Narrowing the gap between supply and demand in heart transplantation

缩小心脏移植供需差距

• 批准号: 10396268
• 负责人: Brian Wayda
• 金额: $ 7.86万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-03-01
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10396268
• 关键词: Adopted; Antibodies; Behavior; Blood; Characteristics; Clinical; Country; Europe; European; Geographic Locations; Grant; Heart; Heart Transplantation; Heart failure; Home; Institution; Logistic Regressions; Measures; Medical; Medical Device; Mentorship; Modeling; Organ; Organ Donor; Outcome; Patients; Phenotype; Physicians; Population; Research; Research Personnel; Resources; Risk; Scheme; Series; Testing; Training; Training Activity; Translating; Transplantation; United States; Universities; Variant; Wait Time; Waiting Lists; Work; alternative treatment; base; career; cohort; data registry; design; disparity reduction; experience; high risk; improved; improved outcome; interest; mechanical device; models and simulation; mortality; patient subsets; post-transplant; simulation; skills; transplant centers; validation studies

Project summary/abstract Demand for heart transplant (HT) in the United States (US) far exceeds the supply of donor organs. Each year, more than 500 patients on the waitlist die or become too sick for transplant. Outcomes are especially poor for patients with high levels of sensitization – the presence of preformed antibodies rendering one incompatible with potential donors. To reduce waitlist mortality, it is essential to narrow the gap between donor heart supply and demand while maintaining fairness. The current study will inform efforts to do so in a series of three aims. The first aim is to show the feasibility and benefits of higher donor heart utilization, that is, the proportion of candidate hearts that are used for transplant. Average donor heart utilization in the US is ~30%. Utilization is higher in Europe and at more “aggressive” centers within the US, who nonetheless achieve acceptable post-transplant outcomes. The current study will use simulation modeling to evaluate hypothetical scenarios in which all US HT centers achieve the same utilization rates as 1) “aggressive” US centers and 2) Europe. Outcomes of interest will include wait times and survival, measured on a population-level. The second aim is to identify patients who would – and would not – benefit from transplant. The hypothesis being tested is that many on the waitlist would fare as well or better with medical or mechanical device therapy in lieu of transplant. Delisting such patients would help alleviate the supply-demand gap, but identifying this subset is challenging. One approach uses multivariate risk scores to measure a patient’s potential benefit from transplant. The current study will systematically test the reliability of post-HT survival scores in historical cohorts. Suspecting their reliability to be poor, an alternative approach will be presented: to estimate the benefit to transplant using blood type as an instrumental variable. The third aim is to demonstrate the benefits of prioritizing sensitized patients. Allocation schemes can be designed that boost priority and reduce waiting times for sensitized patients. The payoff to such schemes, in terms of wait times and population-level survival, will be estimated using simulation modeling and an optimal prioritization scheme will be identified. This work will be conducted at Stanford University, a renowned research institution and home to leaders in HT research. It accompanies a training plan that draws on close mentorship and Stanford’s ample resources to equip the trainee with pertinent and career-advancing skills.

项目摘要/摘要 美国对心脏移植（HT）的需求（美国）远远超过了 捐赠器官。每年，候补名单上有500多名患者死亡或太病了 移植。对于高灵敏度的患者而言，结果尤为差 - 存在预先形成的抗体，使一个与潜在供体不相容。减少 候补名单死亡率，必须缩小供体心脏供应和需求之间的差距 保持公平。当前的研究将为您努力做出三个目标的努力。 第一个目的是展示更高的供体心利用率的可行性和好处， 也就是说，用于移植的候选心脏的比例。普通捐助者心 美国利用率约为30％。欧洲的利用率较高，在更“激进”的中心 在美国，尽管如此，他们仍然可以实现可接受的移植后结果。电流 研究将使用仿真建模来评估所有美国HT中心的假设场景 达到与1）“积极”的美国中心和2）欧洲相同的利用率。结果 兴趣将包括等待时间和生存，以人群级别的衡量。 第二个目的是确定会受益的患者 移植。测试的假设是，候补名单上的许多人的票价也一样好 用医疗或机械设备治疗代替移植。将这些患者推荐 帮助减轻供求差距，但确定该子集是具有挑战性的。一种方法 使用多元风险评分来衡量患者从移植中的潜在益处。 当前的研究将系统地测试历史后HT生存评分的可靠性 同伙。怀疑他们的可靠性是贫穷的，将提出另一种方法： 估计使用血型作为仪器变量移植的好处。 第三个目的是证明优先考虑敏感患者的好处。 可以设计分配方案，以提高优先级并减少敏感的等待时间 患者。就等待时间和人口水平的生存而言，此类计划的回报将 将使用仿真建模和最佳优先级方案进行估算。 这项工作将在斯坦福大学（一家著名的研究机构）进行， HT研究领导者的所在地。它涉及一项训练计划，该计划借鉴了密切的精神制度 以及斯坦福大学的充足资源，可以为实习生提供相关和职业生涯的技能。