Cost-utility of new film-coated tablet formulation of deferasirox vs deferoxamine among major beta-thalassemia patients in Iran
Medicine (Baltimore). 2020;99(28):e20949
OBJECTIVES Thalassemia is a hereditary disease, which caused economic burden in developing countries. This study evaluated the cost utility of new formulation of deferasirox (Jadenu) vs deferoxamine (Desferal) among B-Thalassemia-major patients from payer perspective in Iran. METHODS An economic-evaluation through Markov model was performed. A systematic review was conducted in order to evaluate the clinical effectiveness of comparators. Because of chelating therapy is weight-dependent, patients were assumed to be 2 years-old at initiation in first and 18 years-old in second scenario, and model was estimated lifetime costs and utilities. Costs were calculated to the Iran healthcare system through payer perspective and measured effectiveness using quality-adjusted life years (QALYs). One-way sensitivity analysis and budget impact analysis was also employed. RESULTS The 381 studies were retrieved from systematic searching through databases. After eliminating duplicate and irrelevant studies, 2 studies selected for evaluating the effectiveness. Jadenu was associated with an incremental cost-effectiveness ratio (ICER) of 1470.6 and 2544.7 US$ vs Desferal in first and second scenario respectively. The estimated ICER for Jadenu compared to generic deferoxamine was 2837.0 and 6924.1 US$ for first and second scenario respectively. For all scenarios Jadenu is presumed as cost-effective option based on calculated ICER which was lower than 1 gross domestic product per capita in Iran. Sensitivity analysis showed that different parameters except discount rate and indirect cost did not have impact on results. Based on budget impact analysis the estimated cost for patients using Desferal (based on the market share of brand) was 44,021,478 US$ in 3 years vs 42,452,606 US$ in replacing 33% of brand market share with Jadenu. This replacement corresponded to the cost saving of almost 1,568,872 US$ for the payers in 3 years. The calculated cost of using generic deferoxamine in all patients was 68,948,392 US$. The increase in the cost of using Jadenu for 10% of all patients in this scenario would be 934,427 US$ (1.36%) US$ at the first year. CONCLUSIONS Based on this analysis, film-coated deferasirox appeared to be cost-effective treatment in comparison with Desferal for managing child and adult chronic iron overload in B-thalassemia major patients of Iran.
Avatrombopag and lusutrombopag for thrombocytopenia in people with chronic liver disease needing an elective procedure: a systematic review and cost-effectiveness analysis
Health technology assessment (Winchester, England). 2020;24(51):1-220
BACKGROUND There have been no licensed treatment options in the UK for treating thrombocytopenia in people with chronic liver disease requiring surgery. Established management largely involves platelet transfusion prior to the procedure or as rescue therapy for bleeding due to the procedure. OBJECTIVES To assess the clinical effectiveness and cost-effectiveness of two thrombopoietin receptor agonists, avatrombopag (Doptelet(®); Dova Pharmaceuticals, Durham, NC, USA) and lusutrombopag (Mulpleta(®); Shionogi Inc., London, UK), in addition to established clinical management compared with established clinical management (no thrombopoietin receptor agonist) in the licensed populations. DESIGN Systematic review and cost-effectiveness analysis. SETTING Secondary care. PARTICIPANTS Severe thrombocytopenia (platelet count of < 50,000/µl) in people with chronic liver disease requiring surgery. INTERVENTIONS Lusutrombopag 3 mg and avatrombopag (60 mg if the baseline platelet count is < 40,000/µl and 40 mg if it is 40,000-< 50,000/µl). MAIN OUTCOME MEASURES Risk of platelet transfusion and rescue therapy or risk of rescue therapy only. REVIEW METHODS Systematic review including meta-analysis. English-language and non-English-language articles were obtained from several databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, all searched from inception to 29 May 2019. ECONOMIC EVALUATION Model-based cost-effectiveness analysis. RESULTS From a comprehensive search retrieving 11,305 records, six studies were included. Analysis showed that avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy or rescue therapy only, and mostly with a statistically significant difference (i.e. 95% confidence intervals not overlapping the point of no difference). However, only avatrombopag seemed to be superior to no thrombopoietin receptor agonist in reducing the risk of rescue therapy, although far fewer patients in the lusutrombopag trials than in the avatrombopag trials received rescue therapy. When assessing the cost-effectiveness of lusutrombopag and avatrombopag, it was found that, despite the success of these in avoiding platelet transfusions prior to surgery, the additional long-term gain in quality-adjusted life-years was very small. No thrombopoietin receptor agonist was clearly cheaper than both lusutrombopag and avatrombopag, as the cost savings from avoiding platelet transfusions were more than offset by the drug cost. The probabilistic sensitivity analysis showed that, for all thresholds below £100,000, no thrombopoietin receptor agonist had 100% probability of being cost-effective. LIMITATIONS Some of the rescue therapy data for lusutrombopag were not available. There were inconsistencies in the avatrombopag data. From the cost-effectiveness point of view, there were several additional important gaps in the evidence required, including the lack of a price for avatrombopag. CONCLUSIONS Avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy, but they were not cost-effective given the lack of benefit and increase in cost. FUTURE WORK A head-to-head trial is warranted. STUDY REGISTRATION This study is registered as PROSPERO CRD42019125311. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 51. See the NIHR Journals Library website for further project information.
Modern treatments of haemophilia: review of cost-effectiveness analyses and future directions
BACKGROUND Cost is currently one of the most important aspects in haemophilia care. Factor concentrates absorb more than 90% of healthcare direct costs of haemophilia care, and the debate regarding the high cost of haemophilia treatments and their different use across different countries is increasing. OBJECTIVE The objective of this study was to review cost-effectiveness analyses conducted on treatment options in haemophilia, focusing on their results and their strengths and limitations; to highlight the possible issues associated with economic evaluations of new treatment options. METHODS Electronic searches in PubMed and EMBASE were performed to retrieve papers published between November 2015 and September 2017 to update the previous review of economic evaluations of haemophilia treatments by Drummond et al. Reference lists of included articles and reviews were examined for relevant studies, which were assessed for their quality and their empirical results. RESULTS Twenty-six relevant economic analyses were identified; 15 (57.7%) were conducted in patients with haemophilia with inhibitors while 11 (42.3%) involved patients without inhibitors. There were methodological variations among the included studies, and differences in the treatment schemes make a comparative assessment of interventions for patients with haemophilia difficult. Only immune tolerance induction showed consistent results in its cost-saving profile compared with the treatment with bypassing agents. CONCLUSIONS Economic evaluations of haemophilia treatments are increasing, but the identification of general cost-effectiveness trends is still difficult in these studies. We are now facing a new era in haemophilia management with a soaring need for high-quality economic evaluations, performed through proactive collaboration between clinical experts, budget holders and health economists.
Continuous prophylaxis with recombinant factor IX Fc fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption
Journal of Medical Economics. 2016;:1-30
BACKGROUND Continuous prophylaxis for patients with hemophilia B requires frequent injections that are burdensome and that may lead to suboptimal adherence and outcomes. Hence, therapies requiring less-frequent injections are needed. In the absence of head-to-head comparisons, we compared the first extended-half-life-recombinant factor IX (rFIX) product- recombinant factor IX Fc fusion protein (rFIXFc) - with conventional rFIX products based on annualized bleed rates (ABRs) and factor consumption reported in studies of continuous prophylaxis. METHODS We compared ABRs and weekly factor consumption rates in clinical studies of continuous prophylaxis treatment with rFIXFc and conventional rFIX products (identified by systematic literature review) in previously-treated adolescents and adults with moderate-to-severe hemophilia B. Meta-analysis was used to pool ABRs reported for conventional rFIX products for comparison. Comparisons of weekly factor consumption were based on the mean, reported or estimated from the mean dose per injection. RESULTS Five conventional rFIX studies (injections 1 to >3 times/week) met the criteria for comparison with once-weekly rFIXFc reported by the B-LONG study. The pooled mean ABR for conventional rFIX was slightly higher than but comparable to rFIXFc (difference = 0.71; P = 0.210). Weekly factor consumption was significantly lower with rFIXFc than in conventional rFIX studies (difference in means = 42.8-74.5 IU/kg/week [93-161%], P<0.001). CONCLUSION Comparisons of clinical study results suggest weekly injections with rFIXFc result in similar bleeding rates and significantly lower weekly factor consumption compared with more-frequently-injected conventional rFIX products. The real-world effectiveness of rFIXFc may be higher based on results from a model of the impact of simulated differences in adherence.
Assessing options for treating haemophilia with inhibitors
Cost per responder associated with romiplostim and rituximab treatment for adult primary immune thrombocytopenia in France . French
Transfusion Clinique et Biologique. 2014;21((2):):85-93.
PURPOSE OF THE STUDY This analysis compared the response rates and cost per responder associated with romiplostim and rituximab in adult immune thrombocytopenia from the French National Health System payer perspective. METHODS A decision analytic model was developed to estimate the cost per patient and per responder of treating adult immune thrombocytopenia patients with romiplostim versus rituximab over 6 months. A systematic literature review identified phase 3 randomized controlled trials. Published response rates were extracted (response definition: >50x10(9) platelets/liter). Resource utilization was based on French and international treatment guidelines, and clinical expert opinion. Unit costs were derived from literature and French reimbursement lists, and included the costs of routine physician visits, treatment administration, and emergency care. Non-responders incurred bleeding-related event costs. RESULTS The literature review identified a phase 3 randomized controlled trial for romiplostim with a response rate of 83%. Due to a lack of phase 3 randomized controlled trials for rituximab, a systematic review of studies was selected as the best source, reporting a response rate of 62.5%. Romiplostim and rituximab were associated with similar treatment costs, with an estimated cost per patient for romiplostim of 17,456 and 17,068 for rituximab. Rituximab resulted in a 30% higher cost per responder (27,308 for rituximab versus 21,031 for romiplostim). Romiplostim use reduced drug administration, intravenous immunoglobulin, and bleeding-related hospitalization costs compared to rituximab. CONCLUSIONS Due to its high efficacy leading to lower bleeding-related costs, romiplostim represents an efficient use of resources for adult immune thrombocytopenia patients in the French healthcare system. Copyright 2014 Elsevier Masson SAS. All rights reserved.
A cost-effectiveness study of intravenous immunoglobulin in childhood idiopathic thrombocytopenia purpura patients with life-threatening bleeding
BACKGROUND Although the international guideline recommends intravenous immunoglobulin (IVIG) as the first-line treatment for childhood idiopathic thrombocytopenia purpura (ITP) with life-threatening bleeding, ITP patients may not be able to access IVIG because of the limitation in health benefit packages especially in developing countries. There remains an important policy question as to whether IVIG used as a first-line treatment is worth the money spent. Thus, the objective of this study was to perform a cost-effectiveness analysis of adding IVIG to the standard treatment of platelet transfusion and corticosteroids, for the treatment of childhood ITP with life-threatening bleeding in the context of Thailand. METHODS A cost-effectiveness analysis using a hybrid model consisting of a decision tree and Markov models was conducted with a societal perspective. The effectiveness and utility parameters were determined by systematic reviews, while costs and mortality parameters were determined using a retrospective electronic hospital database analysis. All costs were presented in 2012 US$. The discount rate of 3 % was applied for both costs and outcomes. One-way and probabilistic sensitivity analyses were also performed. RESULTS The incremental cost-effectiveness ratio (ICER) was $3,172 per quality-adjusted life-year gained ($/QALY) for the addition of IVIG versus standard treatment alone. The probability of response to corticosteroids was the most influential parameter on ICER. According to the willingness-to-pay of Thailand, of approximately $3,861/QALY, the probability of IVIG being cost effective was 33 %. CONCLUSIONS The addition of IVIG to standard treatment in the treatment of childhood ITP with life-threatening bleeding is possibly a cost-effective intervention in Thailand. However, our findings were highly sensitive. Policy makers may consider our findings as part of the information for their decision making.
Cost-utility analysis of deferiprone for the treatment of beta-thalassaemia patients with chronic iron overload: a UK perspective
BACKGROUND Patients with beta-thalassaemia major experience chronic iron overload due to regular blood transfusions. Chronic iron overload can be treated using iron-chelating therapies such as desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) monotherapy, or DFO-DFP combination therapy. OBJECTIVES This study evaluated the relative cost effectiveness of these regimens over a 5-year timeframe from a UK National Health Service (NHS) perspective, including personal and social services. METHODS A Markov model was constructed to evaluate the cost effectiveness of the treatment regimens over 5years. Based on published randomized controlled trial evidence, it was assumed that all four treatment regimens had a comparable effect on serum ferritin concentration (SFC) and liver iron concentration (LIC), and that DFP was more effective for reducing cardiac morbidity and mortality. Published utility scores for route of administration were used, with subcutaneously administered DFO assumed to incur a greater quality of life (QoL) burden than the oral chelators DFP and DFX. Healthcare resource use, drug costs (2010/2011 costs), and utilities associated with adverse events were also considered, with the effect of varying all parameters assessed in sensitivity analysis. Incremental costs and quality-adjusted life-years (QALYs) were calculated for each treatment, with cost effectiveness expressed as incremental cost per QALY. Assumptions that DFP conferred no cardiac morbidity, mortality, or morbidity and mortality benefit were also explored in scenario analysis. RESULTS DFP was the dominant strategy in all scenarios modelled, providing greater QALY gains at a lower cost. Sensitivity analysis showed that DFP dominated all other treatments unless the QoL burden associated with the route of administration was greater for DFP than for DFO, which is unlikely to be the case. DFP had >99% likelihood of being cost effective against all comparators at a willingness-to-pay threshold of 20,000 per QALY. CONCLUSIONS In this analysis, DFP appeared to be the most cost-effective treatment available for managing chronic iron overload in beta-thalassaemia patients. Use of DFP in these patients could therefore result in substantial cost savings.
Cost-effectiveness of recombinant activated factor VII vs. plasma-derived activated prothrombin complex concentrate in the treatment of mild-to-moderate bleeding episodes in patients with severe haemophilia A and inhibitors in Spain
Several analyses have shown that recombinant activated factor VII (rFVIIa) is a cost-effective intervention compared with plasma-derived activated prothrombin complex concentrate (pd-aPCC) for the on-demand treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors. The aim of the study was to assess the cost-effectiveness of rFVIIa vs. pd-aPCC in the treatment of bleeding episodes in severe haemophilia A patients with inhibitors in Spain. A decision analytic model was designed to evaluate the costs and clinical outcomes of using rFVIIa or pd-aPCC to treat mild-to-moderate joint bleeds in children (<=14 years old) and adults with inhibitors. Data were obtained from a published meta-analysis and a panel of haemophilia experts. The analysis was conducted from the perspective of the Spanish National Healthcare System. One-way sensitivity analyses were performed to assess the impact of model assumptions on study results. In the Treur meta-analysis, rFVIIa resulted in cumulative joint bleed resolution of 88% and 95% after 24 and 36 h, respectively, compared with 62% and 76%, respectively, with pd-aPCC (Treur et al. Haemophilia 2009; 15: 420-36). Here, the mean cost per bleed was estimated at 8473 and 15 579 in children and adults treated with rFVIIa, vs. 8627 and 15 677 in children and adults treated with pd-aPCC. rFVIIa treatment was found to be the dominating option (cheaper and more effective). The one-way sensitivity analysis also confirmed that rFVIIa was less costly than pd-aPCC. The model suggests that rFVIIa is a cost-effective option compared with pd-aPCC for the treatment of mild-to-moderate bleeding episodes in a Spanish setting. 2013 John Wiley & Sons Ltd.
The clinical effectiveness and cost-effectiveness of primary stroke prevention in children with sickle cell disease: a systematic review and economic evaluation
Health Technology Assessment. 2012;16((43):):1-129.
BACKGROUND Sickle cell disease (SCD) is a recessive genetic blood disorder, caused by a mutation in the -globin gene. For children with SCD, the risk of stroke is estimated to be up to 250 times higher than in the general childhood population. Transcranial Doppler (TCD) ultrasonography is a non-invasive technique which measures local blood velocity in the proximal portions of large intracranial arteries. Screening with TCD ultrasonography identifies individuals with high cerebral blood velocity; these children are at the highest risk of stroke. A number of primary stroke prevention strategies are currently used in clinical practice in the UK including blood transfusion, treatment with hydroxycarbamide and bone marrow transplantation (BMT). No reviews have yet assessed the clinical effectiveness and cost effectiveness of primary stroke prevention strategies in children with SCD identified to be at high risk of stroke using TCD ultrasonography. OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of primary stroke prevention treatments for children with SCD who are identified (using TCD ultrasonography) to be at high risk of stroke. DATA SOURCES Electronic databases were searched from inception up to May 2011, including the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), EMBASE, the Health Technology Assessment (HTA) database, ISI Web of Science Proceedings, ISI Web of Science Citation Index, the NHS Economic Evaluation Database (NHS EED) and MEDLINE. REVIEW METHODS The assessment was conducted according to accepted procedures for conducting and reporting systematic reviews and economic evaluations. A de novo Markov model was developed to determine the cost-effectiveness of TCD ultrasonography and blood transfusion, where clinically appropriate, in patients with SCD. RESULTS Two randomised controlled trials met the inclusion criteria involving a study population of 209 participants. One compared blood transfusion with standard care for children who are identified as being at high risk of stroke using TCD ultrasonography. In this trial, one patient in the transfusion group had a stroke (1/63) compared with 11 children in the standard care group (11/67). The other trial assessed the impact of halting chronic transfusion in patients with SCD. Sixteen patients in the transfusion-halted group had an event (16/41) (two patients experienced stroke and 14 reverted to abnormal TCD velocity); there were no events in the continued-transfusion group (0/38). No meta-analyses of these trials were undertaken. No relevant economic evaluations were identified for inclusion in the review. The de novo modelling suggests that blood transfusions plus TCD scans (compared with just TCD scans) for patients with SCD at high risk of stroke, aged >= 2 years, may be good value for money. The intervention has an incremental cost-effectiveness ratio of 24,075 per quality-adjusted life-year gained, and helps avoid 68 strokes over the lifetime of a population of 1000 patients. The intervention costs an additional 13,751 per patient and generates 0.6 extra years of life in full health per patient. The data available for the economic analysis are limited. Sensitivity analyses and validation against existing data and expert opinion provide some reassurance that the conclusion of the model is reliable but further research is required to validate these findings. LIMITATIONS The main limitations relate to the availability of published clinical data; no completed randomised controlled trials were identified which evaluated the efficacy of either BMT or hydroxycarbamide for primary stroke prevention. Both the clinical and cost data available for use in the economic analysis are limited. Sensitivity analyses and validation against existing data and expert opinion provide some reassurance that the conclusions of the model are reliable, but further research is required to validate these findings. CONCLUSIONS The use of TC