Dose Conversion and Cost???Effectiveness of Erythropoietic???Therapies in Chemotherapy-Related Anaemia

Abstract

To estimate a dose-conversion ratio (DCR) between epoetin alfa (EPO) and darbepoetin alfa (DARB) and compare the costs of both drugs at the estimated DCRs using average wholesale prices (AWPs). A search of PUBMED, CANCERLIT and references for papers and abstracts reporting on clinical trials of DARB or EPO for chemotherapy-related anaemia (CRA) identified 56 publications. A meta-analysis was conducted on the 12 eligible papers to estimate a DCR at which the two drugs were equally effective as measured by the area under the curve of haemoglobin (Hb) change (Hb AUC) at weeks 4 and 13. The DCR is based on the ratio of the coefficients of DARB and EPO doses in a regression of Hb AUC on those two variables, baseline Hb, Hb change calculation method, tumour type, and dosing frequency. Studies were frequency-weighted by the number of subjects. DCRs with confidence intervals (CIs) were calculated using a Monte-Carlo approach. Results from the regression were used to calculate DCRs for different dosing regimen comparisons - EPO three times weekly (TIW) versus DARB once weekly (QW), EPO TIW versus DARB once every 2 weeks (Q2W), EPO QW versus DARB QW, and EPO QW versus DARB Q2W. Relative cost effectiveness (RCE) was assessed by comparing drug costs at the estimated DCRs at $US 2003 AWPs [RCE = DCR . ($/U EPO)/($/mug DARB)]. The regression results suggest an EPO QW : DARB QW DCR of 187 (95% CI 183, 191). Depending on the assumed starting dose, the DCR ranges from 126 to 137 for EPO TIW : DARB QW; from 128 to 139 for EPO TIW : DARB Q2W; and equals 191 for EPO QW : DARB Q2W. RCE was 2.0 for the main regression. The DCR of 330 : 1 estimated for the 2004 Hospital Outpatient Prospective Payment System by the Centers for Medicare and Medicaid Services is greater than the DCRs estimated based on Hb AUC. The DCR estimated in the primary regression suggests that based on AWPs, EPO is 2.0 times more cost effective than DARB.