-
1.
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.
-
2.
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.
-
3.
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.
-
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
-
-
-
Free full text
-
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.
-
5.
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.
-
6.
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.
-
7.
Modern treatments of haemophilia: review of cost-effectiveness analyses and future directions
Cortesi PA, D'Angiolella LS, Lafranconi A, Micale M, Cesana G, Mantovani LG
Pharmacoeconomics. 2017;36((3):):263-284
Abstract
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.
-
8.
Making economic evaluations more helpful for treatment choices in haemophilia
Drummond M, Houwing N, Slothuus U, Giangrande P
Haemophilia : the Official Journal of the World Federation of Hemophilia. 2017;23((2):):e58-e66
Abstract
AIM: Poorly conducted economic evaluations have the potential to mislead both clinicians, leading to inappropriate treatment choices, and payers who must decide on the reimbursement of treatment costs. This paper reviews the methods used in economic evaluations in haemophilia and proposes standards for conducting and reporting such evaluations in the future. METHODS A systematic review of economic evaluations in haemophilia published since 2008 was conducted. The reporting and methods of the studies were assessed using the recently published Consolidated Health Economic Evaluation Reporting Guidelines (CHEERS) checklist. The key methodological deficiencies in the studies were recorded. RESULTS Twenty-one studies met the inclusion criteria, classified as follows: prophylaxis vs. treatment on-demand (five studies); use of bypassing therapy (six); immune tolerance induction (four); and other topics (six). In general, the quality of reporting was good. However, it was poorest for the CHEERS item of patient heterogeneity, with most studies lacking discussion of heterogeneity in the patient population. The main recurring methodological deficiencies were the evaluation of single episodes of care rather than entire treatment strategies; inadequate control for confounders when comparing treatment options; the frequent use of expert opinion to determine drug doses and treatment patterns; lack of consideration of patient heterogeneity; failure to identify patient subgroups; and the inadequate exploration of uncertainty in estimates. CONCLUSIONS A set of 12 standards for future reporting and conduct of economic evaluations within haemophilia is proposed, with the objective of making such evaluations more relevant and reliable for those making treatment and reimbursement decisions in the future.
-
9.
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.
-
10.
Assessing options for treating haemophilia with inhibitors
Farrugia A, Hermans C, Franchini M
Haemophilia. 2015;21((3)):307-9.