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Advisory Committee on Organ Transplantation

ADVISORY COMMITTEE ON ORGAN TRANSPLANTATION
U.S. Department of Health and Human Services
Conference Call * Tuesday, February 28, 2012


Participants: Dr. Barr, Ms. Shih Andrada, Dr. Coleman, Ms. Cornell, Ms. Corning, Dr. Crawford, Dr. Eason, Ms. Finn, Dr. Fong, Dr. Gerber, Ms. Glazier, Dr. Kuehnert, Mr. Lara, Ms. Levine, Ms. McDonald, Dr. Nakagawa, Ms. Puryear, Dr. St. Martin, Dr. Schaeffer. Ms. Stroup

Welcome — Patricia Stroup, Executive Secretary, ACOT

Ms. Stroup welcomed everyone to the ACOT’s winter meeting and conducted a roll call. She then turned the meeting over to Dr. Barr.  

Welcome & Opening Remarks — Mark Barr, M.D., Chairperson, ACOT

Dr Barr welcomed the group; he noted that the agenda was very full and included reports from several workgroups, presentations on projects, an update from the Advisory Committee on Blood Safety and Availability, and a report from Dr. Kuehnert on CDC guidelines. He reminded listeners that the slides are available on-line on the ACOT website.

Program Update – Richard Durbin, Director, Division of Transplantation

Mr. Durbin gave a brief program update. For fiscal year 2012 appropriates, the organ transplantation program is not in the Continuing Resolution and received about $24 million. This is a decrease from FY11 but, in comparison to other programs, it did well for the fiscal year. Funding is down only about $800,000 from FY11. About $7.5 million, or one-third of the funding, is spent on demonstration grants and public education grants – these activities are the largest component of the annual funding. The next largest is the $4.6 million for SRTR, which is 20 percent of the appropriations. The next major initiative is the $2.7 million for the Community of Practice (which used to be called the Collaborative). $2.7 million (12 percent) is spent on Public & Prof. Education Activities; $2.3 million (10 percent) on Travel and Subsistence Grants, and $1.3 million (6 percent) on OPTN.

In terms of program performance, in 2004, goals were established for conversion rates and organs per donor. The conversion rate goal was achieved in the year ending in September 2010; the current rate is 77 percent. There has been less success with the organs per donor goal: it was 3.6 organs per donor at baseline and has only gone up to 3.7 organs/donor. The rate has fluctuated up and down but is around that level.  

In 2010, there were 14,507 donors: 7,943 deceased and 6,564 living; there were 28,662 transplants, an increase of 1 percent from 2009 (22,102 deceased and 6,561 living). The number of 2010 deceased donors is 8/10s of a percent less than the 2009 number; the number of living donors is 7/10s of a percent less, but the number of transplants facilitated has gone up by about 1 percent.

DOT is supporting a Donor Potential Study that is being conducted by the Center for Transplant System Excellence and UNOS. It will look at donor potential in the U.S. and the potential is for the next 5-10 years. The researchers are conducting a very evidence-based study and are working with large group of experts in the field; the report will be completed this fall. HRSA plans to establish performance goals as a result of this study, as part of the community of practice.

HRSA and the FDA have been working on resolving the appropriate approach on VCA (faces, hands, etc.), which are currently considered to be tissues; comments have been accepted on a proposal to characterize VCA as organs. Mr. Durbin described the ways in which VCA more closely resemble traditional organs than tissues. If the approach changes, VCA would be transferred from the FDA to HRSA for the purposes of oversight. Comments are closed now; almost all of the comments were unanimously in support of this change. The comments are being reviewed and the agencies are working with the Secretary to create a final rule on this later this year.

In terms of the Community of Practice, HRSA had worked with the Transplantation Alliance to create activities. HRSA is now trying to make the activities more permanent by awarding a three-year $3 million per year cooperative agreement to the Organ Donation and Transplantation Alliance in order to sustain and improve upon the gains made from the Collaboratives. HRSA is trying to create more permanent infrastructure to build upon.

Mr. Durbin updated the group on the SRTR and the outcomes of the 2010 Appropriations Report; the report included language that barred changes in liver allocation until after an in-depth demonstration study was conducted. The language restricted any changes in the liver allocation policy that were designed to foster broader geographic distribution until certain required OPTN demonstration projects had been conducted and a report on them delivered to Congress. This language has been the subject of much conversation at past ACOT meetings. At the August 2010 meeting, the ACOT responded to this appropriations language and issued Recommendation 51 on the issue. Mr. Durbin read Recommendation 51.  

To follow up, Secretary Sebelius issued a letter to the OPTN, encouraging the OPTN to move forward briskly with a demonstration of the efficacy of broader liver distribution. To help this effort, HRSA provided an additional $1.6 million in direct funding to UNOS’ Center for Transplant System Excellence to conduct a study to evaluate donor potential in the U.S. HRSA also provided $500,000 in additional funding to the Minneapolis Medical Research Foundation to conduct analyses to support OPTN in developing evidence-based approaches for the geographic distribution of livers that are not based on the current artificial boundaries in the system. Mr. Durbin said that he was pleased to report that OPTN satisfied the Appropriations Report requirement in December 2011, and HHS feels that the agency has met the Congressional requirements. OPTN can now continue forward on policymaking on improvements to liver distribution. A report to the liver committee will be forthcoming early this spring.

The OPTN contract is up for renewal this fiscal year. HRSA published an RFI in January 2011 that sought input on the use of subcontracting and other issues. Mr. Durbin also updated the ACOT members on public and professional education efforts including the 50+ Campaign, Workplace Hospital Campaign, Donation Life Month (November 2012), and the use of Social Media. He described the Division’s work with Dr. Howard Koh, Assistant Secretary for Health, to help promote donation.

The other major funding area is the Living Donor Assistance Center, which was authorized in 2004. This is a grant program to provide travel and reimbursement expenses for economically challenged living donors. To date, it has approved over 2,000 requests for funding and paid out $3.75 million. The Cooperative Agreement was awarded to the University of Michigan in 2006, which subcontracted to the American Society of Transplant Surgeons (ASTS) to develop programs and policies to operate the system. The system became operational in October 2007. The average reimbursement to donors and companions is $2,539.

Discussion

Dr. Barr thanked Mr. Durbin for in interesting and informative summary. He asked, on the slide on the FY12 breakdown, if sci-ops initiatives were included in public education efforts. Mr. Durbin confirmed that that amount included a roll up of most grant activities other than the communities of practice and living donor cooperative agreements.

Dr. Barr asked whether the travel and subsistence areas are for the Center with University of Michigan and ASTS and if the budget for this area (living donors) from FY11 had been spent. Mr. Durbin affirmed that there was some financial roll over, but that activities were picking up. The Center now receives about 65 requests per month, an increase from the past. The University of Michigan and ASTS were slow to get this up and running but it is picking up now. There has been a push to also cover lost wages as well, but budget constraints make it hard to do that. Covering lost wages would quickly stretch the program thin. Dr. Barr commented that the ACOT members may have opinions about this issue in terms of how to do the most good for the most people.

Dr. Barr asked, in terms of VCA activities, if there was a possibility to get any assistance from the Department of Defense (DoD) on this area. Mr. Durbin said that this has not been explored but he would talk to counsel to see if it is feasible. There might be some development grants to get this going. VCA will also be revisited in the FY13 budget, and hopefully there will be a bolus to OPTN to get it up and running.

Dr. Fung asked if solid donor organ donors would automatically be considered for VCA? He commented that some people have misinterpreted the issue and believes that, that when one signs up to be an organ donor, it also includes VCA. Mr. Durbin agreed this was an area of confusion and that DOT is very mindful of these issues of patient consent.

Dr. Eason asked how DOT satisfied the Congressional report requirement. Mr. Durbin responded that the report centered on simulation modeling and relevant demonstration projects. It reviewed the analyses that were done for the policy proposals on broader distribution and discussed Region 8’s experience, which demonstrated reduced mortality. The content was framed in light of the proposals that were open for public comment about potential changes in the national allocation process, and talked about what sort of changes might occur with national implementation of the two proposals. The major challenge in using variances in changing distribution systems is that it is hard to demonstrate efficacy of broader distribution on small-scale demonstration projects. There is a need to provide the OPTN liver committee with as much support as possible to get the OPTN seriously thinking about revising the geographic distribution system, and moving away from state boundaries, OPO, regions, etc.

Dr. Barr said that he was pleased the report was completed and the Congressional requirements had been satisfied. He added that the zonal sharing for status 1A-B was done purely by modeling ,by SRTR,  and was conservative in terms of lives saved. If zonal sharing is implemented, there are good reasons to believe that the number of livers saved will be higher than estimated. He noted that Status 2 heart candidates are not dissimilar from low-MELD liver patients; the experience in that area provides additional evidence that the SRTR modeling is very conservative and that the clinical reality will be more important than they look just based on the numbers. In cardiac transplant, this was a game changer that has been dramatic and hugely successful. Dr. Barr noted that there is a local-first aspect to it for high-status patients, which could be the same for livers.

The DOT staff noted that the Congressional requirements have been met and the OPTN is no longer constrained by the need to have small demonstration projects before moving ahead with policy proposals. Hence, modeling would provide the primary support for policy changes.
        
Alignment of CMS Regulatory Requirements with OPTN and HRSA — Workgroup Report, Danielle Cornell, R.N., B.S.N., CPTC, and Consensus Conference Update, Jon Snyder, Ph.D., SRTR Contractor

Ms. Cornell’s working group is exploring the possibility that transplant centers (TCs) have become more conservative due to fears about outcomes data. The Consensus Conference on Transplant Program Quality and Surveillance was held in Arlington on February 13-15, 2012. Funded by HRSA, the conference brought together stakeholders that included: AST, Optum Health, ASTS, OPTN-TAC, CMS, OPTN-MPSC, ACOT, OPTN-PAIS, consumers, and OPTN-POC. They discussed program-specific reports from many angles. Ms. Cornell asked Dr. Snyder to present a summary of the conference so that the working group members can digest the information and assess if there is more work to do.

Dr. Barr clarified that the conference dealt just with TSRs for transplant programs in order to provide focus for the conversation. Down the line, he said, another issue will be to help with the reporting mechanism for OPOs, which may also be creating some of these issues.

Dr. Snyder, an SRTR Contractor, provided an overview of conference and recommendations. The SRTR technical committee reviewed these last week. The committee’s purpose was to address these eight key questions:

1) What is the SRTR’s mandate?
2) Who uses PSRs and why?
3) Are there unintended consequences?
4) What can we learn from others?
5) What statistical methods should we use?
6) How should we adjust for risk?
7) What outcomes should we use?
8) What data should we collect?

Dr. Snyder described the conference agenda and the presentations, which provided different perspectives on these issues. Participants discussed unintended consequences from the PSR and CMS’ conditions of participation. They divided into four breakout groups to address methods, risk adjustment, outcomes, and data. Participants spent a lot of time in breakout groups and then presented their recommendations to the full group. The recommendations are as follows:

Recommendations:

I. Statistical Methods

1. PSRs should be better suited to the needs of users, particularly patients.
2. Rather than refitting each model every 6 months, models could be fitted less often, and the time between reporting periods could be used to more carefully review models.
3. Although the current Cox proportional hazards models (with inclusion of additional comorbidity parameters) will likely be adequate for “flagging”, consider comparing this method with mixed effects methods
4. Consider providing transplant centers with tools like CUSUM and/or PSR forecasting “scorecards” to facilitate Quality Assessment and Performance Improvement (QAPI).
5. Consider increasing the observed-to-expected thresholds and/or using sliding-scale P-values to monitor the outcomes of small-volume centers equitably.
6. Mortality data from the Social Security Administration Death Master File (SSADMF) should continue to be available to the SRTR. (SSA changed policy in 2011 not to report deaths that were reported directly by states, which is a problem.)
7. The SRTR should substitute missing data with values that yield the best outcomes to encourage centers to accurately record data, and should consider including the timeliness and completeness of data submission as a quality indicator.
8. Avoid the conversion of continuous data elements to categorical elements, and use splines in instances where continuous linear values are not appropriate.

II. Adjusting for Risk

1. Consider protecting innovation by excluding patients who are in approved protocols from PSR models in identifying underperforming centers.
2. Identify centers that manage high-risk patients and donors well.
3. Develop more detailed, reliable, organ-specific data on:

a. Coronary heart disease, e.g. revascularizations,
b. Peripheral vascular disease, e.g. revascularizations and amputations,
c. Diabetes mellitus,
d. ZIP code socioeconomic status / race-ethnicity,
e. Donor/organ risk, and
f. Ventricular assist devices
4. Provide more data on waiting list risk and outcomes.

III.  Appropriate Outcomes

1. The composite pre-transplant metric (CPM), combining waiting list mortality, transplantation rate, and organ acceptance rate, is potentially useful.
2. Life-years after listing is a metric that deserves consideration and study.
3. Transplant program risk-tolerance may be a potentially useful metric.
4. Improve the monitoring and reporting of short-term living donor outcomes.
5. Consider providing information on long term outcomes.
6. Study the utility of reporting on outcomes such as:

a)   Life years from transplantation,
b) Quality of life,
c) Serum creatinine as a surrogate for long-term outcomes after kidney transplantation,
d) FEV1 as a surrogate for long-term outcomes after lung transplantation,
e) Acute rejection,
f) Hospitalization, and
g) Rates of candidate acceptance for transplantation.

IV.  Sufficient Data

1. Provide standard definitions and identify source documents for all data elements.
2. Examine whether data in DonorNet® can be used to provide information on donor and organ quality.
3. Consider reducing data by collecting complete data that are needed for organ allocation and in PSR outcomes models, but otherwise use data sampling strategies for other non-essential data.
4. Consider using Medicare claims data to supplement OPTN data.
5. Survey transplant programs to better understand the data collection burden and which data are the most difficult to report.
6. Assist transplant programs in maintaining their OPTN data by:

a) Educating programs about the availability of tools (on the SRTR private sites, Tiedi® export, etc.) to examine missing data and improving the utility of these tools,
b) Developing enhancements that allow programs to more easily monitor their performance,
c) Allowing programs to more easily make corrections when problems are identified, and
d) Offering standardized OPTN training for data entry personnel and a certification process.
7. Use the OPTN policy development process and follow strict criteria for adding new data elements, including:
a) Reasons for each data element,
b) How each data element will be used,
c) Clear definitions,
d) Source documentation requirements,
e) Appropriate populations,
f) Minimizing unproductive data entry categories, e.g. “other” or “unknown”, and
g) Understanding cost implications.

8. The OPTN should explore the feasibility of building data collection interfaces with electronic medical records.
9. Consider allowing the cost of mandated data entry to be placed on the Medicare Cost Report for reimbursement, and not limit this option to the Candidate Registration Form.
10. Consider providing information about paired exchange.

The Consensus Conference recommendations had the following themes: There is strong support for creation of separate reports for public consumption, which would be focused on easy-to-understand metrics that are meaningful for patients and provide the types of information patients are most concerned about (waiting time, life-years from listing, and program consumption). In addition, there was support for reports with a Quality Improvement Focus, which would provide more forward-looking metrics rather than historical performance metrics. Dr. Snyder showed a slide that compared the traditional reports with the new, proposed reports, to demonstrate that the latter are easier to understand. A lot of positive feedback has been received about the revised reports.

There is a need to continue to support OPTN’s MPSC committee and CMS’ Conditions of Participation. The O/E framework is here to stay for the near future. The group recommended studying additional methodologies, including the use of Bayesian hierarchical modeling strategies to determine the probability that program X is underperforming, as well as CUSUM charts for a program’s internal consumption. These are not suitable for public reporting because they are hard to understand. Dr. Snyder provided an example of the use of hierarchical models with Bayesian performance criteria. There were also recommendations to provide more detail on program’s performance relative to their peers; he illustrated one way to do that using a funnel plot to show where each program is and how it fares compared to their peers.

Support for formalizing the SRTR’s risk model development process will include a written “manual of operations” for risk model development, OPTN involvement (via expert review), and set model-building schedules, perhaps in three-year cycles. The use of three-year cycles could engage the organ-specific OPTN committees. Dr. Snyder showed how this could work, such as by looking at thoracic in year one, then living with same model for three years while a different area was studied. The technical advisory committee was very supportive of moving to this sort of format.

Moving forward, the SRTR-STAC discussions are on-going. They are looking to create a PSR subcommittee of the STAC, to focus on performance assessment methodologies. The prioritized list will be settled in the coming days with review by HRSA. SRTR staff will begin researching alternative methods to achieve the stated recommendations.

Discussion

Dr Barr thanked Dr. Snyder and asked if Ms. Cornell had anything to add. Ms. Cornell said Dr. Snyder did a great job of summarizing the meeting. She said she feels positive that the risk adjustment models are being reviewed. The possibility of creating public- vs. program-focused reports is a very positive move. Dr. Snyder stressed that information is not being hidden from the public; rather, the goal is to make the information more useful and more legible. At the end of the day, all information will be in included in public reports and available for those who want it.

Dr. Gerber asked about how mortality that is unrelated to either the disease or the transplant is factored in. For example, how is it captured if a recipient dies in a car wreck, and his/her death is not due to the transplant? Dr. Snyder said that there has been discussion about how to tease out transplant-related vs. -unrelated deaths. Right now, all deaths are considered deaths in the system, but this question was raised at the conference. Some argue that the person who got hit by a bus might have been on too high a dose of steroids, so they failed to see the bus coming — is that a transplant-related or –unrelated death? It’s a complicated question. Dr. Gerber said that potential patients and families will benefit from granular information but need to not be overwhelmed. The speaker agreed.

Dr. Fung added that, in terms of deaths on list, it’s possible to game the system just by limiting the list to those who one believed could be transplanted in a given period, like a year. Dr. Snyder agreed that one unintended consequence is that centers are becoming more selective in who they list. There are no data on the number of patients who were evaluated but turned out. One recommendation made was to improve risk-adjustment methods for waiting list metrics; it should be possible to adjust better for the severity of the patient being listed. Perfect risk adjustment is impossible to achieve, however, and some programs will proactively limit who they list. Dr. Fung commented that it is a disservice to patients if the number of patients being evaluated and/or referred is not captured.

Dr. Barr commented that the meeting was running behind and closed the discussion. He thanked Dr. Snyder and Mr. Cornell for the update and added his personal opinion that the recent conference was amazing and that the SRTR did a great job. The devil is in the details and the path forward will be key, he added. There is a model of the SRTR working closely with HRSA and liaisons on UNOS’ organ-specific committees to help with these issues. Although the issue of CMS’ alignment issues was partly addressed (CMS presented at the meeting), he felt that the ACOT working group still has work to do. Ms. Cornell agreed that there is more to do in the realignment group. ACOT members will hear from her on this.

Dr. Barr said that he encouraged CMS’ work with OPTN to have common definitions and common audit mechanisms. Mr. Durbin said that DOT has discussed this with the Secretary’s office, and is committed to dealing with it from a program standpoint. The challenge is appropriate oversight, while allowing advancement of thinking on metrics.

Policy Proposal to Analyze Travel to U.S. for Transplant — Alexandra Glazier, J.D., M.P.H., Chair, Ethics committee, OPTN, and Gabriel Danovitch, M.D., Chair, Ad Hoc International Relations Committee, OPTN

Dr. Danovitch said that the proposed revisions to Policy 6.0 on the transplantation of non-resident aliens has just gone through a public comment period that has been very useful. The final proposal will go to the board in June, and he thinks the board will be comfortable with it. Policy 6.0 has not been modified in 25 years, although realities have changed dramatically; further, nothing happens with the data and the Policy is misunderstood by the transplant community. Current data collected do not permit adequate evaluation of the number of patients who travel to the U.S. for deceased donor transplantation. There is minimal public transparency. Programs find themselves sorting through immigration status based on current definitions and may be unnecessarily hesitant to transplant non-resident aliens for fear of an audit.

The proposal’s immediate goals are to align Policy 6.0 with current transplantation environment and new data collection points, and to collect data that will more accurately reflect the number of patients that travel to the U.S. for deceased donor transplant. The short-term goal is to provide public transparency of the wait-listing and deceased donor transplant of non-citizen / non-residents. The potential long-term goal is to assess the data to understand the scope of travel to the U.S. for deceased donor transplantation and to inform future policy development when real data are available.

The proposed modifications are:

o Implement new definitions to simplify data collection and focus on patients travelling to the U.S. for transplantation (i.e., resident / non-resident as simplified terms: do you live in the U.S. or not?) This is important because someone who lives here can potentially be an organ donor.
o Be able to collect data and allow the Ad Hoc International Relations Committee to request additional information from transplant centers on listing and transplant of non-citizen/non-resident patients; this will eliminate the “5% rule”, which is really just an audit point and has been misunderstood by the community. This would be voluntary information and will not require any additional work from the transplant programs.
o Provide a public report of transplant center activity regarding listing and transplant by citizen and resident status. This audit of listings and transplants will enable the Committee to distinguish between non-U.S. citizens and non-U.S. residents who traveled to the U.S. for transplant, and why, from those who are residents of the U.S.

New non-citizen definitions (these will be edited on so the language is clearer):

o 6.1.1 — Non-U.S. Citizen / U.S. Resident – A non-citizen of the United States, who is present in the United States, and for whom the United States is the primary place of residence.
o 6.1.2 — Non-U.S. Citizen / Non-U.S. Resident – A non-citizen of the United States who is present in the U.S. but who does not have the United States as his/her primary place of residence.

The goal in creating these categories is to focus on the group of patients who do not reside in the U.S. and are travelling to the U.S. for purposes of transplantation. The proposal changes the current definitions by defining residency simply as whether the patient considers the U.S. to be his/her primary place of residence. The current definition in Policy 6.1 is based on the person’s legal immigration status. The Committees feel that this change is important, given that the purpose in collecting such information is to evaluate the category of non-U.S. citizen patients who travel to the U.S. for transplantation, and to provide transparency regarding the listing and transplantation of these patients. Given that neither the OPTN nor its members are likely to have immigration expertise, the Committees also felt that collecting data on legal immigration status should not be part of the wait-listing process.

The proposed definition of residency is also consistent with the Committees’ conclusion that those individuals who reside in the U.S., regardless of immigration status, may become deceased donors whereas those patients who do not reside in the U.S. may not. The candidate will declare the citizenship or residency categories during the wait listing process — same as today. Self-reporting this type of data has limitations — similar to other demographic information, which is similarly self-reported. The person’s status may be self-evident from demographic information provided.

It is important to note that there are no new data required for this change, which goes into effect on March 7, 2012. OPTN / UNOS data fields have already been already modified. In June 2011, the Board Of Directors approved improvements to data collection, which replace the previous ones, as follows:

o U.S. Citizen
o Non-U.S. Citizen / U.S. Resident
o Non-U.S. Citizen / Non-U.S. Resident
o Traveled to U.S. for Reason Other than Transplant
o Non-U.S. Citizen / Non-U.S. Resident
o Traveled to U.S. for Transplant

Ms. Cornell said that a major proposed change is to eliminate the “5 percent rule” (which is really an audit provision). Currently, the Committee can review and audit programs where more than 5 percent of recipients are non citizens/non-residents. The goal is for the definitions to match the data collection fields and to find out how often and why people travel to the U.S. for transplantation. In identifying the problem that the Committees seek to solve by this proposal, the Committees were influenced by the Declaration of Istanbul on Organ Trafficking and Transplant Tourism, specifically the concepts of travel for transplantation and transplant tourism, which are defined as follows:

“Travel for transplantation is the movement of organs, donors, recipients or transplant professionals across jurisdictional borders for transplantation purposes. Travel for transplantation becomes transplant tourism if it involves organ trafficking and/or transplant commercialism or if the resources (organs, professionals and transplant centers) devoted to providing transplants to patients from outside a country undermine the country’s ability to provide transplant services for its own population.”

In March 2009, the Board of Directors adopted the definitions in the Declaration of Istanbul for “organ trafficking,” “transplant commercialism,” “transplant tourism,” and “travel for transplantation.” (See: http://optn.transplant.hrsa.gov/SharedContentDocuments/Executive_Summary0309.pdf)

The Committees felt that the audit provision was widely misunderstood as a 5 percent cap on a transplant center’s ability to list and transplant non-U.S. citizens. At the same time, the Committees concluded that the current audit provision was ineffectual, as it lacks clarity on the audit’s purpose and any criteria regarding transplantation of non-U.S. citizens against which to evaluate the activities of a transplant program. With the defined goal of collecting information to evaluate the circumstances of patients travelling to the U.S. for transplantation, the Committees concluded that providing a percentage above which audit may be triggered was arbitrary and that transparency required that the ability to audit any time a patient who is a non-U.S. Citizen / Non-resident is listed and transplanted. The purpose of the audit is to discern the circumstances of non-U.S. citizens/Non-residents obtaining deceased donor transplants in the U.S. (for example, did the patient travel to the U.S. for transplantation that was available or unavailable in the patient’s country of residence?), and provide increased transparency regarding these practices. Also, there will be new transparency in the reporting policy that will help increase communication with the public about this issue.

The new Policy 6.3.1, “Transparency in Reporting Listings and Transplants of Non-U.S. Citizens/Non-U.S. Residents” is:

o The Committee shall prepare and provide public access to an annual report of member transplant center activities related to the transplantation of non-U.S. citizens/non-U.S. residents.

Data will be redacted to protect patient privacy. The Proposal does not seek to prohibit non-U.S. citizens/non-residents from being wait-listed and transplanted. It does not alter or impact the allocation of organs based on residency or citizenship status; it does not penalize programs for transplanting non-residents. The changes are designed to collect information and report them in order to foster public transparency and accountability about transplant practices.

The proposal went out for public comment in September 2011, and the comment period is now closed. Almost two-thirds (62%) of the 33 comments received were supportive. Committee leadership, OPTN/UNOS, and HRSA reviewed the proposal and revised it in response to these comments (this revised version is the one shared here). New categories of data collection for citizenship and resident status will go into effect on March 7, 2012. The Full Committees will vote on final proposal and it will be presented to the OPTN/UNOS Board in June 2012.

Ms. Cornell suggested some language for a recommendation and Dr. Crawford proposed a motion:

Recommendation

The ACOT recommends that the Secretary urge the OPTN/UNOS to pass the Policy 6 proposal as an important measure of public transparency.

Discussion

Dr Fung asked if the same sort of information was captured for donors about nationality; the response was that this is currently captured, along with documentation status (i.e., legal / illegal). Ms. Cornell added that undocumented residents of the U.S. donate to the deceased donor pool at about the same rate as they get transplanted; they are defined as “non-resident aliens.” The policy in question only deals with deceased donation, however.

Ms. Stroup asked if it was premature to raise this, as the policy is still in draft format; she noted that the ACOT typically comments on such things after the OPTN/UNOS board has approved them. Dr. Barr agreed that the ACOT could wait. Ms. Cornell clarified that the public comment period is over but the Board has not yet passed the policy proposal; she stated that she felt the policy was unlikely to go back out for public comment.

Dr. Fung asked if an ACOT statement would have any effect on the UNOS board. Ms. Cornell responded that it is impossible to know what, if anything, the Secretary will do with a specific ACOT recommendation; in her view, however, an endorsement from ACOT would reinforce, and align with, the positive comments received from other stakeholders endorsing the policy.

Ms. Levine clarified that the ACOT is an advisory body to the Secretary and it is within the ACOT’s prerogative to make any desired recommendations. The final rule says that the ACOT weighs in on OPTN policies when the board has considered them, however. Ms. Levine said that the ACOT could make a more general recommendation about endorsing the idea of greater data collection and transparency. Dr. Barr suggested that the recommendation wording be changed to take out the specific mention of Policy 6. The speakers suggested: “The ACOT recommends that the Secretary urge the OPTN/UNOS to take measures to increase public transparency with respect to travel to the U.S. for transplant.”

Dr. Barr said this is very broad and is essentially like a recommendation supporting motherhood and apple pie. An alternative would be to have a discussion after the June Board meeting, when the ACOT next meets in the summer. Mr. Durbin noted that there has been a lot of work on this internationally, most recently at the PAHO meeting in Argentina. He asked if there was a statement from WHO or another entity that could be a general principle that the ACOT could recommend. Ms. Cornell said that the Istanbul Declaration would apply but it would be a sideline. Dr. Barr agreed that the Declaration addressed transplant tourism, which is not something that ACOT can address on this call. Mr. Durbin asked if there was anything relevant from the Argentina meeting, such as data transfer and exchange.

Dr. Barr said that he would love to see something done about this; in the interest of time, he suggested that the ACOT return to this issue in the New Business session later on the call. Ms. Cornell said she would work on this over the break. Dr. Crawford withdrew his motion.

OPTN Update — Brian Shepard, Assistant Executive Director, Contract Operations at UNOS and the OPTN Project Director

Mr. Shepard provided an update of the bigger policy issues from the most recent OPTN meeting, and what is coming up. At the OPTN November 2011 Board meeting, there were some key issues addressed, specifically:

o Vessel storage: The board voted to prohibit the storage for subsequent use of specific vessels (i.e., Hep-C, Hep-B infected) due to risk of putting them into an uninfected patient. There have been some cases of this happening, and some near misses that indicate the potential risk. Vessels will be an on-going topic for the board and the Ops and Safety Committee. In the Spring cycle of public comment, there will be another proposed policy to tighten reporting requirements for vessels. The committee is moving to considering vessels to be more like organs in terms of data tracking, in order to support future policies.
o ABO sub-typing: the initial requirements were less stringent because this sub-typing was optional. When sub-typing is used for allocation now, it has to have the same level of rigor of verification as ABO typing does.
o Liver-intestine sharing: The board took a small step to sharing livers more broadly; the policy allows for some national sharing and makes the liver / intestine candidates a national priority before going down local and regionally.

At the June 2012 Board meeting, there are likely to be two more liver-sharing policies to consider, which have gone out for comment.

o Living donor policy: there are three living donor proposals (one apiece on medical evaluation, informed consent, and follow-up) that went out for comment in the fall. The committee is reviewing the comments, some of which raised concerns about the ability to get high enough numbers for effective follow-up.
o Liver-sharing: A proposal to extend regional Share 15 to be national was relatively uncontroversial in the public comments and is likely to go to board in its original format. For regional sharing among those with MELDS over 35, there was more variation in the comments and some concerns were raised; the committee is reviewing this further.

In addition, a bylaws rewrite will be approved at the board meeting that will lead to a head-to-toe rewrite to make the bylaws clearer and more understandable. No policies are changing; the effort just makes language easier to understand.

The Spring public comment period will include policies on:

o Kidney Paired Donation: three levels of policies can apply: living donor guidelines, which apply to all donors; kidney pairs, which apply to all pairs regardless of where the transplant is done (these cover transportation, consent, etc); and operation of OPTN kidney paired donation program, which are specific to OPTN program. There will also be a new policy for bridge donors.  
o Lung Allocation Score (LAS): there is an update for this to be a complete overhaul. There is a need to determine a regular update schedule for the LAS to keep the coefficient current.

Other projects in development, which have not reached public comment or board recommendation stage, include:

o Kidney allocation: A concept paper was published last spring and received a lot of feedback. There is a desire to move ahead with concept that the 20 percent of organs with the longest graft survival should go to the top 20% of patients in terms of longest likely survival. Age bands are not moving ahead, however.
o Practitioner currency: This is an issue that is regularly wrestled with. There is a need for more robust requirements to ensure that leaders at programs are current and able to perform at a high level. This will be driven by MPSC across different organ types
o Histo bylaws: The committee is working on this; one-third of OPTN’s members are histo labs and the bylaws are out of date and need to be revamped.
o The thoracic committee is working on revising the heart status allocation rules.  

Finally, Strategic Planning is in development and will be a broader effort than has been conducted in the past. The process will include allocation and distribution issues that the committees spend a lot of time working on. It will address operational issues such as patient safety, financial stability, and Information Technology priorities. Mr. Shepard said he was happy to answer questions by phone or email.

HLA Update — Laura St. Martin, M.D., FDA Ex Officio Member

Dr. St. Martin noted that the ACOT’s August meeting included a discussion of two FDA guidance document: final guidance on analyte-specific reagents (Sept 2007), and draft guidance on research use only/investigational use only in vitro diagnostics (June 2011).  Concerns were expressed over the FDA proposed plan to provide greater oversight for laboratory-developed tests (LDTs). Specific concerns were expressed about the potential effect on the fields of histocompatibility and immunogenetics.

The FDA has conducted ongoing engagement in public discussion about these issues. It convened a public meeting in July 2010 to gather input on its intent to propose a regulatory framework to address LDTs. In response to draft guidance, the FDA received over 100 comments from stakeholders expressing both support for, and concern over, the proposal. The FDA is reviewing the comments right now.

The agency has repeatedly stated in public that any framework will be phased in according to risk, and there will be ample opportunity for stakeholders to provide input. In fact, stakeholder input is encouraged. The FDA will consider concerns as its develops policies applicable to analyte-specific reagents and laboratory devices indicated for research use only, including concerns that are related to the needs of small patient populations.

The FDA encourages commentary from stakeholders to inform its development of policy related to these reagents, tests, and devices. Dr. St. Martin noted that the comment period deadline is designed to ensure the public’s timely submission of comments, but that the docket is open and new comments will be accepted.

The FDA recognizes the value of high-quality histocompatibility and immunogenetic tests in achieving OPTN goals and the value and need for availability of tests for high-resolution HLA typing in unrelated donor hematopoietic stem cell transplantation. The FDA will provide additional opportunity for input and discussion before taking new steps toward regulation of LDTs that are used in organ and stem cell transplantation. The field’s concerns have been heard and the FDA is considering the impact of any additional oversight.

Discussion

Dr. Barr reminded the listeners that the ACOT had passed a recommendation about this issue at the August meeting.

ACBSA Update — James Berger, MS MT (ASCP) SBB, Executive Secretary, ACBSA

Mr. Berger said that he would address three issues: 1) the duties of the Advisory Committee on Blood Safety and Availability (ACBSA) charter; 2) recommendations and findings from the December meeting on informed consent for recipients of blood, organs and tissues; and 3) a synopsis of the infectious diseases being addressed by HHS.

The ACBSA’s duties are to advise the Secretary through the OASH on a range of policy issues to include: 1) Definition of public health parameters around safety and availability of the blood supply and blood products; 2) Broad public health, ethical and legal issues related to transfusion and transplantation safety; 3) The implications for safety and the availability of various economic factors affecting product cost and safety. Mr. Berger described the members.

The December 2011 meeting was held to discuss the process of informed consent for recipients of blood, organs and tissues and to provide recommendations to the Department regarding the informed consent of those recipients. Over the two-day meeting, the panel of experts convened presented information in the following areas:

o The informed consent process, including the content of those discussions and how complex medical information can be presented in a manner that improves patient comprehension;
o What data about noninfectious and infectious risks are currently available to clinicians for use in informed consent discussions;
o Ways in which available data are accessible to clinicians; and
o What research is needed to better understand both the noninfectious and infectious risks involved in blood transfusion, organ transplantation, and tissue transplantation

After careful consideration and collective input, the Committee developed the following recommendations. Whereas the Committee believes that all patients are entitled to be informed that they are receiving a substance of human origin, such as blood, organs, cells, and tissues; and a robust process of informed consent for recipients of transfusion and transplantation is an ethical imperative, the Committee finds that:

1. Practices of informed consent for transfusion and transplantation are highly variable
2. Practices of informed consent in many instances appear to be inadequate to properly engage patients in shared decision-making
3. Gaps exist in:

a. Data on the risks of transfusion and transplantation and their alternatives
b. Current knowledge and communication of risks, benefits, and options by persons obtaining informed consent for transfusion
c. Current knowledge and communication of donor
d. Derived disease transmission risks by persons
e. Obtaining informed consent for organ transplantation
f. Knowledge of informed consent practices for the wide spectrum of tissues for transplantation.
g. Training (e.g., physician and other health professional) in the need for, and processes to achieve appropriate patient informed consent is inconsistent and generally inadequate

4. CMS requires patient informed consent for organ transplantation, and does not require specific patient informed consent for transfusion and tissue transplantation
5. Disclosures of risk are generally inadequate including

a. The most common transfusion related risks including administration of the incorrect unit, TRALI, TACO, and alloimmunization
b. Infectious and non-infectious risks of tissues
c. Unnecessary transfusions contribute to the risk of transfusion.

The Committee recommends that the Secretary:

1. Direct CMS to establish requirements for patient informed consent for transfusion and tissue transplantation
2. Establish a working group to cooperate with stakeholders to identify opportunities and strategies for improvement in informed consent for recipients of transfusion and transplantation to include:

a. A focus on shared decision making involving the clinicians and patients
b. Assessment of the patient’s needs and competencies
c. Qualitative and quantitative communication of the relative and absolute risks of therapy options and inaction in the specific setting
d. Clarification of the elements of informed consent and the accountability of the primary care provider
e. Two-stage process of education where time permits (once at time the need is identified and again when the procedure is imminent)
f. Standardized documentation of the patient agreement

3. Support research on optimization of patient informed consent for transfusion and transplantation including:

a. Metrics for patient assessment including comprehension
b. Utility of decision aids and media alternatives
c. Medical education and tools for implementing informed consent
d. Public education

4. Provide funds to address identified gaps, including

a. Defining risks associated with blood transfusion and tissue transplantation
b. Defining risks associated with donor-derived disease transmission through organ transplantation
c. The deficiencies in the informed consent process

5. Enhance funding for NHSN, SRTR, and the OPTN to support bio-vigilance efforts (donor and recipient)
6. Promote best practices in patient blood management including CPOE to reduce unnecessary transfusions

The Committee felt that adoption of the recommendations identified will place the Department on firm footing for promoting best practices in the process of informed consent with recipients of blood transfusions, organ transplantation, and tissue transplantation.  The Committee wants to continue working with the Department in guiding and recommending the best path forward in the development of its plans and initiatives for informed consent.

The next meeting will be held on June 15 -- 16, 2012; for more information, see http://www.hhs.gov/ash/bloodsafety/index.html

In addition, he said that HHS is aware that the transplant field is interested in infectious disease tests that meet its unique needs, as well as the use of fourth-generation of tests. To that end, there was a meeting on February 14, 2012, to discuss roles and responsibilities of each agency in examining organ donor testing needs. Many agencies participated in this meeting, and Mr. Berger noted that a working group will address this issue. In addition, there was a meeting of the blood organ and tissue senior executive council last week; the outcome was a recommendation to form a working group to address the needs identified in the recommendations.

Discussion

Dr. Fung asked if any of the policies deal with JCAHO on blood transfusion, since JCAHO has a host of initiatives to address these issues. Mr. Shepard said JCAHO has a representative on the committee. JCAHO can put out recommendations but this is not addressed by HHS. The committee members are looking for something to be equitable between organs, tissues, and blood transfusions.

Dr. Fung noted that on the issue of fourth-generation testing, there are diminishing returns and increasing costs for this. He asked what the impact is of using these expensive and sensitive tests in terms of costs per life years? The response was that this is being looked at. The return on investment is not as large because the pool of users is smaller. But, there is a need for the test and the committee wants to work with industry to see what data they can provide. The working group has to work with industry before the question can be answered, however.

Dr. Barr noted that he had not been aware of the advisory committee and expressed concern that it seems to be making recommendations on solid organs that are more appropriate for the ACOT to address. It is administrative, and would have to be decided by HRSA, but this creates confusion. Blood and tissue safety are good areas of focus, he said, but the ACOT should address the solid organ ones. Mr. Shepard said that he is aware of the issues and overlap; he works closely with solid organ staff and they are working to address this in the committee charter.

CDC Guidelines — Matthew Kuehnert, M.D., CDC Ex Officio Member

Dr. Kuehnert said that he was happy to be able to present this information and to answer any questions the committee members may have.

The last version of the Public Health Service’s (PHS) “Guidelines for Preventing Transmission of Human Immunodeficiency Virus Through Transplantation of Human Tissue and Organs” were published in 1994. A lot has changed and there is broad agreement that the guidelines need revision. In 2008, the Association for Organ Procurement Organizations (AOPO) sent a letter to the CDC suggesting that the guidelines be revised. Other transplant organizations, including AST and ASTS, have done so as well. In response, an objective process was developed for PHS guideline revision and update.

Dr. Kuehnert noted important differences in focus between the 1994 and the Revised Draft Guideline, as noted:

1994: PHS Guideline for Preventing Transmission of Human Immunodeficiency Virus through Transplantation of Human Tissue and Organs

o Organs and tissues; banked breast milk and semen
o Transmission of HIV only addressed
o Were no FDA regulations on tissues back then

Revised Draft: PHS Guideline for Reducing HIV, HBV and HCV Transmission through Solid Organ Transplantation

o Solid organs only
o Transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV)
o Developed through an evidence-based process

The evidence-based process for revision included HHS agencies and external experts from transplant community providing input; then the CDC acted as the lead agency for PHS agencies to develop a draft. 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 University of Pennsylvania and the ECRI Institute/Evidence-based Practice Center (EPC). Advisors for the Guideline development included an Expert Panel (EP) containing experts in consent issues, Hepatitis, HIV, and Laboratory Medicine; an OPO Representative; and physicians from transplant, transplant ID, and transplant surgery. The Review Committee (RC) included representatives from AOPO, AST, ASTS, CSTE, NATCO, UNOS, Industry; and Ad Hoc Members. PHS representatives from CMS, FDA, HHS/OPHS, HRSA, and NIH participated.

Dr. Kuehnert described the five phases of guideline development methodology. The categories of PHS Guideline’s recommendations are as follows:

o Donor Risk Assessment
o Donor Screening (this includes Table of risk factors for recent infection of HIV, HBV, HCV)
o HBV-Infected Donors and Transplantation
o HCV-Infected Donors and Transplantation
o Recipient Informed Consent
o Recipient Testing
o Donor and Recipient Specimen Collection and Storage
o Tracking and Reporting of HIV, HBV and HCV

In the revision process, HHS offices and agencies (including CDC, HRSA, FDA, and CMS) reviewed and approved the draft Guideline. Notice was given in the Federal Register and the draft guideline made accessible at www.regulations.gov. The 90-day public comment period ended in December 2011. All of the approximately 100 comments are being reviewed.

The next steps are for the comments to be mapped to the recommendations and a PHS Revision Task Group convened. The group will review comments and change options and agree on changes to the guideline. Then the Expert Panel and Review Committee will be re-convened to review the guideline and provide input. HHS agencies will consider any suggested changes, then submit the guideline for HHS clearance. The final Guidelines are not regulations and do not replace OPTN policy.

Discussion

Dr. Fung asked if, even though the guidelines are not intended to be regulatory, they could be taken by insurance companies, attorneys, and/or regulators as a standard. And, if so, how will this be addressed? Dr. Kuehnert said that he has heard this question before. On the grading level, it is important to understand that the grades are based on the evaluation of clinical trials. Unless there has been a clinical trail on something specific, there will not be the highest level of evidence, because it’s not possible to do the test.

Dr. Fung asked if there would be another meeting that would include some of those that did not participate for the full process? Dr. Kuehnert said that there were concerns about this and he hoped everyone would come back to the table. There were concerns that some changes were made during the clearance process and that external groups were not able to comment on them. This raised anxiety. He assured the community that the agency is listening and will take comments seriously.

Dr. Barr said that all of those that were engaged are eager and willing to work with the CDC on this, particularly on the issue of accurate data collection on donor information as well as potential recipients. Keep the information going on a two-way street with DTAC. It’s very important and there is a real need to modernize this. He added that the CDC may end up with more people than it wants making comments.

Dr. Kuehnert thanked the members for their interest. The CDC hopes to make this the best document it can be and to address any research gaps to make the recommendation more robust. Dr. Barr suggested that OPTN and UNOS can help in terms of data collection, and Dr. Eison has a lot of experience too. Dr. Barr agreed that everyone wanted the highest level of evidence. He asked Dr. Kuehnert to stay on the call in order to hear Dr. Fung’s presentation.

Organ Donation and Geographic Distribution Workgroup — John Fung, M.D., Ph.D.

Dr. Fung reported on the working group related to organ donation and availability. The estimated incidence of undetected viremia for normal-risk potential donors is 1 in 50,000 for HIV and 1 in 5,000 for HCV. For high-risk potential donors, the incidence of undetected viremia is 1 in 11,000 for HIV and 1 in 1,000 for HCV.

A recent OPO survey found that the percentage of recovered organ donors who were reported as having “increased risk” behaviors varied among these organizations from a range of 2.3% to 26.1% of annual donor volume. Of the 80 potential donor-derived disease transmissions reported to UNOS from 2005-2007, 30 cases were confirmed; HIV, HBV, and HCV were among the top five most reported suspected donor-derived transmissions. Of note, further testing of stored donor specimens were negative using NAT in most cases.

The update to 1994 Public Health Service (PHS) Guidelines for Preventing Transmission of HIV through Transplantation of Human Tissue and Organs, most significant changes involve:

o Expanding the guideline to include hepatitis B virus and hepatitis C virus, in addition to HIV;
o Utilizing factors known to be associated with increased likelihood of HIV, HBV or HCV to identify potential donors at increased risk for transmitting infection;
o Distinguishing between expected and unexpected transmission of HBV and HCV in goals for prevention; and
o Limiting the focus to solid organ transplants and vessel conduits recovered for organ transplant purposes.

Dr. Fung showed comments submitted by AST and other organizations that felt they were not heard. There are issues about categories and the impact on policy and legal issues. The AST did not support the current draft. On the working group call a few months ago, it was noted that, given some of the high technology tests mandated on every donor at the time points recommended, the potential costs per life year would be huge.

Dr. Fung presented a suggested recommendation:

Recommendation

Although ACOT appreciates the efforts made by the CDC and PHS to minimize the risk of transmission of HIV, HBV and HCV through organ donation, the initial intent of the current document was to provide both evidence based and expert input into how best to
implement viral screening into both living and deceased donor solid organ transplantation. Given the limitations of the current draft version, the ACOT recommends to the Secretary of HHS to direct the CDC and PHS to work together with the varied representatives of the transplant and organ donor communities to revise the draft to better address the concerns outlined in their responses.

Discussion

Dr. Kuehnert said he appreciated the time the work group put into this and noted that the public comments received were very thoughtful. He added that it was certainly not the CDC’s intent for groups to either feel excluded, or be excluded. He reminded the group that the PHS documents are not intended to be guidance documents for the public. When he thinks about what happened at the point of clearance, the biggest change made was about the timing for living donor screening, which happened because of a well-publicized HIV transmission case in New York City. In retrospect, Dr. Kuehnert said he wished this had been had run by the panel to get more input. But, that was the only major change made in clearance; there was a misunderstanding about the process and role of input that may have caused the unfortunate withdraw of people from the guideline. He committed to working with the community to reassemble the expert panel and review committees for input in the next few months. Some changes were made based on the public comments.

Dr. Fung agreed that things will get ironed out. There is a desire for people to come back together as a group and address these issues in person rather than through the comments process. Dr. Barr added that such a meeting or discussion could be conducted by web-based slide exchanges or teleconferences. A longer version of the presentation is available on the ACOT website.

Report of the Technical Expert Panel on Uncontrolled Donation after Cardiac Determination of Death — Alexandra Glazier, J.D., M.P.H., James Bernat, M.D., Thomas Nakagawa, M.D.

Dr. Bernat said that he appreciated the opportunity to provide an interim report on what has been accomplished thus far. The charge for the panel was to apply the same type of analysis that had been done on controlled circulatory determination of death to uncontrolled circulatory determination of death (uDCDD) circumstances.

A meeting was held in December 2011 in Arlington, attended by all but two of the panelists. Consensus points were created as a result of a series of emails that followed the December meeting. Dr. Bernat noted that the panelists are listed on page five and expressed his pleasure that Ms. Glazier and Dr. Nakagawa were on the call and could help provide information. Two panelists declined to sign because the process did not reach consensus with them but, he noted, this is not unusual with such controversial questions.   

The first step at the conference was to review the foundational principles to be applied to uncontrolled donation. These principles were laid out in the first report, published in 2010 in Critical Care Medicine, which are being applied to the uncontrolled circumstance. The second step was learning about what the uncontrolled protocols actually mean. The third step was applying those principles to the uncontrolled circumstances. The group was not intended to decide if this process is a good idea, just to consider the death determination of the donor.

The Foundational Principles, which were used for controlled DCDD and applied to the uDCDD circumstance are as follows:

o The way in which cessation of systemic circulation causes death
o Important distinction between permanent (will not) and irreversible (cannot) cessation of circulatory function
o Permanent cessation of circulatory function is a valid criteria for death, if there is no interference by resuscitation technologies and no chance of auto-resuscitation
o If resuscitative technologies restore oxygenated blood flow to the brain, the preceding death declaration might be invalidated.  (If you use permanence, you can’t do something that would negate the permanence.)
o There are differences in death determination in those who are organ donors vs. those who are not donors. Some technology be employed to detect small degrees of blood flow to be certain there is no circulation.

It is important to explicate the temporal and causal relationships between the cessation of systemic circulation and cessation of brain functions. The uncontrolled DCDD donor must have permanent cessation of circulation; there can be no chance of auto-resuscitation occurring to restore circulation (because then it will not have been permanently lost). One has to wait until the period in which auto-resuscitation would be possible to occur has elapsed. Auto-resuscitation is an empirical question that is answerable by data (it’s not a conceptual issue). In all reported cases, retrospectively reviewed, auto-resuscitation never happens with controlled donation. With uncontrolled, it happens up to seven minutes after CPR was abandoned as unsuccessful. Permanent cessation of circulation destroys the brain and, if you provide whole circulation (ECMO), it can retroactively invalidate the death determination unless steps are taken not to perfuse the brain. The meeting participants were not thrilled with the technology but seemed to be unjustified and contrived innovation designed only to meet these requirements. There was not a lot of enthusiasm for that.  

When the panel looked at the relationship between systemic circulation and brain function, they realized that circulatory-respiratory criterion of death (which is one of the two death criteria in the statue) is itself a hybrid of heart circulatory and brain functions. The apnea (breathing) part is a brain function, but the circulation part is circulatory. Brain circulation stops when systemic circulation stops, of course, and actually ceases before there is a complete cessation of brain circulation. Cessation of breathing is tightly linked to cessation of circulation in the absence of resuscitation. In controlled donors, when ventilator support is discontinued, the usual order is that breathing stops first and then the heart stops. In uncontrolled, however, it’s the opposite: there is a cardiac arrest first.

Dr. Bernat showed a table with a diagram on circulatory cessation of death that shows the sequence of events when circulation ceases in uncontrolled donation. The times were arbitrarily named T1 through T6. Sometimes T3 and T5 may follow T6. He discussed the time frames.

Discussion

Ms. Glazier said that Dr. Bernat presented an excellent summary of what was discussed at the conference. As an attorney, she felt that it is difficult to try to tie precise clinical analysis to the Uniform Determination of Death Act’s (UDDA) legal language. Specifically, how to go from an irreversible cessation of circulatory function, and understand that circulation means circulation to the brain. There is some work to do on this in terms of the legal analysis, but the recent effort has furthered the overall goal.

Dr. Barr asked what the points of dissention were from the two who did not sign on to this. Dr. Bernat responded that at the ACOT’s August 2011 meeting. Dr. Halperin had noted that not everyone agrees with the paper published in Crucial Care Medicine. Dr. Halperin had written a paper taking exception with the concept of “permanent cessation” versus “irreversible cessation” and claiming that these patients are all alive at the moment of organ donation during controlled donation. His only solution is to abandon the dead donor rule because the donors are not dead. That was the first person who did not sign on.

The second was Doug White, who was a part of the original document so he has no quarrel over issues of irreversibility. His concern focuses on the President’s Commission on the UDDA, in which the terms “irreversible” and “permanent” were used interchangeably. Appendix F of Defining Death, the medical guidelines for determining death, clearly discusses about “permanent”, not “irreversible” conditions. All death statutes use the term “irreversible”, which creates an interesting ambiguity. The UDDA seems explicit, but the supplementary documentation uses a different word making it hard to determine the framers’ intent.

Dr. Barr noted that the meeting was funded by HRSA and asked if there was an action that the ACOT should take. Ms. Stroup clarified that the presentation was made mainly to provide information. Dr. Bernat said that when the panelists feel there is sufficient consensus to write a paper, they will do so. The first paper was published in Critical Care Medicine, because it was thought that the physicians who are caring for these donors are likely to be ICU doctors. With uncontrolled donation, however, that’s not the case and so the publication might appear in another venue. Dr. Barr agreed that there are two audiences for the document and suggested JAMA. Dr. Bernat noted that he spoke with the JAMA editor, who clarified that the publication doesn’t report on meetings, etc. Dr. Barr suggested the American Journal of Transplantation, which has a high impact factor. Dr. Nakagawa suggested NEJM or Chest.

Ms. Levine clarified that the publication must be clear that this was not approved by the ACOT, and include a disclaimer to that effect. Dr. Bernat agreed and commented that this had been done in the first paper as well. Dr. Barr suggested that the recommendations from the expert panel could potentially impact HRSA with respect to its grant mechanisms. Mr. Durbin agreed.

Dr. Bernat reported that some people in the group had wondered if they should have a second meeting to iron out a few of the issues, such as the relevance of the legal parts. The group only met once the first time and there was enough of a consensus to write by communicating via email. A few points remain to be worked out. Dr. Barr suggested that this could be done as a working group of the ACOT in a conference call. Ms. Glazier agreed.

Dr. Bernat committed to sending the panelists an email updating them and listing the remaining issues. Ms. Glazier added that the legal issues are intricately meshed with the clinical ones and that she was happy to help. Dr. Bernat said he would list a few of the unresolved points and ask panelists to submit additional ones, then, based on how long the list was, determine how long a call was needed. Ms. Stroup said she will distribute the list to the ACOT members.

Brain Death Determination Work Group Report — Thomas Nakagawa, M.D.

At the last ACOT meeting, there was a discussion of inconsistencies on declaration of brain death and a subcommittee formed. Dr. Nakagawa listed the committee’s members and thanked them for their input and expertise in drafting the recommendation. Dr. Nakagawa discussed the draft recommendation, which is as follows:

Recommendation for consideration to standardize brain death testing for children and adults.

The ACOT recognized the importance of this recommendation since no national law exists for determination of brain death.  ACOT encourages adoption of national guidelines for determination and documentation of brain death in infants, children, and adults.  

ACOT recommends the following:

o Medical community use currently accepted guidelines that have been endorsed and supported by multiple national medical organizations for the determination of brain death in infants, children, and adults. ,  These brain death guidelines should be used by clinicians tasked with determining brain death.  National societal guidelines may be updated periodically to reflect currently accepted standards to determine brain death.

o The potential donor patient must have a documented clinical examination (including a valid apnea test) as determined by currently accepted adult and pediatric brain death guidelines to make the determination of death.1, 2 In situations where a complete clinical examination and apnea test cannot be performed, the patient must have an approved ancillary test that is consistent with brain death. Documentation must support the determination of death as outlined in currently accepted adult and pediatric brain death guidelines.   

o All hospitals should have brain death policies in place that reflect currently accepted adult and pediatric brain death guidelines.1, 2 Hospital policies should be reviewed and revised accordingly.  It is recommended that OPOs review hospital brain death policies on a periodic basis and provide the hospital with resource information on currently accepted guidelines for the determination of death in adults and children. These policies will assist by allowing definitive documentation of the specific steps and timeline to determine and declare brain death for clinical and medical legal purposes. The OPO should remain responsible for confirming that the brain death examination and documentation is consistent with applicable hospital policy for all potential organ donors.  

o To maximize the potential for donation opportunities and provide quality end-of-life care, determination of death should be performed in a timely manner in any patient where brain death is suspected.  This includes timely referral to the OPO in an effort to preserve donation options for the family or legal guardian.  In situations where an observation period occurs between examinations, patients should be medically supported until declared dead by neurologic criteria, or until medical support is withdrawn.   

The recommendation has received endorsements from National Organizations – multiple organizations have been involved in them. A letter of endorsement from NATCO was included in the meeting materials. National brain death guidelines have been endorsed and/or supported by the following societies:

o North American Transplant Coordinators Organization (NATCO)
o Association of Organ Procurement Organizations (AOPO) pending letter of support

AAN adult brain death guidelines endorsements

o American Academy of Neurology Society of Critical Care Medicine
o Neurocritical Care Society
o The Child Neurology Society
o The Radiological Society of North America
o The American College of Radiology

SCCM, AAP, and CNS Pediatric brain death guidelines endorsements

o American Academy of Pediatrics
o Sub sections:   

 Section on Critical Care  
 Section on Neurology

o American Association of Critical Care Nurses
o Child Neurology Society
o National Association of Pediatric Nurse Practitioners
o Society of Critical Care Medicine
o Society for Pediatric Anesthesia
o Society of Pediatric Neuroradiology
o World Federation of Pediatric Intensive and Critical Care Societies  
o American Academy of Neurology affirms the value of this manuscript

The following societies have had the opportunity to review and comment on the updated pediatric brain death guidelines.   

o American Academy of Pediatrics

o Sub sections:

 Committee on Bioethics  
 Committee on Child Abuse and Neglect
 Committee on Federal Government Affairs
 Committee on Fetus and Newborn
 Committee on Hospital Care
 Committee on Medical Liability and Risk Management
 Committee on Pediatric Emergency Medicine
 Committee on Practice and Ambulatory Medicine  
 Committee on State Government Affairs
 Council on Children with Disabilities
 Section on Anesthesiology and Pain Medicine
 Section on Bioethics
 Section on Child Abuse and Neglect
 Section on Emergency Medicine
 Section on Hospital Medicine
 Section on Perinatal Pediatrics
 Section on Neurological Surgery
 Section on Pediatric Surgery

The Pediatric Section of the American Association of Neurosurgeons and the Congress of Neurologic Surgeons have had the opportunity to review this document.  

This recommendation was sent to Ms. Levine, who raised questions about to whom, and at what level, the ACOT makes recommendations. The committee was hoping to standardize the definition of brain death, but then had to consider where this would occur, such as in the UDDA, as part of JCAHO accreditation, or through other venues. Based on the most recent conference call, held on February 27, 2012, the subcommittee concluded that the ACOT should recommend that the Secretary consider making a recommendation on this issue.

Discussion
                 
It was noted that death determination is addressed in state law and there is a desire to not re-open the statute. The best place to address this is either through CMS’ interpretive guidelines on hospital COPs, or through JCAHO’s standards.

Dr. Barr asked what the working group’s final output was, where it would be published, and how the ACOT should proceed. Dr. Nakagawa said it would be the recommendation to the Secretary as presented above. Ms. Levine clarified that any recommendation must be discussed at a meeting that is open to the public (such as this call); she noted that the full body cannot “rubber stamp” a work group recommendation, but must rather fully deliberate upon it.

Dr. Barr asked for feedback from other organizations, and was told that AOPO wanted to change the language in the third bullet point from “confirmed” to “verify”. This change was made and is reflected above. Dr. Fung moved to make the recommendation and Dr. Gerber seconded it. The recommendation was approved (see above). Ms. Levine will help create background information to accompany the recommendation when it is conveyed to the Secretary, such as the letter from NATCO.

New Business

Dr. Barr brought the conversation back to the morning session on Policy 6.0. The original recommendation presented was: “The ACOT recommends that the Secretary urge the OPTN/UNOS to take measures to increase public transparency with respect to travel to the US for transplant.” Dr. Barr said that, if the policy in question is going to the June UNOS board of directors’ meeting, it was not clear to him that the ACOT had to act at this time.

Ms. Glazier agreed. She felt that it was important to update the group on the effort, since it dovetails into the ACOT’s past discussions on transplantation and tourism. Dr. Barr asked that the minutes reflect that this issue was presented and discussed, and that there is general approval of the issue of transparency on the part of the ACOT’s members. Specifically, the ACOT members concur that transparency and data collection for categorizing this issue is a good idea. The group agreed with this approach.

Ms. Stroup said she would distribute an email seeking new business or agenda items for the summer meeting.

Public Comment

No one registered for public comment but the microphones were opened in case anyone wanted to comment.

Mr. Brown, the current president of AOPA, thanked the ACOT for accepting the suggested change to the brain death recommendation – the wording is very important to AOPA. Secondly, he asked if the individuals engaged in the organ testing issue included any transplant societies. Dr. St. Martin clarified that the list reflected only internal HHS staff. She said that, when it is appropriate, the FDA will include societies in the larger, external discussion. Ms. Stroup said she would communicate when this might occur to Mr. Brown. Ms. Greenwald clarified that the goal was to let the ACOT know that the FDA realizes that there is a lack of available testing; the department is starting to look at this issue but is not yet in a place where it can involve outside entities. They are committed to doing so as this issue evolves and that is why they wanted to let everyone know what was happening. Please contact her or Mr. Berger with questions or comments.

Mr. Chianchiano, from the National Kidney Foundation, said that the foundation is pleased that the ACOT is looking at problems stemming from the CMS COP and urged the ACOT to continue to do so and work on taking steps to address these unintended consequences.

Ms. Stroup will distribute a Doodle poll for availability for the summer meeting.

The conference call adjourned at 3:15 pm

 


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