Individualized Treatment Strategies and Optimal Hematocrit Target for Complex Dia

描述(由申请人提供)：针对复杂透析患者背景的个体化患者治疗策略和最佳红细胞压积目标。几乎所有的肾功能衰竭患者都会将贫血作为一种重要的合并症。促红细胞生成素疗法是美国食品和药物管理局在批准的，是这一人群中贫血的主要治疗方法。近20年后，有关促红细胞生成素治疗有效性的关键问题仍未得到回答。特别是，在肾功能衰竭合并贫血患者中高度流行的并存疾病的作用尚不清楚。考虑到最近的几项随机试验和FDA的黑匣子警告，患有心血管疾病和糖尿病等并存疾病的患者是否需要不同的治疗终点，以尽可能使用最低剂量的埃博汀。目前，肾病界对于不同患者组的最佳靶向红细胞压积和促红细胞生成素剂量方案似乎存在不确定性。目标。我们提出的研究的目的是解决一个关键问题：基于心血管疾病和糖尿病等并存疾病的存在，最佳治疗策略是什么？仅有的一项针对透析人群的促红细胞生成素随机对照试验表明，心血管疾病患者不应将目标锁定在正常的红细胞压积水平。糖尿病透析患者贫血更严重，对治疗更具抵抗力。为了解决这个研究问题，我们还将研究这种并存的存在如何影响患者对埃博汀治疗的反应性？具体地说，对于对促红细胞生成素治疗有反应(且使用低于平均剂量)的复杂患者，靶向高于FDA推荐的血球压积是否会导致更好的结果？对于没有反应(低血球压积和高剂量)的合并疾病的患者，给予高剂量靶向FDA推荐的红细胞压积是否会导致更差的结果？最后，考虑到糖尿病或心血管疾病的存在，根据种族、性别和年龄等患者人口统计学特征进一步细分的最佳治疗策略是什么？方法：研究方法。我们建议应用因果分析方法(逆概率加权模型)，与标准统计方法不同，这些方法适当地调整了受先前治疗影响的时间相关混杂因素。因此，建议的方法非常适合于解决有关贫血管理和透析患者死亡率的关键问题。意义重大。到目前为止，在评估肾功能衰竭人群中的患者预后时，有限的随机对照试验和观察性研究按患者的并存情况进行了分类。继续对所有透析患者使用单一的红细胞压积目标范围和剂量方案，忽略了糖尿病或心血管疾病患者的个体需求。已经开发了因果推断技术，并使用其他治疗领域的随机临床试验数据进行了验证。在这笔赠款中，我们建议应用这些创新技术，使用联邦医疗保险管理数据，根据常见的患者共病特征，使用个性化的指导方针，为改善患者结果提供基础。研究结果可能为改进临床指南和更具成本效益的支付者政策提供基础。 公共卫生相关性：复杂透析患者的个体化患者治疗策略和最佳红细胞压积目标本提案涉及2009年《美国复苏与再投资法案》第111-5号公法的目标，目的是了解不同策略在预防和管理患有特定并发症的人群中的慢性病的比较价值。本文提出的研究将有助于指导适当整合促红细胞生成素治疗贫血的证据，这种贫血在患有多种慢性病的肾功能衰竭患者中普遍存在。特别是，我们假设接受永久性透析的患者(终末期肾病患者)合并糖尿病或心血管疾病，在安全性和有效性方面都需要不同的治疗终点来治疗贫血。根据国家肾脏基金会(KDOQI)提出的国家指南，使用Epoetin的证据基础“需要贫血管理方案产生的信息，这些方案检查多种干预措施，并明确说明潜在的目标和假设(1)。”在努力涵盖所有药物的过程中，《医疗保险现代化法案》要求确定“提高所用疗法的效率和有效性的战略”(2)。更好地了解促红细胞生成素剂量策略和存活率之间的关系将有助于改进治疗指南，提高终末期肾病患者的存活率。这些信息应该有助于临床医生更好地整合向这类患者提供的护理，帮助患者就医疗保健选择做出明智的决定，并帮助政策制定者找到更好的方法来衡量和促进对复杂患者的高质量护理。1K/DOQI慢性肾脏疾病临床实践指南：评估、分类和分层第7部分：肾脏疾病进展和心血管疾病发展的风险分层指南15.慢性肾脏疾病与心血管疾病的相关性。2 2003年《医疗保险处方药，改进和现代化法案》108-173第108届国会，SEC。1013.医疗保健项目和服务的效果研究

DESCRIPTION (provided by applicant): Individualized Patient Treatment Strategies and Optimal Hematocrit Target for the Complex Dialysis Patient Background. Almost all renal failure patients suffer from anemia as an important co- morbid condition. Epoetin therapy, approved by the FDA in 1989, is the mainstay of treatment for anemia among this population. After almost 20 years, key questions regarding the effectiveness of epoetin therapy remain unanswered. In particular, the role of comorbid conditions highly prevalent among renal failure patients with anemia is unknown. Do patients with co-morbidities including cardiovascular disease and diabetes require a different therapeutic endpoint given several recent randomized trials and Black Box warnings by the FDA to use the lowest dose of epoetin possible. Currently, there appears to be uncertainty in the nephrology community as to the optimal target hematocrit and epoetin dosing protocols for various patient groups. Objectives. The objective of our proposed study is to address the key question: What is the optimal treatment strategy based on the presence of co-morbidities such as cardiovascular disease and diabetes? The only existing epoetin RCT for the dialysis population suggests that patients with cardiovascular disease should not be targeted to normal hematocrit levels. Dialysis patients with diabetes have more severe anemia and are more resistant to treatment. To address this research question, we will also examine how does the presence of such comorbidities affect patient responsiveness to epoetin therapy? Specifically, for complex patients who are responsive to epoetin therapy (and use lower than average dose), does targeting higher than FDA-recommended hematocrits lead to better outcomes? For patients with co-morbid conditions who are not responsive (with low hematocrits and high doses), does administering high doses to target the FDA- recommended hematocrit lead to worse outcomes? Finally, given the presence of diabetes or cardiovascular disease, what is the optimal treatment strategy further disaggregated further by patient demographics such as race, gender and age affect outcome? Methods. We propose to apply causal analytical methods (inverse probability weighting models) that, unlike standard statistical methods, appropriately adjust for time-dependent confounders that are affected by prior treatment. The proposed methods are therefore well suited to address key questions concerning anemia management and mortality of dialysis patients. Significance. To date, limited RCTs and observational studies have been disaggregated by patient co-morbidities when evaluating patient outcomes in the renal failure population. The continuing use of a single hematocrit target range and dosing protocols for all dialysis patients ignores individual patient needs of those with comorbid diabetes or cardiovascular disease. Causal inference techniques have been developed and validated using randomized clinical trial data in other treatment areas. In this grant, we propose to apply these innovative techniques using Medicare administrative data to provide a basis for improved patient outcomes using 'individualized' guidelines based on common patient comorbid characteristics. Study findings might provide the basis for improved clinical guidelines and more cost-effective payer policies. PUBLIC HEALTH RELEVANCE: Individualized Patient Treatment Strategies and Optimal Hematocrit Target for the Complex Dialysis Patient This proposal addresses the goal of the American Recovery & Reinvestment Act of 2009, Public Law 111-5, to understand the comparative value of different strategies in the prevention and management of chronic illness in persons with specific constellations of co-morbid conditions. The research proposed herein will contribute evidence to help guide the appropriate integration of epoetin therapy for the treatment of anemia that is universally found among renal failure patients with multiple chronic conditions. In particular, we hypothesize that patients undergoing permanent dialysis (end-stage renal disease patients) with either comorbid diabetes or cardiovascular disease require a different therapeutic endpoint for treatment of anemia both in terms of safety and effectiveness. According to national guidelines put forth by the National Kidney Foundation (KDOQI), the evidence base for use of epoetin "requires information generated from anemia management protocols that examine multiple interventions and explicitly state underlying goals and assumptions (1)." In its effort to cover all drugs, the Medicare Modernization Act calls for identification of 'strategies for improving the efficiency and effectiveness of' ...therapies used (2). A better understanding of the relationship between epoetin dosing strategies and survival will contribute towards improved treatment guidelines, and improved survival of ESRD patients. This information should help clinicians better integrate care provided to such individuals, help patients make informed decisions about health care choices, and help policymakers identify better ways to measure and promote quality care for complex patients. 1 K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification PART 7. Stratification of Risk for Progression of Kidney Disease and Development of Cardiovascular Disease Guideline 15. Association of Chronic Kidney Disease with Cardiovascular Disease. 2 MEDICARE PRESCRIPTION DRUG, IMPROVEMENT, AND MODERNIZATION ACT OF 2003 Public Law 108-173 108th Congress, SEC. 1013. RESEARCH ON OUTCOMES OF HEALTH CARE ITEMS AND SERVICES