Choosing Immune Suppression in Renal Transplantation by Efficacy and Morbidity

描述(由申请人提供)：肾移植(KTX)专业人员为他们的患者提供多种免疫抑制(IS)药物和方案选择。随着早期急性排斥反应(AR)发生率的降低和移植物短期存活率的提高，个体化的移植物长期存活率取决于患者潜在的IS药物合并症或并发症。然而，关于如何在有效性(预防AR)和并发症(包括感染、癌症和移植后新发糖尿病(NODAT))之间取得平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；但与先前对大型国家数据库的分析一起，也有 有很多限制。在这项研究中，我们建议使用一个新颖的三数据库链接：a)美国国家器官采购和移植网络(OPTN)注册：记录所有KTX和随后的生存结果的初始数据，b)Medicare账单索赔数据库：覆盖KTX后的第一个3年，以及c)一个覆盖美国60%的药物填写的国家药房数据库(PCD)。使用这种集成，我们可以最大限度地减少先前方法的局限性，以开发关于移植程序、使用、生存和非致命性发病率的准确的、纵向的、全国性的数据。我们的研究团队由KTX专家、经济学家和统计学家组成，他们都拥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(根据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注册、更新的Medicare索赔数据集和PCD的数据的新链接，以量化KTX与疗效和发病率的结果指标的关联，并根据人口统计学、医学和免疫学参数进行调整；通过倾向得分和协变量调整的生存模型，量化IS方案或剂量与导致移植物存活和患者存活的硬结果的疗效(AR)或发病率(重大感染、癌症、NODAT)的具体措施之间的关系，并对关键的种族和高风险亚组进行次级分析；2)使用目标1中产生的事件的转移概率，建立马尔科夫模型，计算按总体组和上述关键亚组使用的每个主要IS方案的总体成本效益，包括权衡成本；3)使用AIMS 1和AIMS 2的决策分析，通过免费且可更新的、以患者为中心的、基于网络或移动电话的风险引擎和通信工具，生成不同KTX方案的预测疗效/并发症、结果和成本的个性化实时报告。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成本效益和更知情的方式做出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.