When does economic model type become a decisive factor in health technology appraisals? Learning from the expanding treatment options for relapsing–remitting multiple sclerosis

Objectives: Specific economic model types often become de facto standard for health technology appraisal over time. Markov and discrete event simulation (DES) models were compared to investigate the impact of innovative modeling on the cost-effectiveness of disease-modifying therapies (DMTs) in relapsing–remitting multiple sclerosis (RRMS). Fingolimod was compared to dimethyl fumarate (DMF; in highly active [HA] RRMS), alemtuzumab (in HA RRMS) and natalizumab (in rapidly evolving severe RRMS). Comparator DMTs were chosen to reflect different dosing regimens.

Materials and methods: Markov and DES models used have been published previously. Inputs were aligned in all relevant respects, with differences in the modeling of event-triggered attributes, such as relapse-related retreatment, which is inherently difficult with a memoryless Markov approach. Outcomes were compared, with and without different attributes.

Results: All results used list prices. For fingolimod and DMF, incremental cost-effectiveness ratios (ICERs) were comparable (Markov: £4206/quality-adjusted life year [QALY] gained versus DES: £3910/QALY gained). Deviations were observed when long-term adverse events (AEs) were incorporated in the DES (Markov: £25,412 saved/QALY lost, versus DES: £34,209 saved/QALY lost, fingolimod versus natalizumab; higher ICERs indicate greater cost-effectiveness). For fingolimod versus alemtuzumab, when relapse-triggered retreatment was included in the DES, large cost differences were observed (difference between incremental cost is £35,410 and QALY is 0.10).

Limitations: UK payer perspective, therefore societal approach was not considered. Resource utilization and utilities for both models were not derived from the subpopulations; as the focus is on model type, input limitations that apply to both models are less relevant.

Conclusions: Whilst no model can fully represent a disease, a DES allows an opportunity to include features excluded in a Markov structure. A DES may be more suitable for modeling in RRMS for health technology assessment purposes given the complexity of some DMTs. This analysis highlights the capabilities of different model structures to model event-triggered attributes.     

Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in The Netherlands

Abstract

Objectives:

Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the perspective of the healthcare payer in The Netherlands.

Methods:

A previously constructed Markov state-transition model was adapted and updated with costs and utilities relevant to the Dutch setting. The cost-effectiveness of RDN was compared with standard of care (SoC) for patients with resistant hypertension. The efficacy of RDN treatment was modeled as a reduction in the risk of cardiovascular events associated with a lower systolic blood pressure (SBP).

Results:

Treatment with RDN compared to SoC gave an incremental quality-adjusted life year (QALY) gain of 0.89 at an additional cost of €1315 over a patient’s lifetime, resulting in a base case incremental cost-effectiveness ratio (ICER) of €1474. Deterministic and probabilistic sensitivity analyses (PSA) showed that treatment with RDN therapy was cost-effective at conventional willingness-to-pay thresholds (€10,000–80,000/QALY).

Conclusion:

RDN is a cost-effective intervention for patients with resistant hypertension in The Netherlands.     

Changing costs and the impact on RSV prophylaxis

Abstract

Objective:

Acquisition costs of palivizumab have increased in Canada since 2007. This analysis aims to re-evaluate the cost effectiveness of palivizumab in Canada for premature infants born between 32 and 35 weeks’ gestational age using updated 2010 healthcare costs compared to those used in a 2007 decision analytic model.

Methods:

New costs (CAN$) were acquired from the same Health Canada and Ontario Ministry of Health sources that were utilized in the previously published 2007 model. Palivizumab prices were acquired from Abbott Laboratories Ltd., current as of August 2010.

Results:

Incremental cost-effectiveness ratios (ICERs) rose by $742, going from $30,618/QALY to $31,360/QALY. ICER changes increased from a range of $801,297 to $820,701 for infants with zero risk factors to a decrease from $808 to $192 for infants with four or more risk factors.

Conclusions:

Palivizumab ICERs remained fairly stable from 2007 to 2010. The original recommendation stating that palivizumab is cost effective in infants born between 32 and 35 weeks’ GA with two or more risk factors, or who are at moderate-to-high risk based on a risk assessment model, does not change. Analyses founded on evolving country-specific variables are needed in order to accurately reassess the cost effectiveness of interventions as costs change worldwide.

Limitations:

There are a limited number of publications reporting mortality in premature Canadian infants with RSV as a primary outcome. In addition, conclusions drawn from this analysis are country-specific and limited to premature infants dwelling in Canada.     

艾司西酞普兰与文拉法辛治疗抑郁障碍的成本-效果分析

目的对常用的抗抑郁药物艾司西酞普兰与文拉法辛治疗抑郁障碍进行成本-效果分析。方法将78例符合《中国精神障碍分类与诊断标准》（第三版）抑郁发作诊断标准的抑郁障碍患者随机分为两组,分别给予艾司西酞普兰或文拉法辛治疗8周,观察两组治疗方案的疗效及安全性,运用药物经济学的成本-效果分析方法进行评价。结果艾司西酞普兰、文拉法辛组治疗药品成本分别为663.04元和1164.80元;有效率分别为82.05%和84.62%;不良反应发生率分别为30.77%和28.21%。结论根据药物经济学评价,艾司西酞普兰组优于文拉法辛组。     

EVEREST II high risk study based UK cost-effectiveness analysis of MitraClip® in patients with severe mitral regurgitation ineligible for conventional repair/replacement surgery

Abstract

Objectives:

To evaluate the cost-effectiveness of MitraClip, an interventional procedure for patients with chronic severe mitral regurgitation.

Methods:

A decision analytic model with a lifetime horizon was developed to assess the cost-effectiveness of MitraClip vs conventional medical management in patients with severe mitral regurgitation, ineligible for surgery. The analysis was performed from a UK NHS perspective and the estimates for mortality, adverse events, and cross-sectional NYHA class were obtained from the EVEREST II High Risk Study (HRS). Utility decrements were obtained from a heath technology assessment on Cardiac Resynchronization Therapy, while unit costs were obtained from national databases. The concept model was clinically validated. Costs (2011 £UK) and benefits were discounted at an annual rate of 3.5%.

Results:

Compared to medical management, over 2- and 10-year periods MitraClip had incremental Quality Adjusted Life Year (QALY) gains of 0.48 and 2.04, respectively. The Incremental Cost-Effectiveness Ratios for MitraClip at 2 and 10 years are £52,947 and £14,800 per QALY gained. Overall, the model was most sensitive to the choice of time horizon, the discount rate applied to benefits, the starting age of cohort, the utility decrement associated with NYHA II, and cost of the MitraClip procedure. The model was insensitive to changes in all other parameters. MitraClip was also found to be cost-effective, regardless of the modelling approach, and insensitive to the key assumptions of the procedure cost.

Study limitations:

The primary limitation of the analysis is the reliance on aggregate data from a modestly sized non-randomized study with a short-term follow-up period. Aligned to this was the need to extrapolate survival well beyond the study period in order to generate meaningful results. The impact of both of these limitations was explored via extensive sensitivity analyses.

Conclusion:

Compared to medical management, MitraClip is a cost-effective interventional procedure at conventional threshold values.     

Cost-effectiveness of ceftolozane/tazobactam plus metronidazole compared with piperacillin/tazobactam as empiric therapy for the treatment of complicated intra-abdominal infections based on the in-vitro surveillance of bacterial isolates in the UK

Aims: An increase in the prevalence of antimicrobial resistance among gram-negative pathogens has been noted recently. A challenge in empiric treatment of complicated intra-abdominal infection (cIAI) is identifying initial appropriate antibiotic therapy, which is associated with reduced length of stay and mortality compared with inappropriate therapy. The objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam?+?metronidazole compared with piperacillin/tazobactam (commonly used in this indication) in the treatment of patients with cIAI in UK hospitals.

Methods: A decision-analytic Monte Carlo simulation model was used to compare costs (antibiotic and hospitalization costs) and quality-adjusted life years (QALYs) of patients infected with gram-negative cIAI and treated empirically with either ceftolozane/tazobactam?+?metronidazole or piperacillin/tazobactam. Bacterial isolates were randomly drawn from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database, a surveillance database of non-duplicate bacterial isolates collected from patients in the UK infected with gram-negative pathogens. Susceptibility to initial empiric therapy was based on the measured susceptibilities reported in the PACTS database.

Results: Ceftolozane/tazobactam?+?metronidazole was cost-effective when compared with piperacillin/tazobactam, with an incremental cost-effectiveness ratio (ICER) of £4,350/QALY and 0.36 hospitalization days/patient saved. Costs in the ceftolozane/tazobactam?+?metronidazole arm were £2,576/patient, compared with £2,168/patient in the piperacillin/tazobactam arm. The ceftolozane/tazobactam?+?metronidazole arm experienced a greater number of QALYs than the piperacillin/tazobactam arm (14.31/patient vs 14.21/patient, respectively). Ceftolozane/tazobactam?+?metronidazole remained cost-effective in one-way sensitivity and probabilistic sensitivity analyses.

Conclusions: Economic models can help to identify the appropriate choice of empiric therapy for the treatment of cIAI. Results indicated that empiric use of ceftolozane/tazobactam?+?metronidazole is cost-effective vs piperacillin/tazobactam in UK patients with cIAI at risk of resistant infection. This will be valuable to commissioners and clinicians to aid decision-making on the targeting of resources for appropriate antibiotic therapy under the premise of antimicrobial stewardship.     

Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema

Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME).

Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing ‘death’ state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec.

Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy).

Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy.     

An update to the cost-effectiveness of posaconazole vs fluconazole or itraconazole in the prevention of invasive fungal disease among neutropenic patients in the United States

Abstract

Objectives:

Posaconazole has shown superior clinical efficacy in the prevention of invasive fungal disease (IFD) among neutropenic patients as well as cost-effectiveness in the US healthcare setting vs fluconazole or itraconazole (FLU/ITRA) based on oral suspension formulations of each therapy. This study aims to provide an update on the cost-effectiveness of posaconazole in the current US healthcare setting to reflect bioequivalent tablet formulations of posaconazole and fluconazole, as well as changes in healthcare and drug costs.     

Cost-effectiveness of rosuvastatin 20 mg for the prevention of cardiovascular morbidity and mortality: a Swedish economic evaluation of the JUPITER trial

Abstract

Objective:

This study estimated the long-term health outcomes, healthcare costs, and cost-effectiveness of rosuvastatin 20?mg therapy in primary prevention of major cardiovascular disease (CVD) in a Swedish population.

Methods:

Based on data from the JUPITER trial, long-term CVD outcomes with rosuvastatin vs no active treatment were estimated for patients with an elevated baseline CVD risk (Framingham CVD score >20%, sub-population of JUPITER population) and for a population similar to the total JUPITER population. Using a decision-analytic model, trial CVD event rates were combined with epidemiological and cost data specific for Sweden. First and subsequent CVD events and death were estimated over a lifetime perspective. The observed relative risk reduction was extrapolated beyond the trial duration. Incremental effectiveness was measured as life-years gained (LYG) and quality-adjusted life-years (QALYs) gained.

Results:

Treating 100,000 patients with rosuvastatin 20?mg was estimated to avoid 14,692 CVD events over the lifetime (8021 non-fatal MIs, 3228 non-fatal strokes, and 4924 CVD deaths) compared to placebo. This translated into an estimated gain of 42,122 QALYs and 36,865 total life years (LYG). Rosuvastatin was both more effective and less costly over a lifetime perspective, and rosuvastatin is subsequently a dominant alternative compared to no treatment in the assessed population. Using the overall JUPITER population, rosuvastatin was dominant for the lifetime horizon. In the sensitivity analysis, rosuvastatin was the dominant treatment strategy over a 20-year time horizon, and cost-effective with an incremental cost-effectiveness ratio (cost per QALY) of SEK 1783 over a 10-year time horizon.

Limitations:

Some model inputs were derived from literature or other data sources, but uncertainty was controlled by sensitivity analyses.

Conclusions:

Results indicate that rosuvastatin 20?mg treatment is a cost-effective option vs no-treatment in patients with Framingham CVD risk >20% in Sweden and might even be cost saving if taking a long-term perspective.     

3种质子泵抑制剂联合氟哌噻吨美利曲辛治疗功能性消化不良的成本-效果分析

目的评价艾普拉唑、埃索美拉唑、雷贝拉唑3种质子泵抑制剂（PPI）联合氟哌噻吨美利曲辛（黛力新）治疗功能性消化不良的成本-效果,为临床制定合理用药方案。方法抽取2011年功能性消化不良病例119例随机分为A、B、C三组,三组患者均予黛力新片2片,早晨及中午各服1片。A组45例给予艾普拉唑5mg,早餐前1片,B组40例给予埃索美拉唑20mg,早餐前1片,C组34例给予雷贝拉唑10mg,早餐前1片,三组疗程均为28d。各组结果运用药物经济学原理进行成本-效果分析。结果 A、B、C三组治疗功能性消化不良的有效率分别为95.5%、92.5%、91.2%,三组间无显著性差异（P〉0.05）;成本-效果比（C/E）分别为7.67元、6.06元、6.83元。结论 3种方案治疗功能性消化不良有效率及不良反应发生率无显著性差异,但从药物经济学角度考虑,B组方案较佳。     

Posaconazole vs fluconazole/itraconazole in the prophylaxis of invasive fungal infections in immunocompromised patients: A cost-effectiveness analysis in Greece

Abstract

Background:

Invasive fungal infections (IFIs) present a major issue in clinical practice, due to their high morbidity and mortality rates. In a pivotal multi-centre, randomized clinical trial, posaconazole prophylaxis prevented IFIs more effectively than did either fluconazole or itraconazole, and improved overall survival.

Objective:

The aim of this study was to perform an economic evaluation of the aforementioned therapeutic strategies for IFI prophylaxis in neutropenic patients, in the Greek healthcare setting.

Method:

A decision analytic model was developed, which described the course of neutropenic patients under posaconazole or standard azole (fluconazole or itraconazole) treatment. Effectiveness data for each treatment regimen were derived from published results of a pivotal, multi-centre, randomized clinical trial. Cost and healthcare resources utilization data depict Greek clinical practice and are derived from official Greek sources, from a third party payer perspective.

Results:

Prophylaxis with posaconazole resulted in fewer IFIs (0.05 vs 0.11 per patient) compared to treatment with fluconazole or itraconazole, during the first 100 days from initiation of prophylaxis treatment. The cost per avoided IFI with posaconazole was €6455, while the incremental cost per life year gained (LYG) was estimated at €24,196. Extensive sensitivity analyses corroborated the base-case results. Possible limitations of the study are the exclusion of indirect and outpatient costs from the analysis and the inherent uncertainty with regards to the transferability of the clinical efficacy results of the clinical trial to the Greek healthcare setting.

Conclusions:

The utilization of posaconazole for prophylaxis of IFIs neutropenic patients is a therapeutic strategy that provides superior clinical efficacy, while being cost-effective compared to alternative therapies.     

地特胰岛素注射液的临床效果和经济学评价研究综述

采用文献综述法,系统地分析国外已发表的地特胰岛素注射液（IDet）的临床研究和经济学评价结果,以评估地特胰岛素治疗1型和2型糖尿病患者的临床疗效和经济学价值。研究结果表明,在临床效果方面,患者从应用口服降糖药、中性鱼精蛋白锌胰岛素（NPH）或甘精胰岛素注射液（IGlar）,转换使用IDet后,均有助于进一步降低患者的血糖水平。许多国家的经济学研究显示,与NPH或IGlar相比,IDet是成本节约或具有成本-效果的治疗方案。     

评价疫苗产品对成本-效果的长期影响的必要性探讨——基于儿童七价肺炎结合疫苗的经济性评价

目的从长期研究视角出发,对将七价肺炎链球菌结合疫苗纳入免疫规划方案开展经济学分析,探讨对疫苗产品开展成本-效果分析时进行长期评价的重要性。方法从支付方的研究角度,构建Markov模型,结合北京市的成本数据和我国台湾地区健保局的流行病学数据,模拟在北京市将PCV7纳入免疫规划方案,实施10年后的成本效果进行研究。结果经过成本-效果分析得出,免疫规划方案实施10年期间,在北京市共避免6390人死亡、获得6393个QALYs,其中以2岁以下儿童和65岁以上老人受到的保护效果最显著。而且从长远来看,对全人群而言,方案实施10年使得总成本可节约7.14元/人。结论在进行疫苗类产品成本-效果分析时,关注其对成本、效果长期影响至关重要。     

Operationalising active involvement in the EU Water Framework Directive: Why, when and how?

We identify two key stages in the river basin planning process under the Water Framework Directive: the selection of instruments for a programme of measures to achieve the environmental targets, and disproportionate cost analysis to determine whether selected measures involve high costs. Some EU member states such as Denmark are operationalising these two key stages using cost effectiveness analysis and cost-benefit analysis. However, implementation guidelines encourage the active involvement of all interested parties in the implementation of the Directive. We discuss the potential benefits of actively involving non-state actors, which can be summarised as increasing the effectiveness of policy and improving its implementation. Criticising the emerging economic decision-making approach, we argue that economic analyses could result in a missed opportunity to capitalise on the potential benefits of involvement. The article discusses the appropriateness of actively involving the public during the two aforementioned decision-making stages and suggests concrete ways in which active involvement may be operationalised. We conclude that member states should not implement a minimum form of participation to comply with the statutory requirements of the Directive, but should strive for active involvement due to the potential for increasing the effectiveness of the Water Framework Directive and improving its implementation.     

奇正消痛贴膏治疗急性腰扭伤的药物经济学评价

目的基于社会角度,通过成本-效果分析和成本-效用分析评价奇正消痛贴膏与双氯芬酸钠乙二胺乳胶剂治疗急性腰扭伤的经济学优劣,为急性腰扭伤的治疗方案选择提供依据。方法选取2012年7月至2013年6月来自北京、上海、广州和通辽4个城市5所三级医院的急性腰扭伤患者295例,其中奇正消痛贴膏治疗组152例,双氯芬酸钠乙二胺乳胶剂治疗组143例。选取疼痛消失时间为效果指标,质量调整生命年(QALYs)为效用指标,进行成本-效果分析及成本-效用分析。结果与双氯芬酸钠乙二胺乳胶剂治疗组相比,奇正消痛贴膏治疗组疼痛消失时间显著缩短(8.26 d对9.23 d,P<0.001),且获得更多的QALYs(0.0362对0.0359,P=0.597),但治疗成本也更高(308.52元对297.43元,P=0.697)。增量成本效果比(ICER)为-11.43元/d,即减少1天疼痛时间需多花费11.43元。增量成本效用比(ICUR)为36 966.67元/QALY,低于世界卫生组织(WHO)所建议的成本效用阈值115 000元(人均GDP的3倍)。结论在急性腰扭伤的治疗中,外用止痛药物奇正消痛贴膏是非常具有成本-效益的治疗方案。     

莫西沙星与阿莫西林克拉维酸钾治疗慢性支气管炎急性发作的成本-效果分析

目的：探讨莫西沙星和阿莫西林克拉维酸钾治疗慢性支气管炎急性发作（AECB）的经济性。方法基于全社会角度,选取AECB门诊患者（≥18岁）为研究对象,构建决策树模型,对莫西沙星和阿莫西林克拉维酸钾治疗AECB进行成本-效果分析。疗效和不良反应数据来源于随机对照试验（RCT）文献,药品成本采用广东省医疗机构药品网上采购系统公布的零售价中位数,不良反应治疗成本通过专家问卷调查获得。结果在基础分析中,莫西沙星组的治疗效果优于阿莫西林克拉维酸钾组,且总成本较低,为优势方案,阿莫西林克拉维酸钾组为劣势方案,增量成果比值（ICER）为-1900.08元。在敏感性分析中,结果与基础分析基本一致。结论对于AECB的治疗,莫西沙星的经济性优于阿莫西林克拉维酸钾。