THE OPTIMAL TIMING OF LIVER TRANSPLANTATION

终末期肝病（ESLD）是一个主要的问题， 在美国，肝移植是一种有效的， 昂贵的治疗方法 近期宣传围绕 器官分配和等待时间带来了 最佳选择的候选人和移植的时机 重要的公众监督。 因此，本项目的具体目标 是建立一个复杂的，现实的数学模拟模型， 足够详细的ESLD，以确定 在疾病的自然过程中移植。 因为这些 方法有能力评估几个模型， 同时，该模型将整合自然历史， 生存，成本和生活质量到一个单一的决策分析 框架. 虽然这些模型有大量的数据， 要求，最近的发展和几个大的可用性 一系列肝移植候选者，如NIDDK Liver 移植登记处）进行详细的校准， 模型可能。 这个项目是卫生服务的一个例子 研究旨在利用现有登记册和数据库， 尽可能地。 这项工作分为三个独立的任务：（1）通过 使用在现有技术下开发的技术和基本模型结构， 通过PI的工作，我们将创建疾病特定的模拟模型， ESLD。 将通过使用更好的 支持的建模软件，以及广泛的移植 匹兹堡大学和Deaconess医院的专家。 2)该模型将使用以下随时间变化的估计值进行校准： 预期生存率、资源使用和生活质量， 移植后。 这些估计数各部分的数据 将来自几个现有的大型数据集（匹兹堡和 NIDDK）通过明智的原始数据收集， 现有数据中的某些空白。 3)一旦建立和校准， 模拟模型将被用来调查几个问题， 选择标准对生存、生活质量和费用的影响 移植在终末期肝病中的应用，以及各种标准的影响 器官浪费和等待移植的时间 这项工作将 第一次创建一个完整的模型， 评价不同时间和分配的成本效益 战略布局

End stage liver disease (ESLD) is a problem of major proportions in the United States, and liver transplantation is an effective but expensive therapy for this disease. Recent publicity surrounding organ allocation and waiting times has brought the question of the optimal selection of candidates and timing of transplantation under significant public scrutiny. Therefore, the specific aim of this project is to construct a complex, realistic mathematical simulation model of ESLD that is sufficiently detailed to determine the optimal timing of transplantation during the natural course of disease. Because these methods have the ability to evaluate models across several dimensions simultaneously, the model will integrate natural history, survival, costs, and quality of life into a single decision analytic framework. Although such models have substantial data requirements, the recent development and availability of several large series of liver transplantation candidates such as the NIDDK Liver Transplantation Registry) make the detailed calibration of such models possible. This project is an example of health services research designed to utilize existing registries and databases to the extent possible. The work is divided into three separate tasks: 1) By using techniques and the basic model structure developed under prior work by the PI, we will create disease specific simulation models of ESLD. The effort will be enhanced through the use of better supported modeling software, and the extensive transplantation expertise of the University of Pittsburgh and the Deaconess Hospital. 2) The model will be calibrated with time-varying estimates of expected survival, resource use, and quality of life both before and after transplantation. Data for various portions of these estimates will come from several large existing datasets (Pittsburgh and NIDDK) augmented with judicious primary data collection to fill certain gaps in existing data. 3) Once built and calibrated, the simulation model will be used to investigate several questions about the effect of selection criteria on survival, quality of life and costs in the use of transplantation in ESLD, and the effect of various criteria on organ wasting and transplant waiting times. This work will create, for the first time, a complete model that will allow for the evaluation of the cost-effectiveness of different timing and allocation strategies.