title: Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal.
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.
authors.affiliation: Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland. d.boyers@abdn.ac.uk
authors.forename: Dwayne
authors.initials: D
authors.lastname: Boyers
authors.forename: Xueli
authors.initials: X
authors.lastname: Jia
authors.forename: David
authors.initials: D
authors.lastname: Jenkinson
authors.forename: Graham
authors.initials: G
authors.lastname: Mowatt
mesh_terms: D001565:Benzoates / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D003657:Decision Making; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D018803:Models, Economic; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000191:economics; D011720:Pyrazoles / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D011961:Receptors, Fc / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013156:Splenectomy; D013673:Technology Assessment, Biomedical / Q000379:methods*; D013926:Thrombopoietin / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag