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Advisory Committee on Organ Transplantation
Advisory Committee on Organ Transplantation (ACOT)
Welcome - Patricia Stroup, Executive Secretary, ACOT
Ms. Stroup welcomed the members to the ACOT meeting and updated the attendees on the new policy that food is no longer provided at Federal meetings. She noted that several members were attending by phone due to travel problems stemming from the storm: Danielle Cornell, Matthew Kuehnert, and Jamie McDonald.
Welcome and Opening Remarks, Mark Barr, M.D., Chairperson, ACOT
Dr. Barr welcomed the group and added that the storm was also prompting many flight changes; he expressed the hope that the meeting would end early to accommodate these flight changes. He announced that the agenda had also changed a bit due to the storms. For that reason, public comments would be accepted after each presentation as well as at the end of the meeting.
Program Update - Chris McLaughlin, Chief, Organ Transplantation Branch, Division of Transplantation (DoT), Health Resources and Services Administration (HRSA)
Mr. McLaughlin introduced himself and noted that he manages contracts for the National Organ Transplantation program. He provided an update on activities since the ACOT’s last conference call in February 2012. There would be many other presentations on specific issues noted in this overview, as well.
First, the policy update: at the June meeting, Organ Procurement and Transplantation Network (OPTN) approved a “National Share 15” policy for liver: adult deceased donor livers will be offered to all candidates with MELD/PELD scores of 15 or higher locally, regionally, and nationally before being offered to candidates with lower MELD/PELD scores. OPTN also approved a “Regional Share 35” policy: adult deceased donor livers will be offered to combined local and regional candidates with MELD/PELD scores of 35 or higher (“tiered regional sharing”).
HRSA also provided $500,000 in additional funding to the Scientific Registry of Transplant Recipients (SRTR) to conduct analyses to support OPTN’s development of evidence-based approaches for geographic liver distribution. The goal of the redesign is to use mathematical optimization to aggregate geographical areas into larger units in order to maximize a numerically objective function while satisfying stated constraints (i.e., allowable number of units). Much of this modeling is complete; the SRTR will ask the OPTN Board and the Liver Committee to establish liver policy goals and requirements that will guide the process.
In a related topic, the three living kidney donor policies (Medical and Psychosocial Evaluation, Informed Consent, and Follow-up) received a lot of public comment. These policies were not reviewed by the OPTN Board in June due to procedural issues; it is expected that they would come up to the OPTN Board for review in November 2012. The process to develop analogous Living Liver Donor policies has begun.
The OPTN Kidney Committee is planning to release a public comment proposal on September 21, 2012. The proposal is intended to enhance post-transplant survival benefits, increase utilization of donated kidneys, and increase transplant access for biologically disadvantaged candidates. The proposal will incorporate new features, including: an expanded definition of waiting time based, in part, on the date of initiation of renal dialysis; a sliding scale for assigning points to sensitized patients; expanded access for blood type B candidates who can accept kidneys from subtypes of blood type A donors; broader sharing for extremely highly sensitized candidates; longevity matching of some kidneys; and regional sharing for kidneys with the highest risk of discard.
On Vascularized Composite Allografts (VCA), the NPRM was published on December 17, 2011 and the comment period closed on February 14, 2012. Twenty-eight comments were received, all favorable. The draft Final Rule is undergoing internal HHS review now. An internal/external review work group met in June 2012.
On operational issues, the OPTN contract (in place since 2005) was extended for six months until March 30, 2013. HRSA published an RFI on January 6, 2012, which closed on February 17, 2012, to gather input on: the use of subcontracting, the OPTN National KPD program, ways to enhance public participation, OPTN’s role in educating members, the expansion of compliance on monitoring function (particularly for living donors), expanding OPTN’s research capacity, and enhancing its IT capacity and responsiveness. A Request for Proposals will be posted as soon as possible.
On the Deceased Donor Potential Study, HRSA provided $1.6 million in direct funding to UNOS to conduct a study to evaluate donor potential in the U.S. The findings will serve as basis for evidence-based goal-setting. The study will use rigorous methods and take demographic and epidemiological approaches to set goals and measure variables that affect donor potential.
An SRTR/PSR Transplant Program Quality and Surveillance Conference took place over February 13-15, 2012. Short- and long-term action items were developed and placed on the SRTR web site; they will be updated as work progresses. The SRTR produced a PSR Manual of Operations, detailing the SRTR process for risk model development and oversight. It is moving towards a three-year cycle of model development with formal input and involvement from the OPTN committees. Initial kidney model building steps are underway.
Report improvements are also underway. As of July 2012, the transplant program PSR uses a new color format and enhanced visual display to depict the content. OPO-specific PSRs now contain measures of expected donor yield using the models approved by the OPTN/UNOS Board in 2011. The SRTR released a Donor Yield Calculator tool that is available for download on the secure websites, to help OPOs track observed and expected donor yield using the new models.
Alignment activities: HRSA, CMS, and the OPTN contractor have been working to identify areas of compliance overlap as a first step in the process of better aligning CMS and OPTN requirements. The first product will be a crosswalk of requirements from the CMS Transplant Center Conditions of Participation and the OPTN Bylaws and Policies (with a possible crosswalk and educational webinar in November 2012). The Crosswalk will enhance ongoing efforts to modify OPTN and CMS requirements and survey processes in order to address areas that are similar but not identical. The hope is that the changes would provide clarity and make it easier for transplant centers to comply with both CMS and OPTN requirements.
Next, the Organ Donation and Transplantation Community of Practice, seeks to sustain and improve upon the gains made from the Collaboratives, the 7th National Learning Congress will be held on October 4-5, 2012, in Grapevine, Texas. The theme is “Intentional Integration of Quality Processes;” tracks will address Donor Designation, Advocacy, Donor Management, Pediatrics, Transplantation, and Leadership.
Finally, there have been several public and professional activities of note. DoT is partnering with the Administration on Aging to encourage those over 50 to register as donors. There has been a positive response from a print PSA that ran in Newsweek and Kiplinger’s. The Workplace Hospital Campaign uses a model from Louisiana hospitals and OPOs in order to encourage people to join their state donor registries. There are 10 national partners for this effort, including AHA. Gallup released the National Survey of Donation Attitudes and Practices, which is an expansion and update to the 2005 survey so changes can be compared over time. The survey will over-sample for African Americans, Asians, Hispanics, and Native Americans. The interviews are in progress and will be released in the fall.
Next, a cooperative agreement was awarded to the University of Michigan in 2006 to run the National Living Donor Assistance Center. (Michigan subcontracted with the American Society of Transplant Surgeons to operate the system.) It became operational in October 2007 and has received 2,271 applications. Of these, 2,012 were approved for funding and 1,123 living donations have been completed. The average reimbursement to donors and companions is $2,539. The NLDAC, since its inception, has paid out $3.57 million to donors.
Finally, DoT is participating in a new HHS program designed to increase innovative thinking and problem solving in the Department. An Innovation Fellow will join DoT for a year to help work with the OPTN to develop a new system for electronic identification and tracking of organs.
Dr. Barr thanked Mr. McLaughlin for a very comprehensive overview and invited ACOT members and members of the public to comment.
Dr. Eason asked about the status of the long-awaited kidney allocation policy? The response was that a draft proposal would be released for comment in September 2012; it was approved by the Kidney Committee on August 27, 2012. In the past, when potential concepts were released for comment, they were not officially proposals, but this would be a proposal.
Dr. Barr noted that the CMS alignment is a high-priority and the ACOT is likely to make a recommendation on this.
Alignment of CMS Regulatory Requirements with OPTN and HRSA, Workgroup Report - Danielle Cornell, R.N., B.S.N., CPTC
Ms. Cornell introduced the session by noting that the re-alignment working group was formed to address the need to minimize conflicting performance measures. She thanked the group, whose members include both ACOT members and non-ACOT members. The group has worked on this for two years and the ASTS and AST presidents have given valuable input to its considerations.
As background, donor rates have been flat for about five years; the ACOT members suspected that this was due to conflicting performance measures. For example, HRSA’s goal of “every donor, organ, every time”, while supported by OPO and transplant centers, conflicts with the OPO yield measures. Specifically, there is a penalty for not staying one standard deviation over the national average. So, an OPO that is below the national mean has a disincentive to do a single organ ECD donation, because it prevents them from catching up to the average.
The push to transplant every organ conflicts with penalties for centers that transplant marginal donors. The outcomes data are public and can result in loss of patients, managed care contracts, and even the program as a whole. Transplant programs therefore have less incentive to engage in innovative procedures out of fear of the outcomes – this is a huge loss to the field. The end result will be no increase in transplant rates and the number of donors, too many deaths on the list, and higher discard rates.
The group had a recommendation to present – Ms. Cornell urged the ACOT to vote on it, as it represents two years of hard work. She asked the ACOT members to trust that perfection is not possible here. The timing, however, is critical; in this election year, the work risks being delayed if a new Secretary is appointed in 2013. Ms. Cornell said that she was pleading with the ACOT members to accept this recommendation:
Due to the misalignment and inconsistencies between CMS certification regulations and outcomes requirements for transplant centers (TCs) and organ procurement organizations (OPOs), the ACOT recommends that the Secretary direct CMS to confer with HRSA, OPTN, SRTR, the OPO community, and transplant center representatives to determine appropriate requirements for OPOs and TCs that unify mutual goals of increasing organ donation, improving recipient outcomes and reducing organ wastage. The report will include, but is not limited to, improved risk-adjustment methodologies for TCs and a statistically sound method for yield measure for OPOs.
Dr. Barr reiterated the need to get this recommendation finalized. Dr. Fung said that he was hopeful that this would streamline the review of programs. Other measures of quality (i.e., graft survival, wait list times) are also being developed independently and the SRTR is being used for this. He commented that the goal to reduce and/or condense the amount of administrative oversight was not reflected in the recommendation. Dr. Barr stated that this was implied in the language and that it would be addressed. He asked Mr. McLaughlin to address the comment.
Mr. McLaughlin agreed that the recommendation reflects activities that the DoT is undertaking. DoT is working aggressively with CMS to identify these areas of concern. The language seems appropriate to him. Mr. Durbin added that, in the spirit of what the ACOT is trying to accomplish, it should state “a joint effort with CMS and HRSA,” rather than directing CMS to do something.
Ms. Cornell agreed that was a good point. The rest of the sentence was very important to the transplant community, so this was crafted to include everyone. We can say that the Secretary can direct whatever agency, but the input from the community is important to maintain.
Dr. Fung reiterated that the transplant centers are always under review by entities that are all reviewing the same things. He voiced his view, again, that the goal was to streamline this administrative oversight. Dr. Gerber agreed and suggested language that the agencies should “jointly determine appropriate requirements” in order to address that issue. No one should take the brunt of it but everyone needs to have a fair stake in the process. Not everyone has the same regulatory requirements, so centers have to adapt to the specific regulator, whether that be CMS, or the state, etc. Dr. Eason suggested more working changes about agencies conferring with one another to reduce administrative burden.
Dr. Barr noted that the Secretary cannot direct all of the agencies that are being discussed. Ms. Levine read the ACOT’s Recommendation #52 from March 2011, which was very similar and spoke to the need to resolve regulatory inconsistencies. She added that the recommendation under consideration referenced a “report” but the report was not clearly described. Dr. Fung asked if CMS could deem UNOS to be its auditor. Dr. Gerber agreed that this recommendation would be useful, even if it duplicated past ACOT recommendations.
Dr. Barr commented that the goal was to create language that will actually have an impact on how things are done. He noted that, if the ACOT has to keep repeating itself, it indicates that it did not get the recommendation right the first time. The wording presented here was fairly neutral and reflected sound common sense. He said it was hard to figure out how to prioritize this and triage it to make it happen. He asked for additions to this, language-wise.
Ms. Finn added that, considering what Ms. Levine said about recommendation #52, it might be useful to add a time element into the recommendation to make it more concrete. Ms. Levine stated that it was acceptable to add that the ACOT would like to see something “within X time”, but the ACOT cannot do anything about how and if the Secretary responded to the recommendation. Dr. Barr asked for Mr. McLaughlin’s thoughts on the recommendation.
Mr. McLaughlin raised the issue of the report noted in the recommendation, and asked what the expectation was for it. Ms. Cornell said that the goal was to have something concrete come out of this and to have a way to share what was learned. Otherwise, the agencies will just confer and that will be it. Dr. Barr asked for Mr. McLaughlin’s input.
Mr. McLaughlin stated that DOT could produce a report to update the ACOT on these activities. Dr. Durbin added that the metrics are hard-wired into the regulations; the field uses archaic metrics to measure things that have moved on considerably since then. This is a regulatory issue that cannot be fixed by tweaking at the margins; the recommendation to the Secretary needs to speak to the need for a comprehensive regulatory review of both CMS and HRSA regulations to harmonize them and make them flexible and adaptive to current practices and situations. Dr. Barr suggested using specific language about “regulatory revisions would include, but not be limited to changes in…” and so on. Mr. Durbin added the field has moved on from what was chosen originally; he expressed the view that there was a need for something about how the final rule, as it is structured, envisions that the OPTN would have multiple policies, made enforceable by the Secretary, but the community in general would like this not to be the case. He said some of this is hard wired into the regulations; so if you could remove the hard-wired metrics that are in the CMS regulations, and put them in OPTN policy, then it would enable things to change more rapidly and be more responsive to changes in the field.
Mr. Durbin suggested that the goal be a comprehensive regulatory review of CMS and HRSA policies within two years. Mr. Beyersdorf said that he could support that and it needs to happen; but the discussion was really about performance measurement systems of the oversight agencies (CMS, HRSA, OPTN, ETC) and the ACOT’s desire for them to coalesce on this issue. Ms. Cornell suggested language about a comprehensive regulatory review pertaining to performance measures, but Mr. Durbin said that the issue was bigger. As a result of this discussion, editing changes were made to revise the recommendation as indicated in bold:
Due to misalignment and inconsistencies between CMS certification regulations and outcome requirements for TC and OPOS, the ACOT recommends that the Secretary direct CMS and HRSA to confer with the OPTN, SRTR, the OPO community, and transplant centers representatives, to conduct a comprehensive review of regulatory requirements, and to promulgate regulatory and policy changes to requirements for OPOs and TCs that unify mutual goals of increasing organ donation, improving recipient outcomes, and reducing organ wastage and administrative burden on transplant centers and OPOs. These revisions will include, but not be limited to, improved risk adjustment methodologies for transplant centers and a statistically sound method for yield measures for OPOs. The ACOT recommends that this review be completed within one year and action taken within two years.
Dr. Barr said that he would work on this over lunch and display it later in the day for discussion. The AST representative spoke from the floor to voice the AST’s full support of this recommendation and comment that transplant centers should be actively involved.
OPTN Update, Maureen McBride, OPTN
Ms. McBride provided an update on progress in adopting the OPTN Strategic Plan. The issues have focused on what ends the OPTN needs to achieve in the next three to five years, and how things are likely to change in terms of policy, process, funding, etc. The Board reviewed the vision statement and re-ratified it. Ms. McBride described the OPTN’s key goals (see below) and the measurable and accountable milestones for accomplishing these goals:
1. Increase the number of transplants
The OPTN will report its progress on each of these goals to the Board. It was a monumental task to put it all together so quickly but OPTN is in a stronger position for having prioritized the goals for the future.
Ms. McBride also provided an update on other activities that occurred at the June Board meeting. The bylaws were rewritten to be in plain language and the due process activities changes were approved. The Board passed the revisions to Policy 6 about non-resident aliens; it now has new definitions of citizenship categories and allows for reviews of non-U.S. citizens and residents. Transplant data by citizenship will be available to the public. The changes from the June board meeting go into effect on September 1, 2012.
The fall public cycle will include six items for comment, including requiring reports on islet transplants and changes to neurological death reporting conditions.
Dr. Fung discussed the need for education about adverse events related to living donors. There was a recent kidney death in Ohio that validated the lack of transparency between ASTS and UNOS about adverse events. Dr. Fung expressed surprise that at least 20 kidneys have been removed for living donation but not transplanted. He commented that there was no way to find out about living donors who have died after making a liver or kidney donation. He noted that patients are dying for the same reasons that existed 10 years ago. Ms. McBride agreed and added that this was exactly why more information was needed – to provide this education.
Dr. Fung added that CMS and HHS need to find a way to communicate this; patients should not be dying because of misused clips just like they did 12 years ago. The ASTS leadership has said it was a legal issue but he found that hard to believe.
Dr. Gerber added that there was a need for continued education and asked if the Board was working with other stakeholders. Audits are going to be done across the board for surgical fields and it would be nice to pull things together. He asked if the Board was working with JAHCO. Ms. McBride said not that she knew of, but that this was a great suggestion.
Ms. Glazier said that it was unacceptable that the same issues were happening again. Medical peer review is a matter of state law, so there are more entities engaged here and it is a legally complex area, however. Dr. Fung asked how a living donor could provide informed consent when we cannot give them accurate numbers about outcomes. Ms. Glazier said that she agreed, but that many state laws affect this area.
Dr. Eason said that informed consent is so important, but we cannot specify the risk of making a live donation. It should be possible to both protect the transplant surgeon’s legal due process and have reportable events / incidents that can educate the public. Mr. McLaughlin said that the SRTR is developing metrics on living donation that will be added to program-specific reports in the future. The hope is to provide more information for the public on living donation.
The current ASTS president spoke from the floor and said that this was a big concern for surgeons, who want to know the risk for the donors. Surgeons want a safe forum where death details can be given without creating legal liability. ASTS is developing a patient safety organization that it can lead and use to collect this information. Dr. Barr asked if that had been vetted with HRSA and the response was it stemmed from a request received from the president of OPTN, for ASTS to look into it; they are just starting.
Dr. Eason asked about the proposal to eliminate the DSA as the allocation metric; the ACOT had made a recommendation on this and he wondered if anything happened with it. Mr. McLaughlin said that this was not part of the OPTN strategic plan but noted that the recommendation has traction. Mr. Durbin added that HRSA also gave the SRTR $500,000 to look at distribution boundaries that could be more evidence-based; OPTN will be deliberating on this too.
Living Donor Policy OPTN, Christie Thomas, M.D., Chair, Living Donor Committee, OPTN
Dr. Thomas presented by phone on activities since the last report to the ACOT in November 2008. He introduced the Living Donor Committee’s charge from the OPTN Board: “The Living Donor Committee develops policy and guidance related to the donation and transplantation of organs from living donors to recipients. The goal of the Committee’s work is to continue to improve the informed choice of prospective living donors, and the safety, protection and follow-up of all living donors.”
There have been significant changes in the oversight over living donors. In 2006, the Secretary of HHS directed the OPTN to develop policies regarding living organ donors and organ donor recipients. In 2009, the OPTN/UNOS Board resolved that the Committee should develop a policy proposal to establish a threshold for acceptable submission of living donor follow-up information. At this meeting, the Board also directed the Committee to develop and disseminate a resource outlining best practices for the submission of living donor follow-up based on its review of high performing programs. The OPTN approved “voluntary guidance” for the consent and medical evaluation of living donors that have since been available through the OPTN website. In December 2009, HRSA notified the OPTN that, although helpful, the resources developed to date were insufficient and that additional policies were required.
Dr. Christie showed graphs that illustrated the national numbers for kidney and liver donors who have a patient status (i.e., alive or dead, not lost-to-follow-up) on a one-year LDF form dated within two months of the donation anniversary: 65.6% of kidney donors and 68.9% of liver donors in this cohort had a timely status on their one-year form. Lab value of donated organ (serum creatinine for kidney and bilirubin for liver) was even worse: 40.7% of kidney donors and 54.7% of liver donors in this cohort had a lab value on a form with a status dated within two months of the donation anniversary.
Although the most recent rates are not great, they have improved drastically over the past three years: Kidney status went from about 40% to over 65%; kidney lab value went from 22% to almost 41%; liver status went from 54% to 69%; and liver lab value went from almost 39% to almost 55%. Despite the increase over the past three years, however, there was only a small increase over the past year. Data are highly variable between programs: the best programs have data on 100% on donors, while the worst programs have no information on donors.
In April 2010, representatives of the ASTS, the AST, NATCO, OPTN/UNOS, and HRSA met to discuss and develop a new process for incorporating clinical input into developing OPTN/UNOS policies with the potential to direct or prescribe medical care. The resulting document is known as the “Rockville Document.” According to the document, a Joint Societies Policy Steering Committee (comprised of members from the AST, ASTS, NATCO, OPTN/UNOS, and HRSA) would be given an opportunity to make recommendations on any OPTN policy under development with the potential to prescribe medical care, to include policies for the consent, medical evaluation, and follow-up of living donors. The goal of the new process was to foster earlier involvement from the professional societies in any policy that might impact clinical practice; quicker policy development; and greater acceptance by the transplant community at large.
The Joint Societies Steering Committee established a Joint Societies Workgroup (JSWG) with representation from AST, ASTS, NATCO and the UNOS Living Donor Committee. Its charge was to make recommendations to the Living Donor Committee on consent, medical evaluation, and follow-up of living donors. The JSWG has completed work on three resources representing members’ consensus:
• Guidance Document for the Informed Consent of Living Kidney Donor;
In June 2011, these JSWG resources were approved by the Executive Committees of the parent societies (AST, ASTS, and NATCO) and provided to UNOS and the Living Donor Committee for consideration in policy development. The JSWG recommendation was: “Mandatory follow-up at six months, one year, and two years following surgery is the transplant community’s responsibility to maintaining the public’s trust and demonstrating a sincere interest in that contract we share with current and future living donors.”
Dr. Christie described the comments received on the proposed language. The recommendation was revised as a result of the comments, to require a staggered threshold and delayed implementation. The final language was: “Transplant centers that recover living donor organs must report accurate, complete and timely follow-up data on the LDF form for at least 70% of their living kidney donors who donate between September 1, 2012 and August 31, 2013; 80% of their living kidney donors who donate between September 1, 2013 and August 31, 2014; 90% of their living kidney donors who donate beginning September 1, 2014. Living donor follow-up data within 60 days of the six-month, one-year, and two-year anniversary of donation is considered timely.”
In April 2012, the Committee approved the final language for the three proposals and voted to send the proposals for consideration at the Board’s meeting on June 25-26, 2012. But, before that meeting, the professional societies objected to what were deemed to be “substantive changes” in the proposals and the failure to follow the Rockville Document’s procedures. In response, the OPTN President agreed to table the Board’s consideration of the proposals pending further discussion between JSWG and the Living Donor Committee.
Dr. Fung asked what AST and ASTS objected to. The ASTS president spoke from the floor and clarified that, after the final proposal went back to the committee, it was not also sent back to the Workgroup, which it should have been under the process specified in the Rockville Document. So, the Board’s schedule for reviewing and voting on it did not comply with the Document’s process to discuss the issues before they went to the Board. Changes had been made that should have been discussed before the Board voted. She commented that the ASTS is absolutely in favor of living donor follow-up and would like to require a 100% good faith effort. But, the ASTS does not support making policy without evidence; at this point, no one knows what is feasible, or how hard the programs that lack data had tried to reach their donors for follow up. She noted that some donors were not willing to be engaged.
ASTS has an alternative proposal that the centers have to make a “good faith effort” to contact the donors. This should be documented so it can be audited by OPTN, and there should be some sort of opt-out for the donor. Only after one or two years of collecting these data will there be, in the ASTS’ opinion, enough information to determine a feasible threshold. It may be that a huge number of programs are not in compliance, or that creatinine levels at two years have nothing to do with long-term donor safety. ASTS wants to support living donor programs in their efforts to keep track of donors, but to do so with a sound evidence base.
A speaker commented from the floor that there are efforts to create language that will be accepted by everyone. The living donors on the committee are a constant reminder of the importance of this effort. The OPTN wants minimum threshold for follow up, so the negotiations are delicate and on-going. A minimum threshold for follow-up is based on what has been achieved at the best-performing centers; a level of less than 100% follow-up acknowledges that some programs may not be able to achieve 100%.
Ms. Zill spoke from the floor; she introduced herself as a living donor and past member of the Living Donor Committee. She noted that she has been following the policy proposals since 2002. In her view, the ASTS and the Living Donor Workgroup have a conflict of interest and should not be involved in making these policies. They always say there is an issue with not having enough evidence. As a result, medical criteria have been watered down, and informed consent documents are no better. She noted that there was also a need for long-term data, as short-term data do not tell us anything about long-term survival rates. Living donors are particularly at risk for poor cardiovascular outcomes, for example. She recommended that the ACOT members look at the literature on carcinoma, etc. She also asked Dr. Thomas to look at the allocation concepts being developed to assess where the living donors fit in. Living donors are told they will be “at the top of the list” if they need a donor – but there is no national wait list. Living donors are stuck with the same geographic disparities as everyone else. There needs to be a national program for these donors.
A speaker from the AST commented that he respectfully disagreed with Ms. Zill. In his view, several issues were important: first, the Social Security Master Death File (SSMDF) data are not available for SRTR analysis. Second, although the evidence-based argument was important, why look at data after only two years? When do we transition to longer-term follow up? And, whose responsibility is it?
Mr. McLaughlin said that they are in the midst of work with CMS for the Department to receive the SSMDF data. He added that there is a need for some new verification activities around this and procedural activities that are being addressed.
Liver Allocation Policy Update, OPTN, Kim Olthoff, M.D., Chair, Liver Committee, OPTN
Dr. Olthoff thanked the ACOT for the opportunity to present on this issue. She noted that allocation and distribution are different things. Allocation is based upon the principle of “sickest first”, uses MELD allocation system, and allows for standard and non-standard exceptions. Distribution is based upon the “local first” principle, and fosters broader regional and national sharing for high status and pediatric patients. She provided a timeline of the MELD/PELD system.
Currently, candidates at the regional level with MELD scores less than 15 are offered organs before the Status 1A/Bs and those with MELD scores greater than 15 elsewhere in the nation, sometimes just across a state line (i.e., Regions 2 and 9). There are variation in the MELD score at transplant centers between and within Regions, and variations in waiting list death rates between and within Regions.
Despite improvements in liver allocation and distribution, waitlist mortality remains high for patients with higher MELD scores. Further, there are significant disparities between and within regions for the mean MELD/PELD score at transplant and death rates on the waiting list. The Committee has been exploring how to direct livers to those who are most in need.
Dr. Olthoff described that, in 2009, the Committee circulated a proposal for regional sharing for Status 1s, which was approved and has been implemented, as well as for all MELD scores, which was sent to the Board. The large response to this second proposal led the Committee to request a public forum. A “Request for Information” document and survey was distributed in December 2009 in order to help determine the Forum agenda, which was held in Atlanta in April 2010. In June 2010, the Board directed the Committee “to develop recommendations to reduce geographic disparities in waitlist mortality.” A concept paper and second survey were circulated in December 2010, and the discussions were continued through other mechanisms, such as presentations at AASLD, ASTS Winter Symposium, and the ATC.
Options considered included:
• Full Regional Sharing – there was strong opposition to this option;
Based on a significant amount of feedback, the Committee decided to pursue the two options being proposed: Extension of Regional Share 15 Share 15 National; and Share 35 Regional — Candidates with MELD/PELD scores of 35 and higher. (If both were approved, they could be combined into one algorithm.)
Dr. Olthoff showed a slide to illustrate the process for Share 15 National: following all Regional 1As and Bs, local and Regional patients with MELD scores of 15 and above, and National 1As and 1Bs, livers would be offered to those with MELD/PELD scores greater than 15 nationally before being offered to anyone with a MELD score less than 15.
In June 2012, the two proposals were voted on and approved. Data will be reviewed every six months post-implementation to assess waiting list mortality by MELD score, post-transplant patient and graft survival, percent shared between OPOs, percent shared nationally, and percent of MELD exceptions scores transplanted at high MELDs at 35 and above.
Another forthcoming topic is Hepatocellular carcinoma (HCC): HCC patients get transplanted sooner than non-HCC patients, and HCC patients have lower dropout rate than non-HCC patients across all regions. While MELD, AFP and tumor size are predictors of dropout, non-HCC still has higher drop-out rates.
Through optimized regrouping, the Committee regrouped existing Donor Service Areas (DSAs) into novel regions using an integer programming model. The model assigned each DSA to exactly one region, and includes constraints to ensure that the MELD level at which any region exhausted its supply of livers was similar across regions. The model minimized the sum of the squared distances between all the DSAs and the location of each region. Two optimized maps of the U.S. were shown to illustrate the regrouping.
The Committee is also looking at all the different MELD exceptions, of which there are a huge number, with the goal of standardizing them across the country. A work group will also look at PELD allocation; over half of pediatric cases are done with an exception PELD score, indicating that something was clearly not reflecting the realities of pediatric disease.
Dr. Schaefer commented that the regional design was very exciting and that there were literally a trillion ways to design regions. So, being able to use the data to generate good models was a very good step forward. Dr. Olthoff agreed that the historical ways are probably not the best to use; the DSA can remain as a structure, but the distribution model can do better. DSAs may be important for donor recruitment, but are less important for distribution. She hoped that a new policy proposal would be distributed in the coming year.
A speaker who had been involved in the process commented from the floor that this was just an example and the DSA lines were used to keep the model simple. An important lesson they learned was that, keeping the regional boundaries and using a regional system makes the geographic disparities worse. By redrawing the regions, even maintaining the same DSAs, improved the disparities. The next step was to assess what happens when one ignores all of the lines and past frameworks of the current system.
Update from the Achieving Consensus on Increased Risk Donors to Improve Access to Organ Transplantation Meeting - Michael Ison, M.D., Medical Director, Transplant & Immuno-compromised Host Infectious Disease Service, Northwestern University Comprehensive Transplant Center
Dr. Ison provided an update on the April 2012 meeting that was held in Chicago. He applied to the AHRQ’s Small Grant Program for Conference Support and received the award in September 2011. Organizational calls for the meeting were initiated in October 2011; AST and ASTS agreed to co-sponsor. The goals of the conference were to:
• Disseminate research findings and evidence-based information about optimal evaluation, classification of donors at increased risk of disease transmission in addition to optimal informed consent and post-transplant evaluation of recipients of organs from such donors with the goal of improving the outcomes, quality, access to, and utilization of such organs.
The conference had four aims, each of which was addressed by a workgroup:
• Aim 1. To develop a consensus definition of donors at increased risk of transmission of HIV, HBV, and HCV
Dr. Ison described the workgroup membership and noted that the key findings and workgroup slides were going to be made available to the public. The preliminary findings and the attendee survey have been submitted to AHRQ and are available on the public website. An executive summary of the meeting with all approved recommendations and identified gaps will be submitted to the American Journal of Transplantation; groups may also prepare individual publications based on their own work.
Dr. Ison presented a summary of the workgroup findings. The four workgroups also identified many gaps, which included the lack of data on:
• The optimal screening of live and deceased donors for HIV, HBV and HCV.
Dr. Barr said he had attended the meeting and it was great. Dr. Fung expressed his surprise at the focus on recipient issues for screening and asked if any estimates had been prepared on the costs of implementing the recommendations. The response was that it had been done after the conference, at the request of John Roberts. Dr. Ison noted that just screening for HIV was not cost-efficient (it would take $200 million to identify 1 case) but was cost-effective for Hepatitis C, at a cost of $74,000 per case detected.
Update on PHS Guidelines - Matthew Kuehnert, M.D., CDC ex officio member, ACOT
Dr. Kuehnert presented by phone – he noted that there was one clarification to make on the title that appeared in the agenda: the guidelines are Public Health Service (PHS) guidelines, not CDC guidelines. Although the CDC has taken a lead in their development, the guidelines were for the public health service agencies as a whole, including HRSA and the FDA. He noted that the slides would be familiar to members, as he was providing an update from the ACOT’s last meeting and the ACOT membership is largely the same.
The PHS published the “Guidelines for Preventing Transmission of Human Immunodeficiency Virus Through Transplantation of Human Tissue and Organs” in 1994. There has been broad agreement that these guidelines needed to be revised; for example, the Association for Organ Procurement Organizations (AOPO) and other transplant organizations sent letters to the CDC suggesting guidelines’ revision in 2008.
There are important differences in the focus of the old and new guidelines: The 1994 guidelines for preventing HIV transmission addressed HIV transmission with respect to organs and tissues, banked breast milk, and semen. The Revised Draft is broader; the “PHS Guideline for Reducing HIV, HBV and HCV Transmission through Organ Transplantation” addresses organs only but considers transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV).
HHS agencies and external experts from the transplant community provided input and the CDC acted as the lead for PHS agencies to develop a draft. The recommendations were based on systematic review of the best available evidence. The evidence review was conducted by the Center for Evidence-based Practice (CEP) at the University of Pennsylvania and the ECRI Institute/Evidence-based Practice Center (EPC). Dr. Kuehnert described the many entities that participated in this process.
The HHS offices and agencies (including CDC, HRSA, FDA, and CMS) reviewed and approved the draft Guideline. The 90-day comment period that was announced in the Federal Register ended on December 23, 2011. Approximately 100 comments were received and all were reviewed. The PHS Guideline Revision Work Group convened to review and discuss and agree upon changes to the recommendations. The major changes made in response to public comment were:
• Number of recommendations decreased from 54 to 32;
The next steps were to reconvene the Expert Panel and the Review Committee, submit the Guideline for HHS clearance, and then publish the final Guideline in late 2012 or early 2013. He closed by saying that it was important to clarify that the final guideline would not be regulation or policy, it is just a guideline.
Dr. Kuehnert responded that he certainly understood that PHS statements were often seen as a standard of care; the agencies take seriously that it will impact the standard of practice.
Dr. Fung described a case where he got a notification about post-test positive in kidney transplant recipient in North Carolina that turned out to be a false positive. Damage occurred from the resulting costs and anxiety, but the organs had already been transplanted. He asked about the false-positive rates. The response was that false-positives do occur; it depends on the lab.
Dr. Ison advocated for collecting these data. He described an effort to collect them from three OPOs that was very hard; the effort needs to be a national one. He added that no one had raised the issue of false-positive serologic testing – this can be safely used but was not being used.
Vascular Composite Allografts Informed Consent, Alexandra Glazier, J.D., M.P.H., New England Organ Bank; Kurt Shutterly, RN, Chief Operating Officer, Center for Organ Recovery and Education
Alexandra Glazier, J.D., M.P.H., New England Organ Bank
Ms. Glazier provided an update on the field of VCA, which is moving forward despite the fact that there has yet to be any action on it from the Secretary. The Uniform Anatomical Gift Act (UAGA) is model law that is enacted by the states; currently, 46 states have passed the 2006 update. The UAGA is based on “gift law”; this was a purposeful and important choice that best fits the realities of organ donation.
The law for gifts includes three primary elements: intent, transfer, and acceptance. She noted that informed consent was not one of these elements. The law defines the gift as a voluntary and legally binding uncompensated transfer. There are two ways to transfer something – by selling it (this is governed by contract law) or by giving it (this is governed by gift law). Since Federal law prevents compensation for organs, gift law has to be used. It is important that the gift be legally binding, so people cannot take their organ donations back at some future time. When the organ is gifted and accepted, then it is legally binding.
From the law’s perspective, informed consent is designed to provide the risks and benefits to the patient; it exists within the context of the doctor-patient relationship. But, deceased donors do not fit here – they have no risks or benefits stemming from organ donation, and they lack an active doctor-patient fiduciary relationship. Decisions are made well before the person actually donates, usually. So, this falls outside the informed consent box.
There are two ways the authorization to make the gift can happen: the first is first-person consent which is irrevocable; it applies to adults, and is usually done through registries. The second way is through a surrogate decision being made in the absence of first-person consent; this applies to minors. Ms. Glazier described proxies in terms of who can make decisions in this area.
Applying this to VCA is fairly simple because the UAGA says that an anatomical gift applies to any “part” of the human body, and then further defines “part” as any organ, eye, or tissue or component thereof. There is not a lot of debate in legal fields about VCA failing under the UAGA as being some part of a human body.
Ms. Glazier said that she was often asked about donor registries, and whether they authorize VCA donations. She commented that the UAGA includes something called a “general consent registry.” This is what one thinks of when a person goes to the DMV and checks the box: the person saying they will donate “any needed organ or tissue” – it is all encompassing. There is no way to be more specific about what organs to donate because general intent registries include “any” donation, and therefore include VCA as well. Some registries, however, allow the person to put limitations or restrictions on the donation; this is more often the case in web-based registries where someone can restrict the gift, such as by donating their liver but not their kidney. This varies by region.
In addition, thus far, the VCA protocols have been experimental and go through an IRB approval process and involve data collection. To this end, they might be considered to be “research”; some donor registries include the option to allow the gift to be used for research, while others do not.
Given those factors, the New England Organ Bank decided to ask for additional permission from the agent, next of kin, etc. Even if the person is in the registry and has given first-person consent, in her view, there were sound reasons to do this. First, there are privacy considerations, specifically with facial VCA. The newness of this area means that people may not have considered this use when they made their donation, so one cannot assume first-person consent. Media attention on the recipient is likely to occur, which will alert the donor’s family about the recipient very quickly, which is very unusual in the field of transplantation. For these reasons, her organization only approaches families after they have made the decision to donate organs. It also uses a special form for VCA that is very long and includes much more information, such as describing what the grafts are and the need for photographs to match skin tone.
The New England Organ Bank has coordinated six VCA donations so far (4 face, 2 hands); it has had no post-donation issues. Most of the families have met the recipient and most have agreed to talk to the media.
In the future, there will be a need to worry about allocation, so Ms. Glazier expressed the hope that the Secretary will act soon on the regulations. There are three VCA programs in Boston, so her organization had to come up with its own regional allocation system. Matching criteria for the VCA donor and recipient are significant and include a lot of factors, such as size (which is a very significant issue for extremities), gender, age range (there is about a 10-year range), and skin tone.
Given the limitations and complications of matching, she said it was not clear when there will be a need for allocation, but the organization has started a list. Time since the injury may be an issue, as could be the need for multiple VCA transplants, and/or the need for other organs. Ms. Glazier said she was looking forward to the official designation of VCA in order to provide the regulatory infrastructure that her organization has already been following. Allocation issues will change as this evolves; she expected that, one day, there would not be a need for separate authorization forms for VCA donations.
Kurt Shutterly, RN, Chief Operating Officer, Center for Organ Recovery and Education
Mr. Shutterly provided the OPO perspective on VCA. The OPOs use the same screening process described by Ms. Glazier. They learned early on that bringing up VCA at the same time as organ donation complicated matters. Organs are the priority; his organization strives to get the family on board for that and then use the time during which organs were being allocated to seek a match and then talk to the family about VCA. His organization has 100% acceptance of VCA. His organization also obtains written authorization from the family regardless of whether or not first-person authorization exists.
Families are concerned about additional costs and the OPO picks up all costs for VCA. Families can be concerned about viewings at the funeral home, so they use a prosthesis that is very realistic. In three-fifths of cases, the family chooses direct cremation, however, making this less of an issue. Reconstructions and funeral homes have not presented any problems. The donor’s family knows who the recipient is within days because of the media attention; it is important to be up-front about this.
Coordination is not very complicated and the OPO does it. His organization could do more VCAs than they have – he agreed that there was a need for an allocation system.
The OPO conducts post-donor reviews and have found the OR and other staff to be very supportive. Mr. Shutterly showed a photograph of a hand transplant recipient and described the very personal connections that were made by this patient. The hospital has been very supportive and the process has been special for the staff. He showed pictures of recipients and described some of their stories.
Dr. Barr noted that the ACOT’s Recommendation #52 addressed VCA and asked where that was in the process. The response from DOT was that everyone was just waiting. Dr. Barr noted that the complexities with VCA are very different than with solid organ transplantation and suggested that there was a need to share best practices. Ms. Glazier added that facial graft donation is much more complex than limbs, in terms of recovery.
A representative from AST spoke from the floor to comment that, as the field matures, data should be collected so that everyone can benefit.
Dr. Nakagawa asked about pediatric cases. Ms. Glazier responded that no pediatric cases have been done yet, but will be shortly. One of the three Boston centers is a pediatric center. Dr. Barr added that pediatric cases have been done in France.
Alignment of CMS Regulatory Requirements with OPTN and HRSA: ACOT Recommendation
The recommendation from before lunch was displayed for comment:
The ACOT recognizes that the current CMS and HRSA/OPTN structure creates unnecessary burdens and inconsistent requirements on transplant centers (TCs) and organ procurement organizations (OPOs) and that the current system lacks responsiveness to advances in TC and OPO performance metrics. The ACOT recommends that the Secretary direct CMS and HRSA to confer with the OPTN, SRTR, the OPO community, and TC representatives, to conduct a comprehensive review of regulatory and other requirements, and to promulgate regulatory and policy changes to requirements for OPOs and TCs that unify mutual goals of increasing organ donation, improving recipient outcomes, and reducing organ wastage and administrative burden on TCs and OPOs. These revisions should include, but not be limited to, improved risk adjustment methodologies for TCs and a statistically sound method for yield measures for OPOs. The ACOT recommends that this review be completed within one year and that action be taken within two years.
Members expressed their support for this language and Ms. Cornell expressed her appreciation for their input. A motion to approve the recommendation was made and seconded. The recommendation was passed unanimously.
Ms. Stroup took the opportunity to introduce Cheryl Dammons, the new Deputy Associate Administrator of the Healthcare Systems Bureau who joined the Bureau after the last ACOT meeting.
CMS Conditions of Participation Outcomes on Kidney Transplant: Impact on Center Volume and Donor Selection - John Fung, M.D., Ph.D., Cleveland Clinic
There has been an unprecedented attenuation of the growth of kidney transplantation in the U.S. While this stagnation in national kidney transplant volume may have multiple causes, it is of concern to prospective transplant recipients and caregivers alike. One source of the stagnant growth might be associated with increased emphases on regulatory oversight of centers’ performance. Dr. Fung and his partners hypothesized that centers with low performance evaluations may respond by becoming more conservative and thereby limited transplant growth.
To explore this question, his group evaluated data directly from archived SRTR performance reports from 2007 to 2009. They compared the change in transplant volume for each kidney transplant center over this period with respect to the incidence of low performance evaluation. In addition, they evaluated changes in recipient and donor characteristics between centers based on the receipt of a low performance evaluation. They then tested the association between changes in kidney transplant volume with incidence of low performance evaluations.
They looked at 46 centers: 5 centers had 6 out of 6 reporting periods with lower-than-expected outcomes. They did not see a correlation with volume and deficiency in graft survival or patient survival: all do about the same. They also looked at change in kidney volume by performance. Centers with no issues grew by 7%, while those with low performance in terms of graft survival had a net volume decrease of 27%.
The group believes that there is a significant association between changes in transplant volume and receipt of low performance evaluations for kidney transplant centers. The results may suggest that centers that receive low performance evaluations react by reducing their transplant volume and changing selection criteria of donors and candidates.
The group discussed the fact that a center getting flagged and reducing its volume may not completely describe the situation. The center could have bad outcomes that were flagged, or they could have acceptable outcomes and have taken on risks that are not accommodated in the models. Or, they could have acceptable outcomes but be flagged due to statistical artifacts –analysis indicates that the centers in the last group have an 11% chance of getting flagged, which is a problem.
Dr. Fung noted that there were also data indicating that the centers might be doing the wrong thing – Expanded Criteria Donors provide a buffer. So, if the centers get rid of them, the outcomes get worse. Centers need to see where they were failing and not assume it was due to higher risk donors/recipients.
Dr. Snyder added that the SRTR did a study in which it found the flag and then looked both before and after the flag; this review found little evidence in decreased volume. The SRTR is trying to see why the two studies got different outcomes. He added that SRTR provides the data sheets that are used; the centers can see where they have events and if it is about an ECD. They have the tools.
Update and Challenges of Kidney Paired Donation (KPD) - Dorry Segev, M.D., Ph.D., Johns Hopkins University
Dr. Segev began by noting that KPD is a complex field right now and he would refer to simple exchanges, or dominoes, in this presentation. To date, there have been over 2,000 patients transplanted through KPD. This number is not as high as many thought it would be; KPD should comprise something more like one-third of all live donor transplants. KPD represents 12% of live donor transplants in the U.S. A key issue is that, as a result, for 12% of U.S. live donor transplants, someone other than the donor is deciding the recipient.. Does this make KPD allocation?
Several decision paradigms exist for who determines the recipient:
• Single-center paradigm in which the physician running the KPD program decides;
There has been progress made in KPD. Thanks to the Charlie W. Norwood Living Organ Donation Act, KPD is legal. It is now clear that the donor and recipient operations do not need to occur at the same time, or in the same hospital. And, live donor kidneys can be shipped; most multi-center exchanges now ship the kidney.
KPD is not just for incompatible pairs anymore. Compatible pairs can benefit both in terms of finding a younger donor and in terms of the KPD pool because of blood type distributions. A problem is that, once one gets over the period of matching all the easy matches, what’s left are the very difficult pairs to match and one has to do KPD with a goal that is more amenable to desensitization.
Key issue areas include:
• Chains: are longer chains really better, or do they just attract more media? When do you stop the chain? To whom does the last kidney go? Critically, is the non-directed donor the resource of the center, or a national resource?
The mathematics will follow from this as role of chains and priorities evolve.
• Evaluation of incompatible donors
KPD financing seeks to accomplish several goals including to: transfer the costs from the donor hospital to the recipient hospital; eliminate the volume disparity between different centers; provide reimbursement for donor services by out-of-network providers; present consistent and predictable expenses for payers; and remain compliant with CMS regulations.
Mike Reese and colleagues have suggested the use of a national Standard Acquisition Charge (SAC) to improve upon the need for individual negotiations between KPD transplant centers. A SAC would also avoid volume-related discrepancies because all centers pay the same amount for a KPD transplant, representing an average of all the possible charges from a center-specific approach. SAC is assessed only to those centers and payers who benefited through completed KPD transplants. The SAC is preferred by private payers. It is not trivial to define the fee. A center-specific SAC disincentivizes centers from practices that benefit the patient. With a national SAC, someone would have to say when is enough or the costs will be huge.
To address these issues, a conference was held in March 2012 to address donor evaluation, histocompatibility, geographic barriers, financial issues, allocation policies, and implementation.
The resulting consensus statement was that:
• All potential living donors should be informed about KPD early in the educational process, prior to compatibility testing.
Too many people still do not know about KPD, so the clear message is the need to do better at educating the public about KPD. A national SAC was the conference recommendation. This is dependent upon having one national program; without it, a national SAC would be nearly impossible. The payor recommendations are for a national SAC as well. Questions remain, such as whether CMS would lead this effort.
Dr. Barr asked Dr. Segev’s opinion about these questions. Dr. Segev responded that, personally, he felt there was a need to slowly move to a national program; this cannot happen tomorrow but the field should head this way. It should be run by a contractor through HRSA, like the OPTN is. This will make the payors happy, enable centers to do KPD without losing money, save CMS money, and increase transplants via KPD. At the conference, there was a clear consensus for a single national registry as the best way to serve patients, payors, and CMS alike. Moving slowly enables people to start thinking this way and make it easier for them to work together.
Mr. Beyersdorf noted that, if the field moves too slowly, it may end up with boundaries that do not help. Dr. Segev clarified that he was talking about something like a two-year time frame. Dr. Beyersdorf joked that that’s not “slow”.
Dr. Schaefer said that the number of transplants would go up a lot with a national list, but seconded the concern raised in the talk: that the easy transplants would get done and the nation would be left with just the hard-to-match patients. Dr. Segev said that a national system would help identify these issues and identify more donors for those patients.
Dr. Fung asked about a system where there was a hard-to-transplant patient for whom a potential match was found in the KPD pool, and the patient was asked to bring someone in to continue the chain. Dr. Segev responded that he could not comment on the ethics of something like that, but can comment on the “coolness” of it. This could be done; where it lies on the coercion scale he could not address, but he noted that national lists foster creativity.
Dr. Crawford asked about the role of the OPTN in KPD living donation. All of the language was pre-KPD; it seems like, on the authority of the Secretary, the OPTN could gain the authority to regulate KPD. Dr. Segev said that this is a question for HRSA; he has heard different things about it. We could decide whether the process of taking an organ from a live donors and putting it into a recipient is allocation – it would be a big deal.
Dr. Feng added that the national system described has many advantages but may not solve all of the problems. Many of the problems are at the grassroots, where transplant centers fail to tell patients about KPD and cannot perform it. Even with the perfect national system, there was still a need to think about this as a national effort that engages the whole community: centers, donors, potential donors, etc. This has to be discussed early on in order to disseminate the success of the process. Dr. Segev noted that patients sign an informed consent form for ECDs, infectious risk donors, etc… there may be a way to have patients sign something to confirm they were told about KPD.
Ms. Levine noted that NOTA does not differentiate between living and deceased donations. The Secretary can direct OPTN to issue policies on any matter on which the Secretary provides direction. So, the Secretary’s direction that OPTN should work on living donor policies could extend to KPD as well; there is probably authority for this. Dr. Barr added that, with 12% of donations being KPD, it probably is allocation. The ACOT cannot do anything about it at this meeting, but should follow up on the subject to see if it wanted to make a recommendation on this area.
Ms. Glazier agreed that this absolutely raises allocation issues that people struggle with on the deceased side; in her view, KPD was no different. Dr. Barr suggested that the ACOT form a work group on this. ACOT now only meets face-to-face once a year due to budget issues, but could hold conference calls and then present at the meeting next year. Dr. Segev agreed that this is timely; there is a publication coming out soon in AJT. Dr. Barr committed to talking to Ms. Stroup about setting up calls and generating a recommendation for future consideration.
Mr. Durbin added that the CMS/ HRSA coordinating group needs to really look at it too.
Donor Management Research and Innovation - Peter Abt, M.D. and Sandy Feng, M.D., Ph.D., American Society of Transplant Surgeons; Claus Neimann, M.D., University of California San Francisco
Challenges to Research and Innovation to Optimize Deceased Donor Organ Quality and Quantity Peter Abt, M.D., American Society of Transplant Surgeons
There is a need for innovation and research in donor intervention and treatment in order to increase the number of organs available for transplantation; mitigate waitlist morbidity and mortality; improve the quality of organs used for transplantation; and reduce recipient morbidity and mortality. There are many barriers to doing this work, however. Dr. Abt described the timeline of ASTS efforts and the two face-to-face meetings that have been conducted recently.
As described, organ donation and associated research is based on “gift law”; the donation is viewed as a gift, not as an informed decision regarding health care by the deceased or their next of kin. There are issues of transparency and some circumstances require informed consent, as with genetic studies.
Does authorization achieve maximum transparency? The public perception of and trust in donation is very important. There is, however, a lack of awareness that donation may be associated with research, and there is the potential risk for research to alter the intention of the gift.
Hospitals face regulatory and logistical challenges too: most lack a policy for assessing clinical trial protocols in deceased donors. If an investigator has to approach each hospital on an individual basis – the current approach – donor-based research is not feasible. There is a vacuum related to research in deceased donors. Federal regulations governing research in human subjects do not apply. The role of the institutional review board, if any, in the evaluation of donor intervention / treatment trials is unclear, as well.
Sandy Feng, M.D., Ph.D., American Society of Transplant Surgeons
Challenging problems have dissuaded insurance payors and others from supporting this research.
• Organ offers are made to waitlist candidates through their transplant physicians;
Receiving an organ that has been involved in a donor-based research protocol does not obligate the recipient to participate in the research. Donor-based research questions the necessity of recipient consent under specific circumstances. There are many informed consent issues.
There is a need for better communication and coordination, such as a single repository that provides standardized information related to all donor-based studies (as is provided by www.clinicaltrials.gov). There is a need for a mechanism to expeditiously distribute detailed information about study interventions / treatments to the physicians of all candidates offered an organ from a donor that has participated in an intervention or treatment trial. This is essential for final decisions regarding organ acceptance and to support the informed consent discussion with the recipient regarding research participation. Such a mechanism can also optimally and safely provide data regarding the recipient and/or transplant outcomes to the investigator.
We lack a framework for approaching this issue and for determining whose obligation it is to track the impact on the other organs. There are a host of potential impacts on donors, centers, researchers, etc.
The ASTS has a recommendation it would like to suggest that the ACOT make. The ASTS requests that the ACOT recommend to the Secretary that HRSA leadership should work with the donation and transplantation community to provide recommendations that address the complex and multi-disciplinary challenges that obstruct the safe and optimal design and execution of innovative clinical trials in deceased brain dead organ donors. We need a broad assessment of this area of innovation.
Claus Neimann, M.D., University of California San Francisco
Dr. Niemann attended by phone and commented that, from an investigator’s perspective, this was a good summary. The problems that he has experienced are exactly those outlined by the other speakers. In fact, he just received an email from a pharmaceutical company that is worried about clinical trials.
Dr. Barr noted that there was a HRSA funding mechanism for research. He asked Ms. Beigay, who manages the DoT special donation initiatives, to address this. Ms. Beigay said there were several things to consider; logistics were as important as IRB approval. It is important to consider that, when an IRB looks at studies, it looks at the standard of practice, to assess the risk of the study or technique.
Dr. Niemann commented that the study he mentioned is looking at mild hypothermia in donors. The IRB process considered both donor and recipient and the ethicists said there was minimal risk. This was circulated in all transplant centers (although he was not sure who read it). The transplant centers were concerned about liability, so he met with them too. This process was very time-consuming and would be impossible to do outside of the DSA.
Dr. Feng noted that the concepts are easily embraceable. But, when one considers the extent of what the National Institutes of Health are doing — things like molecular targets, totally investigational drugs — and then layers this onto organ transplantation, there is a large risk of everything coming to standstill while we figure out how to address it. This will impact public perceptions. Dr. Niemann agreed.
Ms. Glazier expressed her appreciation that the ACOT is talking about this very important issue. She added that one problem stems from the fact that we do not know who the subjects are in advance. The Federal Office of Human Research Protections (OHRP) is responsible for oversight of human subject regulations; it should connect with the FDA and HRSA to have conversations about guidance in this area. An interagency discussion is needed. Ms. Beigay suggested some activities to make this easier, such as consenting the recipient at the time of transplant as a second level for a research organ.
Dr. Barr agreed this was a very complicated issue and complimented the speakers on doing such a good job of explaining it. He suggested that this was an appropriate issue for the ACOT to consider and that there was a need for a consensus meeting with an algorithm to think about it. After such a meeting, the ACOT could do something with the outcomes. In his view, an ACOT work group was not going to cut it – something more is needed to engage scientists, IRB, OPOs, etc. We need more background that lays out potential solutions.
Dr. Feng stated that the challenge was getting the right group together. Whether it was the Office of Human Research Protections or some other people in a room, there is a need for some more vested authority to be able to say something definitive. Dr. Abt agreed that there was a need for input from HRSA and from other governmental agencies. He noted that a consensus conference had already been held, and Dr. Barr withdrew that recommendation.
Dr. Barr suggested that the ACOT could try to get OHRP and HRSA together to communicate; Ms. Glazier added the FDA to that list, since they are involved in device trials and other areas. Dr. Barr added all of NIH and said that HRSA should make the decision. He said that he would send an email to ACOT members about working on this with the goal of getting HRSA to interact with OHRP regarding obstacles to donor-interventional research and improving donor quality. HRSA has already tried this; pharmaceuticals are interested but are overwhelmed by the complexity of this. Dr. Feng and Dr. Abt said that they were also working on something that they would share with Dr. Barr.
Ms. Levine reminded the group that a formal recommendation must be made in public and cannot be done by email. It can be done on a conference call, as long as a notice is placed in the Federal Register about the call. Dr. Barr asked members to let him know if they were interested in the KPD work group and/or the research workgroup.
Dr. Barr announced a big “thank you” to Mr. Durbin for everything he has done for the community over the years; Mr. Durbin is retiring in November 2012. He has worked with OPTN and ACOT and been a major champion of the field of transplantation throughout his time at DOT and HRSA.
Report of the Technical Expert Panel on Uncontrolled Determination of Death
Dr. Nakagawa said that the group has grappled with this; there is almost a unified theory of death based on circulation, which presents a stumbling block. An uncontrolled circulatory determination of death may not be feasible in the U.S. There is a need for boundaries for when patients are declared dead. Ms. Glazier noted that the clinical clarity and legal clarity must mesh.
Dr. Bernat stated that part of the problem stems from the UDDA language, which does not clarify the relationship between the two standards. This clarification does exist in the background document that was published in 1981. He noted that international groups are working on this as well; the World Health Organization, for example, was engaged. He expressed the hope that there would be something of substance to discuss at the next meeting of the ACOT.
Dr. Barr asked ACOT members and members of the public to send agenda item ideas to Ms. Stroup; the staff will work on getting the right person to speak and collect background information for the ACOT members.
Ms. Stroup noted that public comments would be shared with the members and made part of the record.
The AST representative brought up the UNOS rewrite of the policies that had been mentioned in the strategic plan overview. The AST was concerned that some of the plain language rewriting might not reflect the original language so it was submitting comments about its concerns. It was noted that the comment period ends on September 1, 2012.
Dr. Fung asked what HRSA was funding in terms of studies. The response was that all of the studies are listed on the website along with the abstract (www.organdonor.gov, under “legislation and grants”). All the grantee-stimulated publications are there too (about 100 of them). Dr. Barr asked about Clinical Interventions to Increase Organ Procurement (CIOP) funding and was told that there would not be a new cycle of CIOP grants in FY 2013 due to budget issues.
Ms. Zill spoke from the floor, noting that she is a living kidney donor, and former member of the Living Donor Death Task Force. She has concluded, with sadness, that the U.S. transplantation system is not high-quality and is out-of-step with international consensus. She implored Secretary Sebelius to review the OPTN policies around ethical conduct, international activities and living donors. The following question should be central to review: Are UNOS and OPTN’s policies designed to meet the needs of the public or the desires of private sector stakeholders? The NOTA was created in 1984 and included a system for sharing organs and the OPTN was created to be a self-governing agency to be managed by a non-profit tax-exempt private contractor, UNOS. Although created to be separate organizations, UNOS and the OPTN have shared the same board since 1986. Concerns about this were raised immediately, including by legal scholars. Ms. Zill read a quotation from one such legal scholar.
Ms. Zill continued, 12 years later, during controversy over the final rule, Representative Dingell of Michigan referred to UNOS as “shabby contractor who seeks an absolute monopoly over their handling of organs in this nation, and which spreads deceit, misrepresentation, and falsehood.” Congress intended OPTN to be a national resource; however, a recent 2011 policy UNOS/OPTN policy proposal ostensibly on data collection about U.S. nationals, contains options about NOTA and does not provide any authority for basing policy on U.S. citizenship and residency. Regarding the final rule, the regulations provide no basis for the use of citizenship or residency status in the allocation formulas. Why were these opinions sought and included in a policy on data collection?
Ms. Zill continued, despite recent international consensus meetings in Istanbul and Madrid, which stressed the importance of national self-sufficiency in transplantation to decrease organ trafficking, the opinions undermine our national self-sufficiency and have been rendered in the context of a global market approximately $54 billion in 2010 and is projected to reach $80 billion in 2018. And, she added, as she reads it, the same proposal does not enhance data on foreign nationals coming to the U.S. and being placed on the list. Rather, it is more of a “don’t ask, don’t tell” policy because residency is to be self-selected by the patient without verification. The five percent policy that used to trigger the system has been eliminated and the ability to track those coming to the U.S. so tracing this will be difficult because the data used to audit transplants for foreign nationals will be of limited value. Ms. Zill noted that she had copies of her public comment available.
The meeting adjourned.