Organ Allocation In Transplantation Research Articles

Toward Equity in Global Access to SoHO-based Therapies: Recommendations for Action.

Therapies derived from substances of human origin (SoHOs) such as organs, cells, and tissues provide life-saving or life-changing treatment for millions of people worldwide each year. However, many people lack timely access to SoHO-based therapies because of insufficient supplies of these exceptional health resources and/or broader barriers in access to healthcare. Despite well-established governmental commitments to promote health equity in general and equity of access to SoHOs in particular, information about inequities in access to most SoHO-based therapies is scarce. Furthermore, the issue of equitable allocation of SoHO-based therapies has received little attention from policymakers and ethicists, except in the context of organ allocation for transplantation. Consequently, the extent and nature of potential inequities within and between countries are largely unknown, and few sources of guidance are available to support progress toward equity in global access to SoHO-based therapies. We present here the findings of an international ethics working group convened in preparation for the 2023 Global Summit on Convergence in Transplantation, organized in Santander, Spain. The group sought to assess potential gaps in knowledge about inequities involving SoHO-based therapies, to elucidate systemic factors that may influence access to these therapies, and to consider how policies and frameworks governing access to and allocation of SoHO-based therapies may promote equity when it is necessary to define boundaries in access because of insufficiency of supply. In discussing these challenges, we also outline several recommendations for action by governments and health authorities.

Prevalence of Human Leukocyte Antigen Alleles Polymorphism in North Indian Population

Background Human leukocyte antigens (HLA) are highly polymorphic glycoproteins required for immune response and recognizing self or non-self. Knowing the HLA diversity in a population may be helpful in the selection of organ allocation for transplantation. We aimed to retrospectively analyze the prevalence of HLA, A, B, C, DRB1, and DQA1 alleles frequency in the north Indian population. Materials and Methods HLA antigen allele data were retrospectively analyzed from a transplant cohort of 2259 subjects. HLA-A, B, and DRB1 frequency were determined in 2259, HLA-C in 759 and DQA1 in 751 subjects. Results The most abundant HLA-A antigen alleles were HLA-A*01(25.41%), HLA-A*02 (24.83%), HLA-A*11 (17.53%), HLA-A*24 (10.27%), HLA-A*03 (9.07%). HLA-B antigen alleles were HLA-B*35 (20.54%), HLA-B*15 (15.36%), HLA-B*40 (13.59%), HLA-B*07 (10.14%), HLA-B*44 (7.79). HLA-C antigen alleles were HLA-C*07 (28.06%), HLA-C*04 (20.42%), HLA-C*03 (15.55%), HLA-C*06 (13.04%), HLA-C*12 (5.27%). HLA-DRB1 alleles were HLA-DRB1*07 (21.60%), HLA-DRB1*04 (19.74%), HLA-DRB1*10 (13.15%), HLA-DRB1*03 (10.80%), HLA-DRB1*11 (8.63%). HLA-DQA1 antigen alleles were HLA-DQA1*03 (35.42%), HLA-DQA1*02 (30.89%), HLA-DQA1*05 (21.84%), HLA-DQA1* 06 (10.12%), HLA-DQA1*04 (1.07%). Conclusion The most frequent HLA alleles were HLA-A*01(25.41%), HLA-B*35 (20.54%), HLA-C*07 (28.06%), HLA-DRB1*07(21.60%), HLA-DQA1*03(35.42%) in north Indian population.

The history of ethical principles in liver transplant organ allocation in the united states: how historical and proposed allocations system fare in balancing utility vs. urgency and justice vs. pragmatism.

The United States (US) liver transplant community is processing changes to the allocation system and developing a new proposal that will result in even greater change. This review evaluates the ethical implications of these decisions, focusing on two sets of competing ethical principles (Urgency vs. Utility and Justice vs. Pragmatism). About four years ago, the Organ Procurement and Transplantation Network (OPTN) implemented the Acuity Circle Model to replace the geographic boundaries of organ procurement organizations (OPOs). Here, we review how effectively this model reduced regional variation in access and improved waitlist survival. Likewise, the OPTN is planning to transition to a continuous distribution model which will redefine the scoring systems for allocation. We will discuss how the ethical priorities discussed above should be considered while developing the new system. Every change in organ allocation policy must balance competing ethical imperatives. Although our community's emphasis on urgency over utility is appropriate, we should study the potential benefits of considering utility in the system. Meanwhile, our push for more Justice in the system should remain our imperative and Pragmatism should only be considered to minimize the costs of these changes.

Is the Affordable Care Act Moving the Needle for Advanced Heart Failure Therapies for Black Patients?

Is the Affordable Care Act Moving the Needle for Advanced Heart Failure Therapies for Black Patients?

Public preferences for the allocation of donor organs for transplantation: A discrete choice experiment

This study aimed to assess public preferences for the allocation of donor organs in Germany with the focus on ethical principles of distributive justice. We performed a discrete choice experiment (DCE) using a self-completed online questionnaire. Based on a systematic review and focus group discussions, six attributes, each with two–four levels, were selected (corresponding principle of distributive justice in brackets), including (1) life years gained after transplantation (principle of distributive justice: effectiveness/benefit – utilitarianism), (2) quality of life after transplantation (effectiveness/benefit – utilitarianism), (3) chance for a further donor organ offer (principle of distributive justice: medical urgency – favouring the worst-off), (4) age (medical and social risk factors: sociodemographic status), (5) registered donor (principle of distributive justice: value for society), and (6) individual role in causing organ failure (principle of distributive justice: own fault). Each respondent was presented with eight choice sets and asked to choose between two hypothetical patients without an opt-out. Data were analysed using conditional logit, mixed logit and latent class models. The final sample comprised 1028 respondents. Choice decisions were significantly influenced by all attributes except chance for a further donor organ offer. The attributes of good quality of life after transplantation, younger age, and no individual role in causing organ failure had the greatest impact on choice decisions. Life years gained after transplantation and being a registered donor were less important for the public. The latent class model identified four classes with preference heterogeneities. Respondents preferred to allocate deceased donor organs by criteria related to effectiveness/benefit, whereas medical urgency was of minor importance. Therefore, a public propensity for a rational, utilitarian, ethical model of allocation could be identified. Public preferences can help to inform policy to warrant socially responsible allocation systems and thus improve organ donation rates.

Evolution of liver transplant organ allocation policy: Current limitations and future directions.

Since the adoption of the model for end-stage liver disease (MELD) score for organ allocation in 2002, numerous changes to the system of liver allocation and distribution have been made with the goal of decreasing waitlist mortality and minimizing geographic variability in median MELD score at time of transplant without worsening post-transplant outcomes. These changes include the creation and adoption of the MELD-Na score for allocation, Regional Share 15, Regional Share for Status 1, Regional Share 35/National Share 15, and, most recently, the Acuity Circles Distribution Model. However, geographic differences in median MELD at time of transplant remain as well as limits to the MELD score for allocation, as etiology of liver disease and need for transplant changes. Acute-on-chronic liver failure (ACLF) is a subset of liver failure where prevalence is rising and has been shown to have an increased mortality rate and need for transplantation that is under-demonstrated by the MELD score. This underscores the limitations of the MELD score and raises the question of whether MELD is the most accurate, objective allocation system. Alternatives to the MELD score have been proposed and studied, however MELD score remains as the current system used for allocation. This review highlights policy changes since the adoption of the MELD score, addresses limitations of the MELD score, reviews proposed alternatives to MELD, and examines the specific implications of these changes and alternatives for ACLF.

UNOS Match Runs for Pediatric Heart Transplant Organ Allocation—How Well Do They Sequence Patients Based on Medical Urgency?

<h3>Purpose</h3> The match run is the automated mechanism by which UNOS prioritizes donor hearts to waitlist candidates for heart transplant (HT) based on medical urgency. We sought to determine how well match runs perform in sequencing patients according to their medical urgency after implementation of the 2016 pediatric heart allocation revisions. <h3>Methods</h3> OPTN data were used to identify all match runs between March 21, 2016 and June 9, 2020 for each pediatric donor heart offered through UNOS to US waitlist candidates. The rank-order of candidates on the match run was compared to the rank-order based on medical urgency alone defined as the probability of survival on the day of the match run using a risk prediction model developed and validated during the prior 6 years. <h3>Results</h3> Overall, 634 donors generated 2,524 unique match runs during the study period when a total of 2,608 candidates were listed for pediatric HT. The median age of donors was 5 years (Q1, Q3, 1, 13), median weight 21 (11, 54) kg with the most common cause of death natural causes (26%), non-motor vehicle accidents (MVA) (22%) and MVA (16%). The risk-prediction model for death or deterioration included 8 variables (age, weight, cardiac diagnosis and cardiac support). When the survival model was applied to the match run candidates within zone, 26% of candidates were ranked out of survival order (i.e. had a rank-reversal) (<b>Table</b>). Of these, 69% of rank-reversals involved candidates <i>within</i> the same UNOS status levels whereas 41% involved candidates spread across UNOS status levels. <h3>Conclusion</h3> There is evidence to suggest that the 2016 revision to the pediatric donor heart allocation system fails to sequence waitlisted candidates according to medical urgency, which affects a substantial fraction of match runs. Misclassification of patient risk by UNOS status level and within UNOS status levels each contribute rank-reversals. Rank-ordering patients based on a continuous survival probability model could address both problems.

French People’s Views on the Allocation of Organs for Transplantation

BackgroundFrench laypeople’s views on the allocation of organs for transplantation were examined. MethodsA total of 199 adults make judgments of priority for a liver transplant in 48 realistic scenarios composed of all combinations of 4 factors: 1. probability of success, 2. life expectancy without transplant, 3. level of responsibility for liver failure (eg, substance abuse in the past), and 4. social situation (eg, young mother with 2 young children). In all scenarios, the patients were in need of liver transplant. The ratings were subjected to cluster analysis and analyses of variance. ResultsSix qualitatively different positions were found that were termed Probability of Success and Life Expectancy (6%), Family Responsibilities (8%), Family Responsibilities and Risky Behavior (28%), Risky Behavior and Family Responsibilities (22%), Risky Behavior (11%), and Always a Priority (25%). Regular church attendees expressed more often the Risky Behavior and Family Responsibilities position and less often the Always a Priority position than atheists. Female participants expressed more often the Risky Behavior position than male participants. ConclusionsThe French laypeople in our sample think that when assessing priority for transplant, criteria additional to medical urgency or the estimated utility in terms of expected life span after transplant should be taken into account. These criteria are the patient’s lack of responsibility for the liver failure (ie, not causing it by drinking or using drugs) and the extent of the patient’s social responsibilities (with active employment and dependents to care for).

Attitudes, knowledge, and preferences of the Israeli public regarding the allocation of donor organs for transplantation

BackgroundThere is a stark disparity between the number of patients awaiting deceased-donor organ transplants and the rate at which organs become available. Though organs for transplantation are assumed to be a community resource, and the organ supply depends on public willingness to donate, current allocation schemes do not explicitly incorporate public priorities and preferences. This paper seeks to provide insights regarding the Israeli public’s preferences regarding criteria for organ (specifically, kidney) allocation, and to determine whether these preferences are in line with current allocation policies.MethodsA market research company administered a telephone survey to 604 adult participants representing the Jewish-Israeli public (age range: 18–95; 50% male). The questionnaire comprised 39 questions addressing participants’ knowledge, attitudes, and preferences regarding organ donation and criteria for organ allocation, including willingness to donate.ResultsThe criteria that respondents marked as most important in prioritizing waitlist candidates were maximum medical benefit (51.3% of respondents) and waiting time (21%). Donor status (i.e., whether the candidate is registered as an organ donor) was ranked by 43% as the least significant criterion. Most participants expressed willingness to donate the organs of a deceased relative; notably, they indicated that they would be significantly more willing to donate if organ allocation policies took their preferences regarding allocation criteria into account. Unlike individuals in other countries (e.g., the UK, the US, and Australia) who responded to similar surveys, Israeli survey respondents did not assign high importance to the candidate’s age (24% ranked it as the least important factor). Interestingly, in some cases, participants’ declared preferences regarding the importance of various allocation criteria diverged from their actual choices in hypothetical organ allocation scenarios.ConclusionsThe findings of this survey indicate that Israel’s citizens are willing to take part in decisions about organ allocation. Respondents did not seem to have a strict definition or concept of what they deem to be just; yet, in general, their preferences are compatible with current policy. Importantly, participants noted that they would be more willing to donate organs if their preferences were integrated into the allocation policy. Accordingly, we propose that allocation systems must strive to respect community values and perceptions while maintaining continued clinical effectiveness.

Public preferences for the allocation of donor organs for transplantation: Focus group discussions.

BackgroundDeceased donor organs are scarce resources because of a large supply‐and‐demand mismatch. This scarcity leads to an ethical dilemma, forcing priority‐setting of how these organs should be allocated and whom to leave behind.ObjectiveTo explore public preferences for the allocation of donor organs in regard to ethical aspects of distributive justice.MethodsFocus groups were facilitated between November and December 2018 at Hannover Medical School. Participants were recruited locally. Transcripts were assessed with content analysis using the deductive framework method. All identified and discussed criteria were grouped according to the principles of distributive justice and reported following the COREQ statement.ResultsSix focus groups with 31 participants were conducted. Overall, no group made a final decision of how to allocate donor organ; however, we observed that not only a single criterion/principle but rather a combination of criteria/principles is relevant. Therefore, the public wants to allocate organs to save as many lives as possible by both maximizing success for and also giving priority to urgent patients considering the best compatibility. Age, waiting time, reciprocity and healthy lifestyles should be used as additional criteria, while sex, financial status and family responsibility should not, based on aspects of equality.ConclusionsAll participants recognized the dilemma that prioritizing one patient might cause another one to die. They discussed mainly the unclear trade‐offs between effectiveness/benefit and medical urgency and did not establish an agreement about their importance. The results suggest a need of preference studies to elucidate public preferences in organ allocation.

Risk Indices in Deceased-donor Organ Allocation for Transplantation: Review From an Australian Perspective.

Over the last decade, organ donation and transplantation rates have increased in Australia and worldwide. Donor and recipient characteristics for most organ types have generally broadened, resulting in the need to consider more complex data in transplant decision-making. As a result of some of these pressures, the Australian software used for donor and recipient data management is currently being updated. Because of the in-built capacity for improved data management, organ allocation processes will have the opportunity to be significantly reviewed, in particular the possible use of risk indices (RIs) to guide organ allocation and transplantation decisions. We aimed to review RIs used in organ allocation policies worldwide and to compare their use to current Australian protocols. Significant donor, recipient, and transplant variables in the indices were summarized. We conclude that Australia has the opportunity to incorporate greater use of RIs in its allocation policies and in transplant decision-making processes. However, while RIs can assist with organ allocation and help guide prognosis, they often have significant limitations which need to be properly appreciated when deciding how to best use them to guide clinical decisions.

Systematic Review of Public Preferences for the Allocation of Donor Organs for Transplantation: Principles of Distributive Justice.

Solid organ transplantation is the treatment of choice for organ failure, but donor organs are a scarce resource because of a large mismatch between supply and demand. This scarcity leads to an ethical dilemma, forcing priority setting in organ allocation to individual patients. Little is known about public preferences regarding priority setting in organ allocation. A systematic review was performed to review the existing evidence and provide an overview of the criteria and criterion levels in regard to ethical aspects of distributive justice. The PubMed, Web of Science, EBSCO and PsycINFO databases were searched for literature published between January 2000 and December 2018. Only original studies were selected. The criteria were identified, extracted and grouped into a self-developed matrix according to the principles of distributive justice to ascertain public preferences. Overall, 9645 references were identified, and 15 studies were included. In total, 27 criteria clustered in seven theory-guided groups could be identified: "equality", "effectiveness/benefit", "medical urgency", "own fault", "value for society", "medical background" and "sociodemographic status". It was shown that not only a single principle but rather a combination of principles are relevant for the allocation. Therefore, a public propensity towards a rational utilitarian ethical model of allocation could be recognised. The general public not only wanted to allocate organs mainly to those with a good probability of having a successful transplantation but also wanted to consider those who need an organ most urgently to prevent fatal consequences, resulting in unclear trade-offs between effectiveness/benefit and medical urgency. Public preferences for organ allocation are therefore complex, and data regarding clear trade-offs are still lacking.

Unintended consequences of changes to lung allocation policy.

Organ allocation for transplantation aims to balance the principles of justice and medical utility to optimally utilize a scarce resource. To address practical considerations, the United States is divided into 58 donor service areas (DSA), each constituting the first unit of allocation. In November 2017, in response to a lawsuit in New York, an emergency action change to lung allocation policy replaced the DSA level of allocation for donor lungs with a 250 nautical mile circle around the donor hospital. Similar policy changes are being implemented for other organs including heart and liver. Findings from a recent US Department of Health and Human Services report, supplemented with data from our institution, suggest that the emergency policy has not resulted in a change in the type of patients undergoing lung transplantation (LT) or early postoperative outcomes. However, there has been a significant decline in local LT, where donor and recipient are in the same DSA. With procurement teams having to travel greater distances, organ ischemic time has increased and median organ cost has more than doubled. We propose potential solutions for consideration at this critical juncture in the field of transplantation. Policymakers should choose equitable and sustainable access for this lifesaving discipline.

Public, medical professionals’ and patients’ preferences for the allocation of donor organs for transplantation: study protocol for discrete choice experiments

IntroductionOrgan transplantation is the treatment of choice for patients with severe organ failure. Nevertheless, donor organs are a scarce resource resulting in a large mismatch between supply and demand. Therefore,...

Liver transplant organ allocation; preliminary results using the ISO score system

Liver transplant organ allocation; preliminary results using the ISO score system

Regional Differences in Communication Process and Outcomes of Requests for Solid Organ Donation.

Although federal mandate prohibits the allocation of solid organs for transplantation based on "accidents of geography," geographic variation of transplantable organs is well documented. This study explores regional differences in communication in requests for organ donation. Administrative data from nine partnering organ procurement organizations and interview data from 1339 family decision makers (FDMs) were compared across eight geographically distinct US donor service areas (DSAs). Authorization for organ donation ranged from 60.4% to 98.1% across DSAs. FDMs from the three regions with the lowest authorization rates reported the lowest levels of satisfaction with the time spent discussing donation and with the request process, discussion of the least donation-related topics, the highest levels of pressure to donate, and the least comfort with the donation decision. Organ procurement organization region predicted authorization (odds ratios ranged from 8.14 to 0.24), as did time spent discussing donation (OR = 2.11), the number of donation-related topics discussed (OR = 1.14), and requesters' communication skill (OR = 1.14). Standardized training for organ donation request staff is needed to ensure the highest quality communication during requests, optimize rates of family authorization to donation in all regions, and increase the supply of organs available for transplantation.

The brain gets its say: Hepatic encephalopathy and its evolving role in transplant priority

Potential conflict of interest: Nothing to report. See Article on Page 1333 Hepatic encephalopathy (HE), overt and even covert, has a major impact on patient morbidity1 and survival.3 In recent years, the rapidly changing impact of HE on transplant priority and survival on the waiting list has been studied extensively using the United Network for Organ Sharing (UNOS) database and through well‐characterized cohorts.5 The subjective nature of clinical assessment of HE makes including it in organ allocation a divisive issue. Lucidi et al.7 in 2 large cohorts from Italy and Canada defined 1 approach toward solving this issue. Specifically, the authors used HE‐related hospitalizations with grade 2 or higher, that is, overt HE defined by the European Association for the Study of the Liver/American Association for the Study of Liver Diseases guidelines using asterixis and disorientation as diagnostic of HE.8 Stages lower than grade 2 were bundled into a user‐friendly pragmatic no‐HE group that included covert HE.9 A key strength of the study was validation across 2 separate continents with diverse populations and varying transplant organ allocation systems. The authors demonstrated that the contribution of HE to mortality was equivalent to 7 points of Model for End‐Stage Liver Disease (MELD) score. Interestingly, the impact on mortality was independent of the maximum grade of HE achieved beyond grade II, the proximity of the HE episode to enrollment, and the number of recent HE episodes. These findings point toward a biological "“crossing of the Rubicon"” that occurs when a patient reaches grade 2 HE in cirrhosis. The consequences of an overt HE (grade 2 or higher) episode requiring hospitalization are important from a psychosocial and clinical perspective.8 The incorporation of these findings by Lucidi et al.7 into organ allocation remains difficult. The advantages of the MELD score include its objectivity. In contrast, when the Child‐Pugh score was the basis of organ allocation assessment of HE, in the listing the clinician's word was paramount and could not be challenged due to the waxing and waning nature of HE. Interestingly, when HE lost its role in organ allocation after the introduction of the MELD score, the proportion of listed patients coded as grade 3/4 HE in the UNOS database dropped precipitously at a rate far higher than that expected biologically.10 These findings indicate that a portion of the "HE" patients in the Child‐Pugh era were likely overcoded. Ultimately, regardless of which definition of HE is used, it will remain difficult to clinically justify its use. Therefore, as prior studies have demonstrated, corroboration with cognitive, neuropsychological, and neurophysiological techniques may be important objective techniques that could help in the appeal to regional review boards regarding potential listing priority changes in affected patients.3 Moreover, with the introduction of MELD score with sodium for organ allocation, the numeric value to be assigned to HE > grade 2 needs to be recalculated.12 An increase in priority listing for patients with advanced HE is also relevant from a posttransplant recovery standpoint because pretransplant cognitive impairment with HE is consistently associated with a relatively lower recovery after transplant compared with those without these issues.13 Posttransplant liver recovery may not necessarily translate into return to the workforce and independence if cognitive recovery is not complete.15 Therefore, it may be important to consider that “time is brain” when HE patients on the transplant list are considered. This will require objective and reproducible assessment of HE rather than the time‐honored clinical evaluation.

Decade-Long Trends in Liver Transplant Waitlist Removal Due to Illness Severity: The Impact of Centers for Medicare and Medicaid Services Policy

The central tenet of liver transplant organ allocation is to prioritize the sickest patients first. However, a 2007 Centers for Medicare and Medicaid Services regulatory policy, Conditions of Participation (COP), which mandates publically reported transplant center performance assessment and outcomes-based auditing, critically altered waitlist management and clinical decision making. We examine the extent to which COP implementation is associated with increased removal of the "sickest" patients from the liver transplant waitlist. This study included 90,765 adult (aged 18 years and older) deceased donor liver transplant candidates listed at 102 transplant centers from April 2002 through December 2012 (Scientific Registry of Transplant Recipients). We quantified the effect of COP implementation on trends in waitlist removal due to illness severity and 1-year post-transplant mortality using interrupted time series segmented Poisson regression analysis. We observed increasing trends in delisting due to illness severity in the setting of comparable demographic and clinical characteristics. Delisting abruptly increased by 16% at the time of COP implementation, and likelihood of being delisted continued to increase by 3% per quarter thereafter, without attenuation (p < 0.001). Results remained consistent after stratifying on key variables (ie, Model for End-Stage Liver Disease and age). The COP did not significantly impact 1-year post-transplant mortality (p= 0.38). Although the 2007 Centers for Medicare and Medicaid Services COP policy was a quality initiative designed to improve patient outcomes, in reality, it failed to show beneficial effects in the liver transplant population. Patients who could potentially benefit from transplantation are increasingly being denied this lifesaving procedure while transplant mortality rates remain unaffected. Policy makers and clinicians should strive to balance candidate and recipient needs from a population-benefit perspective when designing performance metrics and during clinical decision making for patients on the waitlist.

From Child-Pugh to Model for End-Stage Liver Disease: Deciding Who Needs a Liver Transplant.

This article reviews the historical evolution of the liver transplant organ allocation policy and the indications/contraindications for liver transplant, and provides an overview of the liver transplant evaluation process. The article is intended to help internists determine whether and when referral to a liver transplant center is indicated, and to help internists to counsel patients whose initial evaluation at a transplant center is pending.

Grouping Promotes Equality

Decisions about allocation of scarce resources, such as transplant organs, often entail a trade-off between efficiency (i.e., maximizing the total benefit) and fairness (i.e., dividing resources equally). In three studies, we used a hypothetical scenario for transplant-organ allocation to examine allocation to groups versus individuals. Study 1 demonstrated that allocation to individuals is more efficient than allocation to groups. Study 2 identified a factor that triggers the use of fairness over efficiency: presenting the beneficiaries as one arbitrary group rather than two. Specifically, when beneficiaries were presented as one group, policymakers tended to allocate resources efficiently, maximizing total benefit. However, when beneficiaries were divided into two arbitrary groups (by hospital name), policymakers divided resources more equally across the groups, sacrificing efficiency. Study 3 replicated this effect using a redundant attribute (prognosis) to create groups and found evidence for a mediator of the grouping effect—the use of individualizing information to rationalize a more equitable allocation decision.