Epoetin Therapy and Survival of Hemodialysis Patients

描述(由申请人提供)：我们的目标是使用边际结构模型(MSM)来探索接受这种疗法的血液透析患者中促红细胞生成素剂量与死亡率之间的因果关系。MSM将使我们能够通过创建一个伪总体来区分因果影响，该伪总体有效地随机地根据医生对有观察到的病史的患者所做的治疗决定。目前增加埃博汀剂量和增加红细胞压积的趋势尚未显示出对ESRD人群死亡率的影响。超过2000万美国人患有慢性肾脏疾病，同样数量的人面临着更高的风险。大约378,000名美国人进展为终末期肾病(ESRD)，需要进行常规透析或接受肾脏移植。贫血是终末期肾病患者的常见情况，超过90%的中心血液透析患者接受埃普汀治疗。尽管红细胞压积从1993年的30%上升到2000年的34.5%，每周平均埃博汀剂量从大约8500个单位/ADM增加到13400个单位/ADM，但在过去两年半的时间里，大约有155,000名ESRD患者死亡。事实上，调整后的一年死亡率仍然有增无减；在此期间基本保持在每千人230人死亡。根据NIDDK的说法，这个比率“高得令人无法接受”。K/DOQI临床实践指南引用了几项研究，这些研究报告了较高的血细胞比容与存活率之间的关联。然而，其中一些研究也报道了红细胞压积和促红细胞生成素剂量之间的负相关，强调红细胞压积实际上是促红细胞生成素剂量和对促红细胞生成素敏感性的结果，混淆了红细胞压积和存活率的分析。因此，将已发表的红细胞压积和存活率之间的关联解释为因果关系是不合适的。更好地了解促红细胞生成素剂量与生存之间的关系将为改进目前的治疗指南提供基础，从而可能降低这些患者的死亡率。结果将通过同行评议的期刊向公众传播。我们的目标是确保为这一高危人群提供合理的治疗模式，为患者提供最好的生存可能性。

DESCRIPTION (provided by applicant): Our objective is use a Marginal Structural Model (MSM) to explore the causal relationship of epoetin dose on mortality for hemodialysis patients receiving this therapy. The MSM will enable us to distinguish causal effects by creating a pseudo-population that is effectively randomized on the treatment decisions made by physicians for patients with the observed histories. The current trend of increasing epoetin doses and increasing hematocrits has yet to show an impact on the ESRD population's mortality rates. More than 20 million Americans have chronic kidney disease and an equal number are at increased risk. Approximately 378,000 Americans progress to end-stage renal disease (ESRD) and require routine dialysis or undergo a kidney transplant. Anemia is a common occurrence in patients with ESRD and over 90% of in-center hemodialysis patients receive epoetin treatment for this condition. Despite the fact that hematocrit increased from 30 percent in 1993 to 34.5 percent in 2000 and mean epoetin dose per week increased from approximately 8,500 units/adm to 13,400 units/adm over this time, approximately 155,000 ESRD patient deaths have occurred over the last two and one half years. In fact, the adjusted one-year death rate remains unabated; essentially constant at 230 deaths per thousand during this time. This rate is, according to NIDDK, "unacceptably high". K/DOQI clinical practice guidelines cited several studies that report an association between higher hematocrits and survival. However, some of these studies also report a negative association between hematocrit and epoetin dose highlighting that hematocrit is actually an outcome of both epoetin dosing and sensitivity to epoetin, confounding the analysis of hematocrit and survival. Therefore, it is not appropriate to interpret the published associations between hematocrit and survival as a causal relationship. A better understanding of the relationship between epoetin dose and survival will provide a basis for improving current treatment guidelines and may thereby decrease the mortality rate of these patients. The results will be disseminated to the public through peer-reviewed journals. Our goal is to insure that treatment !patterns for this high-risk population are rationally based to provided the patients with the best possibilities for survival.