CANADIAN COST-UTILITY ANALYSIS OF INTRAVENOUS IMMUNOGLOBULIN FOR ACUTE CHILDHOOD IDIOPATHIC THROMBOCYTOPENIC PURPURA
Main Article Content
Keywords
Purpura, thrombocytopenic, idiopathic, cost benefit-economics, immunoglobulins, intravenous
Abstract
Background
Idiopathic thrombocytopenic purpura (ITP) is a hematological disorder and can be classified as acute or chronic. The main goal of treatment for acute childhood ITP is the prevention of potentially fatal bleeding complications, the most serious of which is intracranial hemorrhage (ICH). Treatment options for acute childhood ITP include splenectomy, corticosteroids, and blood products such as intravenous immunoglobulin.
Objectives
The objective was to evaluate, from a Canadian perspective, the cost-effectiveness of intravenous immunoglobulin (IVIG) compared to alternative inpatient treatments for acute childhood idiopathic thrombocytopenic purpura (ITP).
Methods
A Markov model with a lifelong time horizon was used to evaluate the costs and quality-adjusted life years (QALYs) for 5 treatments for children hospitalized for ITP: 1) no treatment; 2) IVIG; 3) Anti-D; 4) prednisone; and 5) methylprednisolone. The model predicted the probability of intracranial hemorrhage for each treatment strategy based on the time children spent with platelet counts <20,000?L. The time patients spent with platelet counts <20,000?L with each treatment was estimated by pooling data from published randomized clinical trials. In the basecase analysis, the cohort was assumed to weigh 20kg. Cost and utility model variables were based upon various literature sources. Parameter uncertainty was assessed using probabilistic sensitivity analysis.
Results
The treatment strategies that comprised the efficiency frontier were prednisone, Anti-D and IVIG. The incremental cost per QALY was $53,333 moving from prednisone to Anti-D and $53,846 moving from Anti-D to IVIG. Results were sensitive to patient weight. If patient weight is 10kg, IVIG dominates all other strategies and if weight is increased to 30kg, the cost per QALY of IVIG is $163,708.
Conclusion
Based on common willingness to pay thresholds, IVIG might be considered a cost effective treatment for acute childhood ITP. Cost effectiveness is highly dependent on patient weight.
References
2. Medeiros D, Buchanan GR. Major hemorrhage in children with idiopathic thrombocytopenic purpura: immediate response to therapy and long-term outcome. J Pediatr 1998;133(3):334- 9.
3. Anderson D, Ali K, Blanchette V, Brouwers M, Couban S, Radmoor P, Huebsch L, Hume H, McLeod A, Meyer R, Moltzan C, Nahirniak S, Nantel S, Pineo G, Rock G. Guidelines on the use of intravenous immune globulin for hematologic conditions. Transfus Med Rev 2007;21(2 Suppl 1):S9-56.
4. George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, Blanchette VS, Bussel JB, Cines DB, Kelton JG, Lichtin AE, McMillan R, Okerbloom JA, Regan DH, Warrier I. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996;88(1):3-40.
5. Beck CE, Nathan PC, Parkin PC, Blanchette VS, Macarthur C. Corticosteroids versus intravenous immune globulin for the treatment of acute immune thrombocytopenic purpura in children: a systematic review and meta-analysis of randomized controlled trials. J Pediatr 2005;147(4):521-7.
6. El Alfy MS, Mokhtar GM, El-Laboudy MA, Khalifa AS. Randomized trial of anti-D immunoglobulin versus low-dose intravenous immunoglobulin in the treatment of childhood chronic idiopathic thrombocytopenic purpura. Acta Haematol 2006;115(1-2):46-52.
7. Plasma products & services: per capita IVIg issues in selected countries (2005-2006). Int Blood/Plasma News 2007;24(11):157. Available: http://www.blood.ca/CentreApps/Internet/UW_ V502_MainEngine.nsf/resources/Plasma+Produ cts+and+Services/$file/ivig_issues_intl_comp20 08.pdf (accessed 2008 Jul 3).
8. Plasma products & services: overall IVIG issues by Canadian Blood Services. Ottawa: Canadian Blood Services; 2008. Available: http://www.blood.ca/CentreApps/Internet/UW_ V502_MainEngine.nsf/resources/Plasma+Produ cts+and+Services/$file/ivig_issues_overall2008. pdf (accessed 2008 Jul 3).
9. Kumar M, Vik TA, Johnson CS, Southwood ME, Croop JM. Treatment, outcome, and cost of care in children with idiopathic thrombocytopenic purpura. Am J Hematol 2005;78(3):181-7.
10. Kuhne T, Imbach P, Bolton-Maggs PH, Berchtold W, Blanchette V, Buchanan GR. Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study. Lancet 2001;358 (9299):2122-5.
11. Chen S, Pi D, Ansari M, Puil L, Desjardins B, Banks R. Polyclonal intravenous immunoglobulin in patients with immune thrombocytopenic purpura: clinical systematic review [Technology report no 108]. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2008. Available: http://www.cadth.ca/media/pdf/298A_Polyclona l-Intravenous-Immunoglobulin_tr_e.pdf.
12. Blanchette VS, Luke B, Andrew M, Sommerville-Nielsen S, Barnard D, de Veber B, Gent M. A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura. J Pediatr 1993;123(6):989-95.
13. Duru F, Fisgin T, Yarali N, Kara A. Clinical course of children with immune thrombocytopenic purpura treated with intravenous immunoglobulin G or megadose methylprednisolone or observed without therapy. Pediatr Hematol Oncol 2002;19(4):219- 25.
14. Ancona KG, Parker RI, Atlas MP, Prakash D. Randomized trial of high-dose methylprednisolone versus intravenous immunoglobulin for the treatment of acute idiopathic thrombocytopenic purpura in children. J Pediatr Hematol Oncol 2002;24(7):540-4.
15. Moser AM, Shalev H, Kapelushnik J. Anti-D exerts a very early response in childhood acute idiopathic thrombocytopenic purpura. Pediatr Hematol Oncol 2002;19(6):407-11.
16. Erduran E, Aslan Y, Gedik Y, Orhan F. A randomized and comparative study of intravenous immunoglobulin and mega dose methylprednisolone treatments in children with acute idiopathic thrombocytopenic purpura. Turk J Pediatr 2003;45(4):295-300.
17. Tarantino MD, Young G, Bertolone SJ, Kalinyak KA, Shafer FE, Kulkarni R, Weber LC, Davis ML, Lynn H, Nugent DJ, Acute ITP Study Group. Single dose of anti-D immune globulin at 75 microg/kg is as effective as intravenous immune globulin at rapidly raising the platelet count in newly diagnosed immune thrombocytopenic purpura in children. J Pediatr 2006;148(4):489-94.
18. Benesch M, Kerbl R, Lackner H, Berghold A, Schwinger W, Triebl-Roth K, Urban C. Lowdose versus high-dose immunoglobulin for primary treatment of acute immune thrombocytopenic purpura in children: results of a prospective, randomized single-center trial. J Pediatr Hematol Oncol 2003;25(10):797-800.
19. Blanchette V, Imbach P, Andrew M, Adams M, McMillan J, Wang E, Milner R, Ali K, Barnard D, Bernstein M. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet 1994;344(8924):703-7.
20. Newman GC, Novoa MV, Fodero EM, Lesser ML, Woloski BM, Bussel JB. A dose of 75 microg/kg/d of i.v. anti-D increases the platelet count more rapidly and for a longer period of time than 50 microg/kg/d in adults with immune thrombocytopenic purpura. Br J Haematol 2001;112(4):1076-8.
21. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7(3):177- 88.
22. Lilleyman JS. Intracranial haemorrhage in idiopathic thrombocytopenic purpura. Paediatric Haematology Forum of the British Society for Haematology. Arch Dis Child 1994;71(3):251-3.
23. Lilleyman JS. Management of childhood idiopathic thrombocytopenic purpura. Br J Haematol 1999;105(4):871-5.
24. Ontario Ministry of Health and Long-Term Care. e-Formulary. Ontario drug benefit formulary / comparative drug index: electronic version. Version 1.4. Toronto: Queen's Printer for Ontario; 2007. Available: https://www.healthinfo.moh.gov.on.ca/formular y/index.jsp (accessed 2008 Apr 24).
25. OCCI costing analysis tool. In: Ontario Case Costing Initiative (OCCI) [website]. Toronto: Ontario Case Costing Initiative; 2007. Available: http://www.occp.com/.
26. Hopkins R, O'Reilly D, Blackhouse G, Tarride J-E, Bowen J, Campbell K, Patterson L, Goeree R. Potential systematic bias in the estimation of cost-effectiveness that result from using non disease-specific costs of complications: demonstration with a population-based diabetes and matched non-diabetes cohort in the province of Ontario [poster presentation]. In: SMDM 29th Annual Meeting. Pittsburgh (PA); 2007.
27. Complete life table, Canada, 2000-2002. Male and female. In: Life tables, Canada, provinces and territories. Ottawa: Statistics Canada; 2006. Available: http://dsppsd. pwgsc.gc.ca/Collection/Statcan/84-537- X/84-537-XIE.html.
28. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project--1981- 86. 2. Incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 1990;53(1):16-22.
29. Kind P, Hardman G, Macran S. UK population norms for EQ-5D [Discussion paper 172]. York (UK): University of York, Centre for Health Economics; 1999.
30. Shin AY, Porter PJ, Wallace MC, Naglie G. Quality of life of stroke in younger individuals. Utility assessment in patients with arteriovenous malformations. Stroke 1997;28(12):2395-9.
31. O'Brien SH, Ritchey AK, Smith KJ. A costutility analysis of treatment for acute childhood idiopathic thrombocytopenic purpura (ITP). Pediatr Blood Cancer 2007;48(2):173-80.