Comparative Effectiveness and Safety of Newer Agents for Anemia Treatment in HD

描述（由申请人提供）：超过57.5万美国人患有终末期肾病，通常伴有贫血，其中大多数患者接受维持性透析治疗。拟议的工作将比较darbepoetin alfa（一种治疗贫血的新型注射药物）与已有的同类药物epoetin alfa的有效性和安全性。同样，阿魏木糖醇，一种用于治疗贫血的新的静脉补铁剂，将与一种已建立的补铁剂，铁蔗糖进行比较。这两种药物都是根据随机研究的信息获得批准的，这些研究评估了它们减少贫血的疗效。然而，关于这两种药物的长期疗效和安全性的信息非常有限。我们建议研究这两种药物的有效性和安全性，并将其与已有的同类药物进行比较。具有科学意义的事件包括短期结果（过敏反应、血红蛋白、铁饱和度、铁蛋白等实验室参数）和长期结果（感染、心血管事件、癌症和死亡率）。我们将使用已经从医疗保险账单索赔和透析提供者的电子医疗记录中收集的数据来解决这些研究问题。由于医疗机构根据其处方中可用的药物选择这些治疗方案，而不一定基于患者的特征，我们可以利用自然实验，当医疗机构为其整个患者群体切换其ESA或铁剂时发生的实验。我们将运用现代流行病学技术来消除偏见，并力求提供对相对收益和风险的有效估计。这项工作的发现有可能立即影响和改善终末期肾病患者接受的护理。我们的研究结果可能会提高接受治疗的质量，从而改善这一弱势患者群体的预后。工作的目标和范围与国家糖尿病、消化和肾脏疾病研究所的使命完全一致，更具体地说，是肾脏、泌尿和血液疾病部门的使命，该部门将考虑这项申请的资助。

DESCRIPTION (provided by applicant): More than 575,000 Americans have end-stage renal disease, which is typically complicated by anemia, and most of these patients receive maintenance dialysis treatment. The proposed work will compare the effectiveness and safety of darbepoetin alfa, a novel injectible drug for the treatment of anemia, with its established cousin, epoetin alfa. Similarly, ferumoxytol, a new intravenous iron supplement for the treatment of anemia will be compared with an established iron supplement, iron sucrose. Both drugs were approved using information from randomized studies that evaluated their efficacy on reducing anemia. Very limited information, however, is available for either drug regarding their longer-term efficacy and safety. We are proposing to study the effectiveness and safety of these two medications when compared to their established cousins. Events of scientific interest include short-term outcomes (anaphylaxis, laboratory parameters including hemoglobin, iron saturation, ferritin) and longer- term outcomes including infection, cardiovascular events, cancer, and mortality. We will use already collected data from Medicare billing claims and electronic medical records of dialysis providers to address these research questions. Since facilities choose among these treatment options based on what is available in their formulary, and not necessarily based on patient characteristics, we can exploit natural experiments that occur when facilities switch their ESA or iron agent for their entire patient population. We will apply modern epidemiological techniques to eliminate bias and aspire to provide valid estimates of relative benefits and risks. Findings from the proposed work have the potential to immediately impact and improve the care that patients with end-stage renal disease receive. Our results may improve the quality of care received and, thus, the outcomes of this vulnerable patient population. The aims and scope of work are in full congruence with the mission of the National Institutes of Diabetes and Digestive and Kidney Diseases, and more specifically the Division of Kidney, Urologic, and Hematologic Diseases, which will consider this application for funding.