Clinical and economic evaluation of exenatide for formulary decisions

Summary

This study was designed to provide an assessment for healthcare organisations to make formulary decisions on Byetta®* (exenatide).

The drug was shown to be efficacious in treating type 2 diabetes mellitus when used as adjunctive therapy with other oral antidiabetic drugs. The Centre for Outcomes Research Diabetes Model analyses suggested that the drug treatment fails to achieve a threshold level of the incremental cost-effectiveness ratio until 50 years have passed. Sensitivity analyses suggested that maintaining an appropriate haemoglobin A_1c level is essential for the treatment to be cost effective. A budget impact analysis with a hypothetical plan produced a 2.1 cent base case compliance-adjusted, per member per month cost in Year 1. One-way sensitivity analyses indicated that the two major determinants are compliance and the percentage of individuals expected to be on exenatide.

The author's conclude that further research is needed to include exenatide for the formulary decision.     

Addressing shortfalls in TIA care in the UK: an economic perspective

Abstract

Objective: To estimate the clinical outcomes and costs associated with reconfiguring the management of TIA in the UK to offer patients rapid access to outpatient clinics for specialist assessment and treatment.

Methods: An economic deterministic model was run comparing two pathways – one arm representing current clinical care based on national guidelines and clinical practice and patient referral to a weekly outpatient clinic, and a revised care pathway replicating phase 2 of the EXPRESS study with patient referral to a daily outpatient clinic. The outcomes of the model were measured in terms of recurrent strokes avoided and net budget impact to secondary care.

Results: Reconfiguring TIA care pathways in the UK could result in the avoidance of 8,164 recurrent stroke events. The model predicts savings of £25,573,279 for the UK healthcare system over 12 months. Annual net savings are predicted in England (£24,916,011), Scotland (£80,554) and Northern Ireland (£1,041,817). In Wales, increased costs of £450,435 are estimated.

Limitations: Using the data published from the EXPRESS study, it is not possible to model a stepwise approach to implementing the revised TIA care pathway. It is therefore assumed that it would be possible to implement the revised TIA care pathway as detailed in the EXPRESS study across the UK and achieve the reduction in recurrent stroke risk that was reported.

Conclusions: The model suggests that the reconfiguration of TIA care pathways in the UK to offer rapid access to treatment and assessment could prevent TIA-related future stroke events and potentially result in cost savings to the healthcare system.     

Budget impact model in moderate-to-severe psoriasis vulgaris assessing effects of calcipotriene and betamethasone dipropionate foam on per-patient standard of care costs

Aims: To develop a budget impact model (BIM) for estimating the financial impact of formulary adoption and uptake of calcipotriene and betamethasone dipropionate (C/BD) foam (0.005%/0.064%) on the costs of biologics for treating moderate-to-severe psoriasis vulgaris in a hypothetical US healthcare plan with 1 million members.

Methods: This BIM incorporated epidemiologic data, market uptake assumptions, and drug utilization costs, simulating the treatment mix for patients who are candidates for biologics before (Scenario #1) and after (Scenario #2) the introduction of C/BD foam. Predicted outcomes were expressed in terms of the annual cost of treatment (COT) and the COT per member per month (PMPM).

Results: At year 1, C/BD foam had the lowest per-patient cost ($9,913) necessary to achieve a Psoriasis Area and Severity Index (PASI)-75 response compared with etanercept ($73,773), adalimumab ($92,871), infliximab ($34,048), ustekinumab ($83,975), secukinumab ($113,858), apremilast ($47,960), and ixekizumab ($62,707). Following addition of C/BD foam to the formulary, the annual COT for moderate-to-severe psoriasis would decrease by $36,112,572 (17.91%, from $201,621,219 to $165,508,647). The COT PMPM is expected to decrease by $3.00 (17.86%, from $16.80 to $13.80).

Limitations: Drug costs were based on Medi-Span reference pricing (January 21, 2016); differences in treatment costs for drug administration, laboratory monitoring, or adverse events were not accounted for. Potentially confounding were the definition of “moderate-to-severe” and the heterogeneous efficacy data. The per-patient cost for PASI-75 response at year 1 was estimated from short-term efficacy data for C/BD foam and apremilast only.

Conclusions: The introduction of C/BD foam is expected to decrease the annual COT for moderate-to-severe psoriasis treatable with biologics by $36,112,572 for a hypothetical US healthcare plan with 1 million plan members, and to lower the COT PMPM by $3.00.     

Clinical and economic impact of rivaroxaban on the burden of atrial fibrillation: The case study of Japan

Objectives: Atrial fibrillation (AF) affects an estimated 1.5 million individuals in Japan, increasing their stroke risk and imposing considerable costs on the Japanese healthcare system. To reduce stroke incidence, guidelines recommend using anticoagulants in moderate-to-high risk non-valvular AF (NVAF) patients; however, many patients receive no treatment, aspirin only, or remain poorly-controlled on vitamin K antagonists (VKAs) due to high VKA discontinuation rates and non-adherence to guidelines. A prevalence-based Markov model was developed to estimate the clinical and budgetary impact of treating these patients with Xarelto^TM (rivaroxaban, Bayer AG) in Japan.

Methods: Population, baseline risk of events, and associated management costs were estimated using data from Japanese publications where available. Treatment efficacy and safety were derived from published data and the J-ROCKET AF trial. Drug and physician visit costs were based on data from the Ministry of Health, Labor, and Welfare, the J-ROCKET AF trial, and Japanese clinical guidelines.

Results: This model demonstrates that increased use of rivaroxaban in inadequately-managed NVAF patients could avoid 456 081 non-fatal ischemic strokes (IS) and 76 975 cardiovascular deaths over 10 years in Japan. This clinical benefit offsets the increased incidence of myocardial infarctions and anticoagulant-related bleeding. Decreased event costs could lead to a ¥188.4 billion decrease in net spending over the analysis time horizon.

Conclusions: Introducing rivaroxaban may decrease the burden of NVAF in Japanese society. From a clinical perspective, the reduction in IS and embolic events outweighs the increased risk of anticoagulant-related bleeding; from an economic perspective, reduced event costs offset drug and physician visit costs, resulting in cost savings.     

Ulipristal acetate for pre-operative treatment of moderate-to-severe uterine fibroids in women of reproductive age in The Netherlands: cost minimization analysis and budget impact analysis

Objective: Ulipristal acetate has been found to be non-inferior to other pre-operative treatments of uterine fibroids, particularly leuprolide. The objective of this study was to assess the pharmacoeconomic profile of ulipristal acetate compared to leuprolide for the pre-operative treatment of moderate-to-severe uterine fibroids in women of reproductive age in The Netherlands. The analysis was performed and applied within the framework of the ulipristal acetate submission for reimbursement in 2012.

Methods: A decision model was developed to compare the total costs of ulipristal acetate compared to leuprolide, the standard care in The Netherlands. The target population of this study corresponded to the type of patients included in the PEARL II clinical trial; i.e. women of reproductive age requiring pre-operative treatment for uterine fibroids. Sensitivity analysis was implemented to assess uncertainties. Data regarding costs, effects, and other input parameters were obtained from relevant published literatures, the Dutch Healthcare Insurance Board, and expert opinion obtained by means of a panel of experts from several medical centers in The Netherlands.

Results: In The Netherlands, the total costs of ulipristal acetate and leuprolide were estimated at €4,216,027 and €4,218,095, respectively. The annual savings of ulipristal acetate were, therefore, estimated at €2,068. The major driver of this cost difference was the cost of administration for leuprolide. Sensitivity analyses showed that ulipristal acetate mostly remained cost-saving over a range of assumptions. The budget impact analysis indicated that the introduction of ulipristal acetate was estimated to result in cost savings in the first 3 years following the introduction. The results of this study were used in the decision on reimbursement of ulipristal acetate according to the Dutch Reference Pricing system in 2012.

Conclusion: Ulipristal acetate was cost saving compared to leuprolide and has the potential to provide substantial savings on the healthcare budget in The Netherlands.     

On the economic impacts of COVID-19: A text mining literature analysis

The COVID-19 outbreak has affected everyday lives worldwide. As governments started to implement confinement and business closure measures, the economic impact was felt by entire societies immediately. The urgency of such a theme has led researchers to study the phenomenon. Accordingly, the purpose of this research is to provide the state of the art on relevant dimensions and hot topics of research to understand the economic impacts of COVID-19. In this survey, we conduct a text mining analysis of 301 articles published during 2020 which analyzed such economic impacts. By defining a set of relevant dimensions grounded on existing literature, we were able to extract a set of coherent topics that aggregate the collected articles, characterized by the predominance of a few sets of dimensions. We found that the impact on “financial markets” was widely studied, especially in relation to Asia. Next, we found a more diverse range of themes analyzed in Europe, from “government measures” to “macroeconomic variables.” We also discovered that America has not received the same degree of attention, and “institutions,” “Africa,” or “other pandemics” were studied less. We anticipate that future research will proliferate focusing on several themes, from environmental issues to the effectiveness of government measures.     

Correlates of economic growth in developing countries: a panel cointegration approach

The inflow of foreign direct investment (FDI) has been found to play a crucial role in the economic growth of receiving countries. Using panel cointegration techniques, this perception was found to be mitigated by an empirical approach that yields different results from previous studies. While the growth in real FDI has an influence on real GDP growth across developing countries in the short-run, year-to-year periods, it does not explain real GDP in the long-run. Rather, it appears to be the economic factors internal to a country that have the most influence on real GDP over time: human capital (measured by literacy rates), export trade, and monetary and fiscal policy.     

Costs of in-house genomic profiling and implications for economic evaluation: a case example of non-small cell lung cancer (NSCLC)

Abstract

Objectives

Genomic profiling in oncology is vital for determining eligible patients for mutation-specific targeted therapies. Use of commercial genomic testing has the potential to improve patient outcomes. Economic evaluations of in-house genomic profiling typically only include material costs while external commercial services include many other factors. Using non-small cell lung cancer (NSCLC) as an example, this study sought to characterize the unique challenges of costing testing services and their impact on results of economic evaluations.     

How complicated skin and soft tissue infections are treated in Italy: economic evaluation of inpatient intravenous antibiotic treatment in seven hospitals

Abstract

Objectives: Complicated skin and soft tissue infections (cSSTIs) are a common cause of morbidity at hospital level. This study aimed to evaluate the costs and outcomes of inpatient intravenous antibiotic therapy for the treatment of cSSTI in seven Italian hospitals.

Methods: A total of 307 patients were enrolled in a retrospective, multicentre, incidence-based, observational study. The target population consisted of hospitalised patients eligible to receive intravenous antibiotic therapy for cSSTI. Direct hospital costs were measured through a microcosting approach.

Results: Failure of initial antibiotic therapy occurred in 23% of patients. Average antibiotic treatment lasted 12.2 days; the average full cost of admission totalled €5,530. If the initial antibiotic regimen fails to eradicate the infectious organism, the length of stay extends for 7 days and costs increase by €2,850 per patient. Nevertheless, when taking into account the lower intensity of care during the last days of treatment, savings reduce costs to €671 per patient. These could be increased by €74 for each hospital day avoided because of faster antibiotic action.

Conclusions: Efforts should be made to minimise the risk of selecting wrong antibiotics and to identify the quickest antibiotic in eradicating the infection.     

Assessing the economic impact of entrepreneurship on a regional economy using social accounting matrices: the case of Andalusia

This article analyses the impact that entrepreneurial activity has, from the economic point of view, on a regional economy (Andalusia), based on a Social Accounting Matrix linear model. Moreover, to measure entrepreneurship at regional level, it is defined what can be considered an entrepreneurial initiative company from a quantitative point of view. The results obtained, in terms of Production, GDP and job creation, show how entrepreneurship, in the case of Andalusia, contributes to the sustainability of the economy, its growth and, above all, the reduction of unemployment in the short term.     

Clinical and economic impact of mirabegron compared with antimuscarinics for the treatment of overactive bladder in Canada

Background: The β₃-adrenoceptor agonist, mirabegron, and antimuscarinic agents provide similar efficacy for the treatment of overactive bladder (OAB), but mirabegron appears to be associated with better persistence, perhaps due to an absence of anticholinergic side-effects. This study estimated the expected costs associated with the management of OAB in Canada from a societal perspective by utilizing real-world evidence.

Methods: An economic model with monthly cycles and a 1-year time horizon was developed to depict a treatment pathway for a hypothetical cohort of 100 patients with OAB. At model entry, patients receive mirabegron or an antimuscarinic. Patients who do not persist may switch treatment, undergo a minimally invasive procedure, or remain symptomatic (uncontrolled). The model includes direct costs (e.g. physician visits) and indirect costs (e.g. lost productivity). A one-way univariate sensitivity analysis assessed a ±20% variation in each of the key model inputs.

Results: At 1 year, a greater proportion of patients persisted on treatment with mirabegron compared with antimuscarinics (33% vs 15–23%), and a smaller proportion switched treatment (17% vs 20–22%). The number of healthcare visits (292 vs 299–304), pads used (74,098 vs 77,878–81,669), and work hours lost (4,497 vs 5,372–6,249) were all lower for mirabegron vs antimuscarinics. The estimated total annual cost of treatment per patient with mirabegron was $2,127.46 Canadian dollars (CAD) ($5.82 CAD/day) compared with $2,150.20–$2,496.69 CAD ($5.89–$6.84 CAD/day) for antimuscarinics. The one-way sensitivity analysis indicated the results are robust.

Conclusions: Improved persistence observed in routine clinical practice with mirabegron appears to translate into benefits of reduced healthcare resource use, and lower direct and indirect costs of treatment compared with antimuscarinics. Overall, these data suggest that mirabegron may offer clinical and economic benefits for the management of patients with OAB in Canada.     

疫苗药物经济学评价中有关成本和效果的测算方法探讨

与一般药物相比,疫苗具有外部性、保护率和作用时间不确定等特性,因此疫苗的经济学评价应当有其特殊性.本文回顾了近十几年世界有关疫苗经济学评价的研究报道,综合概括了疫苗经济学评价方法的最新进展.本文讨论的主要内容包括间接成本法、边际成本法、选择合适流行病学模型测量健康结果、成本和效果的贴现等.     

Economic evaluation of ramipril in the treatment of patients at high risk for cardiovascular events

SUMMARY

Cardiovascular disease (CVD) is a primary cause of death and morbidity in the United Kingdom (UK). Recently, the Heart Outcomes Prevention Evaluation (HOPE) trial demonstrated significant survival and morbidity benefits associated with ramipril use in the treatment of patients at high risk for cardiovascular events. The purpose of this paper is to assess whether and to what extent, these clinical benefits might translate into economic benefits from the perspective of the UK NHS. Using trial data and a decision-analytic model, our base case estimate of cost-effectiveness is £4,406 per life-year saved (undiscounted) and £5,544 per life-year saved (discounted). The extreme values of our sensitivity analyses ranged from a best case of £2,814 per life-year saved (undiscounted) to a worst case of £10,291 per life-year saved (undiscounted). Our base case estimate of cost-effectiveness suggests that treating patients at high risk for CVD events with ramipril is likely to be a good investment of NHS resources.     

Budget impact analysis of secukinumab versus adalimumab in the treatment of ankylosing spondylitis

Background: Biologic treatments have enhanced the treatment outcomes of patients with active ankylosing spondylitis (AS). Until recently, TNF-alpha-inhibitors have been the only biologics approved for the treatment of active AS. The objective of this study was to assess the potential financial impact of the first non-TNF-alpha biologic secukinumab (fully human IL-17A-inhibitor) vs adalimumab (TNF-alpha-inhibitor) in the treatment of AS in Finland.

Materials and methods: In this model-based budget impact analysis, patients were treated either with secukinumab (150?mg) or adalimumab (40?mg). The number of patients and market share of different biologics were based on national reimbursement registry data. Adalimumab was the most commonly used biologic treatment for AS, and in the base case analysis all adalimumab patients are assumed to switch to secukinumab. Response rates were based on a matching-adjusted indirect comparison between secukinumab and adalimumab. Patients not achieving response were switched to another biologic treatment.

Results: Treating AS patients with secukinumab instead of adalimumab leads to potential savings of 18.2 million euros within a 5-year time period. The total costs within the follow-up time were 59.5 million euros and 77.7 million euros with and without secukinumab, respectively. According to sensitivity analyses, a higher adoption rate of secukinumab corresponds to higher potential savings.

Conclusions: Secukinumab is a cost-saving treatment option compared with adalimumab in the treatment of AS in Finland. More patients could be treated with a biologic by allocating resources more efficiently.     

Measuring the total impact of demographic and behavioural factors on the risk of obesity accounting for the depression status: a structural model approach using new BMI

Building upon previous studies that highlight considerable overlap in the influential factors of both obesity and depression, we employ a structural model to investigate the direct and indirect impacts of behavioural and demographic factors on obesity. We use new body mass index (BMI) to calculate the obesity status and find a significant relationship between an individual’s depression status and his/her obesity status. The results and simulations imply that demographic and behavioural factors can significantly influence the obesity status both directly and indirectly through their impact on depression. Therefore, this study suggests that models which do not account for these various pathways of influence are most likely misrepresenting the impact of these factors on obesity.     

Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding. This study assessed the long-term clinical and economic benefits of extending treatment with apixaban when clinical equipoise exists compared to standard of care with enoxaparin/warfarin and other novel oral anti-coagulants (NOACs) for the treatment and prevention of recurrent VTE in Canada.

Methods A Markov model was developed to follow patients with VTE over their lifetimes. Efficacy and safety for apixaban and enoxaparin/warfarin were based on AMPLIFY and AMPLIFY-EXT, while relative efficacy to other NOACs was synthesized by network meta-analysis (NMA). Dosages for NOACs and enoxaparin/warfarin were based on their respective trials and were given up to 18 months and up to 6 months, followed by no treatment, respectively. Patient quality adjusted life years (QALYs) were based on published studies, and costs for resource utilization were from a Ministry of Health perspective, expressed as 2014 CAD ($).

Results Extended treatment with apixaban compared to enoxaparin/warfarin resulted in fewer recurrent VTEs, VTE-related deaths, and bleeding events, but at slightly increased cost. The incremental cost-effectiveness ratio was $4828 per QALY gained. Compared to other NOACs, apixaban had the fewest bleeding events, similar recurrent VTE events, and the lowest overall cost, which was driven by the strong bleeding profile. In scenario analyses of acute and lifetime treatments, apixaban was cost-effective against all strategies.

Conclusions Extended treatment with apixaban can offer substantial clinical benefits and is a cost-effective alternative to enoxaparin/warfarin and other NOACs.     

Economic evaluation of tocilizumab combination in the treatment of moderate-to-severe rheumatoid arthritis in Italy

Abstract

Objective:

This study was designed to evaluate the cost utility of tocilizumab in rheumatoid arthritis (RA) patients, with inadequate responses to traditional disease-modifying anti-rheumatic drugs (tDMARDs) from a payer’s perspective in Italy.

Methods:

An individual patient simulation model was used to project lifetime medical costs (payer’s perspective) and quality-adjusted life-years (QALYs). Treatment sequences starting with tocilizumab or the most commonly prescribed biologics (etanercept, adalimumab, or infliximab) were compared. The addition of tocilizumab to standard of care, without the replacement of anti-tumor necrosis factor (TNF)-α treatments, was also evaluated. Patient characteristics, treatment efficacy, and quality-of-life data were based on three phase 3 tocilizumab clinical trials (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders [OPTION], Tocilizumab in cOmbination With traditional DMARD therapy [TOWARD], and TociLIzumab Safety and THE Prevention of Structural Joint Damage [LITHE]). Mixed-treatment comparison was used to estimate response probabilities. Resource utilization, treatment acquisition, administration, and monitoring costs were estimated using Italian secondary sources. Uncertainty in model parameters was evaluated by probabilistic sensitivity analysis.

Results:

Replacement of anti-TNF-α treatments with tocilizumab reduced total costs over a patient’s lifetime (base-case analysis: tocilizumab sequence, €141,100 vs standard of care sequence, €143,500). Patients receiving tocilizumab realized more QALYs than patients receiving standard of care (9.8881 vs 9.3502 QALYs). Therefore, according to the base-case analysis, the tocilizumab sequence dominated the standard of care. In a sensitivity analysis, the model base-case result was robust to input changes. When tocilizumab was added to standard of care, without replacing anti-TNF-α treatments, the incremental cost-effectiveness ratio was €17,100 per QALY.

Conclusion:

The analysis demonstrates that, in Italy, replacing another biologic DMARD with tocilizumab or adding tocilizumab to the current standard of care is a cost-effective strategy in the treatment of RA patients with inadequate responses to tDMARDs.     

转轨进程中国有企业改革与财政约束关系研究——补贴还是课税

财政约束硬化是国有企业转换机制的重要前提条件,但是经济转轨国家的实践表明,财政约束硬化在大部分转轨国家都没有做到。尽管产权学论者和外部环境论者都给出了自己的解释,但都不说明政府为什么对硬化国有企业财政约束“知而不能为之”的原因。文章通过建立了政府、国有企业和民营企业三者间动态博弈模型研究发现,政府对国有企业预算约束是“软”或“硬”不能简单地一概而论,财政对国有企业的预算是“硬”还是“软”内生于经济体制改革的进程和改革的方式选择,以及国有企业本身的竞争能力。因此,转轨国家应该考虑国有企业自身竞争能力情况,在改革不同阶段采取灵活的财政手段,保证转轨过程中全社会福利水平的提高,从而顺利推进国有企业改革的进行。     

Modeling the fiscal costs and benefits of alternative treatment strategies in the United Kingdom for chronic hepatitis C

Background: Hepatitis C (HCV) infection causes substantial direct health costs, but also impacts broader societal and governmental costs, such as tax revenue and social protection benefits. This study investigated the broader fiscal costs and benefits of curative interventions for chronic Hepatitis C (CHC) that allow individuals to avoid long-term HCV attributed health conditions.

Methods: A prospective cohort model, assessing the long-term fiscal consequences of policy decisions, was developed for HCV infected individuals, following the generational accounting analytic framework that combines age-specific lifetime gross taxes paid and governmental transfers received (i.e. healthcare and social support costs). The analysis assessed the burden of a theoretical cohort of untreated HCV infected patients with the alternative of treating these patients with a highly efficacious curative intervention (ledipasvir/sofosbuvir [LDV/SOF]). It also compared treating patients at all fibrosis stages (Stages F0–F4) compared to late treatment (Stage F4).

Results: Based on projected lifetime work activity and taxes paid, the treated cohort paid an additional £5,900 per patient compared to the untreated cohort. Lifetime government disability costs of £97,555 and £125,359 per patient for treated cohort vs no treatment cohort were estimated, respectively. Lifetime direct healthcare costs in the treated cohort were £32,235, compared to non-treated cohort of £26,424, with an incremental healthcare costs increase of £5,901 per patient. The benefit cost ratio (BCR) of total government benefits and savings relative to government treatment costs (including LDV/SOF) ranged from 1.8–5.6. Treating patients early resulted in 77% less disability costs, 43% lower healthcare costs, and 33% higher tax revenue.

Conclusion: The ability to cure Hepatitis C offers considerable fiscal benefits beyond direct medical costs and savings attributed to reduced disability costs, public allowances, and improved tax revenue. Changes in parameters, such as productivity, wage growth, and tax rates, can influence the conclusions described here.