Epoetin Therapy and Survival of Hemodialysis Patients

依泊汀治疗和血液透析患者的生存

• 批准号: 6953551
• 负责人: Dennis Joseph Cotter
• 金额: $ 36.47万
• 依托单位: MEDICAL TECHNOLOGY AND PRACTICE PATTERNS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6953551
• 关键词: anemia; blood cell count; chronic renal failure; data collection methodology /evaluation; erythropoietin; hemodialysis; human data; human mortality; human therapy evaluation; mathematical model; outcomes research; recombinant proteins

DESCRIPTION (provided by applicant): Our objective is to 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 ensure that treatment patterns for this high-risk population are rationally based to provide the patients with the best possibilities for survival.

描述（由申请方提供）：我们的目的是使用边缘结构模型（MSM）探索接受该治疗的血液透析患者中依泊苷剂量与死亡率的因果关系。MSM将使我们能够通过创建一个伪人群来区分因果效应，该伪人群根据医生对具有观察到的病史的患者所做的治疗决定进行有效随机化。目前依泊苷剂量增加和血细胞比容增加的趋势尚未显示对ESRD人群死亡率的影响。超过2000万美国人患有慢性肾脏疾病，同等数量的人面临更高的风险。大约有378，000名美国人进展为终末期肾病（ESRD），需要常规透析或接受肾移植。贫血是ESRD患者的常见事件，超过90%的中心血液透析患者因这种情况接受依泊苷治疗。尽管红细胞压积从1993年的30%增加到2000年的34.5%，并且在此期间，每周平均依泊苷剂量从约8，500单位/给药增加到13，400单位/给药，但在过去的两年半中，仍有约155，000例ESRD患者死亡。事实上，调整后的一年死亡率仍然没有减少;在此期间基本上保持在每千人230人死亡。据NIDDK称，这一比率“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生存率之间的相关性。然而，其中一些研究也报告了红细胞压积和依泊苷剂量之间的负相关性，强调红细胞压积实际上是依泊苷剂量和对依泊苷敏感性的结果，混淆了红细胞压积和生存期的分析。因此，将已发表的红细胞压积和生存率之间的关系解释为因果关系是不合适的。更好地了解依泊苷剂量和生存率之间的关系将为改善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。研究结果将通过同行评审期刊向公众传播。我们的目标是确保这种高危人群的治疗模式是合理的，为患者提供最佳的生存可能性。