Choosing Immune Suppression in Renal Transplantation by Efficacy and Morbidity

描述（由申请人提供）：肾移植（KTx）专业人员为患者提供多种免疫抑制（IS）药物和治疗方案。随着早期急性排斥反应（AR）率的降低和短期移植物存活率的提高，个体化的长期移植物存活率取决于患者的潜在合并症或IS药物的并发症。然而，关于如何平衡IS疗效（预防AR）与并发症（包括感染，癌症和移植后新发糖尿病（NODAT））之间的权衡的研究或数据很少。随机试验或FDA批准的风险评估和缓解策略有助于非常具体的情况;但沿着先前对大型国家数据库的分析， 很多限制。 在这项研究中，我们建议使用一种新的三个数据库链接：a）美国国家器官采购和移植网络（OPTN）登记处：记录所有KTx和随后生存结果的初始数据，B）医疗保险账单索赔数据库：涵盖了KTx后的前3年，以及c）覆盖美国所有药物填充的60%的国家药房交换所数据库（PCD）。使用该集成，我们可以最小化现有方法的限制，关于移植手术、IS使用、生存率和非致死性发病率的国家级纵向数据。我们的KTx专家，经济学家和统计学家的调查团队，都具有移植数据库和结果研究专业知识，然后可以以比以前更严格的方式评估IS方案和剂量的疗效和发病率权衡。在拟议的CISTEM研究中，（通过疗效和发病率选择肾移植中的免疫抑制），我们将完成以下三个目标：1）构建来自OPTN登记处、更新的医疗保险索赔数据集和PCD的数据的新链接，以量化KTx IS与疗效和发病率的结果指标的关联，针对人口统计学、医学和免疫学参数进行调整;通过倾向评分和协变量校正的生存模型，量化IS方案或剂量与疗效（AR）或发病率的特定指标之间的相关性（主要感染，癌症，NODAT），有助于移植物生存和患者生存的硬结果，对关键种族和高风险亚组进行亚组分析; 2）使用目标1中产生的事件转移概率，建立马尔可夫模型，并计算总体成本效益，包括按总体组和上述关键子组计算的使用中的每种主要体制建设方案的权衡成本;和3）使用目标1和2的决策分析，通过免费和可更新的以患者为中心的网络或移动的电话，生成不同KTx IS方案的预测疗效/并发症结局和成本的个性化和实时报告。基于风险引擎和沟通工具。其长期意义在于，医生和患者将能够以比目前可用的任何其他策略更具有成本效益和更明智的方式做出IS选择。

DESCRIPTION (provided by applicant): Kidney transplant (KTx) professionals have many choices of immunosuppressive (IS) medications and regimens for their patients. With early acute rejection (AR) rates now low and short term graft survival high, individualized long-term graft survival depends on patients' underlying co-morbidities or complications of IS medications. Yet few studies or data exist on how to balance the trade-offs between IS efficacy (in preventing AR) versus complications, including infections, cancers and new onset diabetes after transplant (NODAT). Randomized trials or FDA-sanctioned Risk Evaluation and Mitigation Strategies help with very specific situations; but along with prior analyses of large national databases, also have many limitations. In this study, we propose to use a novel, three-database linkage of the a) U.S.A. national Organ Procurement and Transplant Network (OPTN) registry: recording initial data on all KTx and subsequent survival outcomes, b) a Medicare billing claims database: covers the first 3 years post-KTx, and c) a national Pharmacy Clearinghouse Database (PCD) that covers 60% of all medication fills in the U.S.A. Using this integration, we can minimize limitations of prior approaches to develop accurate, longitudinal, national level data on the transplant procedures, IS use, survival and non-fatal morbidity. Our investigative team of KTx specialists, economists and statisticians, all with transplant database and outcomes research expertise, can then assess in a more rigorous way than previously possible, the efficacy and morbidity tradeoffs of the IS regimens and doses. In the proposed CISTEM study (Choosing Immune Suppression in Renal Transplantation by Efficacy and Morbidity), we will complete the following three aims: 1) To construct a novel linkage of data from the OPTN registry, an updated Medicare claims dataset and the PCD to quantify the associations of KTx IS with outcome metrics of efficacy and morbidity, adjusted for demographic, medical and immunologic parameters; through propensity-score and covariate-adjusted survival models that will quantify the association between IS regimen or dose and specific measures of efficacy (AR) or morbidity (major infections, cancers, NODAT) that contribute to the hard outcomes of graft survival and patient survival, with sub-analyses for key racial and high-risk subgroups; 2) To use the transition probabilities of events, generated in aim 1, to develop Markov models and calculate the overall cost-effectiveness, including trade-off costs, for each of the major IS regimens in use, by overall group and in the key sub-groups mentioned above; and 3) To use the decision analytics from Aims 1 and 2 to generate individualized and real-time reports of the predicted efficacy/complications outcomes and costs of different KTx IS regimens through a free and updateable patient-focused web- or mobile phone-based risk engine and communication tool. The long-term significance is that physicians and patients will be able to make IS choices in a more cost-effective and better informed manner than any other strategy currently available.