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Health care costs and resource use of managing hemophilia A: A targeted literature review
Chen, Y., Cheng, S. J., Thornhill, T., Solari, P., Sullivan, S. D.
Journal of managed care & specialty pharmacy. 2023;29(6):647-658
Abstract
BACKGROUND Hemophilia A (HA) is a rare, inherited, serious bleeding disorder characterized by a deficiency of blood clotting factor VIII (FVIII). HA is associated with considerable economic burden. OBJECTIVE To identify, review, and summarize published studies on the health care resource use and costs of managing HA in the United States using a targeted literature review. METHODS A comprehensive and targeted literature search was conducted in Embase, MEDLINE, and Cochrane Database of Systematic Reviews covering the period 2010 to 2022. We supplemented the search by searching gray literature (relevant abstracts, posters, and presentations of relevant scientific conferences from the past 6 years [2016 to 2022], reference lists, the Institute for Clinical and Economic Review reports, and other sources). Eligibility criteria were developed based on the population, interventions, comparators, and outcomes framework. For comparability, costs were adjusted to 2021 US dollars. RESULTS A total of 40 publications, including 17 full-text papers, 21 abstracts, and 2 Institute for Clinical and Economic Review reports, met eligibility criteria. Total annual health care costs per patient ranged from $213,874 to $869,940 and are mainly driven by the cost and intensity of prophylaxis with FVIII replacement concentrates, bypassing agents, and, most recently, emicizumab. Generally, we observed substantial heterogeneity in estimated treatment costs for HA, which varied depending on HA severity, treatment type and intensity, age, weight, and inhibitor status. Patients with inhibitors incurred much higher costs, but annual FVIII treatment costs are increasing over time among a subset of adult patients without inhibitors. Only 2 studies reported indirect costs; these were $13,220 and $27,978 annually among patients without and with inhibitors, respectively. Parents of children with HA spent $8,252 on non-mental health services and $258 on mental health services annually. CONCLUSIONS The annual health care costs of managing HA are substantial and vary widely, depending on the study population definitions and intensity of prophylaxis. Total health care costs are dominated by the cost of prophylaxis. Indirect costs are also important. More robust studies in various settings, subpopulations, and assessing the impact of emerging therapies are required to fully elucidate the changing societal and economic impact, particularly regarding indirect costs and productivity loss for individuals living with HA. DISCLOSURES Drs Solari and Thornhill are employees of Spark Therapeutics and Roche Group Shareholders. Ms Chen and Drs Cheng and Sullivan are employees of Curta, Inc. Spark Therapeutics paid Curta, Inc., to conduct the literature search. This study was funded by Spark Therapeutics. Spark Therapeutics was involved in the study design, collection, analysis and interpretation of data, article review, and the decision to submit the report for publication. Medical writing support was provided by Ashfield MedComms, an Inizio company.
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Medical and Non-medical Costs of Sickle Cell Disease and Treatments from a US Perspective: A Systematic Review and Landscape Analysis
Baldwin Z, Jiao B, Basu A, Roth J, Bender MA, Elsisi Z, Johnson KM, Cousin E, Ramsey SD, Devine B
PharmacoEconomics - open. 2022
Abstract
BACKGROUND Sickle cell disease (SCD) is a complex genetic disorder that manifests in infancy and progresses throughout life in the form of acute and chronic complications. As the upfront costs of potentially curative, genetic therapies will likely be high, an assessment and comprehensive characterization of the medical and non-medical cost burden will inform future decision making. OBJECTIVE We sought to systematically summarize the existing literature surrounding SCD medical and non-medical costs. METHODS We searched MEDLINE and EMBASE (2008-2020) and identified US-based studies that detailed medical or non-medical costs. Eligible studies provided empirical estimates about any aspect of cost or SCD individuals of all ages and their caregivers. Study quality was assessed using the Newcastle-Ottawa Scale, and costs were adjusted to 2019 US$. RESULTS Search queries returned 479 studies, with 342 from medical burden searches and 137 from non-medical burden searches, respectively. Herein, we report the results of the 40 studies that contained relevant cost information: 39 detailed medical costs and 1 detailed non-medical costs. Costs were higher for SCD patients when compared with non-SCD individuals (cost difference range: $6636-$63,436 annually). The highest medical cost component for SCD patients was inpatient ($11,978-$59,851 annually), followed by outpatient and then pharmacy. No studies characterized the cost burden throughout the lifetime disease trajectory of an SCD individual, and no studies captured caregiver or productivity costs. CONCLUSION Our results reveal an incomplete characterization of medical and non-medical costs within SCD. A deeper understanding of the medical and non-medical cost burden requires completion of additional studies that capture the burden across the patient's lifetime, in addition to expression of the impact of existing and emergent health technologies on disease trajectory.
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The Use of Cost-Effectiveness Analysis in Sickle Cell Disease: A Critical Review of the Literature
Jiao B, Basu A, Roth J, Bender M, Rovira I, Clemons T, Quach D, Ramsey S, Devine B
PharmacoEconomics. 2021
Abstract
Novel interventions for sickle cell disease (SCD) bring hope to patients, yet concern about the associated economic costs exists. Cost-effectiveness analysis (CEA) uses standardized methods, with robust underpinnings in health economics, to estimate the value of these interventions compared with usual care. However, because of the complexity and lifetime trajectory of SCD, CEAs are challenging to conduct. The objectives of this rapid review were to summarize the main characteristics, components, and results of published CEAs of existing interventions for SCD, identify research gaps, and provide directions for future analyses. We identified records through searches of bibliographic databases, from reference lists of relevant review articles, and through consultation with experts. A total of 13 CEAs met our inclusion criteria and were qualitatively synthesized. These evaluated blood transfusions (n = 2), hematopoietic stem cell transplantation (n = 1), pharmaceuticals (n = 2), hypothetical cell or genetic therapy (n = 1), screening programs (n = 4), and interventions for SCD treatment complications (n = 3). A limited number of potential SCD and treatment complications were evaluated. No study adopted a societal perspective in the base case, six studies examined lifetime cost-effectiveness, seven studies employed a Markov or discrete-event simulation model, and eight studies used an outcome metric that captured both quality and length of life. To better compare the value of emerging and current therapies, future CEAs should adopt a societal perspective incorporating both medical and nonmedical costs, comprehensively model SCD complexity using robust health economic simulation models over the patient's entire lifespan, and capture the intervention's effect on both survival and quality of life.
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4.
Patient-Reported Outcomes and Economic Burden of Adults with Sickle Cell Disease in the United States: A Systematic Review
Lee S, Vania DK, Bhor M, Revicki D, Abogunrin S, Sarri G
Int J Gen Med. 2020;13:361-377
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Editor's Choice
Abstract
PURPOSE To systematically estimate the patient-reported outcomes (PROs) and economic burden of sickle cell disease (SCD) among adults in the United States (US). PATIENTS AND METHODS Two systematic literature reviews (SLRs), one each for the PROs and economic topics, were performed using MEDLINE and Embase to identify observational studies of adults with SCD. Included studies were published between 2007 and 2018 and evaluated health-related quality of life (HRQL), function, healthcare resource utilization (HCRU), or costs. Given the high degree of clinical and methodological heterogeneity, findings were summarized qualitatively. RESULTS The SLRs identified 7 studies evaluating the PROs and 15 studies evaluating the economic burden meeting the pre-specified selection criteria. The PRO evidence showed the prevalence of depression and anxiety to be 21-33% and 7-36%, respectively, in adults with SCD. The mean SF-36 physical summary scores ranged from 33.6 to 59.0 and from 46.3 to 61.5 for the mental summary scores. Overall HRQL for adults with SCD was poor and significantly worse in those with opioid use. Adult SCD patients were found to have varying rates of emergency department (ED) utilization (0.3-3.5 annual ED visits), hospitalizations (0.5-27.9 per patient per year), and/or readmission (12-41%). Key factors associated with significant HCRU were age, dental infection, and SCD-related complications. SCD specialized care settings and SCD intensive management strategy were reported to significantly decrease the number of hospitalizations. CONCLUSION This systematic evidence synthesis found that disease burden measured by PROs and economic burden of SCD on adults in the US are substantial despite the availability of approved SCD treatments during 2007-2018. The use of hydroxyurea, optimal management with opioids, and employing intensive treatment strategies may help decrease the overall burden to patients and healthcare systems. Published data on costs associated with SCD are limited and highlight the need for more economic studies to characterize the full burden of the disease.
PICO Summary
Population
Adults with sickle cell disease (SCD) in the United States (22 studies).
Intervention
Two systematic literature reviews to estimate the patient-reported outcomes and economic burden of SCD.
Comparison
Outcome
The prevalence of depression and anxiety was 21-33% and 7-36%, respectively. Overall health-related quality of life for adults with SCD was poor and significantly worse in those with opioid use. Adult SCD patients were found to have varying rates of emergency department (ED) utilization (0.3-3.5 annual ED visits), hospitalizations (0.5-27.9 per patient per year), and/or readmission (12-41%). Key factors associated with significant healthcare resource utilization were age, dental infection, and SCD-related complications. SCD specialized care settings and SCD intensive management strategy were reported to significantly decrease the number of hospitalizations.
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Cost-utility of new film-coated tablet formulation of deferasirox vs deferoxamine among major beta-thalassemia patients in Iran
Saiyarsarai P, Khorasani E, Photogeraphy H, Ghaffari Darab M, Seyedifar M
Medicine (Baltimore). 2020;99(28):e20949
Abstract
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.
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Avatrombopag and lusutrombopag for thrombocytopenia in people with chronic liver disease needing an elective procedure: a systematic review and cost-effectiveness analysis
Armstrong N, Büyükkaramikli N, Penton H, Riemsma R, Wetzelaer P, Huertas Carrera V, Swift S, Drachen T, Raatz H, Ryder S, et al
Health technology assessment (Winchester, England). 2020;24(51):1-220
Abstract
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.
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Continuous prophylaxis with recombinant factor IX Fc fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption
Iorio A, Krishnan S, Myren KJ, Lethagen S, McCormick N, Yermakov S, Karner P
Journal of Medical Economics. 2016;:1-30
Abstract
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.
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Cost-utility analysis of deferiprone for the treatment of beta-thalassaemia patients with chronic iron overload: a UK perspective
Bentley A, Gillard S, Spino M, Connelly J, Tricta F
Pharmacoeconomics. 2013;31((9):):807-22.
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Abstract
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.
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The clinical effectiveness and cost-effectiveness of primary stroke prevention in children with sickle cell disease: a systematic review and economic evaluation
Cherry MG, Greenhalgh J, Osipenko L, Venkatachalam M, Boland A, Dundar Y, Marsh K, Dickson R, Rees DC
Health Technology Assessment. 2012;16((43):):1-129.
Abstract
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
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Systematic literature review of economics analysis on treatment of mild-to-moderate bleeds with aPCC versus rFVIIa
Hay JW, Zhou ZY
Journal of Medical Economics. 2011;14((4):):516-25.
Abstract
Objective: Two bypassing agents, activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa (rFVIIa), have shown similar efficacy and safety in the treatment of bleeding episodes in patients with hemophilia and inhibitors as demonstrated through the only two head-to-head clinical trials. Given the economic burden of bypassing treatment, it is crucial to have a valid estimate of cost effectiveness of alternative treatments. The aims of this study were to conduct a systematic review of published pharmacoeconomic literature on the cost-effectiveness of aPCC versus rFVIIa to treat mild-to-moderate bleeds in patients with hemophilia and inhibitors, with a focus on the model assumptions and their impact on results. Methods: An English language search was conducted for original economic studies comparing aPCC and rFVIIa published between 1995 and July 2010. Detailed information on sponsorship, study design, assumptions and their impact on results was collected for each study. Results: A total of 11 economic studies were included in the review. Nine studies assessed cost per bleeding episode (eight cost-minimization analysis (CMA) and one cost-effectiveness analysis (CEA)). Two studies were from longitudinal perspective. Studies on cost per bleeding episode were evaluated and systematically compared. All studies were from a third-party payer perspective. Most analyses, except one study, used a similar decision-tree model. The assumptions for all CMA studies were obtained from non-comparable single-armed trials or observational data. All studies were sponsored by the two competing manufacturers of rFVIIa (seven studies) and aPCC (two studies). The crucial parameter assumptions on treatment efficacy and dosing drove their reported findings. Eight of these nine studies favored their sponsor's product. Conclusion: With one exception, published economic studies tend to favor their sponsor's product primarily by assuming a higher efficacy and lower dosing for the sponsored agent, even though the two existing head-to-head clinical studies do not support superior efficacy for either product.