Dose Conversion for Patients Receiving Hemodialysis
In his recent article in Pharmacotherapy, Dr. Shane Scott estimated an epoetin alfa:darbepoetin alfa dose conversion ratio (DCR) by comparing week 0 epoetin alfa doses with week 24 darbepoetin alfa doses from several studies in which patients receiving hemodialysis were converted from epoetin alfa to darbepoetin alfa. Based on evidence in Table 1 and Figure 3 of his article (replicated as Table 1 and Figure 1), Dr. Scott concluded that the DCR is nonlinear and increases with epoetin alfa dose and that there is "large interpatient variability" in DCRs. He therefore recommended that no fixed DCR between epoetin alfa and darbepoetin alfa be used when converting patients from epoetin alfa to darbepoetin alfa. This recommendation contrasts with the Centers for Medicare and Medicaid Services (CMS) recent adoption of a fixed DCR of 260:1.


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Relationship between week-24 darbepoetin alfa dose and previous weekly r-HuEPO dose in patients with chronic kidney disease. Linear regression of data combined across three studies in which patients were converted from r-HuEPO to darbepoetin alfa. Relating previous r-HuEPO dose (x axis) with week-24 darbepoetin alfa dose (y axis). Observed data also show 95% confidence intervals of the regression fit. Adapted from references 3-7.

Dr. Scott's findings are inconclusive for two reasons. First, he failed to provide statistically significant evidence against using a linear model with a 260:1 DCR. Second, his calculations about interpatient variation in DCRs posit that a patient's appropriate epoetin alfa dose is constant over time, an assumption that is inconsistent with his data. His observations of a nonlinear DCR and large interpatient variability of DCRs could be construed as artifacts of variation over time in an individual patient's dosing requirements. The current presumption of a fixed 260:1 DCR therefore should not be rejected on the basis of Dr. Scott's evidence.