrete categories that one opts into or out of at the time of listing. The problem with option 1 is that consent at the time of listing is not really consent at all because it does not promote individual’s autonomy. These decisions are made under hurried circumstances and create false trust that the risks of all the possible organs are well-defined, but this is not true and the information on the organs may not be precise. It can be inefficient because having the conversation when an organ is offered can be a barrier to matching on well-defined criteria. Providing too much information about organs under hurried conditions is likely to create information-overload for the patient, and may erode donors’ quality of choice. It has the potential for social biases rather than true risks to drive organ allocation.

The problem with option 2 is that it creates false trust that the risks are well-defined and that “other” organs are risk-free. It can be burdensome for clinicians who do not know what categories to create and the categories may be arbitrarily defined. It is likely to create information-overload for patients.

The third option is the best because it enables truly informed consent to be made and fosters shared and goal-oriented decision-making that builds upon the lessons learned in other domains (e.g., End of Life choices). It promotes efficiency in organ distribution while being flexible enough to encompass inevitable changes in definitions of “standard” organs. Patients would have the right to declare whether their decision would change if their clinical status deteriorated and/or they lost any decisional capacity. Patients would have the right to revisit their decision at any time but would not be mandated to do so. The transplant physicians would continue to retain the discretion to use their judgment on each offer.

Discussion

Dr. Fung said that there are some risks (disease transmission) that are not really clear until after the event has occurred. Cancer is one thing but West Nile virus is different. Yet, even when there are very slim odds of getting such a disease, the risk has to be incorporated into IC. Dr. Halpern responded that this fact drives the need for less specific, more general risk categories to address such once-in-a-lifetime risks. These risks would be incorporated into the “standard” or “very low-risk” categories. If one thinks of the laundry list of potential diseases that could be transmitted by transplantation, it clearly does not do patients a great service to to receive such precise information when there is such a low-probability level (particularly as more and more diseases are identified).

Dr. Barr commented that two issues are being mixed in this presentation: disease transmission and ECD — but the latter is not usually related to disease transmission. ECD is different from after-the-fact diseases and some organs have no ECD definition at all. He asked if Dr. Halpern was on the OPTN Disease Transmission Advisory Committee (DTAC) and suggested that Dr. Halpern connect with Brian Shepherd about this. The OPTN Ethics Committee is another good venue for these ideas. Ms. Glazier reported that she is the Vice Chair of the OPTN Ethics Committee and agreed that it was a good venue. From a donor community perspective, disease risks are identified even if they are not diagnosed. The expectation in the OPO community around waivers and forms is that the recipient does get this information in real time prior to the transplant.

Dr. Barr asked what useful feedback ACOT could provide. Dr. Halpern responded that it would be useful to know how to get these ideas to decision-makers. In many cases, the potential disease risks are known before the fact but a true consideration of how patients can construe risks and benefits requires that multiple different categories be considered together and presented appropriately.

Dr. Kuehnert, CDC ex officio member, suggested that a larger discussion be scheduled for ACOT’s next in-person meeting. This is an important issue, and there has been some interest expressed at other advisory committees in a standard IC form. DTAC is more focused on disease transmission and less focused on IC. It’s unclear what committee should address this but the CDC is concerned about IC for both living and deceased donors.

Dr. Barr agreed to check with Dr. Scantlebury and Ms. Stroup about putting this on agenda for the ACOT summer meeting; he asked members to email him other suggested meeting topics.

Transplant Tourism — Francis Delmonico, M.D., President-Elect, The Transplantation Society; WHO Advisory for Human Transplantation; Medical Director, New England Organ Bank

Dr. Delmonico spoke on transplant tourism and the U.S., specifically, although he noted the issue impacts the whole world. It includes both U.S. patients going elsewhere for organ transplants, and American transplant centers that receive foreign patients. His goal is to achieve awareness of, and transparency about, both aspects of this practice.

The Health Resources and Services Administration (HRSA) has informed the Transplantation Society about sites that are soliciting patients to undergo transplantation in Tijuana, Mexico. The peril for U.S. patients is the risk of being a carrier of infectious disease and of getting an unsafe transplant in a center that lacks regulation and oversight. The public health risk is the possibility that an individual could bring infectious diseases into the U.S. as a sentinel carrier. West Nile and HIV provide examples of this happening before.

There are no OPTN data on U.S. transplants occurring outside this country. Patients may come home with infections that have to be addressed using U.S. resources, either private insurance or public coverage, through CMS. A recent UCLA report addressed a single-center experience with outcomes such as disease transmission, organ rejection, infection, and the need to treat the person for complications.

Dr. Delmonico described a recent time when Americans were heading to Mexico for kidney transplants. The Mexican authorities stopped these transplants from occurring, but other transplants occur. He describes a woman who went to Calcutta and advertised for a kidney; a person who just came home with TB from the Philippines; and the fact that, in China, an executed prisoner is likely to be the donor source. In Costa Rica, a recent proposal to bring Americans in to the country for transplant stated that there were over 1,000 patients available for transplantation (particularly in Arizona). Where would these organs come from? What about prohibition on organ sales?

The other issue is when foreign patients come to the U.S. for transplantation. This often happens and the field should be paying more attention. Many years ago, before organ demand became an international concern, UNOS created a policy as a condition of membership, stating that member transplant centers agree to allow the OPTN Ad HocInternational Relations Committee to review and audit activities around transplantation of non-resident aliens. It also says that, when the transplants performed on non-resident aliens is a cohort of more than 5% of any type of deceased organ transplants, that center may be audited to examine why the number is so high.

UNOS has reviewed the data and found that less than 1% of transplants performed in the U.S. involve non-resident aliens. But this does not provide sufficient information because it is not “transparent to realities.” A non-resident alien is someone who is allowed to be here temporarily; there is no clarity about who they are, where they are from, and why they came here. Foreign patients do come here and get organs, which leaves fewer organs for our citizens.

Both the Centers for Medicare and Medicaid Services (CMS) and transplant center resources are expanded in these situations. HHS, ACOT and OPTN should know about this and the U.S. should keep track of who is getting what organs in center-specific results. The residency of donors and recipients should be tracked. National organ self-sufficiency is undermined if residents can go to a foreign destination and get organs, and if our organs are donated to foreigners. There is no reason for a country to develop its own donation system if its citizens can just go to another country for treatment. Dr. Delmonico expressed the hope that the ACOT and HHS would both address this problem.

Discussion

Dr. Ettenger said that, ever since the American Journal of Transplantation (AJT) viewpoint on China and executed prisoners, he has been thinking about this a lot. Part of the problem with transplant tourism is that a patient can go elsewhere and buy an organ (which is illegal in the U.S.) and then come to a U.S. center for care. Dr. Ettenger has had this experience, personally. He said that American professionals are willing to take care of these patients because they feel an obligation to care for patients regardless of how they came to the center. This is problematic because it encourages transplant tourism in a tacit way. The field itself is culpable, but the alternative is unclear; could these patients be sent to county facilities? Something creative needs to be done to take the centers out of the loop of transplant tourism.

Dr. Delmonico noted that the Canadians have written about this. He cautioned that the goal is not to be punitive, but to be aware about the magnitude of this problem. The need is for transparency, not punishment. An ACOT recommendation that there be greater awareness of patients who are coming and going would help assess the situation. The field would start to know more about who is leaving the country for transplantation and how problematic it is in terms of these patients returning with poor outcomes.

Dr. Barr commented that these problems could be the subject of an entire conference. The AJT article referenced by Dr. Ettenger is by Gabe Danovich, at UCLA, who chairs the OPTN Ad Hoc International Relations Committee, on which several ACOT members also serve. Dr. Barr recommended that ACOT members review this part of the meeting notes carefully, and then think about this issue further. Dr. Barr added that the problem is compounded by the fact that these patients are not registered in the system and so UNOS does not have a mechanism to capture data on them.

This could be an agenda item for the ACOT’s next meeting. Dr. Barr asked Dr. Delmonico to write up the key issues for ACOT’s consideration, and committed to giving ACOT members the information Dr. Delmonico referenced in this discussion. Ms. Stroup noted that ACOT already has two recommendations on this issue: numbers 47 and 48 from 2007. She committed to sharing these recommendations with the group. Dr. Barr asked for the next meeting to include an update on the outcome of these recommendations.

OPO Performance Metrics for Quality Improvement — Charlie Alexander, R.N., M.S.N., M.B.A., CPTC; President, OPTN/UNOS Board of Directors; CEO, Living Legacy Foundation of Maryland

As background, Mr. Alexander noted that this was a mandate from the former OPTN President to the OPO Committee to better quantify OPO performance, develop OPO metrics, assist in benchmarking OPO/DSA performance, and focus on improvement. The goals are to evaluate current metrics; identify opportunities for DSA improvement; identify areas that are currently not working well for measuring OPO/DSA performance; and identify areas where transplant centers, OPOs, and donor hospitals could improve outcomes, increase donations, and/or make more organs available for waiting recipients.

A data-driven metric is needed (in terms of organs per donor) that moves away from ECD and DCD, since these describe kidneys, not donors. The project recognizes that variability in donor co-morbidities and access to health care exist. ECD, SCD, and DCD definitions are fundamentally flawed in their ability to describe OPO performance, donor populations, and expected outcomes (beyond kidney). There is great variability in donors per population, donors per in-patient deaths, and eligible donors per population throughout the country. These variations contribute greatly to donor health and waitlist variability in the U.S.

The Yield Project s a joint OPTN Membership and Professional Standards Committee/Organ Procurement Organizations Committee Work Group with a large number of participants and broad representation, including representatives from OPOs, SRTR, transplant surgery, transplant medicine, UNOS, and HRSA. This diverse group of people reviewed reliably reported donor-specific data from DonorNet and Death Donor Rule (DDR) and created a 4-year cohort of every OPO to model “the national experience.” The model includes every organ donor in the U.S. including all OPOs, from 2006 through June 2010, and uses all donors (with or without transplanted organ) as its basis. This helped to determine the “expected yield of organs transplanted per donor.” The Work Group took the unique characteristics of each OPO and plugged those into the 4-year aggregate model in order to assess OPOs, based on their specific populations’ complexities.

The results showed a natural bell curve: many OPOs are around the national averages, while a handful are statistically significant on either end of the curve (not meeting and exceeding the measure). In 2009, the first year the model ran (using 2005-2009 data), the National Expected Organs Transplanted Per Donor (eOTPD) (e.g., yield) was 3.02. OPOs have been working with the model for about a year, during which time the national average has improved to 3.12, although it is not clear why. There are many potential reasons for this improvement but the hope is that the model will continue to drive improvements.

The variability slide shows the narrow bands of variability for some organs. This denotes more of a national resource and a decreased variability among OPOs for organs like kidneys and livers. For these organs, the range of high to low is very narrow; this suggests that, when these organs are recovered and transplantable, they are transplanted even if it’s not done locally. This is true for kidney and liver, due to the organs’ high tolerance to travel. Moving to other organs like pancreas, heart, and lung, there is more variability. This may be due to placement practice than medical management – but there is greater variability in these organs.

The Work Group has conducted this analysis for the aggregate, as well as for organ-specific outcomes. It can tell if a DSA in one place is exceeding the aggregate for one organ, but not for another. It can also look at which strategies will help increase the yield. The model combines statistical and clinical significance. The model can be used to identify DSAs with exceptional yields through statistical significance (p 0.05 or some other level); the ratio of observed-to-expected (O/E); and the relative difference between O/E and average O/E.

The current status is that every OPO has received their OPO-specific data and improvement projects are underway in many OPOs as a result. The O/E metric is being used as an internal performance measure across the country. The Work Group has proposed formation of a flagging methodology that would identify high performers as well as OPOs/DSAs with lower-than-expected yields, to evaluate donor management, allocation practices, acceptance practices, and donor hospital factors that may contribute to the gap. The Work Group is particularly interested in places where the system is in place for greater yield and the yield can be increased.

The other project is the Donor Potential Study, which is in the early stages. This study looks at variability in donor potential and takes an epidemiological approach to evaluating populations and how variations contribute to greater and/or lesser amounts of donors. Understanding the variability in donor potential in the U.S. will help define regions, DSA/OPO performance, and organ availability.

Discussion

Dr. Fung commented that some say the system is not as rigorous as could be, i.e., using 90th percentile E/O vs. 95th. There’s been an online discussion about putting the onus on the OPOs to hold up their end. Shifting to 95th percentile might generate more buy-in. Mr. Alexander agreed that this issue has generated a lot of discussion. The Work Group thought it was more credible to cast the net this way so as not to bring in OPOs that had very little variability to the national model—the focus was on the outliers first. It was important to minimize the workload at the start. That’s not the only reason but it is one reason – the Work Group needed to be able to get through the first cases and then, if there is not a false positive rate, expand the net.

Dr. Fung noted that interactions and competitions between OPOs and the transplant centers serve to drive up utilization rates; he recommended the Work Group get out of the OPO/transplant center relationship and look at models that would allow for more expedited placement of lungs. It does not seem to be a model that works well using the centers. Mr. Alexander unofficially agreed. The Work Group does not want to suggest a policy that bypasses the waiting list, but there is a need for an urgent allocation process for some organs. When livers or kidneys are accumulating cold time, going back to DonorNet and going out to the next 10 centers is not the best way to get the organ placed. There is a need for data to drive the policy change, however; it’s been very anecdotal to-date. This model will help drive an emergency allocation procedure.

Dr. Barr added that the thoracic community will also support this. Mr. Alexander noted that the Association of Organ Procurement Organizations (AOPO) has been a strong supporter of this project, which supports the desire to make things better.

Work Group Report on Alignment of CMS Regulatory Requirements with the OPTN — Danielle Cornell, R.N., B.S.N., CPTC

Dr. Scantlebury joined the call and thanked Dr. Barr for chairing the meeting in her absence.

Ms. Cornell began by thanking those who are on the call today and who participated in the Work Group’s calls and email discussions. The Work Group narrowed its concerns to a few observations:

• Regulatory documentation: This works one way for CMS and another for UNOS, sometimes in entirely different manners. The Work Group believes that required regulatory documentation should satisfy both agencies.
• HRSA’s push for more marginal organs to be transplanted: National learning conferences and the goal of “every donor every organ every time” mean that more marginal donors are getting transplanted (i.e., ECD, DCD). At the same time, centers are being more conservative in order to stay at or above expected outcome measures and so do not transplant these organs.
• SRTR risk adjustment: There are arguments that there is little or no risk adjustment in the SRTR model for transplants from DCD donors or centers with large waiting lists that may want to use ECD organs.
• ECD definition: There is a lack of a good ECD definition from the donor perspective, since we are using a kidney measure. This definition applies even when no kidney is involved (as with a liver transplant).

The law of unintended consequences really applies here. OPOs have higher discard rates in all categories of donors. Transplant centers are increasingly conservative, due to fear of outcomes data, fewer referrals, loss of contracts and revenue, additional CMS site visits, increased expenses, and lower incentives for experimental procedures. In 2008, the U.S. discarded 343 kidneys from DCD donors, which increased to 403 kidneys in 2009. In 2008, the U.S. discarded 1,360 kidneys from ECD donors, which increased to 1,372 in 2009. Over 5,000 kidneys were discarded in just those two years, and that’s just one organ. The bottom line is that there is less incentive for innovation, and fewer transplants are occurring, resulting in more deaths on the waiting list.

Ms. Cornell showed a bar graph of deceased donor transplants from 1996 to 2010 that indicates a pattern of growth until 2007. Looking at 5-year segments, there was a 9% growth in deceased donor organs transplanted during the first 5-year group (1996-2001), and 20% growth in the second group. The past 5 years, however, have been flat. The field had 20 years of sustained growth but, once the new CMS regulations were published, there was no growth.

Ms. Cornell showed a bar graph of deceased donors and noted that the centers are inextricably caught between supporting the goal of “every donor every time” and the real possibility that meeting it involves sacrificing their own existence. It’s not reasonable to penalize centers for expansion and innovation. The dilemma can be resolved, however. Everyone believes there should be performance measures and that HRSA’s goals are valuable. The OPTN does a great job collecting data and the SRTR does a wonderful job of building models based on those data. This problem deserves a strong sense of urgency and the recognition that regulations must not reduce the number of transplants that occur.

The Work Group’s proposed recommendation is as follows:
In order to resolve the regulatory inconsistencies between CMS and UNOS policy, and the unintended consequences that the performance measures portion of the CMS Regulations for OPOs and Transplant Centers has created, the ACOT recommends that the Secretary appoint a Task Force that includes representatives from the CMS, HRSA, UNOS, SRTR, and members from the OPO and transplant center communities—such as AOPO, AST/ASTS and the Alliance—to work together to find an appropriate balance between regulation and national goals to increase the number of organs transplanted and lives saved. This Task Force should have oversight from the Secretary or her designee, and due to the urgency of the matter, a firm, swift deadline should be set for completion.

Ms. Cornell said she would spell out the acronyms, and invited comment from ACOT members.

Discussion

Dr. Ettenger applauded the group for its presentation. Dr. Fung asked, when looking at outcomes, whether there was risk adjustment for donor characteristics. One gets fewer organs from older donors, so he wanted to know if this was age risk-adjusted in OPOs—otherwise OPOs that pursue older donors are penalized for falling below national expectations. Ms. Cornell answered that there is equal outcomes data pressure for OPOs and transplant centers. This does not happen today for OPOs. The Yield Model, which was presented earlier, does adjust substantially for age, and age is a big determining factor so it would have a huge impact.

Ms. Cornell said that the Work Group was open to suggestions; one idea was for ACOT to put together a task force on this issue so the right people would be at the table. Her Work Group did not feel that ACOT represents all of the necessary experts; it would be important to also have CMS, HRSA, OPTN, SRTR, American Society of Transplant Surgeons (ASTS), and AOPO. at the table.

Dr. Barr agreed that unintended consequences certainly apply here; while well-intended, the effect has been for OPOs and centers to pull back. This is an urgent issue. He thanked Ms. Cornell for her presentation that very clearly distilled ACOT’s concerns. He suggested that ACOT was a viable mechanism to draw these various entities together in a rapid fashion.

Ms. Cornell added that she has heard from transplant center medical staff that the selection committee’s conversations have changed; centers are concerned about taking a risk on someone because he or she may have co-morbidities that might impact outcomes. This is a perfect storm that affects selection and prevents growth. Dr. Barr noted that it was important to not reward bad behavior, however. There is a need for data and not to swing too far the other way and end up with organ wastage.

Dr. Ettenger commented that the first responsibility is the care of patients and not to place inappropriate organs with co-morbidities because they lead to diminished outcomes. Ms. Cornell said there is a need to change CMS’ regulations. She added that Mr. Alexander’s presentation on metrics should also be considered. The issue is whether the SRTR models are the best or if there is a need to risk-adjust more on the transplant side. Dr. Barr added the need for buy-in from the centers on data entry, since a lot of data on donors and recipients are needed to make these decisions. This is a major area where ACOT could make a difference.

Ms. Stroup commented that the HRSA’s Division of Transplantation (DoT) sees ACOT itself as being the task force. She suggested that ACOT could pull people into the Work Group and accomplish the goals outlined in the proposed recommendation. Sven Peterson, from the Office of the General Counsel, expressed concerns with the recommendation language as presented. He said that, given ACOT’s function and charter, ACOT can do much of this on its own and could put a task force together as a Work Group. The Work Group could provide information to ACOT, which could make recommendations to the Secretary. ACOT can bring in entities and expertise to get the needed data. Recommending to the Secretary that she create what is, in some resects, another advisory committee is not an appropriate approach.

Dr. Scantlebury asked what ACOT’s limitations are and how much of a free hand it has in bringing the necessary parties together. Ms. Stroup responded that ACOT has a free hand to bring in speakers and outside experts to advise ACOT Work Groups. Ms. Cornell rescinded the recommendation and asked those who are interested in being part of the new Work Group to let Dr. Scantlebury know.

Work Group Report on Declining Rates of Donation/Geographical and Other Variations in Organ Distribution — John Fung, M.D.

Dr. Fung presented a document summarizing the Work Group’s discussions:

While much has been written about disparities in receiving a transplant based on economic, geographic, and medical referral for patients with end-stage organ failure, one pressing controversy in transplantation is the documented disparities in waitlist outcomes. Differences in deaths, waiting times, likelihood of receiving a transplant within a given period of time, and severity of medical illness at the time of transplantation have been clearly demonstrated. This was the basis for the 1999 HHS Final Rule,which directed the OPTN to address arbitrary geographic barriers that restrict the allocation of organs to patients who have the greatest medical urgency.

It has been argued that geographic disparities are related to differences in regional medical practice, incidence of diseases leading to end-stage organ failure, and OPO performance. Studies have clearly noted regional differences in the incidence of disease that are related to ethnic background and racial prevalence. Standardized guidelines have sought to minimize differences in medical practices. But, insufficient analysis has been placed on OPO performance and observed differences in metrics (i.e., organs per 100 donors, conversion rates, organs per donor, etc.). These statistics assume that donor deaths and characteristics are uniform and that OPOs located in high-demand, low-availability areas are simply not providing sufficient procurement rates.

In a recent analysis, Dr. Ellen Sheehy, as part of a four OPO collaborative, used the National Center for Health Statistics Detailed Mortality File database to create OPO service area level death data. Inter-DSA differences were examined, using in-hospital CVA and trauma deaths as an indicator of brain deaths. A three-fold variation in state level deaths for CVA has been previously noted but, when analyzed by DSA, variations in CVA and trauma deaths accounted for 70% of the variation in eligible deaths per million population. (“Eligible deaths” were defined as age between 0 and 70, no absolute contraindication to organ donation, being declared brain dead, and excluding DCD.)

Dr. Sheehy concluded that there is an inherent geographic inequity in donor pools that impact DSA performance and that conversion rates are a more meaningful measure of OPO performance. This suggests that, in order to improve the allocation system’s fairness, increased sharing in larger units (i.e., regional, supra-regional) should be considered.

The last sentence is the Work Group’s findings: “In order to improve the allocation system’s fairness, increased sharing in larger units (i.e., regional, supra-regional) should be considered.”

Discussion

Dr. Ettenger noted that CVA-plus-trauma made up 89%, but the other 11% was relatively undefined and might be more pristine organs. He said he thought that Dr. Sheehy was going to do further analysis on the points the group brought up, in terms of characteristics of trauma deaths and the other 11% that were non-CVA and non-trauma deaths. Dr. Fung said he remembered looking at other factors; the Southeast has the most favorable donor-recipient ratio and has the highest quartile of CVA deaths. There may be a need to break trauma out of CVA to see different donor characteristics and the organs produced. Dr. Fung said that he did not know what Dr. Sheehy has done and asked if anyone else remembered. A group member commented that she thought Dr. Sheehy was working on this, but that the ACOT group was not clear about whether it wanted a report back and, if so, in what format.

Dr. Fung said it is revealing that there is clear correlation and commented that he was recently at a meeting with an OPO director from Denver who had also looked at this. Denver has looked at its deaths versus OPO performance and come to the same conclusion. This issue is being discussed in a forthcoming article in the New England Journal of Medicine (NEJM), and Dr. Sheehy shared the findings pre-publication. Tweaking the percentiles will generate a few more donors but will not address disparities or the need for more organs.

Dr. Ettenger said that Dr. Sheehy showed a revealing map that clustered CVA-plus- trauma in the Southeast; he added that regional sharing is not helpful if all of the conjoining states have the same characteristics. Dr. Fung said he did not know where ACOT want to go from here and asked the other members if they wanted to ask Dr. Sheehy to further assess trauma vs. CVA.

Dr. Wiesner had participated in the conference call with Dr. Sheehy as well and commented that the group discussed the heart transplant example, which has concentric circles going from 500-1,000 miles. The death rate drops by two- to three-fold. He stated that it was unclear how DSAs and regions were picked initially, as they are not based on transplant centers or population. There is a real need to deal with the geographic differences. This is not a new issue, however, it has been looked at by the Institute of Medicine as far back as 2000.

Dr. Fung mentioned a philosophical discussion about blaming transplant centers that are located in donor under-privileged regions and how they are over-listing patients for organs, but should actually be being more selective and not listing them. There should be a realistic ratio of the number of organs to the number of patients who are listed. It’s unconscionable that a person cannot be listed merely because the quota for patients on the list has been met. Dr. Wiesner added that some DSAs and regions are under-listing. Dr. Fung and Dr. Wiesner discussed guidelines on when people should be listed.

Dr. Barr commented that this issue is easily applicable to all organ programs. People need to drop their egos and their financial interests and allocate organs by the confines of cold ischemic times. There are ways to make sure that smaller and more rural programs still get organs. Dr. Barr said that the field would never be able to get away from locality, but there is a need to broaden from locality to zone and move away from gerrymandered lines drawn all over the United States. He noted that UNOS wants to see this as well. Everyone wants to see a rational approach to this issue. We have identified a problem, we all know it, and we need to address it with a data-driven and rationale approach.

Dr. Ettenger expressed the view that an ACOT recommendation could address the egos and financial interests at play. There are some organ disciplines that do things better than others and it makes sense to have a recommendation that articulates the need to address this problem. Dr. Wiesner added that an outrageous example of this, at least in liver, is that there are several single-center OPOs where they do low MELDs of 16 while everyone else is doing them at 29. There should be a mechanism to promote broader sharing and a broader pool among OPOs.

Mr. Durbin commented that ACOT made a recommendation at the August 2010 meeting on taking steps to create evidence-based allocation policies that are not determined by arbitrary boundaries like OPO regions or state boundaries. This was in response to congressional involvement in the field by preventing any changes to liver allocation policy from being implemented until an extensive analysis and demonstration project have been conducted. He said that the field is dealing with the self-interest of transplant centers and of Congress, as well. Dr. Fung added that the congressional wording applies only to livers so it might be possible to move ahead on other organs. Mr. Durbin agreed and said that HHS needs to push this forward.

Dr. Fung said that another conversation occurred recently concerning the declining rates of living donations, in light of the recent living donor liver deaths, two of which occurred in 2010. Four patients who donated kidneys died last year and there was a highly publicized kidney donor death in 2001. Yet, it’s not possible to find out the number of donors who died from the SRTR. It’s hard to get a set of numbers to present risks to patients, or for people who are considering donation to find on their own. A commentary appeared in the AJT a few months ago about how much information can be released and what would happen if it were more highly publicized. The two deaths were from the same root cause that also caused a death in 2008. People do not feel confident in the system; this also prevents people from analyzing and growing from one another’s mistakes.

Dr. Wiesner said that it was important to discuss bad outcomes so they can be prevented; there is a reluctance to do so. Dr. Barr asked if Dr. Fung’s statement referred to the hemolock clip issue and reminded the group that the ASTS issued a warning not to use the clip and the FDA also issued a warning. This is a professional society issue, medical malpractice, and an FDA issue. Creating awareness in the community is half the battle but not an OPTN issue.
Mr. Durbin added that DoT was in discussion with the SRTR on this issue and is working on the ability to track living donor deaths. Dr. Fung suggested that complications are another important issue to track. Dr. Barr said that the Renal and Lung Living Donor Evaluation (RELIVE) research project is happening at five centers to look at this very question. The OPTN Living Donor Committee has been talking about this too and now requires immediate deaths be reported within the first 2 years. Donors are not followed long-term so it’s hard to collect data on their outcomes.

Dr. Scantlebury added that having centers report information is an issue and stated the view that there are no repercussions for not doing so. Dr. Barr clarified that this is not true. The living donor recommendations have been endorsed and there are ramifications for not reporting data on them. The problem is one of long-term follow up but, over the short-term, there are strict requirements. UNOS is trying to lengthen the time over which living donors are followed.

The group discussed the fact that information is solely gathered as part of a research protocol (i.e., RELIVE); it cannot be used by SRTR, although the bureaucracy around haring research in clinical databases is being worked on. Dr. Barr cautioned that this is a very small sample. If RELIVE does nothing else, it will provide guidance on this area and about living donation. RELIVE is fostering examination of long-term complication rates for living donors; hopefully, UNOS can get behind these data in terms of key issues. It might also help fund a registry of key issues.

Opportunities for Organ Donation: Expanding the Right to Donate Organs Following Uncontrolled Circulatory Determination of Death — Stephen P. Wall, M.D., MS, MAEd; Department of Emergency Medicine, New York University School of Medicine

Dr. Wall noted that, in the U.S., only those who die in hospital settings are currently able to donate organs, unlike in other countries. As an Institute of Medicine report noted, uncontrolled donation after circulatory determination of death (UDCDD) would provide 22,000 more U.S. donors annually. For liver this is still experimental but for kidneys this is more feasible.

The goal of the HRSA grant was to create an out-of-hospital UDCDD program that would be accepted and sustained by New York City (NYC) residents; and to evaluate the impact of the new UDCDD program on both members of the public who were approached for organ donation and transplant recipients.

The Protocol Derivation Study used participatory action research methods and the SEED-SCALE process for social change to guide the development of the NYC UDCDD protocol. This process, which occurred from July 2007 through September 2010, fosters an equal partnership between experts, community members, and government representatives so each has an equal stake in the outcome. The main categories of concerns were clinical, organizational, legal, ethical and public. Many activities were held to gather data through focus groups, town hall meetings, etc., in order to balance these various concerns.

The protocol starts with a cardiac arrest that occurs outside hospital at a private location, when 911 is called and NYC EMS responds. A lot of personnel are involved, including firefighters and police. An on-line medical control physician is responsible for care and transmits orders to the advanced life support personnel who are on-scene to follow termination and resuscitation guidelines.

There is a separate team called the Organ Preservation Vehicle (OPV) team, which includes a family service specialist, an emergency physician, and two EMTs who act as organ preservation technicians. There is no communication between the treating team and the OPV team. The OPV parks near to the treating team and then, if termination is called, they enter the dwelling. Under public health law, the team can enter a dwelling only when the person had already signed up for donation; in this case, the team is entering to protect the person’s stated right to be a donor. Dr Wall noted that the project lost a year and a half of time due to recommendations about Extra Corporeal Membrane Oxygenation (ECMO) catheters and how to obtain consent for those who were not already registered for donation. Eventually, they worked out a tri-partite consent process; but, once this passed HRSA’s levels, the State Health Department restricted the project to first-person consent. Now the team needs to have proof of first-person consent through the registry.

A medical screening is conducted based on specific criteria modified for the program. A big issue was that of a focused neurological exam. The main difference between controlled and uncontrolled donation is that after the patient has been declared to be dead, cardio-pulmonary support must be reinstated, the person taken to the hospital, and ECMO established.

With controlled donation the patient is in the OR or very nearby. When an event happens outside the hospital, however, there is a need to infuse and circulate Heparin and to maintain some baseline of profusion during transit because of warm ischemic time. Originally, HRSA said that nothing could be done to support circulation after death; but in the end, a compromise was reached: before starting chest compressions, the team does a baseline brain stem assessment and a second one is done before ECMO is established. (This explains the need to have a physician on the team, which added $400,000 in costs and shortened the project period.) The NYC team assesses whether reinstitution of cardio-pulmonary support impairs “the natural progression to brain death in the newly deceased” – this prohibits uncontrolled donation after death programs from occurring. Their paper has been accepted and will be published shortly.

Discussion

Dr. Fung asked how far along the team was in getting the prototype going. Dr. Wall responded that it is in the streets now. The probability of recovering an organ is low, however. New York City has 25 eligible cases a week; of those, there is a 5% chance the person is registered as an organ donor. This means that, the way the protocol is now, there is a very low chance of capturing someone who is a donor. The team has entered at least four locations and everyone been overwhelmingly supportive in what they are trying to do. It is hoped that the public will get more comfortable with this and the ethics of the program; hopefully, eventually the requirement for the individual to be registered as an organ donor can be relaxed, which would increase the numbers.

Dr. Wall noted that the Pittsburgh system is an in-hospital program and that a hybrid approach is probably needed. That’s the only way it can be cost-effective and sustainable. EMS has done a great job of increasing survival after cardiac arrest, so the patients are being transported to the ER, and dying there, and may be lost as donors. Dr. Scantlebury asked if the idea of taking potential donors from the ER to a referral center might backfire and increase public distrust. Dr. Wall responded that the public was very engaged in designing the protocol and many iterative sessions were held to refine it. He felt that, if this was done right, the answer would be no — public distrust would not be increased. In the beginning the program received a lot of negative media coverage (many articles got the details wrong), but now they coverage is positive. Uncontrolled donation has a huge potential to help meet the need for organ transplantation. France has reduced its waiting time for kidneys using such a system – the fact is that more people die in an uncontrolled situation than in a hospital setting. It must be done in a way that is ethically, legally and morally responsible.

The HHS grant enabled New York City to do the necessary social, political and cultural work and to get the project signed off on. It’s not an efficient program, but it’s a good first step to help build support for this sort of work that hopefully can lead either to changing the protocol or encouraging more people to register as an organ donor.

The group discussed the benefits of out-of-hospital deaths vs. trying to capture those who die in the ER. There are nuances of trust in the latter due to the fact that there is less separation of the teams outside the ER. Someone else asked what the project is doing to address the determination of death issue from a legal standpoint. Dr. Wall answered that the group was writing a paper on just this issue. Dr. Wall described the various permutations the process took around legal issues and the way in which the paper got accepted. He noted that, with controlled donation, someone dies and afterwards they are prepping the person for donation. With uncontrolled donation, under their protocol, the patient is worked on for over half an hour and determined to have no meaningful brain activity. Death is determined by circulatory/respiratory definition; there is about 10 minutes where the team is confirming the person is an organ donor, during which no CPR occurs. Then, they do chest compressions and mechanical ventilation for another 25 minutes. When the team gets to the hospital, they do a balloon occlusion before ECMO to ensure there is absolutely no chance of resuscitating the patient. Dr. Wall described this process and its underlying logic in some detail.

Committee Discussion on Meeting Proceedings

Dr. Scantlebury noted that Dr. James Bernat gave a presentation on circulatory/respiratory determination of death at the August 2010 meeting, and recommended using the term “DCDD” and really looking at uniformity in death determination. He pointed out that different centers and hospitals vary in the amount of time used to make this determination. Dr. Scantlebury asked if ACOT wanted to reconvene Dr. Bernat’s panel to address some of the outstanding issues, including those surrounding uncontrolled donations.

Ms. Stroup commented that part of Dr. Bernat’s recommendation was to reconvene his panel, and he can be invited back to the next meeting to discuss uncontrolled DCD issues. The members agreed that this panel should reconvene. Ms. Stroup said that the ACOT had to make a motion on this, so Dr. Scantlebury moved that Dr Bernat’s panel be reconvened to address some of the dilemmas raised in his and this most recent presentation. The motion was seconded and passed unanimously.

Ms. Stroup brought the group’s attention back to the recommendation from Ms. Cornell’s Work Group. She commented that there are two aspects to the Work Group recommendation; one is the legal part of how one would structure such a Work Group and the second is on the need to harmonize HRSA and CMS regulations and policies. Mr. Peterson sought clarification that these are two separate issues, and Ms. Cornell confirmed that they are two different issues. Dr. Barr added that, for those on the phone representing CMS, there are volunteers who are willing to help with this issue.

Dr. Scantlebury said that it makes sense for CMS and HRSA to resolve their issues. Ms. Cornell and Dr. Barr offered to draft a statement encouraging this, to be presented at the next ACOT meeting. Mr. Peterson read a sample statement:

The ACOT recommends that the Secretary encourage HRSA and CMS to resolve the regulatory inconsistencies between CMS and OPTN policies.

The group members discussed the use of the word “encourage” and were informed by general counsel that this is the preferable term. A motion in favor of this recommendation was made, seconded, and passed unanimously.

Public Comment

John Snyder from the Minneapolis Medical Research Foundation/Chronic Disease Research Group (current SRTR contractor) commented that they have inherited the yield calculator from the Arbor Research Collaborative for Health and he hopes to have something more user-friendly to share soon.

Dr. Halpern commented that there is substantial controversy and disagreement over definitions of death (specifically around DCDD) and how these definitions are used to promote transplantation. He suggested that it would be good to invite a variety of groups to participate in the ACOT discussions. A paper will be published shortly by several notable medical societies and other entities, taking a different view on this issue, which might also be interesting for ACOT’s work. Dr. Scantlebury thanked Dr. Halpern for this suggestion.

The meeting adjourned at 4:05 pm.