Dataset Information

Relationship between epoetin alfa dose and mortality: findings from a marginal structural model.

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.

SUBMITTER: Wang O

PROVIDER: S-EPMC2827587 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Publications

Relationship between epoetin alfa dose and mortality: findings from a marginal structural model.

Wang Ouhong O Kilpatrick Ryan D RD Critchlow Cathy W CW Ling Xiang X Bradbury Brian D BD Gilbertson David T DT Collins Allan J AJ Rothman Kenneth J KJ Rothman Kenneth J KJ Acquavella John F JF

Clinical journal of the American Society of Nephrology : CJASN 20091217 2

<h4>Background and objectives</h4>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.<h4>Design, setting, participants, & measurements</h4>This retrospective cohort study included 27,791 hemodialysis patients between July 2000 and ...[more]

PMID: 20019122

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Project description:BACKGROUND AND OBJECTIVES:This study was conducted to compare the safety and efficacy of intravenous epoetin alfa-epbx, an epoetin alfa biosimilar, to epoetin alfa in patients on hemodialysis with ESKD and anemia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:In this 24-week, multicenter, double-blind comparative efficacy and safety study, 612 patients on hemodialysis with ESKD and anemia who had stable hemoglobin and were receiving stable doses of intravenous epoetin alfa were randomized (1:1) to intravenous epoetin alfa or epoetin alfa-epbx. Dosing was adjusted according to the epoetin alfa prescribing information. The coprimary efficacy end points were the least squares mean difference between the two treatments in mean weekly hemoglobin level and mean weekly epoetin dose per kilogram of body weight during the last 4 weeks of treatment. RESULTS:The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly hemoglobin was -0.12 g/dl and the 95% confidence interval (-0.25 to 0.01) was contained within the prespecified equivalence margin (-0.5 to 0.5 g/dl). The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly epoetin dose per kilogram of body weight was 0.37 U/kg per week, and the 95% confidence interval (-10.40 to 11.13) was contained within the prespecified equivalence margin (-45 to 45 U/kg per week). Incidences of adverse events (77.1% versus 75.3%), serious adverse events (24.9% versus 27.0%), and deaths (n=5 versus 6) were similar between the epoetin alfa-epbx and epoetin alfa groups, respectively. Five patients tested positive for anti-recombinant human erythropoietin antibodies at baseline, and two additional patients (n=1 per group) developed anti-recombinant human erythropoietin antibodies while on study treatment. All patients tested negative for neutralizing antibodies, and no patient in either group experienced an event of pure red cell aplasia. CONCLUSIONS:This 24-week, comparative, clinical trial in patients on hemodialysis with ESKD and anemia demonstrated there is no clinically meaningful difference in efficacy or safety between epoetin alfa-epbx and epoetin alfa.

Dataset Information

Relationship between epoetin alfa dose and mortality: findings from a marginal structural model.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Publications

Relationship between epoetin alfa dose and mortality: findings from a marginal structural model.

Similar Datasets

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