Skip to main content
SpringerLink
Log in

Economic Evaluation of Weekly Epoetin Alfa versus Biweekly Darbepoetin Alfa for Chemotherapy-Induced Anaemia

Evidence from a 16-Week Randomised Trial

  • Original Research Article
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Introduction: A 16-week, open-label, multicentre, randomised trial of weekly epoetin alfa 40 000 units versus biweekly darbepoetin alfa 200µg among 358 patients with solid-tumour cancers and chemotherapy-induced anaemia demonstrated superior haematological outcomes with epoetin alfa. We sought to compare resource use, costs and clinical outcomes between treatment groups and report the results using a cost-consequences framework.

Methods: Pre-specified methods were used to assign costs ($US, year 2004–5 values) to medical resources and patient time using a societal perspective. Costs for inpatient care, outpatient care and physician services were based on US Medicare reimbursement rates. Indirect costs assigned to patient time spent receiving study medication were based on the mean hourly wage in the US. In the base-case analysis, the average wholesale price was used to assign costs to medications. Clinical outcomes included all haemoglobin levels and transfusions recorded throughout the trial. Sensitivity analyses were performed to evaluate the impact of different costing methods, cost sources, perspectives and methods to assign haemoglobin values following a blood transfusion.

Results: Over a mean follow-up duration of 11.8 weeks, the average cost of study medications and their administration was the single largest component of total costs and was similar between groups (epoetin alfa $US5979 and darbepoetin alfa $US5935, difference $US44; 95% CI −590, 692). There were no significant differences in the proportions of patients hospitalised (epoetin alfa 24.6%, darbepoetin alfa 22.0%; p = 0.57). Patients randomised to epoetin alfa experienced more inpatient days, on average, than patients randomised to darbepoetin alfa (2.6 vs 1.6, 95% CI for the difference, 0.07, 2.27). However, with regard to transfusions, patients in the epoetin alfa arm required fewer units of blood than patients in the darbepoetin alfa arm (0.46 vs 0.88, 95% CI for the difference −0.77, −0.08). Mean total costs, comprising costs for study medications and their administration, inpatient care, transfusions, unplanned radiation therapy, haematology and laboratory services, chemotherapy and non-chemotherapy drugs and indirect costs were $US14 976 in the epoetin alfa arm compared with $US14 101 in the darbepoetin alfa arm, a difference of $US875 (95% CI for difference −849, 2607), of which 98% of the difference was attributable to higher inpatient costs in the epoetin alfa arm ($US2374 vs $US1520; 95% CI for difference −33, 1955). Assessments of multiple clinical measures demonstrated improved outcomes with epoetin alfa relative to darbepoetin alfa.

Conclusion: Most clinical outcome measures suggested greater improvement with epoetin alfa relative to darbepoetin alfa, but most costs for both agents appeared similar. Decision makers must evaluate the differences in costs and efficacy measures that are most relevant from their perspectives.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV
Table V
Table VI

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

  2. First, the costs (from table IV) for study drugs and administration were added together for each treatment group ($US5781 + 98 = $US5979 for epoetin, and $US5824 + 111 = $US5935 for darbepoetin). Then these numbers were multiplied by 0.2 to represent the patient co-payment. Then the co-payment was divided by the proportion of patients experiencing a haematological response in each treatment group (1196/0.474 = $US2523 for epoetin, and 1187/0.350 = $US3391 for darbepoetin). From an incremental perspective, this would result in an estimate of approximately $US75 per additional patient experiencing a haematological response ($US1196 − 1187)/(0.474 − 0.350) = $US73.

References

  1. Knight K, Wade S, Balducci L. Prevalence and outcomes of anemia in cancer: a systematic review of the literature. Am J Med 2004 Apr 5; 116 Suppl. 7A: 11S–26S

    Article  Google Scholar 

  2. Cella D. The Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale: a new tool for the assessment of outcomes in cancer anemia and fatigue. Semin Hematol 1997 Jul; 34 (3 Suppl. 2): 13–19

    PubMed  CAS  Google Scholar 

  3. Groopman JE, Itri LM. Chemotherapy-induced anemia in adults: incidence and treatment [published erratum appears in J Natl Cancer Inst 2000 Mar 15; 92 (6): 497]. J Natl Cancer Inst 1999 Oct 6; 91 (19): 1616–1634

    Article  PubMed  CAS  Google Scholar 

  4. Rizzo JD, Lichtin AE, Woolf SH, et al. Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol 2002 Oct 1; 20 (19): 4083–4107

    Article  PubMed  CAS  Google Scholar 

  5. Cancer and treatment-related anemia. In: Rodgers GM, Cella D, Chanan-Khan A, et al. NCCN clinical practice guidelines in oncology, version 1. Jenkintown (FA): National Comprehensive Cancer Network, 2005 [online]. Available from URL: http://www.nccn.org/professionals/physician_gls/PDF/anemia.pdf [Accessed 2005 Oct 11]

  6. Littlewood TJ, Nortier J, RapoportB, et al. Epoetin alfa corrects anemia and irq)foves quality of life in patients with hematologic malignancies receiving non-platinum chemotherapy. Hematol Oncol 2003 Dec; 21 (4): 169–180

    Article  PubMed  Google Scholar 

  7. Littlewood TJ, Bajetta E, Nortier JW, et al. Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001 Jun 1; 19: 2865–2874

    PubMed  CAS  Google Scholar 

  8. Vansteenkiste J, Pirker R, Massuti B, et al. Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alia in lung cancer patients receiving chemotherapy. J Natl Cancer Inst 2002 Aug 21; 94: 1211–1220

    Article  PubMed  CAS  Google Scholar 

  9. KotasekD, Steger G, Faught W, et al. Darbepoetin alfa administered every 3 weeks alleviates anaemia in patients with solid tumours receiving chemotherapy: results of a double-blind, placebo-controlled, randomised study. Eur J Cancer 2003 Sep; 39 (14): 2026–2034

    Article  Google Scholar 

  10. Witzig TE, Silberstein PT, Loprinzi CL, et al. Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy. J Clin Oncol 2005 Apr 20; 23 (12): 2606–2617

    Article  PubMed  CAS  Google Scholar 

  11. Case DC, Bukowski RM, Carey RW, et al. Recorminant human erythropoietin therapy for anemic cancer patients on combination chemotherapy. J Natl Cancer Inst 1993 May 19; 85 (10): 801–806

    Article  PubMed  Google Scholar 

  12. Henry DH, Brooks BJ, Case DC, et al. Recorminant human erythropoietin therapy for anemic cancer patients receiving cisplatin chemotherapy. Cancer J Sci Am 1995 Nov; 1 (4): 252

    PubMed  CAS  Google Scholar 

  13. Cascinu S, Fedeli A, Del Ferro E, et al. Recorminant human erythropoietin treatment in cisplatin-associated anemia: a randomized, double-blind trial with placebo. J Clin Oncol 1994-May; 12 (5): 1058–1062

    PubMed  CAS  Google Scholar 

  14. Kurz CH, Marth CH, Windbichler G, et al. Erythropoietin treatment under polychemotherapy in patients with gynecologic malignancies: a prospective, randomized, double-blind placebo-controlled multicenter study. Gynecol Oncol 1997 Jun; 65 (3), 461–466

    Article  PubMed  CAS  Google Scholar 

  15. Oberhoff C, Neri B, Amadori D, et al. Recombinant human erythropoietin in the treatment of chemotherapy-induced anemia and prevention of transfusion requirement associated with solid tumors: a randomized, controlled study. Ann Oncol 1998 Mar; 9 (3): 255–260

    Article  PubMed  CAS  Google Scholar 

  16. Glaspy J, Berg R, Tomita D, et al. Final results of a phase 3, randomized, open-label study of darbepoetin alfa 200µg every 2 weeks (Q2W) versus epoetin alfa 40 000 U weekly (QW) in patients with chemotherapy-induced anemia (CIA) [abstract]. Proc Am Soc Clin Oncol 2005; 23 (165 Pt I of II): 760s

    Google Scholar 

  17. Waltzman R, Croot C, Justice G, et al. Randomized comparison of epoetin alfa (40 000 U weekly) and darbepoetin alfa (200 microg every 2 weeks) in anemic patients with cancer receiving chemotherapy. Oncologist 2005; 10 (8): 642–650

    Article  PubMed  CAS  Google Scholar 

  18. Beveridge RA, Rifkin RM, Moleski RJ, et al. Impact of long acting growth factors on practice dynamics and patient satisfaction. Pharmacotherapy 2003 Dec; 23 (12 Pt 2): 101S–109S

    Article  PubMed  CAS  Google Scholar 

  19. Luce BR, Manning WG, Siegel JE, et al. Estimating costs in cost-effectiveness analysis. In: Gold MR, Siegel JE, Russell LB, et al., editors. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996

    Google Scholar 

  20. DRG expert: a comprehensive reference to the DRG classification system. 20th ed. Salt Lake City (UT): Ingenix Inc., 2004

  21. Reed SD, Friedman JY, Gnanasakthy A, et al. A comparison of hospital costing methods for multinational economic evaluations. Int J Technol Assess Health Care 2003; 19 (2): 396–406

    Article  PubMed  Google Scholar 

  22. Centers for Medicare and Medicaid Services. Acute inpatient prospective payment system: DRG relative weights [online]. Available from URL: http://www.cms.hhs.gov/providers/hipps/ippspufs.asp [Accessed 2004 Jul 20]

  23. Centers for Medicare and Medicaid Services. National physician fee schedule payment amount file [online]. Available from URL: http://www.cms.hhs.gov/providers/pufdownload/carrpuf.asp [Accessed 2005 Jun 14]

  24. Red Book. March 2005 ed. Montvale (NJ): Thomson Healthcare, 2005

  25. 69 Federal Register 65864 (2004; codified at 42 CFR 419). Addendum A. List of armulatory payment classifications (APCs) with status indicators, relative weights, payment rates, and copayment amounts: calendar year 2005. Fed Regist 2004 Nov 15; 69 (219): 65864–65880 [online]. Available from URL: http://www.cms.hhs.gov/providerupdate/regs/cms1427fc_4.pdf [Accessed 2006 Apr 12]

    Google Scholar 

  26. 69 Federal Register 66405 (2004; codified at 42 CFR 419, 405, 410, et al.). Table 40. Impact of final rule and physician fee schedule update on Medicare payment for selected drug administration services including the effect of the 32 and 3% transition adjustments and demonstration project. Fed Regist 2004 Nov 15; 69 (219): 66405 [online]. Available from URL: http://www.cms.hhs.gov/providerupdate/regs/cms1427fc_4.pdf [Accessed 2006 Apr 12]

    Google Scholar 

  27. Data on file, Ortho Biotech Products, LP, 2005 Mar

  28. Cremieux PY, Barrett B, Anderson K, et al. Cost of outpatient blood transfusion in cancer patients. J Clin Oneol 2000 Jul; 18 (14), 2755–2761

    CAS  Google Scholar 

  29. US Department of Labor, Bureau of Labor Statistics. Consumer price index: all urban consumers [online]. Available from URL: http://146.142.4.24/cgi-hin/surveymost?.cu [Accessed 2005 Jun 10]

  30. Centers for Medicare and Medicaid Services. Clinical laboratory fee schedule for CY 2004 [online]. Available from URL: http://www.cms.hhs.gov/clinicallabfeesched/02_clinlab.asp [Accessed 2006 Apr 12]

  31. US Department of Labor, Bureau of Labor Statistics. National corr:pensation survey: occupational wages in the United States, July 2003. Summary 04-03 [online]. Available from URL: http://www.bls.gov/ncs/ocs/sp/ncbl0635.pdf. [Accessed 2005 Jun 10]

  32. Schwartzberg LS, Yee LK, Senecal FM, et al. A randomized comparison of every-2-week darbepoetin alfa and weekly epoetin alfa for the treatment of chemotherapy-induced anemia in patients with breast, lung, or gynecologic cancer. Oncologist 2004; 9 (6): 696–707

    Article  PubMed  CAS  Google Scholar 

  33. Drummond MF, O’Brien B, Stoddart GL, et al., editors. Methods for the economic evaluation of health care programmes. 2nd ed. New York: Oxford University Press, 1997

    Google Scholar 

  34. Medi-Span electronic drug file. Health facts and comparisons. Philadelphia (PA): Lippincott Williams & Wilkins, 2005

    Google Scholar 

  35. US Department of Veterans Affairs. Pharmacy benefits management, strategic health group, drugs and pharmaceutical prices [online]. Available from URL: http://www.pbm.va.gov/PBM/prices.htm [Accessed 2006 Apr 12]

  36. Centers for Medicare and Medicaid Services, Hospital Outpatient PPS, Addendum A and Addendum B updates, Addendum A, October 2005 [online]. Available from URL: http://www.cms.hhs.gov/hospitaloutpatientpps/au/list.asp [Accessed 2006 Apr 11]

  37. Centers for Medicare and Medicaid Services. April 2005 payment allowance limits for Medicare Part B drugs effective April 1, 2005 through June 30, 2005 [online]. Available from URL: http://www.cms.hhs.gov/providers/drugs/asp.asp [Accessed 2005 Apr 4]

  38. Efron B, Tibshirani RJ. Bootstrap methods for standard errors, confidence intervals, and other measures of statistical accuracy. Stat Sci 1986; 1: 54–77

    Article  Google Scholar 

  39. Harley C, Muser E, Nelson M, et al. Resource use and anemia-related treatment costs among cancer patients treated with epoetin alfa ordarbepoetin alfa [poster]. Academy of Managed Care Pharmacy 2005 Educational Conference; 2005 Oct 5–8; Nashville (TN)

    Google Scholar 

  40. Gosselin A, Lefevbre P, Dub M, et al. Dosing patterns and transfusion use in cancer patients treated with erythropoietic agents: results of an observational study of over 8000 patients [poster]. American Society of Hematology Meeting; 2005 Dec 10–13; Atlanta (GA)

    Google Scholar 

  41. Barosi G, Marchetti M, Liberato NL. Cost-effectiveness of recorminant human erythropoietin in the prevention of chemotherapy-induced anaemia. Br J Cancer 1998 Sep; 78 (6): 781–787

    Article  PubMed  CAS  Google Scholar 

  42. Martin SC, Gagnon DD, Zhang L, et al. Cost-utility analysis of survival with epoetin-alfa versus placebo in stage IV breast cancer. Pharmacoeconomics 2003; 21 (16): 1153–1169

    Article  PubMed  Google Scholar 

  43. Cremieux PY, Finkelstein SN, Berndt ER, et al. Cost effectiveness, quality-adjusted life-years and supportive care: recorminant human erythropoietin as a treatment of cancer-associated anaemia. Pharmacoeconomics 1999 Nov; 16 (5 Pt 1): 459–472

    Article  PubMed  CAS  Google Scholar 

  44. Foley RN, Parlrey PS, Morgan J, et al. Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy. Kidney Int 2000 Sep; 58 (3): 1325–1335

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The economic evaluation was sponsored through a research agreement between Duke University Medical Center and Ortho Biotech Clinical Affairs, LLC. The authors had access to all trial data, independently conducted all study analyses and retained publication rights. Representatives of the sponsor responded to queries from the authors regarding trial data and procedures. They also reviewed and commented on the final manuscript.

We thank John Fastenau from Ortho Biotech Products, LP, for assistance with data acquisition and conceptualisation of the study during early phases of the project, and Damon Seils from Duke University for editorial assistance and manuscript preparation. All authors were involved in the conceptualisation and design of the study. Reed and Radeva developed the analysis plan, analysed the data and drafted the manuscript. All authors revised the manuscript for important intellectual content and approved the final manuscript.

Co-authors S.H. Mody, J.B. Forlenza and R.S. McKenzie are employees of Ortho Biotech Clinical Affairs, LLC, which develops and provides clinical information on Procrit® (epoetin alfa). They also own stock in Johnson and Johnson.

Author information

Authors and Affiliations

  1. Center for Clinical and Genetic Economics, Duke Clinical Research Institute, Duke University Medical Center, PO Box 17969, Durham, North Carolina, 27715, USA

    Shelby D. Reed, Jasmina I. Radeva &  Kevin A. Schulman

  2. Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA

    Shelby D. Reed, Davey B. Daniel &  Kevin A. Schulman

  3. Clinical Affairs, Ortho Biotech Clinical Affairs, LLC, Bridgewater, New Jersey, USA

    Samir H. Mody, Jamie B. Forlenza & R. Scott McKenzie

Authors
  1. Shelby D. Reed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jasmina I. Radeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Davey B. Daniel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Samir H. Mody
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jamie B. Forlenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Scott McKenzie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kevin A. Schulman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kevin A. Schulman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reed, S.D., Radeva, J.I., Daniel, D.B. et al. Economic Evaluation of Weekly Epoetin Alfa versus Biweekly Darbepoetin Alfa for Chemotherapy-Induced Anaemia. Pharmacoeconomics 24, 479–494 (2006). https://doi.org/10.2165/00019053-200624050-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00019053-200624050-00006

Keywords

Search

Navigation