Relationship between Epoetin Alfa Dose and Mortality
Open Access
- 1 February 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Clinical Journal of the American Society of Nephrology
- Vol. 5 (2), 182-188
- https://doi.org/10.2215/cjn.03040509
Abstract
Background and objectives: Observational studies relating epoetin alfa (EPO) dose and mortality frequently use analytic methods that do not control time-dependent confounding by indication (CBI). The relationship between EPO dose and 1-year mortality, adjusting for the effects of time-dependent CBI, was examined using a marginal structural model. Design, setting, participants, & measurements: This retrospective cohort study included 27,791 hemodialysis patients between July 2000 and June 2002. Patients were grouped at successive 2-wk intervals into a zero-dose category or four nonzero-dose categories. Ordinal regression was used to calculate inverse probability of treatment weights of patients receiving their own dose level given their covariate and treatment history. Three treatment models with an increasing number of treatment predictors were evaluated to assess the effect of model specification. A small number of excessively large patient weights were truncated. Relative hazards for higher-dose groups compared with the lowest nonzero-dose group varied by treatment model specification and by level of weight truncation. Results: Results differed appreciably between the simplest treatment model, which incorporated only hemoglobin and EPO dosing history with 2% weight truncation (hazard ratio: 1.51; 95% confidence interval: 1.09, 1.89 for highest-dose patients), and the most comprehensive treatment model with 1% weight truncation (hazard ratio: 0.98; 95% confidence interval: 0.76, 1.74). Conclusions: There is appreciable CBI at higher EPO doses, and EPO dose was not associated with increased mortality in marginal structural model analyses that more completely addressed this confounding.Keywords
This publication has 26 references indexed in Scilit:
- Predictors of Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Hemodialysis PatientsAmerican Journal of Kidney Diseases, 2009
- Estimated Effect of Epoetin Dosage on Survival among Elderly Hemodialysis Patients in the United StatesClinical Journal of the American Society of Nephrology, 2009
- Effect of Epoetin Alfa Dose Changes on Hemoglobin and Mortality in Hemodialysis Patients with Hemoglobin Levels Persistently below 11 g/dLClinical Journal of the American Society of Nephrology, 2009
- Impact of elevated C-reactive protein levels on erythropoiesis- stimulating agent (ESA) dose and responsiveness in hemodialysis patientsNephrology Dialysis Transplantation, 2008
- Constructing Inverse Probability Weights for Marginal Structural ModelsAmerican Journal of Epidemiology, 2008
- History-Adjusted Marginal Structural Analysis of the Association between Hemoglobin Variability and Mortality among Chronic Hemodialysis PatientsClinical Journal of the American Society of Nephrology, 2008
- Estimating causal effects from epidemiological dataJournal of Epidemiology and Community Health, 2006
- Associations between Changes in Hemoglobin and Administered Erythropoiesis-Stimulating Agent and Survival in Hemodialysis PatientsJournal of the American Society of Nephrology, 2006
- Clinical Significance of C-Reactive Protein in Patients on Hemodialysis: A Longitudinal StudyNephron Clinical Practice, 2005
- Epoetin requirements predict mortality in hemodialysis patientsAmerican Journal of Kidney Diseases, 2004