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Applied Health Economics and Health Policy

, Volume 11, Issue 6, pp 619–637 | Cite as

Are the True Impacts of Adverse Events Considered in Economic Models of Antineoplastic Drugs? A Systematic Review

  • Alison Pearce
  • Marion Haas
  • Rosalie Viney
Systematic Review

Abstract

Background

Antineoplastic drugs for cancer are often associated with adverse events, which influence patients’ physical health, quality of life and survival. However, the modelling of adverse events in cost-effectiveness analyses of antineoplastic drugs has not been examined.

Aims

This article reviews published economic evaluations that include a calculated cost for adverse events of antineoplastic drugs. The aim is to identify how existing models manage four issues specific to antineoplastic drug adverse events: the selection of adverse events for inclusion in models, the influence of dose modifications on drug quantity and survival outcomes, the influence of adverse events on quality of life and the consideration of multiple simultaneous or recurring adverse events.

Methods

A systematic literature search was conducted using MESH headings and key words in multiple electronic databases, covering the years 1999–2009. Inclusion criteria for eligibility were papers covering a population of adults with solid tumour cancers, the inclusion of at least one adverse event and the resource use and/or costs of adverse event treatment.

Results

From 4,985 citations, 26 eligible articles were identified. Studies were generally of moderate quality and addressed a range of cancers and treatment types. While the four issues specific to antineoplastic drug adverse events were addressed by some studies, no study addressed all of the issues in the same model.

Conclusion

This review indicates that current modelling assumptions may restrict our understanding of the true impact of adverse events on cost effectiveness of antineoplastic drugs. This understanding could be improved through consideration of the selection of adverse events, dose modifications, multiple events and quality of life in cost-effectiveness studies.

Keywords

Economic Evaluation Febrile Neutropenia Dose Modification Antineoplastic Therapy Antineoplastic Drug 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors would like to acknowledge the contribution of Liz Chinchen in conducting the literature search for this review.

Funding

Alison Pearce was supported by a University of Technology, Sydney Doctoral Scholarship, and a PhD top-up scholarship within an NHMRC Health Services Research Grant (ID455366) through the Centre for Health Economics Research and Evaluation; neither funding organisation had any role in the study.

Contributorship

Alison Pearce: Contributed to the planning of the study, designed the search strategy, conducted the literature searches, reviewed the retrieved articles for eligibility, completed and documented data extraction, and wrote the paper for publication. Alison Pearce is the guarantor for the overall content of the paper.

Marion Haas: Contributed to the planning of the study, advised on the design of the search strategy, reviewed the eligibility of articles where eligibility was uncertain, advised on data extraction and interpretation of results, and reviewed the publication.

Rosalie Viney: Contributed to the planning of the study, advised on the design of the search strategy, advised on data extraction and interpretation of results, and reviewed the publication

Liz Chinchen: Contributed to advising on search strategy techniques, conducted the literature searches and retrieved the eligible articles

Conflict of interest

All authors have declared no conflict of interest.

References

  1. 1.
    Australian Institute of Health and Welfare. Australia’s Health 2010. 12th ed. Canberra: Australian Institute of Health and Welfare; 2010.Google Scholar
  2. 2.
    National Cancer Institute. Common Terminology Criteria for Adverse Events v4.03. National Institute of Health; 2010.Google Scholar
  3. 3.
    Liou SY, Stephens JM, Carpiuc KT, Feng W, Botteman MF, Hay JW. Economic burden of haematological adverse effects in cancer patients: a systematic review. Clin Drug Investig. 2007;27(6):381–96.PubMedCrossRefGoogle Scholar
  4. 4.
    Neymark N. Assessing the economic value of anticancer therapies. Berlin: Springer; 1998.CrossRefGoogle Scholar
  5. 5.
    Philipson TJ, Becker G, Goldman D, Murphy KM. Terminal care and the value of life near its end. NBER Working paper 15649. Cambridge: National Bureau of Economic Research; 2010.Google Scholar
  6. 6.
    Briggs A, Sculpher MJ, Claxton K. Decision modelling for health economic evaluation. Oxford: Oxford University Press; 2006.Google Scholar
  7. 7.
    de Raad J, van Gool K, Haas M, Haywood P, Faedo M, Gallego G, et al. Nursing takes time: workload associated with administering cancer protocols. Clin J Oncol Nurs. 2010;14(6):735–41.PubMedCrossRefGoogle Scholar
  8. 8.
    Tappenden P, Chilcott J, Ward S, Eggington S, Hind D, Hummel S. Methodological issues in the economic analysis of cancer treatments. Eur J Cancer. 2006;42(17):2867–75.PubMedCrossRefGoogle Scholar
  9. 9.
    Cancer Institute NSW. EviQ: cancer treatments online. [cited 2011 November 21]; EviQ version 1.4.0. https://www.eviq.org.au/Home.aspx.
  10. 10.
    Hryniuk W, Bush H. The importance of dose intensity in chemotherapy of metastatic breast-cancer. J Clin Oncol. 1984;2(11):1281–8.PubMedGoogle Scholar
  11. 11.
    Hershman DL, Unger JM, Barlow WE, Hutchins LF, Martino S, Osborne CK, et al. Treatment quality and outcomes of African American versus white breast cancer patients: retrospective analysis of Southwest Oncology Studies S8814/S8897. J Clin Oncol. 2009;27(13):2157–62.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Lepage E, Gisselbrecht C, Haioun C, Sebban C, Tilly H, Bosly A, et al. Prognostic significance of received relative dose intensity in non-Hodgkin’s lymphoma patients: application to LNH-87 protocol. The GELA (Groupe d’Etude des Lymphomes de l’Adulte). Ann Oncol. 1993;4(8):651–6.PubMedGoogle Scholar
  13. 13.
    Bonadonna G, Valagussa P. Dose–response effect of adjuvant chemotherapy in breast cancer. N Engl J Med. 1981;304(1):10–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995;332(14):901–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Wood WC, Budman DR, Korzun AH, Cooper MR, Younger J, Hart RD, et al. Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med. 1994;330(18):1253–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Budman DR, Berry DA, Cirrincione CT, Henderson IC, Wood WC, Weiss RB, et al. Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. J Natl Cancer Inst. 1998;90(16):1205–11.PubMedCrossRefGoogle Scholar
  17. 17.
    Hryniuk W, Levine MN. Analysis of dose intensity for adjuvant chemotherapy trials in stage-I breast-cancer. J Clin Oncol. 1986;4(8):1162–70.PubMedGoogle Scholar
  18. 18.
    Kuo SH, Lien HC, You SL, Lu YS, Lin CH, Chen TZ, et al. Dose variation and regimen modification of adjuvant chemotherapy in daily practice affect survival of stage I–II and operable stage III Taiwanese breast cancer patients. Breast. 2008;17(6):646–53.PubMedCrossRefGoogle Scholar
  19. 19.
    Lyman GH, Dale DC, Crawford J. Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices. J Clin Oncol. 2003;21(24):4524–31.PubMedCrossRefGoogle Scholar
  20. 20.
    Henry DH, Viswanathan HN, Elkin EP, Traina S, Wade S, Cella D, et al. Symptoms and treatment burden associated with cancer treatment: results from a cross-sectional national survey in the US. Support Care Cancer. 2008;16(7):791–801.PubMedCrossRefGoogle Scholar
  21. 21.
    Coates A, Abraham S, Kaye SB, Sowerbutts T, Frewin C, Fox RM, et al. On the receiving end: patient perception of the side-effects of cancer chemotherapy. Eur J Cancer Clin Oncol. 1983;19(2):203–8.PubMedCrossRefGoogle Scholar
  22. 22.
    de Boer-Dennert M, de Wit R, Schmitz PIM, Djontono J, Beurden VV, Verweij J. Patient perceptions of the side-effects of chemotherapy: the influence of 5HT3 antagonists. Br J Cancer. 1997;76(8):1055–61.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Carelle N, Piotto E, Bellanger A, Germanaud J, Thuillier A, Khayat D. Changing patient perceptions of the side effects of cancer chemotherapy. Cancer. 2002;95(1):155–63.PubMedCrossRefGoogle Scholar
  24. 24.
    Milton CW, Bernie OB, John H, Joseph J, Magnus J, Chris M, et al. Principles of good practice for decision analytic modeling in health-care evaluation: report of the ISPOR Task Force on good research practices: modeling studies. Value Health. 2003;6(1):9–17.CrossRefGoogle Scholar
  25. 25.
    Graves N, Walker D, Raine R, Hutchings A, Roberts JA, Graves N, et al. Cost data for individual patients included in clinical studies: no amount of statistical analysis can compensate for inadequate costing methods. Health Econ. 2002;11(8):735–9.PubMedCrossRefGoogle Scholar
  26. 26.
    NSW Department of Health. Issues in the costing of large projects in health and healthcare. Sydney: NSW Department of Health; 2008.Google Scholar
  27. 27.
    Borg S, Glenngard AH, Osterborg A, Persson U. The cost-effectiveness of treatment with erythropoietin compared to red blood cell transfusions for patients with chemotherapy induced anaemia: a Markov model. Acta Oncol. 2008;47(6):1009–17.PubMedCrossRefGoogle Scholar
  28. 28.
    Eldar-Lissai A, Cosler LE, Culakova E, Lyman GH. Economic analysis of prophylactic pegfilgrastim in adult cancer patients receiving chemotherapy. Value Health. 2008;11(2):172–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Annemans L, Strens D, Lox E, Petit C, Malonne H. Cost-effectiveness analysis of aprepitant in the prevention of chemotherapy-induced nausea and vomiting in Belgium. Support Care Cancer. 2008;16(8):905–15.PubMedCrossRefGoogle Scholar
  30. 30.
    Lordick F, Ehlken B, Ihbe-Heffinger A, Berger K, Krobot KJ, Pellissier J, et al. Health outcomes and cost-effectiveness of aprepitant in outpatients receiving antiemetic prophylaxis for highly emetogenic chemotherapy in Germany. Eur J Cancer. 2007;43(2):299–307.PubMedCrossRefGoogle Scholar
  31. 31.
    Cantor SB, Elting LS, Hudson DV Jr, Rubenstein EB. Pharmacoeconomic analysis of oprelvekin (recombinant human interleukin-11) for secondary prophylaxis of thrombocytopenia in solid tumor patients receiving chemotherapy. Cancer. 2003;97(12):3099–106.PubMedCrossRefGoogle Scholar
  32. 32.
    Lyman GH. Balancing the benefits and costs of colony-stimulating factors: a current perspective. Semin Oncol. 2003;30(4 Suppl 13):10–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Lundkvist J, Wilking N, Holmberg S, Jonsson L. Cost-effectiveness of exemestane versus tamoxifen as adjuvant therapy for early-stage breast cancer after 2–3 years treatment with tamoxifen in Sweden. Breast Cancer Res Treat. 2007;102(3):289–99.PubMedCrossRefGoogle Scholar
  34. 34.
    Tumeh JW, Shenoy PJ, Moore SG, Kauh J, Flowers C. A Markov model assessing the effectiveness and cost-effectiveness of FOLFOX compared with FOLFIRI for the initial treatment of metastatic colorectal cancer. Am J Clin Oncol. 2009;32(1):49–55.PubMedCrossRefGoogle Scholar
  35. 35.
    Cosler LE, Calhoun EA, Agboola O, Lyman GH. Effects of indirect and additional direct costs on the risk threshold for prophylaxis with colony-stimulating factors in patients at risk for severe neutropenia from cancer chemotherapy. Pharmacotherapy. 2004;24(4):488–94.PubMedCrossRefGoogle Scholar
  36. 36.
    Danova M, Chiroli S, Rosti G, Doan QV. Cost-effectiveness of pegfilgrastim versus six days of filgrastim for preventing febrile neutropenia in breast cancer patients. Tumori. 2009;95(2):219–26.PubMedGoogle Scholar
  37. 37.
    Liu Z, Doan QV, Malin J, Leonard R. The economic value of primary prophylaxis using pegfilgrastim compared with filgrastim in patients with breast cancer in the UK. Appl Health Econ Health Policy. 2009;7(3):193–205.PubMedCrossRefGoogle Scholar
  38. 38.
    Kurian AW, Thompson RN, Gaw AF, Arai S, Ortiz R, Garber AM. A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer. J Clin Oncol. 2007;25(6):634–41.PubMedCrossRefGoogle Scholar
  39. 39.
    Norum J, Risberg T, Olsen JA. A monoclonal antibody against HER-2 (trastuzumab) for metastatic breast cancer: a model-based cost-effectiveness analysis. Ann Oncol. 2005;16(6):909–14.PubMedCrossRefGoogle Scholar
  40. 40.
    Touchette DR, Stevenson JG, Jensen G. Cost effectiveness of amifostine (Ethyol) in patients with non-small cell lung cancer. J Aging Pharmacother. 2006;13(2):109–26.CrossRefGoogle Scholar
  41. 41.
    Wolowacz SE, Cameron DA, Tate HC, Bagust A. Docetaxel in combination with doxorubicin and cyclophosphamide as adjuvant treatment for early node-positive breast cancer: a cost-effectiveness and cost-utility analysis. J Clin Oncol. 2008;26(6):925–33.PubMedCrossRefGoogle Scholar
  42. 42.
    Risebrough NA, Verma S, Trudeau M, Mittmann N. Cost-effectiveness of switching to exemestane versus continued tamoxifen as adjuvant therapy for postmenopausal women with primary breast cancer. Cancer. 2007;110(3):499–508.PubMedCrossRefGoogle Scholar
  43. 43.
    Dedes KJ, Matter-Walstra K, Schwenkglenks M, Pestalozzi BC, Fink D, Brauchli P, et al. Bevacizumab in combination with paclitaxel for HER-2 negative metastatic breast cancer: an economic evaluation. Eur J Cancer. 2009;45(8):1397–406.PubMedCrossRefGoogle Scholar
  44. 44.
    Le QA, Hay JW. Cost-effectiveness analysis of lapatinib in HER-2-positive advanced breast cancer. Cancer. 2009;115(3):489–98.PubMedCrossRefGoogle Scholar
  45. 45.
    Bristow RE, Santillan A, Salani R, Diaz-Montes TP, Giuntoli RL 2nd, Meisner BC, et al. Intraperitoneal cisplatin and paclitaxel versus intravenous carboplatin and paclitaxel chemotherapy for Stage III ovarian cancer: a cost-effectiveness analysis. Gynecol Oncol. 2007;106(3):476–81.PubMedCrossRefGoogle Scholar
  46. 46.
    Lidgren M, Jönsson B, Rehnberg C, Willking N, Bergh J. Cost-effectiveness of HER2 testing and 1-year adjuvant trastuzumab therapy for early breast cancer. Ann Oncol. 2008;19(3):487.PubMedCrossRefGoogle Scholar
  47. 47.
    Eniu A, Carlson RW, El Saghir NS, Bines J, Bese NS, Vorobiof D, et al. Guideline implementation for breast healthcare in low- and middle-income countries: treatment resource allocation. Cancer. 2008;113(8 Suppl):2269–81.PubMedCrossRefGoogle Scholar
  48. 48.
    Delea TE, Karnon J, Sofrygin O, Thomas SK, Papo NL, Barghout V. Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in hormone receptor-positive postmenopausal women with early-stage breast cancer. Clin Breast Cancer. 2007;7(8):608–18.PubMedCrossRefGoogle Scholar
  49. 49.
    Hillner BE, Schrag D, Sargent DJ, Fuchs CS, Goldberg RM. Cost-effectiveness projections of oxaliplatin and infusional fluorouracil versus irinotecan and bolus fluorouracil in first-line therapy for metastatic colorectal carcinoma. Cancer. 2005;104(9):1871–84.PubMedCrossRefGoogle Scholar
  50. 50.
    Karnon J, Delea T, Barghout V. Cost utility analysis of early adjuvant letrozole or anastrozole versus tamoxifen in postmenopausal women with early invasive breast cancer: the UK perspective. Eur J Health Econ. 2008;9(2):171–83.PubMedCrossRefGoogle Scholar
  51. 51.
    Ojeda B, de Sande LM, Casado A, Merino P, Casado MA. Cost-minimisation analysis of pegylated liposomal doxorubicin hydrochloride versus topotecan in the treatment of patients with recurrent epithelial ovarian cancer in Spain. Br J Cancer. 2003;89(6):1002–7.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Ramsey SD, Clarke L, Kamath TV, Lubeck D. Evaluation of erlotinib in advanced non-small cell lung cancer: impact on the budget of a U.S. health insurance plan. J Manag Care Pharm. 2006;12(6):472–8.PubMedGoogle Scholar
  53. 53.
    Main C, Bojke L, Griffin S, et al. Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation. Health Technol Assess. 2006;10(9):1–132, iii–iv.Google Scholar
  54. 54.
    Wilson J, Yao GL, Raftery J, et al. A systematic review and economic evaluation of epoetin alpha, epoetin beta and darbepoetin alpha in anaemia associated with cancer, especially that attributable to cancer treatment. Health Technol Assess. 2007;11(13):1–202, iii–iv.Google Scholar
  55. 55.
    Bennett CL, Calhoun EA. Evaluating the total costs of chemotherapy-induced febrile neutropenia: results from a pilot study with community oncology cancer patients. Oncologist. 2007;12(4):478–83.PubMedCrossRefGoogle Scholar
  56. 56.
    Dranitsaris G, Maroun J, Shah A. Severe chemotherapy-induced diarrhea in patients with colorectal cancer: a cost of illness analysis. Support Care Cancer. 2005;13(5):318–24.PubMedCrossRefGoogle Scholar
  57. 57.
    Dranitsaris G, Maroun J, Shah A. Estimating the cost of illness in colorectal cancer patients who were hospitalized for severe chemotherapy-induced diarrhea. Can J Gastroenterol. 2005;19(2):83–7.PubMedGoogle Scholar
  58. 58.
    Minisini A, Spazzapan S, Crivellari D, Aapro M, Biganzoli L. Incidence of febrile neutropenia and neutropenic infections in elderly patients receiving anthracycline-based chemotherapy for breast cancer without primary prophylaxis with colony-stimulating factors. Crit Rev Oncol Hematol. 2005;53(2):125–31.PubMedCrossRefGoogle Scholar
  59. 59.
    Arbuckle RB, Huber SL, Zacker C. The consequences of diarrhea occurring during chemotherapy for colorectal cancer: a retrospective study. Oncologist. 2000;5(3):250–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Fortner BV, Tauer K, Zhu L, Okon TA, Moore K, Templeton D, et al. Medical visits for chemotherapy and chemotherapy-induced neutropenia: a survey of the impact on patient time and activities. BMC Cancer. 2004;20(4):22.CrossRefGoogle Scholar
  61. 61.
    Calhoun EA, Chang CH, Welshman EE, Fishman DA, Lurain JR, Bennett CL. Evaluating the total costs of chemotherapy-induced toxicity: results from a pilot study with ovarian cancer patients. Oncologist. 2001;6(5):441–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Liu C-Y, Liu T-W, Liu J-S, Hsaio C-F, Chen L-T. Medical resource utilizations and economic burden in Chinese cancer patients with chemotherapy-induced anemia: a population database study. Chin J Cancer Res. 2008;20(4):307–15.CrossRefGoogle Scholar
  63. 63.
    Caggiano V, Weiss RV, Rickert TS, Linde-Zwirble WT. Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy. Cancer. 2005;103(9):1916–24.PubMedCrossRefGoogle Scholar
  64. 64.
    Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357(20):2040–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Mittmann N, Au HJ, Tu D, O’Callaghan CJ, Isogai PK, Karapetis CS, et al. Prospective cost-effectiveness analysis of cetuximab in metastatic colorectal cancer: evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 trial. J Natl Cancer Inst. 2009;101(17):1182–92.PubMedCrossRefGoogle Scholar
  66. 66.
    Craig D, McDaid C, Fonseca T, Stock C, Duffy S, Woolacott N. Are adverse effects incorporated in economic models? An initial review of current practice. Health Technol Assess. 2009;13(62):1–71.Google Scholar
  67. 67.
    Weinstein M, O’Brien B, Horberger J, Jackson J, Johannesson M, McCabe C. Principles of good practice for decision analytic modelling in health-care evaluation: report of the ISPOR task force on good research practices: modelling studies. Value Health. 2003;6:9–17.PubMedCrossRefGoogle Scholar
  68. 68.
    Lyman GH. Chemotherapy dose intensity and quality cancer care. Oncology (Williston Park). 2006;20(14 Suppl 9):16–25.Google Scholar
  69. 69.
    Shabaruddin FH, Chen LC, Elliot R, Payne K. A systematic review of utility values for chemotherapy-related adverse events. Pharmacoeconomics. 2013;31(4):277–88.PubMedCrossRefGoogle Scholar
  70. 70.
    Beusterien KM, Szabo SM, Kotapati S, Mukherjee J, Hoos A, Hersey P, et al. Societal preference values for advanced melanoma health states in the United Kingdom and Australia. Br J Cancer. 2009;101(3):387–9.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Flanagan W, McIntosh C, Le Petit C, Berthelot J-M. Deriving utility scores for co-morbid conditions: a test of the multiplicative model for combining individual condition scores. Popul Health Metr. 2006;4(1):13.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Dale W, Basu A, Elstein A, Meltzer D. Predicting utility ratings for joint health states from single health states in prostate cancer: empirical testing of 3 alternative theories. Med Decis Making. 2008;28(1):102–12.PubMedCrossRefGoogle Scholar
  73. 73.
    Carlson JJ, Reyes C, Oestreicher N, Lubeck D, Ramsey SD, Veenstra DL. Comparative clinical and economic outcomes of treatments for refractory non-small cell lung cancer (NSCLC). Lung Cancer. 2008;61(3):405–15.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Centre for Health Economics Research and EvaluationUniversity of Technology, SydneyBroadwayAustralia

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