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 美国对心脏移植的需求远远超过心脏移植的供应 捐献器官。每年，等待名单上的500多名患者死亡或病情严重 移植。高致敏水平的患者预后尤其差-- 预制抗体的存在使一个人与潜在的捐赠者不相容。减少 在等待死亡的同时，缩小供者心脏供需之间的差距是至关重要的 维护公平。目前的研究将为实现这一目标的一系列三个目标提供信息。 第一个目标是显示更高的供体心脏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。平均供心 美国的利用率约为30%。欧洲的使用率更高，而且是在更“积极”的中心 在美国，尽管如此，他们仍然取得了可接受的移植后结果。海流 研究将使用模拟建模来评估假设的场景，在这些场景中，美国所有的HT中心 达到与1)“积极进取”的美国中心和2)欧洲中心相同的利用率。结果： 利息将包括等待时间和存活率，以人口水平衡量。 第二个目标是确定哪些患者将受益，哪些患者不会受益。 移植。正在检验的假设是，等待名单上的许多人也会过得不错，甚至更好。 用医疗或机械设备治疗来代替移植。将这类患者除名将 有助于缓解供需缺口，但确定这一子集是具有挑战性的。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好处。这个 目前的研究将系统地检验高血压术后生存评分在历史上的可靠性 一群人。如果怀疑它们的可靠性较差，将提出另一种方法： 使用血型作为辅助变量来评估移植的益处。 第三个目标是证明优先处理敏感患者的好处。 可以设计分配方案，以提高优先级并减少敏感化的等待时间 病人。在等待时间和人口水平的生存方面，这种计划的回报将是 将使用模拟建模进行估计，并将确定最佳优先排序方案。 这项工作将在著名的研究机构斯坦福大学进行， 这里是HT研究领域的领军人物之家。它伴随着一项利用密切指导的培训计划 斯坦福大学拥有充足的资源，可以让学员掌握相关的职业发展技能。