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.

项目概要/摘要 美国（US）对心脏移植（HT）的需求远远超过心脏移植的供应 捐赠器官。每年，超过 500 名等候名单上的患者死亡或病情严重而无法接受治疗。 移植。对于过敏程度高的患者来说，结果尤其糟糕—— 预制抗体的存在使得抗体与潜在的供体不相容。减少 等待名单死亡率，缩小捐赠心脏供需之间的差距至关重要，同时 维护公平。当前的研究将为实现这一目标的一系列三个目标提供信息。 第一个目标是展示更高的供体心脏利用率的可行性和好处， 即用于移植的候选心脏的比例。平均捐献心脏 美国的利用率约为 30%。欧洲和更“激进”的中心的利用率更高 在美国，他们仍然获得了可接受的移植后结果。目前的 研究将使用模拟模型来评估假设场景，其中所有美国 HT 中心 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率，以人口水平来衡量。 第二个目标是确定哪些患者会（或不会）受益于 移植。正在测试的假设是，候补名单上的许多人也会有同样或更好的表现 用医疗或机械设备治疗代替移植。将此类患者除名将 有助于缓解供需缺口，但识别这一子集具有挑战性。一种方法 使用多变量风险评分来衡量患者从移植中获得的潜在益处。这 当前的研究将系统地测试历史上 HT 后生存评分的可靠性 队列。怀疑它们的可靠性很差，将提出另一种方法： 使用血型作为工具变量来估计移植的益处。 第三个目标是证明优先考虑敏感患者的好处。 可以设计分配方案来提高优先级并减少敏感对象的等待时间 患者。就等待时间和人口水平生存而言，此类计划的回报将 使用仿真模型进行估计，并确定最佳优先级方案。 这项工作将在著名研究机构斯坦福大学进行 HT 研究领域领导者的所在地。它附带一个基于密切指导的培训计划 斯坦福大学拥有充足的资源，可以为学员提供相关的职业发展技能。