PharmacoEconomics

, Volume 22, Issue 16, pp 1029–1045

Clinical and economic impact of epoetins in cancer care

Review Article

Abstract

Anaemia develops in most patients undergoing cancer therapy and invariably induces fatigue, which is a major determinant of QOL. Blood transfusions are reserved for patients with severe anaemia, since blood is a scarce resource and provides a short-lived benefit. Epoetins are recombinant proteins capable of alleviating therapy-related anaemia in 40–60% of cancer patients. The number of patients needed to be treated with epoetins to avoid the transfusion of one unit of blood ranges from 2.6 to 5.2; however, the absolute risk reduction depends on patients’ characteristics and dose-escalation.

The ratio between acquisition costs of epoetins and blood transfusion requirement is very high; thus, many thousands of dollars needs to be spent on epoetins to save 1 blood unit. Despite this, epoetins have been widely adopted by industrialised countries, where cancer patients are about 2% of the total population. The resulting budget impact of epoetins can be calculated at about 10% of the overall direct cost for cancer care, and it is expected to continue growing by about 20% each year, due to the expanding cancer population and the intensification of cancer therapies. The economic burden of epoetins needs to be weighed against the improvement of patients’ QOL and society’s willingness to pay for a non-life-saving therapy. All published economic evaluations of epoetins invariably report that this supportive therapy is not cost effective.

Society should be made aware of the opportunity cost of treatments and should be allowed to elicit preferences for healthcare interventions and prioritisation criteria. In the near future we expect that a wider range of epoetins, drug patent expiry, a more appropriate patient selection criteria and an improved dosage schedule may help increase the efficiency of cancer-related anaemia management.

References

  1. 1.
    Groopman JE, Itri LM. Chemotherapy-induced anaemia in adults: incidence and treatment. J Nall Cancer Inst 1999; 91: 1616–34CrossRefGoogle Scholar
  2. 2.
    Denton TA, Diamond GA, Matloff JM, et al. Anaemia therapy: individual benefit and societal cost. Semin Oncol 1994; 21 Suppl. 3: 29–35PubMedGoogle Scholar
  3. 3.
    Capocaccia R, Colonna M, Corazziari I, et al. Measuring cancer prevalence in Europe: the EUROPREVAL project. Ann Oncol 2002; 13: 831–9PubMedCrossRefGoogle Scholar
  4. 4.
    Miller CB, Joner RJ, Piantadosi S, et al. Decreased erythropoietin response in patients with the anaemia of cancer. N Engl J Med 1990; 322: 1689–92PubMedCrossRefGoogle Scholar
  5. 5.
    Fein DA, Lee WR, Hanlon AL, et al. Pretreatment haemoglobin level influences local control and survival of TI -T2 squamous cell carcinomas of the glottic larynx. J Clin Oncol 1995; 13: 2077–83PubMedGoogle Scholar
  6. 6.
    Caro JJ, Salas M, Ward A, et al. Anaemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer 2001; 91: 2214–21PubMedCrossRefGoogle Scholar
  7. 7.
    Annual Meeting of the American Society of Hematology, 2001, abstract 2656 [online]. Available from URL: http://www. abstracts2view.com/hemOl/ [Accessed 2003 Mar]Google Scholar
  8. 8.
    Smaniotto D, Luzi S, Morganti A, et al. Prognostic significance of anaemia and the role of erythropoietin in radiation therapy. Tumori 2000; 86: 17–23PubMedGoogle Scholar
  9. 9.
    Levine EA, Vijayakumar S. Blood transfusion in patients receiving radical radiotherapy: a reappraisal. Onkologie 1993; 16: 79–87CrossRefGoogle Scholar
  10. 10.
    Okamoto H, Saijo N, Shinkai T, et al. Chemotherapy-induced anaemia in patients with primary lung cancer. Ann Oncol 1992; 3: 819–24PubMedGoogle Scholar
  11. 11.
    NCI classification of anemia. National Cancer Institute. Available from URL: http//www.nei.nih.org [Accessed 2003 May 20]Google Scholar
  12. 12.
    WHO classification of anemia. World Health Organisation, Available from URL: http//www.who.int/en/for English language [Accessed 2003 May 20].Google Scholar
  13. 13.
    Ray-Coquard I, Le Cesne A, Rubio MT, et al. Risk model for severe anaemia requiring red blood cell transfusion after cytotoxic conventional chemotherapy regimens. The Elypsel Study Group. J Clin Oncol 1999; 17: 2840–6PubMedGoogle Scholar
  14. 14.
    Coiffier B, Guastalla JP, Pujade-Lauraine E, et al. Predicting cancer-associated anaemia in patients receiving non-platinum chemotherapy: results of a retrospective survey. Fur J Cancer 2001; 37: 1617–23Google Scholar
  15. 15.
    Barrett-Lee PJ, Bailey NP, O’Brien ME, et al. Large-scale UK audit of blood transfusion requirements and anaemia in patients receiving cytotoxic chemotherapy. Br J Cancer 2000; 82: 93–7PubMedCrossRefGoogle Scholar
  16. 16.
    Skillings JR, Sridhar FG, Wong C, et al. The frequency of red cell transfusion for anaemia in patients receiving chemotherapy: a retrospective cohort study. Am J Clin Oncol 1993; 16: 22–5PubMedCrossRefGoogle Scholar
  17. 17.
    Cella D. Factors influencing QOL in cancer patients: anaemia and fatigue. Semin Oncol 1998; 25 (3 Suppl. 7): 43–6PubMedGoogle Scholar
  18. 18.
    Curt GA, Breibart W, Cella D. Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition. Oncologist 2000; 5: 353–60PubMedCrossRefGoogle Scholar
  19. 19.
    Vogelzang NJ, Breitbart W, Cella D, et al. Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. Semin Hematol 1997; 34 Suppl. 2: 4–12PubMedGoogle Scholar
  20. 20.
    Stone P, Richardson A, Ream E, et al. Cancer-related fatigue: inevitable, unimportant, and untreatable? Results of a multicentre patient survey. Cancer Fatigue Forum. Ann Oncol 2000; 11: 971–5PubMedCrossRefGoogle Scholar
  21. 21.
    Glaspy JA, Jadeja IS, Justice G, et al. Darbapoetin every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy. Br J Cancer 2002; 87: 268–76PubMedCrossRefGoogle Scholar
  22. 22.
    Cella D, Zagari MJ, Vandoros C, et al. Epoetin-alpha treatment results in clinically significant improvements in QOL in anemic cancer patients when referenced to the general population. J Clin Oncol 2003; 21: 366–73PubMedCrossRefGoogle Scholar
  23. 23.
    Patrick DL, Gagnon DD, Zagari MJ, et al. Assessing the clinical significance of health-related QOL (HrQOL) improvements in anaemic cancer patients receiving Epoetin-alpha; Fur J Cancer 2003; 39: 335–45Google Scholar
  24. 24.
    Quirt I, Robeson C, Lau CY, et al. Epoetin alpha in patients not on chemotherapy: Canadian data. Semin Oncol 2002; 29 Suppl. 8: 75–80PubMedGoogle Scholar
  25. 25.
    Crawford J, Cella D, Cleeland CS, et al. Relationship between changes in haemoglobin level and QOL during chemotherapy in anemic cancer patients receiving Epoetin-alfa; therapy. Cancer 2002; 95: 888–95PubMedCrossRefGoogle Scholar
  26. 26.
    Demetri GD, Kris M, Wade J, et al. Quality-of-life benefit in chemotherapy patients treated with epoetin-alpha; is independent of disease response or tumor type: results from a prospec tive community oncology study. J Clin Oncol 1998; 16: 3412–25PubMedGoogle Scholar
  27. 27.
    Gabrilove JL, Cleeland CS, Livingston RB, et al. Clinical evaluation of once-weekly dosing of epoetin-alfa; in chemotherapy patients: improvements in haemoglobin and QOL are similar to three-times weekly dosing. J Clin Oncol 2001; 19: 2875–82PubMedGoogle Scholar
  28. 28.
    Cleeland CS, Demetri GD, Glaspy J, et al. Identifying haemoglobin level for optimal QOL: an incremental analysis [abstract 2215]. ASCO General Meeting 1999. Available from URL: http://www.asco.org/ac/1,1003, 12-002643 -00_18-0017-00_19-0016461,00.asp [Accessed 2003 May]Google Scholar
  29. 29.
    Scagliotti GV, Novello S. Role of erythropoietin in the treatment of lung cancer associated anaemia. Lung Cancer 2001; 34 Suppl. 4: S 91–4Google Scholar
  30. 30.
    Fallowfield L, Gagnon D, Zagari M, et al. Multivariate regression analyses of data from a randomised, double-blind, placebo-controlled study confirm QOL benefit of epoetin-alpha; in patients receiving non-platinum chemotherapy. Br J Cancer 2002; 87: 1341–53PubMedCrossRefGoogle Scholar
  31. 31.
    Wallace EL, Churchill WH, Surgenor DM, et al. Collection and transfusion of blood components in the United States 1994. Transfusion 1998; 38: 625–36PubMedCrossRefGoogle Scholar
  32. 32.
    Wells PS. Safety and efficacy of methods for reducing perioperative allogeneic transfusion: a critical review of the literature. Am J Ther 2002; 9: 377–88PubMedCrossRefGoogle Scholar
  33. 33.
    Zimmermann R, Buscher M, Linhardt C, et al. A survey of blood component use in a Germany university hospital. Transfusion 1997; 37: 1075–83PubMedCrossRefGoogle Scholar
  34. 34.
    Shireman TI, Hilsenrath PE, Strauss RG, et al. Recombinant human erythropoietin vs transfusions in the treatment of anemia of prematurity: a cost-benefit analysis. Arch Pediatr Adolesc Med 1994 Jun; 148 (6: 582–8PubMedCrossRefGoogle Scholar
  35. 35.
    Tretiack R, Laupacis A, Riviere M, et al. Cost of allogeneic and autologous transfusion in Canada. CMAJ 1996; 154: 1501–8Google Scholar
  36. 36.
    Sheffield R, Sullivan SD, Saltiel E, et al. Cost comparison of recombinant human erythropoietin and blood transfusion in cancer chemotherapy-induced anaemia. Ann Pharmacother 1997; 31: 15–22PubMedGoogle Scholar
  37. 37.
    Kavanagh BD, Fischer IV BA, Segred EM, et al. Cost analysis of erythropoietin versus blood transfusions for cervical cancer patients receiving chemoradiotherapy. Int J Radial Oncol Biol Phys 2001; 51: 435–4CrossRefGoogle Scholar
  38. 38.
    Chapman J. The national blood stocks project [abstract]. Br J Haematol 2001; 113 Suppl. 1: 58Google Scholar
  39. 39.
    Cremieux PY, Barrett B, Anderson K, et al. Cost of outpatient blood transfusion in cancer patients. J Clin Oncol 2000 Jul; 18 (14): 2755–61Google Scholar
  40. 40.
    Finlay IG, Jenkins MI. Six-year audit of blood transfusion for hospice patients: simple criteria increase benefit. Fur J Palliat Care 1997Google Scholar
  41. 41.
    Cantor SB, Hudson DV Jr, Lichtiger B, et al. Related articles, links costs of blood transfusion: a process-flow analysis. J Clin Oncol. 1998 Jul; 16 (7): 2364–70PubMedGoogle Scholar
  42. 42.
    Herold M, Hieke K. Costs of toxicity during chemotherapy with CHOP, COP/CVP, and fludarabine. Fur J Health Econ 2002; 3: 166–72CrossRefGoogle Scholar
  43. 43.
    Hill SR, Carless PA, Henry DA, et al. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 1. Oxford: Update Software, 2003Google Scholar
  44. 44.
    British Committee for Standards in Haematology, Blood Transfusion Task Force. Guidelines for the clinical use of red blood cell transfusions. Br J Haematol 2001; 113: 24-31Google Scholar
  45. 45.
    NIH. Consensus conference. Perioperative red blood cell transfusion. JAMA 1988; 260: 2700-3Google Scholar
  46. 46.
    Barosi G, Marchetti M, Liberato NL. Cost-effectiveness of recombinant human erythropoietin in the prevention of chemotherapy-induced anaemia. Br J Cancer 1998; 78: 781–7PubMedCrossRefGoogle Scholar
  47. 47.
    Finucane ML, Slovic P, Mertz CK. Public perception of the risk of blood transfusion. Transfusion 2000; 40: 1017–22PubMedCrossRefGoogle Scholar
  48. 48.
    Eastbough SR. Valuation of the benefits of risk-free blood. Int J Technol Assess Health Care 1991; 7: 51–7CrossRefGoogle Scholar
  49. 49.
    Chamberland ME. Emerging infectious agents: do they pose a risk to the safety of transfused blood and blood products? Clin Infect Dis 2002; 34: 797–805PubMedCrossRefGoogle Scholar
  50. 50.
    Van Hulst M, de Wolf JTM, Staginnus U, et al. Pharmacoeconomics of blood transfusion safety: review of the available evidence. Vox Sang 2002; 83: 146–55PubMedCrossRefGoogle Scholar
  51. 51.
    Lubarsky DA, Hahn C, Bennett DH, et al. Related articles, links the hospital cost (fiscal year 1991/1992) of a simple perioperalive allogeneic red blood cell transfusion during elective sur gery at Duke University. Anesth Analg 1994 Oct; 79 (4): 629–37PubMedCrossRefGoogle Scholar
  52. 52.
    Etchason J, Petz L, Keeler E, et al. The cost effectiveness of preoperative autologous blood donations. N Engl J Med 1995; 332: 719–24PubMedCrossRefGoogle Scholar
  53. 53.
    Sonnenberg FA, Gregory P, Yomlovian RA, et al. The costeffectiveness of autologous transfusion revisited: implications of an increased risk of bacterial infection with allogeneic transfusion. Transfusion 1999; 39: 808–17PubMedCrossRefGoogle Scholar
  54. 54.
    Marchetti M, Barosi G. Cost-effectiveness of epoetin and autologous blood donationin reducing allogeneic blood transfusions in coronary artery bypass graft surgery. Transfusion 2000; 40: 673–81PubMedCrossRefGoogle Scholar
  55. 55.
    Healy JC, Frankforter SA, Graves BK, et al. Preoperative autologous blood donation in total-hip arthroplasty: a cost-effectiveness analysis. Arch Pathol Lab Med 1994; 118: 465–70PubMedGoogle Scholar
  56. 56.
    Macdougall JC. Novel erythropoiesis stimulating protein. Semin Nephrol 2000; 20: 375–81PubMedGoogle Scholar
  57. 57.
    Thatcher N, De Campos ES, Bell DR, et al. Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer. Br J Cancer 1999; 80: 396–402PubMedCrossRefGoogle Scholar
  58. 58.
    Amgen Inc. Aranesp physical package insert. Thousand Oaks (CA): Amgen Inc., 2001 Sep 14Google Scholar
  59. 59.
    Ortho Biotech Inc. Procrit prescribing information. Raitan (NJ): Ortho Biotech Inc., 2000 MarGoogle Scholar
  60. 60.
    Amgen Inc. Epogen prescribing information. Thousand Oaks (CA): Amgen Inc., 1999 Jul 26Google Scholar
  61. 61.
    Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339: 584–90PubMedCrossRefGoogle Scholar
  62. 62.
    Casadevall N, Nataf J, Viron B, et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 2002; 346: 469–75PubMedCrossRefGoogle Scholar
  63. 63.
    Smith Jr RE, Jaiyesimi IA, Meza LA, et al. Novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia of chronic disease associated with cancer. Br J Cancer 2001; 84 Suppl. 1: 24–30PubMedCrossRefGoogle Scholar
  64. 64.
    Macdougall IC, Gray SJ, Elston O, et al. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin-alpha; in dialysis patients. J Am Soc Nephrol 1999; 10: 2392–5PubMedGoogle Scholar
  65. 65.
    Lawless G, Wilson-Royalty M, Meyers J. epoetin alfa; practice pattern usage in community practice sites [abstract]. Blood 2000; 96: 390bGoogle Scholar
  66. 66.
    Adams JR, Elting LS, Lyons T, et al. Evaluation of EPO use and direct-to-consumer marketing effects: results from a survey of American and international hematologists and oncologists [abstract 994]. ASCO General Meeting 2001 Proc Am Soc Clin Oncol 2001 Available from URL: http://www.asco.org/ac/1,1003,_12-002643-00_18-0010-00_19-00994,00.asp [Accessed 2003 May]Google Scholar
  67. 67.
    Marchetti M, Colombo G, Carruggi M. Propensity analysis of epoetin use and its impact of overall costs of cancer care [abstract]. Value Health 2002; 5: 540CrossRefGoogle Scholar
  68. 68.
    Lawless G, Daniel GW, Baron JJ, et al. Probability of initiating epoetin-alpha; therapy [abstract]. Value Health 2003; 6: 740CrossRefGoogle Scholar
  69. 69.
    Turner R, Anglin P, Burkes R, et al. Canadian Cancer and Anaemia Guidelines Development Group. epoetin-alpha; in cancer patients: evidence-based guidelines. J Pain Symptom Manage 2001; 22: 954–65PubMedCrossRefGoogle Scholar
  70. 70.
    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. Blood 2002; 100: 2303–20PubMedCrossRefGoogle Scholar
  71. 71.
    Available online from URL: http://www.cancereare.on.ca/access PEBC.htm [Accessed 2003 May]Google Scholar
  72. 72.
    National Comprehensive Cancer Network (NCCN) Practice guidelines v1.2003. Avialable from URL: http//www.neen.org [Accessed 2003 May]Google Scholar
  73. 73.
    Ludwig H, Sundal E, Percherstorfer M, et al. Recombinant human erythropoietin for the correction of cancer associated anaemia with and without concomitant cytotoxic chemotherapy. Cancer 1995; 76: 2319–29PubMedCrossRefGoogle Scholar
  74. 74.
    Prontuario Farmaceutico nazionale 2003 [online]. Italian Drug Formulary 2003. Available from URL: http://www.ministerosalute.it/imgs/C 17 bif editoriale_5 listaFile itemName_0 filePdf.pdf [Accessed 2003 May]Google Scholar
  75. 75.
    Shah ND, Hoffman JM, Vermeulen LC, et al. Projecting future drug expenditures: 2003. Am J Health Syst Pharm 2003; 60: 137–49PubMedGoogle Scholar
  76. 76.
    Brown ML, Riley GF, Schussler N, et al. Estimating health care costs related to cancer treatment from SEER-medicare data. Med Care 2002; 40 Suppl. IV: 104–17Google Scholar
  77. 77.
    Spiridonidis H, Brinkmann K, Gore K, et al. Evaluating the “effectiveness” of epoetin-alpha; in oncology [abstract 1482]. Proc Am Soc Clin Oncol 2002Google Scholar
  78. 78.
    Seidenfeld J, Piper M, Flamm C, et al. Epoetin treatment of anaemia associated with cancer therapy: a systematic review and meta-analysis of controlled clinical trials. J Nall Cancer Inst 2001; 93: 1204–14CrossRefGoogle Scholar
  79. 79.
    Marsch WA, Rascati KL. Meta-analyses of the effectiveness of erythropoietin for end-stage renal disease and cancer. Clin Ther 1999; 21: 1443–55CrossRefGoogle Scholar
  80. 80.
    Clark O, Adams JR, Bennett CL, et al. Erythropoietin, uncertainty principles and cancer related anaemia. BMC Cancer 2002; 2: 23–31PubMedCrossRefGoogle Scholar
  81. 81.
    Estrin IT, Schocket L, Kregenow R, et al. A restospective chart review of blood transfusions in cancer patients with anaemia. Oncologist 1999; 4: 318–24PubMedGoogle Scholar
  82. 82.
    Beguin Y. Prediction of response and other improvements on the limitations of recombinant human erythropoietin therapy in anemic cancer patients. Haematologica 2002; 87: 1209–21PubMedGoogle Scholar
  83. 83.
    Engert A. Recombinant human Erythropoietin as an alternative to blood transfusion in cancer-related anaemia. Dis Manage Health Outcomes 2000; 8: 259–72CrossRefGoogle Scholar
  84. 84.
    Littlewood TJ, Bajetta E, Nortier JWR, et al. Effects of epoetinalpha; on hematologic parameters and QOL in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001; 19: 2865–74PubMedGoogle Scholar
  85. 85.
    Gonzalez-Baron M, Ordonez A, Franquesa R, et al. Response predicting factors to recombinant human erythropoietin in cancer patients undergoing platinum-based chemotherapy. Cancer 2002; 95: 2408–13PubMedCrossRefGoogle Scholar
  86. 86.
    Glaspy J, Bukowski R, Steinberg D, et al. Impact of therapy with epoetin-alpha; on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. J Clin Oncol 1997; 15: 1218–34PubMedGoogle Scholar
  87. 87.
    Abets R. Erythropoietin for anaemia in cancer patients. Fur J Cancer. 1993; 29A Suppl. 2: S2–8Google Scholar
  88. 88.
    Abets RI. Recombinant human erythropoietin in the treatment of anaemia of cancer. Acta Haematol 1992; 87 Suppl. 1: 4–11Google Scholar
  89. 89.
    Quirt I, Robeson C, Lau CY, et al. epoetin-alpha; therapy increases haemoglobin levels and improves QOL in patients with cancer-related anaemia who are not receiving chemotherapy and patients with anaemia who are receiving chemotherapy. J Clin Oncol 2001; 19 Suppl. 4: 4126–34PubMedGoogle Scholar
  90. 90.
    Yount S, Lai J-S, Cella D. Methods and progress in assessing the QOL effects of supportive care with erythropoietin therapy. Curr Opin Hematol 2002; 9: 234–40PubMedCrossRefGoogle Scholar
  91. 91.
    Henry DA, Abets RI. Recombinant human erythropoietin in the treatment of cancer and chemotherapy-induced anaemia: results of double-blind and open-label follow-up studies. Semin Oncol 1994; 21 Suppl. 3: 21–8PubMedGoogle Scholar
  92. 92.
    Shasha D, George MJ, Harrison LB. Once-weekly dosing of epoetin-alpha increases hemoglobin and improves QOL in anemic cancer patients receiving radiation therapy either con comitant or sequentially with chemotherapy. Cancer 2003; 98: 1072–9PubMedCrossRefGoogle Scholar
  93. 93.
    Shasha D, Belani CP, George MJ, et al. Epoetin alpha once weekly increases haemoglobin and improves QOL in anemic lung cancer patients receiving chemotherapy with or without concomitant or sequential radiation therapy [abstract 3000]. Proc Am Soc Clin Oncol 2001 [online]. Available from URL: http://www.asco.org/ac/1,1003,12-002643-00_18-0010-00_19-003000,00.asp [Accessed May 2003]Google Scholar
  94. 94.
    Meadowcroft AM, Gilbert CJ, Maravich-May D, et al. Costs of managing anaemia with and without prophylactic epoetinalpha; therapy in breast cancer patients receiving combination chemotherapy. Am J Health Syst Pharm 1998; 55: 1898–902PubMedGoogle Scholar
  95. 95.
    Remak A, Hutton J, Zagari M. Changes in cost-effectiveness over time: the case of epoetin-alpha; for renal replacement therapy patients in the UK [abstract]. Value Health 2002; 5: 458CrossRefGoogle Scholar
  96. 96.
    Cremieux PY, Finkelstein SN, Berndt ER, et al. Cost effectiveness, quality-adjusted life-years and supportive care. Recombinant human erythropoietin as a treatment of cancer-associated anaemia. Pharmacoeconomics 1999; 16: 459–72PubMedCrossRefGoogle Scholar
  97. 97.
    Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 2003; 362: 1255–60PubMedCrossRefGoogle Scholar
  98. 98.
    Ortega A, Dranitsaris G, Puodziunas ALV. What are cancer patients willing to pay for prophylactic epoetin-alpha;? A costbenefit analysis. Cancer 1998; 83: 2588–96PubMedCrossRefGoogle Scholar
  99. 99.
    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: 1153–69PubMedCrossRefGoogle Scholar
  100. 100.
    Liljas B, Lindgren B. On individual preferences and aggregation in economic evaluation in healthcare. Pharmacoeconomics 2001; 19: 323–35PubMedCrossRefGoogle Scholar
  101. 101.
    Meehan K, Tchekmedyian S, Ciesla G, et al. ASCO annual meeting.The burden of epoetin-alpha: injections to patients and their caregivers (abstract no. 2186). Proc An Soc Clin Oncol 2003; 22 [online]. Available from URL: http://www.asco.org/ac/1,1003,_12-002643-00_18-0023-00_19-00100768,00.asp [Accessed 2003 Mar]Google Scholar
  102. 102.
    Straus DJ, Testa M, Riggs SA, et al. Early treatment with epoetin-alpha; improves anemia, quality of life (QOL), and productivity in patients (pts) with hematologic malignancies and mild anemia during chemotherapy (CT). Annual Meeting of the American Society of Hematology, 2003, abstract 1811 [online]. Available from URL: http://www.hematology.org/ meeting/abstracts.cfm [Accessed 2003 Nov]Google Scholar
  103. 103.
    Vansteenkiste J, Pirker R, Massuti B, et al. Double-blind, placebo-controlled, randomized phase III trial of darbepoetin-alpha; in lung cancer patients receiving chemotherapy. J Nall Cancer Inst 2002; 94: 1211–20CrossRefGoogle Scholar
  104. 104.
    Pirker R, Vansteenkiste J, Gateley J, et al. A phase III, doubleblind, placebo-controlled, randomized study of novel erythropoiesis stimulating protein (NESP) in patients undergoing platinum-treatment for lung cancer [abstract 981]. Fur J Cancer 2001; 37: 264Google Scholar
  105. 105.
    Kotasek D, Steger G, Faught W, et al. Darbepoetin-alpha; administered every 3 weeks alleviates anaemia inpatients with solid tumors receiving chemotherapy; results of a double blind, placebo-controlled, randomised study. Fur J Cancer 2003; 39: 2026–34Google Scholar
  106. 106.
    Hedenus M, Adriansson M, San Miguel J, et al. Efficacy and safety of darbepoetin-alpha; in anaemic patients with lymphoproliferative malignancies: a randomized, double blind, placebo-controlled study. Br J Haematol 2003; 122: 394–403PubMedCrossRefGoogle Scholar
  107. 107.
    Kotasek D, Albertsson M, Mackey J, Darbepoetin-alpha; 980291 Study Group. Randomized, double-blind, placebocontrolled, dose-finding study of darbepoetin-alpha; adminis tered once every 3 (Q3W) or 4 (Q4W) weeks in patients with solid tumors [abstract 1421] ASCO General Meeting 2002. Proc Am Soc Clin Oncol 2002. Available from URL: http://www.asco.org/ac/1,1003,_12-002643-00_18-0016-00_ 19001421,00.asp [Accessed 2003 May]Google Scholar
  108. 108.
    Smith Jr RE, Tchekmedyian NS, Chan D, et al. A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer. Br J Cancer 2003; 88: 1851–8PubMedCrossRefGoogle Scholar
  109. 109.
    Glaspy J, Jadeja J, Justice G, et al. Randomized, active-controlled, phase 1/2, dose-comparison study of NESP administered weekly or every 2 weeks in patients with solid tumors [abstract 1315]. Fur J Cancer 2001; 37: 353Google Scholar
  110. 110.
    Glaspy JA, Jadeja IS, Justice G, et al. A randomized, activecontrol, pilot trial of front-loaded dosing regimens of darbepoetin-alfa for the treatment of patients with anaemia during chemotherapy for malignant disease. Cancer 2003; 97: 131220Google Scholar
  111. 111.
    Smith R. Applications of darbepoetin-alpha, a novel erythropoiesis-stimulating protein, in oncology. Curr Opin Hematol 2002; 9: 228–33PubMedCrossRefGoogle Scholar
  112. 112.
    Kallich J, Erder H, Glaspy JA, Tchekmedyian S. Darbepoetinalpha; has higher observed improvements in fatigue and physical. well-being than epoetin-alpha; [abstract 1466]. Proc Am Soc Clin Oncol 2002Google Scholar
  113. 113.
    Glaspy JA, Jadeja IS, Justice G, et al. Darbepoetin-alpha; given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy. Br J Cancer 2002; 87: 268–76PubMedCrossRefGoogle Scholar
  114. 114.
    Rosberg J, Oster EF, Wu EQ, et al. Dose conversion of erythropoietic agents in chemotherapy-induced anemia: a meta-analysis [abstract]. Value Health 2003; 6: 229CrossRefGoogle Scholar
  115. 115.
    Glaspy J, Tchekedyian N, Gupta S. Comparing the cost-effectiveness of 3gg/kg Q2W darbepoetin-alpha; with standard dose epoetin-alpha; in chemotherapy-treated cancer patients in the United States [abstract]. Value Health 2002; 5: 543CrossRefGoogle Scholar
  116. 116.
    Cremieux P, Greenberg P, Piech CT. epoetin-alpha; is more effective and less costly relative to darbepoetin-alpha; in lung cancer patients receiving treatment for chemotherapy-induced anaemia [abstract 2248]. Proc Am Soc Clin Oncol 2003; 22: 559 Available from URL: http://www.asco.org/ac/1,1003,_ 12-002643-00 18-0023-00_19-00104250,00.asp [Accessed 2003 Mar]Google Scholar
  117. 117.
    Drug Topics Red Book. 106th ed. Montvale (NJ): Medical Economics Co. Inc., 2002Google Scholar
  118. 118.
    Oxfordshire NHS [online]. Available from URL: http://www. oha.org.uk subsequently moved to http://www.oxfordshire.nhs [Accessed 2003 May]Google Scholar
  119. 119.
    Osterborg A, Boogaerts MA, Cimino R, et al. Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin’s lymphoma: a randomized multicenter study. Blood 1996; 87: 2675–82PubMedGoogle Scholar
  120. 120.
    Osterborg A, Brandberg Y, Molostova V, et al. Randomized, double-blind placebo-controlled trial of recombinant human erythropoietin, epoetin beta, in hematologic malignancies. J Clin Oncol 2002; 20: 2486–96PubMedCrossRefGoogle Scholar
  121. 121.
    Johansson JE, Wersall P, Brandberg Y, et al. Efficacy of epoetin beta on haemoglobin, QOL, and transfusion needs in patients with anaemia due to hormone-refractory prostate cancer: a randomized study. Scand J Urol Nephrol 2001; 35: 288–94PubMedCrossRefGoogle Scholar
  122. 122.
    Glimelius B, Linne T, Hoffman K, et al. Epoetin beta in the treatment of anaemia in patients with advanced gastrointestinal cancer. J Clin Oncol 1998; 16: 434–40PubMedGoogle Scholar
  123. 123.
    OSMED report [online]. Available from URL: blip:// www.ministerosalute.it/medicinali/resources/documenti/ osmed/ rapporti/osmed 2003.pdf)” [Accessed 2003 May]Google Scholar
  124. 124.
    Coiffier B. Epoetin beta (Neorecormonc) improved QOL in cancer-associated anemia to a similar degree in patients with lymphoid malignancies or solid tumors [abstract 0153]. 8th Congress of the European Haematology Association; 2003 Jun 12-15; Lyon. Abstract available from URL:http://whaweb.org/ [Accessed 2003 May]Google Scholar
  125. 125.
    Cazzola M, Beguin Y, Kloczko J, et al. Once-weekly epoetin beta is highly effective in treating anaemic patients with lymphoproliferative malignancy and defective erythropoietin production. Br J Haematol 2003; 122: 386–93PubMedCrossRefGoogle Scholar
  126. 126.
    Ludwig H, Birgegard G, Barrett-Lee P, Krakowski K. Prevalence and management of anaemia in patients with hematologic malignancies and solid tumors: results from the European Cancer Anaemia Survey (ECAS) [abstract 884]. Proc Am Soc Clin Oncol 2002Google Scholar
  127. 127.
    Shahn ND, Hoffman JM, Vermeulen LC, et al. Projectiong future drug expenditures-2003. Am J Health Syst Pharm 2003; 60: 137–49Google Scholar
  128. 128.
    Kind P, Macran S, Christie A. A weighted index form of the FACT-L for use in economic evaluation [abstract]. Value Health 2003; 6: 234CrossRefGoogle Scholar
  129. 129.
    Owens DK. Interpretation of cost-effectiveness analyses. J Gen Intern Med 1998; 13: 716–7PubMedCrossRefGoogle Scholar
  130. 130.
    Tengs TO, Adams ME, Pliskin IS, et al. Five-hundred lifesaving interventions and their cost-effectiveness. Risk Anal 1995; 15: 369–90PubMedCrossRefGoogle Scholar
  131. 131.
    Lee SJ, Neumann PJ, Churchill WH, et al. Patients’ willingness to pay for autologous blood donation. Health Policy 1997; 40: 1–12PubMedCrossRefGoogle Scholar
  132. 132.
    Hoffer S, Berardino F, Smith J, Rubin S. Economic values for evaluation of FAA investment and regulatory decisions. Washington, DC, Federal Aviation Administration, Office of Avia tion Policy, Plans and Management Analysis. Publication FAA-APO-98-8Google Scholar
  133. 133.
    Holtgrave DR, Qualls NL. Threshold analysis and programs for prevention of HIV infection. Med Decis Making 1995; 15: 311–7PubMedCrossRefGoogle Scholar
  134. 134.
    Dranitsaris G, Leung P, Ciotti R, et al. A multinational study to measure the value that patients with cancer place on improved emesis control. Pharmacoeconomics 2001; 19: 955–67PubMedCrossRefGoogle Scholar
  135. 135.
    Lee DH, Paling JE, Blajchman MA. A new tool for communication transfusion risk information. Transfusion 1998; 38: 184–8PubMedCrossRefGoogle Scholar
  136. 136.
    Leese B, Hutton J, Maynard AK. A comparison of the costs and benefits of recombinant human erythropoietin (Epoetin) in the treatment of chronic renal failure in 5 European countries. Pharmacoeconomics 1992; 1: 346–56PubMedCrossRefGoogle Scholar
  137. 137.
    Nicholls AJ. Enhanced QOL in dialysis patients treated with erythropoietin: are the benefits worth the costs? Erythropoiesis 1992; 3: 46–9Google Scholar
  138. 138.
    Cantor SB, Carson RW, Spann SJ. A cost-effectiveness analysis of epoetin usage for patients with AIDS. Pharmacoeconomics 1993; 3: 244–9PubMedCrossRefGoogle Scholar
  139. 139.
    Sullivan PW, McLaren R. Cost-effectiveness of recombinant human erythropoeitin for preventing transfusions in critically ill patients [abstract]. Value Health 2003; 6: 338CrossRefGoogle Scholar
  140. 140.
    Coyle D, Lee KM, Fergusson DA, et al. Economic analysis of erythropoietin use in orthopedic surgery. Transfus Med 1999; 9: 21–30PubMedCrossRefGoogle Scholar
  141. 141.
    AuBuchon JP, Birkmeyer JD. Safety and cost-effectiveness of solvent-detergent-treated plasma: in search of a zero-risk blood supply. JAMA 1994 Oct; 272 (15): 1210–4PubMedCrossRefGoogle Scholar
  142. 142.
    AuBuchon JP, Birkmeyer JD, Busch MP. Cost-effectiveness of expanded human immunodeficiency virus-testing protocols for donated blood. Transfusion 1997; 37: 45–51PubMedCrossRefGoogle Scholar
  143. 143.
    Blumberg N, Heal JM, Kirkey SA, et al. Leukodepleted-ABOidentical blood components in the treatment of haematologic malignancies: a cost analysis. Am J Hematol 1995; 48: 108–15PubMedCrossRefGoogle Scholar
  144. 144.
    Lopez-Plaza I, Weissfeld J, Triulzi DJ. The cost-effectiveness of reducing donor exposures with single-donor versus pooled random donor platelets. Transfusion 1999; 39: 925–32PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Laboratory of Medical InformaticsIRCCS Policlinico San MatteoPaviaItaly

Personalised recommendations