Abstract
The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE’s subsequent decisions.
The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses.
Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50×10^9/L and 400×10^9/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients.
For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed before the incremental cost per QALY is less than £30 000. There was significant uncertainty, with the incremental cost-effectiveness ratio (ICER) reported varying from £33 561 to £103 500 per QALY (splenectomized) and £39 657 to £150 245 per QALY (non-splenectomized). All costs are presented in £, year 2008 values, as this was the costing year for the manufacturer’s model. Other than bleeding, no adverse events were modelled. In relation to the long-term treatment model, the ERG questioned the robustness of the use of non-randomized non-comparative data. The base-case results restricting the time horizon to 2 years and prescribing eltrombopag as second-line treatment post-rituximab were found to be favourable towards eltrombopag. As rituximab is not a licensed treatment for ITP, the ERG were concerned that its inclusion may not be reflective of clinical practice. None of the treatment sequences resulted in an ICER approaching the recommended threshold of £30 000 per QALY gained.
Eltrombopag appears to be a safe treatment for ITP (although long-term follow-up studies are awaited) and has short-term efficacy. However, NICE found based on the evidence submitted and reviewed that there was no robust evidence on the long-term efficacy or cost effectiveness of eltrombopag and a lack of direct evidence for eltrombopag tested against other relevant comparators.
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Notes
Durable response was defined as a weekly platelet count ≥50×109/L during 6 or more weeks of the last 8 weeks of treatment excluding those who received rescue medication at any time during the study, while overall response was durable plus transient response (four or more weekly responses ≥50×109/L during the study without a platelet response from week 2 to 25).
References
National Institute for Health and Clinical Excellence. Guide to the single technology appraisal process. London: NICE, 2009 [online]. Available from URL: http://www.nice.org.uk/media/42D/B3/STAGuideLrFinal.pdf [Accessed 2011 Jan 10]
Sculpher M. Single technology appraisal at the UK National Institute for Health and Clinical Excellence: a source of evidence and analysis for decision making internationally. Pharmacoeconomics 2010; 28 (5): 347–9
Rodgers M, Griffin S, Paulden M, et al. Alitretinoin for severe chronic hand eczema: a NICE single technology appraisal. Pharmacoeconomics 2010; 28 (5): 351–62
Bagust A, Greenhalgh J, Boland A, et al. Cetuximab for recurrent and/or metastatic squamous cell carcinoma of the head and neck: a NICE single technology appraisal. Pharmacoeconomics 2010; 28 (6): 439–48
Stevenson M, Pandor A. Febuxostat for the management of hyperuricaemia in patients with gout: a NICE single technology appraisal. Pharmacoeconomics 2011; 29 (2): 133–40
Scotland G, Waugh N, Royle P, et al. Denosumab for the prevention of osteoporotic fractures in post-menopausal women: a NICE single technology appraisal. Pharmacoeconomics 2011; 29 (11): 951–61
Dickson R, Bagust A, Boland A, et al. Erlotinib monotherapy for the maintenance treatment of non-small cell lung cancer after previous platinum-containing chemotherapy: a NICE single technology appraisal. Pharmacoeconomics 2011; 29 (12): 1051–62
McKenna C, Maund E, Sarowar M, et al. Dronedarone for the treatment of atrial fibrillation: a NICE single technology appraisal. Pharmacoeconomics 2012; 30 (1): 35–46
Holmes M, Carroll C, Papaioannou D. Dabigatran etexilate for the prevention of venous thromboembolism in patients undergoing elective hip and knee surgery: a NICE single technology appraisal. Pharmacoeconomics 2012; 30 (2): 137–46
Yang H, Craig D, Epstein D, et al. Golimumab for the treatment of psoriatic arthritis: a NICE single technology appraisal. Pharmacoeconomics 2012; 30 (4): 257–70
Burch J, Griffin S, McKenna C, et al. Omalizumab for severe and persistent asthma in children aged 6 to 11 years: a NICE single technology appraisal. Pharmacoeconomics. In press
Whyte S, Pandor A, Stevenson M. Bevacizumab for metastatic colorectal cancer: a NICE single technology appraisal. Pharmacoeconomics. In press
Kilonzo M, Hislop J, Elders A. Pazopanib for the first-line treatment of patients with advanced and/or metastatic renal cell carcinoma: a NICE single technology appraisal. Pharmacoeconomics. In press
Craig D, Rice S, Paton F, et al. Retigabine for the adjunctive treatment of adults with partial onset seizures in epilepsy with and without secondary generalisation: a NICE single technology appraisal. Pharmacoeconomics. In press
National Institute for Health and Clinical Excellence. Thrombocytopenic purpura: eltrombopag. London: NICE, 2010 [online]. Available from URL: http://guidance.nice.org.uk/TA/Wave17/14 [Accessed 2011 Jan 10]
Neylon AJ, Saunders PW, Howard MR, et al. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol 2003; 122: 966–74
George JN, El-Harake MA, Aster RH. Thrombocytopenia due to enhanced platelet destruction by immunologic mechanisms. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, editors. Williams hematology. New York: McGraw-Hill, 1995: 1315–55
Cheng G, Saleh MN, Bussel JB, et al. Oral eltrombopag for the long-term treatment of patients with chronic idiopathic thrombocytopenic purpura: results of a phase III, double-blind, placebo-controlled study (RAISE) [abstract]. Blood 2008; 112:400
Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007; 357: 2237–47
Bussel JB, Provan D, Shamsi T, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373: 641–8
GlaxoSmithKline Inc. Product monograph: Revolade™ eltrombopag tablets 25mg and 50mg eltrombopag (as eltrombopag olamine), thrombopoietin receptor agonist. Mississauga (ON): GSK, 2011 [online]. Available from URL: http://www.gsk.ca/english/docs-pdf/Revolade_2011.pdf [Accessed 2012 Jan 19]
Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 2008; 371: 395–403
George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996; 88: 3–40
Chen S, Pi D, Ansari M, et al. Polyclonal intravenous immunologlobulin in patients with immune thrombocytopenic purpura: clinical systematic review [report no. 108]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health, 2008 [online]. Available from URL: http://www.cadth.ca/index.php/en/publication/809 [Accessed 2011 Jan 10]
Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from the SF-36. J Health Econ 2002; 21: 271–92
Bruneneberg D, Joore MA, Boonen A, et al. Comparing SF-6D and EQ-5D: data from 4 patient populations [abstract]. 6th World Congress on Health Economics; 2007 Jul 8–11; Copenhagen [online]. Available from URL: http://papers.ssrn.com/sol3/papers.cfm?abstract_id=992656 [Accessed 2011 Jan 10]
Seymour J, McNamme P, Scott A, et al. Shedding new light onto the ceiling and floor? A quantile regression approach to compare EQ-5D and SF-6D responses. Health Econ 2009; 19: 683–96
National Institute for Health and Clinical Excellence. Romiplostim for the treatment of chronic immune (idiopathic) thrombocytopenic purpura [guidance no. 221]. London: NICE, 2011 [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/13467/54219/54219.pdf [Accessed 2011 Oct 10]
Boyers D, Jia X, Crowther M, et al. Eltrombopag for the treatment of chronic idiopathic (immune) thrombocytopenic purpura (ITP): a single technology appraisal. Aberdeen: Aberdeen HTA Group, Institute of Applied Health Sciences, University of Aberdeen, 2009 Dec [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/12025/49132/49132.pdf [Accessed 2012 Jan 19]
Acknowledgements
This project was funded by the NIHR Health Technology Assessment Programme (project number 08/81/01) and will be published as part of a compendium of ERG articles in Health Technology Assessment (HTA). See the HTA programme website for further project information (http://www.hta.ac.uk). This summary of the ERG report was compiled after the appraisal committee’s review. This summary has not been externally peer reviewed by PharmacoEconomics.
Professor Luke Vale, Health Economics Research Unit and Health Services Research Unit at the University of Aberdeen, acted as guarantor and advised and commented on work throughout the project. Dr Mark Crowther, Department of Haematology at Aberdeen Royal Infirmary, provided clinical guidance and Ms Cynthia Fraser (information specialist), Health Services Research Unit at the University of Aberdeen, conducted literature searches and commented on drafts of the report to HTA.
Further acknowledgements and contributions are detailed in the ERG report.[29]
The views and opinions expressed therein are those of the authors and do not necessarily reflect those of NICE or the Department of Health.
Dwayne Boyers completed an internship (3-month student placement in Dublin, Ireland) with GlaxoSmithKline as part of an MSc in Economics from the National University of Ireland (NUI), Galway, during which time he completed a minor dissertation on the supply and reimbursement of medicines in Ireland. As part of the programme between NUI Galway and GlaxoSmithKline, he received a small stipend to cover living expenses while on placement in Dublin in 2009. The remaining authors have no conflicts to report.
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Boyers, D., Jia, X., Jenkinson, D. et al. Eltrombopag for the Treatment of Chronic Immune or Idiopathic Thrombocytopenic Purpura. PharmacoEconomics 30, 483–495 (2012). https://doi.org/10.2165/11591550-000000000-00000
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DOI: https://doi.org/10.2165/11591550-000000000-00000