A cost-effectiveness and budget impact analysis of apremilast in patients with psoriasis in the Italian setting

Abstract

Aims: The aim of this study was to conduct a cost-effectiveness analysis, as well as a budget impact analysis, on the use of apremilast for the treatment of adult patients with moderate-to-severe plaque psoriasis (defined as a psoriasis area severity index [PASI]?≥?10), who failed to respond to, had a contraindication to, or were intolerant to other systemic therapies, within the Italian National Health Service (NHS).

Materials and methods: A Markov state-transition cohort model adapted to the Italian context was used to compare the costs of the currently available treatments and of the patients’ quality of life with two alternative treatment sequences, with or without apremilast as pre-biologic therapy. Moreover, a budget impact model was developed based on the population of patients treated for psoriasis in Italy, who would be eligible for treatment with apremilast.

Results: Over 5?years, the cost-effectiveness analysis showed that the strategy of using apremilast before biologic therapy was dominant compared with the sequence of biologic treatments without apremilast. In addition, it is important to underline that the use of apremilast slightly increases the quality-adjusted life years gained over 5?years. Furthermore, within the budget impact analysis, the strategy including apremilast would lead to a saving of €16 million within 3?years. Savings would mainly be related to a reduction in pharmaceutical spending, hospital admissions and other drug administration-related costs.

Conclusion: These models proved to be robust to variation in parameters and it suggested that the use of apremilast would lead to savings to the Italian healthcare system with potential benefits in terms of patients’ quality of life.     

The cost-effectiveness of celecoxib vs diclofenac in the treatment of osteoarthritis in the UK; an update to the NICE model using data from the CONDOR trial

Abstract

Objectives:

The National Institute for Health and Clinical Excellence (NICE) health economic model for assessing the cost-effectiveness of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus PPI in the treatment of osteoarthritis has been updated using new adverse event (AE) risks from the CONDOR trial. In light of this new information, this study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus PPI compared to diclofenac plus PPI.

Methods:

NICE developed a health economic model as part of their 2008 multiple technology assessment of treatments for osteoarthritis. The model was adapted for this study to update the relative risks of adverse events, using data from the CONDOR trial.

Results:

Using the AE data from the CLASS trial alone, celecoxib plus PPI has an ICER of £9538 per QALY when compared to diclofenac plus PPI. When the AE data from CONDOR alone is used, this ICER decreases to £4773 per QALY. Using the pooled data from both trials, celecoxib plus PPI has an ICER of £9377 per QALY compared to diclofenac plus PPI.

Discussion:

The results suggest that when new AE risks are used, celecoxib plus PPI remains a cost-effective treatment for OA when compared to diclofenac plus PPI. However, this analysis is limited by the short time horizon, and additional AEs that have not been considered.     

剖宫产产妇抗菌药物使用疗程的成本-效果分析

目的:寻找广州市妇婴医院剖宫产产妇术后预防性使用抗菌药物的最佳疗程。方法:采用回顾性研究,收集和整理该院2006年6月至2007年5月493例剖宫产产妇相关资料,利用成本-效果分析方法对剖宫产产妇术后预防性使用抗菌药的不同疗程进行分析。结果:剖宫产产妇预防性使用抗菌药的疗程A组((d<3)天)、B组((3≤d<4)天)、C组((4≤d<5)天)、D组((d≥5)天)的有效率分别为:66.67%、85.12%、89.5%、85.19%;以抗菌药费用作为成本计算的成本-效果比分别为:9.21、7.22、8.62、14.32;以西药费作为成本计算的成本-效果比分别为:13.92、15.29、16.89、21.89;以住院费作为成本计算的成本-效果比分别为:61.15、67.09、66.78、79.96。结论:剖宫产产妇术后预防性使用抗菌药物,最经济、有效、合理的使用时间为术后3天(B组),增加用药天数并不能增加治疗效果,而费用却明显增加。     

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.     

The cost-effectiveness of dulaglutide versus insulin glargine for the treatment of type 2 diabetes mellitus in Japan

Aims: Dulaglutide is a new once weekly glucagon-like peptide-1 (GLP-1) receptor agonist administered via a disposable auto-injection pen for the management of type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the cost-effectiveness of dulaglutide vs insulin glargine for the management of T2DM from a Japanese healthcare perspective, in accordance with recently approved Japanese Cost-Effectiveness Guidelines.

Methods: The IQVIA CORE Diabetes Model (version 9) was used to estimate the long-term costs and effects of treatment with dulaglutide and insulin glargine. Direct comparative data from the Araki 2015 trial (NCT01584232) was used to inform the analysis. Costs associated with treatment and complications were derived from Japanese sources wherever possible and inflated to 2015 Japanese Yen (JPY). Utilities were based upon a European systematic review of diabetes utilities and adjusted for use in a Japanese population. One-way and probabilistic sensitivity analyses (OWSA and PSA) were conducted on all inputs and key modeling assumptions.

Results: Dulaglutide 0.75?mg was associated with higher quality-adjusted life years (QALYs), life years (LYs), and total costs, compared to insulin glargine, resulting in an incremental cost-effectiveness ratio (ICER) of 416,280 JPY/QALY gained. Treatment with dulaglutide increased the time alive and free from diabetes-related complications by 4 months. OWSA and PSA indicated that results were robust to plausible variations in input parameters and modeling assumptions.

Limitations: Key limitations of this study are similar to other cost-utility analyses of diabetes, including the extrapolation of short-term clinical trial data into lifelong durations. In addition, due to the lack of robust published Japanese data, some values were derived from non-Japanese sources.

Conclusions: This analysis suggests that dulaglutide 0.75?mg may be a cost-effective treatment alternative to insulin glargine for patients with T2DM in Japan.     

Modeling the cost-effectiveness of ilaprazole versus omeprazole for the treatment of newly diagnosed duodenal ulcer patients in China

Objectives: To evaluate the cost-effectiveness of 10?mg ilaprazole once-daily vs 20?mg omeprazole once-daily to treat newly-diagnosed duodenal ulcer patients in China.

Methods: A decision tree model was constructed and the treatment impact was projected up to 1 year. The CYP2C19 polymorphism distribution in the Chinese population, the respective cure rates in the CYP2C19 genotype sub-groups, the impact of Duodenal Ulcer (DU) on utility value and drug-related side-effect data were obtained from the literature. The total costs of medications were calculated to estimate the treatment costs based on current drug retail prices in China. Expert surveys were conducted when published data were not available. Probabilistic sensitivity analysis was performed to gauge the robustness of the results.

Results: Ilaprazole, when compared with omeprazole, achieved a better overall clinical efficacy. For the overall population, ilaprazole achieved an incremental cost effectiveness ratio (ICER) of ¥132 056 per QALY gained. This is less than the WHO recommended threshold of 3-times the average GDP per capita in China (2014). Furthermore, sub-group analysis showed that ilaprazole is cost-effective in every province in CYP2C19 hetEM patients and in the most developed provinces in CYP2C19 homEM patients. Probabilistic sensitivity analysis suggests that the results are robust with 97% probability that ilaprozole is considered cost-effective when a threshold of 3-times China’s average GDP per capita is considered.

Limitation: This study didn’t have the data of ilaprazole combined with Hp eradication therapy. Caution should be taken when extrapolating these findings to DU patients with an Hp eradication therapy.

Conclusions: The cost-effectiveness analysis results demonstrated that ilaprazole would be considered a cost-effective therapy, compared with omeprazole, in Chinese DU patients based on the efficacy projections in various CYP2C19 polymorphism types.     

Modelling the cost-effectiveness of nevirapine triple combination therapy and dual combination therapy for the treatment of HIV disease in the United Kingdom

Summary

Recent advances in HIV antiretroviral therapy together with limited budgets have forced payers to look for evidence that new combinations provide good value for money. Using a public financing perspective, two Markov models are employed to evaluate the first-year outcomes and costs and the long-term cost-effectiveness of adding nevirapine (NVP) to dual combination therapy with zidovudine (ZDV) and didanosine (ddI) in the United Kingdom.

First-year medical care savings are estimated to be £2,122 (103.8% of NVP cost). In the longer term, NVP/ZDV/ddI therapy yields £6,186 per life year saved (costs discounted at 6%). The model is moderately sensitive only to duration of therapy effects and the therapy initiation time. These model estimates suggest that policy makers may expect to observe superior initial health outcomes and substantial medical cost savings during the first year of therapy, as well as acceptable long-term cost-effectiveness, when NVP/ZDV/ddI is used in place of dual therapy.     

Comparison of costs and outcomes of dapagliflozin with other glucose-lowering therapy classes added to metformin using a short-term cost-effectiveness model in the US setting

Objective: To compare 1-year costs and benefits of dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, with those of other treatments for type 2 diabetes (T2D), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), sulfonylureas (SUs), thiazolidinediones (TZDs), and dipeptidyl peptidase-4 inhibitors (DPP-4i), all combined with metformin.

Methods: A short-term decision-analytic model with a 1-year time horizon was developed from a payer’s perspective in the United States setting. Costs and benefits associated with four clinical end-points (glycated hemoglobin [A1C], body weight, systolic blood pressure [SBP], and risk of hypoglycemia) were evaluated in the analysis. The impact of DAPA and other glucose-lowering therapy classes on these clinical end-points was estimated from a network meta-analysis (NMA). Data for costs and quality-adjusted life-years (QALYs) associated with a per-unit change in these clinical end-points were taken from published literature. Drug prices were taken from an annual wholesale price list. All costs were inflation-adjusted to December 2016 costs using the medical care component of the consumer price index. Total costs (both medical and drug costs), total QALYs, and incremental cost-effectiveness ratios (ICERs) were estimated. Sensitivity analyses (SA) were performed to explore uncertainty in the inputs. To assess face validity, results from the short-term model were compared with long-term models published for these drugs.

Results: The total annual medical cost for DAPA was less than that for GLP-1RA ($186 less), DPP-4i ($1,142 less), SU ($2,474 less), and TZD ($1,640 less). Treatment with DAPA resulted in an average QALY gain of 0.0107, 0.0587, 0.1137, and 0.0715 per treated patient when compared with GLP-1RA, DPP-4i, SU, and TZD, respectively. ICERs for DAPA vs SU and TZD were $19,005 and $25,835, respectively. DAPA was a cost-saving option when compared with GLP-1RAs and DPP-4is. Among all four clinical end-points, change in weight had the greatest impact on total annual costs and ICERS. Sensitivity analysis showed that results were robust, and results from the short-term model were found to be similar to those of published long-term models.

Conclusion: This analysis showed that DAPA was cost-saving compared with GLP-1RA and DPP-4i, and cost-effective compared with SU and TZD in the US setting over 1 year. Furthermore, the results suggest that, among the four composite clinical end-points, change in weight and SBP had an impact on cost-effectiveness results.     

Mirabegron for the treatment of overactive bladder: cost-effectiveness from US commercial health-plan and Medicare Advantage perspectives

Background and objective: The first class of oral pharmacologic treatments for overactive bladder (OAB) are antimuscarinics that are associated with poor persistence, anticholinergic adverse events, and increased anticholinergic burden (ACB) with risk of cognitive impairment. Mirabegron, a β3-adrenoceptor agonist, is an oral treatment that does not contribute to ACB and has early evidence of improved persistence. The objective of the analysis was to assess the cost-effectiveness of mirabegron for OAB vs six antimuscarinics in the US.

Methods: A Markov state-transition model assessed US commercial health-plan and Medicare Advantage perspectives over a 3-year time horizon in an OAB patient population. Transition probabilities between five micturition and five incontinence severity states were derived from a network meta-analysis of 44 trials of oral OAB treatments. Therapy beginning with an oral OAB agent could discontinue or switch to another oral agent and could be followed by tibial nerve stimulation, sacral neuromodulation, or onabotulinumtoxinA. The primary outcome was cost per quality-adjusted life year (QALY). Utilities were mapped from incontinence and micturition frequencies as well as demographics. Based on analysis of data from a large healthcare system, elevated ACB was associated with increased healthcare utilization and probability of cognitive impairment.

Results: From both commercial and Medicare Advantage perspectives, mirabegron was the most clinically effective treatment, while oxybutynin was the least expensive. Tolterodine immediate release (IR) was also on the cost-effectiveness frontier. The analysis estimated costs per QALY of $59,690 and $66,347 for mirabegron from commercial health plan and Medicare Advantage perspectives, respectively, compared to tolterodine IR. Other antimuscarinics were dominated.

Conclusions: This analysis estimated that mirabegron is a cost-effective treatment for OAB from US commercial health plan and Medicare Advantage perspectives, due to fewer projected adverse events and comorbidities, and data suggesting better persistence.     

Evaluating the cost-effectiveness of percutaneous closure of a patent foramen ovale versus medical management in patients with a cryptogenic stroke: from the UK payer perspective

Aims: Percutaneous closure of a patent foramen ovale (PFO) is known to lower the risk of recurrent stroke in patients with a cryptogenic stroke. However, the economic implications of transcatheter PFO closure are less well known. From a UK payer perspective, a detailed economic appraisal of PFO closure was performed for prevention of recurrent ischemic stroke in patients with a PFO who had experienced a cryptogenic stroke.

Materials and methods: A Markov cohort model was constructed using a 5-year time-horizon with a patient mean age of 45.2 years, reflecting the characteristics reported in the REDUCE trial. Transition probabilities, clinical inputs, costs, and utility values were ascertained from published and national costing sources. Total costs, incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were calculated, utilizing a discount rate of 3.5%. A range of univariate and probabilistic sensitivity analyses were also performed.

Results: When applying a willingness-to-pay (WTP) threshold of £20,000/QALY in accordance with NICE guidelines, PFO closure compared with antiplatelet therapy alone showed a beneficial cost/QALY of £18,584, attained at 4 years. Applying discount rates of 0% and 6% had a negligible effect on the base-case model findings. PFO closure demonstrated a 76.9% probability of being cost-effective at a WTP threshold of £20,000/QALY at a 5-year time-horizon.

Limitations: This model focused specifically on UK stroke patients and typically enrolled young (mean age <65 years old) patients. Hence, caution should be taken when comparing data vs non-UK populations, and it remains unclear how older patients might have affected cost-effectiveness findings, as the risk of paradoxical embolism can persist as patients age.

Conclusion: Percutaneous closure of a PFO is cost-effective compared with antiplatelet therapy alone, underlining the economic benefits potentially afforded by this treatment in selected patients.     

Cost-effectiveness of rivaroxaban versus apixaban for the initial treatment of venous thromboembolism and extended prevention of recurrences in the UK

Abstract

Aim: To evaluate the relative cost-effectiveness of using rivaroxaban vs apixaban for the initial treatment plus extended prevention of venous thromboembolism (VTE) in the UK. Extended prevention was assessed using a 10-mg rivaroxaban dose, as the 20-mg dose has already been evaluated.

Methods: A Markov model compared the health outcomes and costs of treating VTE patient cohorts with either rivaroxaban (15?mg twice daily for 3 weeks, followed by 20?mg once daily for 6 months, then extended prevention with 10?mg once daily) or apixaban (10?mg twice daily for 1 week, followed by 5?mg twice daily for 6 months, then extended prevention with 2.5?mg twice daily) over a lifetime horizon. The model included an initial acute treatment and prevention phase (0–6?months) and an extended prevention phase (6–18 months). Efficacy and safety data were derived from two network meta-analyses. Reference treatment comparators were derived from the EINSTEIN-Pooled study and EINSTEIN-CHOICE trial. Healthcare costs and utility data were derived from published literature.

Results: The rivaroxaban regimen was associated with increased quality-adjusted life years (QALYs) and slightly lower total costs compared with apixaban over a lifetime horizon. Deterministic and probabilistic sensitivity analyses demonstrated that rivaroxaban remained a cost-effective alternative to apixaban over a wide range of parameters. Incremental cost-effectiveness ratio estimates were below the £20,000 per QALY threshold in 74.1% of 2,000 model simulations. Scenario analyses further supported that rivaroxaban is a cost-effective alternative to apixaban.

Limitations: Clinical and safety inputs were derived from network meta-analysis, which are subject to inherent limitations whereby small differences between study designs may severely impact efficacy and safety outcomes. Furthermore, these inputs were based on data from clinical trials, which may not reflect real-world data.

Conclusions: Rivaroxaban was associated with a slightly lower total cost and increased QALYs compared with apixaban for VTE management in the UK over a lifetime horizon.     

Cost-effectiveness analysis of rivaroxaban for treatment and secondary prevention of venous thromboembolism in the Netherlands

Background: Until recently, standard treatment of venous thromboembolism (VTE) concerned a combination of short-term low-molecular-weight heparin (LMWH) and long-term vitamin-K antagonist (VKA). Risk of bleeding and the requirement for regular anticoagulation monitoring are, however, limiting their use. Rivaroxaban is a novel oral anticoagulant associated with a significantly lower risk of major bleeds (hazard ratio?=?0.54, 95% confidence interval?=?0.37–0.79) compared to LMWH/VKA therapy, and does not require regular anticoagulation monitoring.

Aims: To evaluate the health economic consequences of treating acute VTE patients with rivaroxaban compared to treatment with LMWH/VKA, viewed from the Dutch societal perspective.

Methods: A life-time Markov model was populated with the findings of the EINSTEIN phase III clinical trial to analyze cost-effectiveness of rivaroxaban therapy in treatment and prevention of VTE from a Dutch societal perspective. Primary model outcomes were total and incremental quality-adjusted life years (QALYs), as well as life expectancy and costs.

Results: Over a patient’s lifetime, rivaroxaban was shown to be dominant, with health gains of 0.047 QALYs and cost savings of €304 compared to LMWH/VKA therapy. Dominance was robustly present in all sensitivity analyses. Major drivers of the differences between the two treatment arms were related to anticoagulation monitoring (medical costs, travel costs, and loss of productivity) and the occurrence of major bleeds.

Conclusion: Rivaroxaban treatment of patients with venous thromboembolism results in health gains and cost savings compared to LMWH/VKA therapy. This conclusion holds for the Dutch setting, both for the societal perspective, as well as the healthcare perspective.     

A within-trial cost-effectiveness analysis of panitumumab compared with bevacizumab in the first-line treatment of patients with wild-type RAS metastatic colorectal cancer in the US

Abstract

Aims: This analysis investigated the cost-effectiveness of panitumumab plus mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) compared with bevacizumab plus mFOLFOX6 in the first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC).

Materials and methods: The cost-effectiveness analysis was developed from a third-party payer perspective in the US and was implemented using a partitioned survival model with health states for first-line treatment (progression-free), disease progression with and without subsequent active treatment, and death. Survival analyses of patients with wild-type RAS mCRC from the PEAK head-to-head clinical trial of panitumumab vs bevacizumab were performed to estimate time in the model health states. Additional data from PEAK informed the amount of each drug consumed, duration of therapy, subsequent therapy use, and toxicities related to mCRC treatment. Literature and US public data sources were used to estimate unit costs associated with treatment and duration of subsequent active therapies. Utility weights were calculated from patient-level data from panitumumab trials in the first-, second-, and third-line settings. A life-time perspective was taken with future costs and outcomes discounted at 3% per annum. Scenario, one-way, and probabilistic sensitivity analyses were performed.

Results: Compared with bevacizumab, the use of panitumumab resulted in an incremental cost of US $60,286, and an incremental quality-adjusted life-year (QALY) of 0.445, translating into a cost per QALY gained of US $135,391 in favor of panitumumab. Results were sensitive to wastage and dose rounding assumptions modeled.

Limitations: Progression-free and overall survival were extrapolated beyond the follow-up of the primary analysis using fitted parametric curves. Costs and quality of life were estimated from multiple and different data sources.

Conclusions: The efficacy of panitumumab in extending progression-free and overall survival and improving quality of life makes it a cost-effective option for first-line treatment of patients with wild-type RAS mCRC compared with bevacizumab.     

Peginterferon beta-1a versus other self-injectable disease-modifying therapies in the treatment of relapsing-remitting multiple sclerosis in Scotland: a cost-effectiveness analysis

Aims: Peginterferon beta-1a 125?mcg administered subcutaneously every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22?mcg, 30?mcg, and 44?mcg], interferon beta-1b, and glatiramer acetate 20?mg) in the treatment of RRMS, from the National Health Service and Personal Social Services perspective in Scotland.

Methods: A previously published, validated Markov cohort model was adapted for this analysis. The model estimates changes in patient disability, occurrence of relapses, and other adverse events, and translates them into quality-adjusted life years and costs. Natural history data came from the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database, and a large population-based MS survey in the UK. The comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (2015 British Pounds) were obtained from public databases and literature. Clinical and economic outcomes were projected over 30 years and discounted at 3.5% per year.

Results: Over 30 years, peginterferon beta-1a was dominant compared with interferon beta-1a (22, 30, and 44?mcg), and interferon beta-1b, and cost-effective compared with glatiramer acetate 20?mg. Results were most sensitive to variations in each DMT’s efficacy and acquisition costs. Deterministic and probabilistic sensitivity analyses confirmed the robustness of the results.

Limitations: The impact of improved adherence with peginterferon beta-1a on clinical and economic outcomes and the impact of subsequent DMTs after treatment discontinuation were not considered. Oral and infused DMTs were not included as comparators.

Conclusion Long-term treatment with peginterferon beta-1a improves clinical outcomes, while its cost profile makes it either dominant or cost-effective compared with other self-injectable DMTs for the treatment of RRMS in Scotland.     

Costs and effectiveness of fingolimod versus alemtuzumab in the treatment of highly active relapsing-remitting multiple sclerosis in the UK: re-treatment,discount, and disutility

Objective: Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod, or may be considered for alemtuzumab. Previous economic modeling used Markov models; applying one alternative technique, discrete event simulation (DES) modeling, allows re-treatment and long-term adverse events (AEs) to be included in the analysis.

Methods: A DES was adapted to model relapse-triggered re-treatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous 1-year Markov cycles. As the price to the NHS of fingolimod in the UK is unknown, due to a confidential patient access scheme (PAS), a variety of possible discounts were tested. The interaction of re-treatment assumptions for alemtuzumab with the possible discounts for fingolimod was tested to determine which DMT resulted in lower lifetime costs. The lifetime QALY results were derived from modeled treatment effect and short- and long-term AEs.

Results: Most permutations of fingolimod PAS discount and alemtuzumab re-treatment rate resulted in fingolimod being less costly than alemtuzumab. As the percentage of patients who are re-treated with alemtuzumab due to experiencing a relapse approaches 100% of those who relapse whilst on treatment, the discount required for fingolimod to be less costly drops below 5%. Consideration of treatment effect alone found alemtuzumab generated 0.2 more QALYs/patient; the inclusion of AEs up to a duration of 1 year reduced this advantage to only 0.14 QALYs/patient. Modeling AEs with a lifetime QALY decrement found that both DMTs generated very similar QALYs with the difference only 0.04 QALYs/patient.

Conclusions: When the model captured alemtuzumab re-treatment and long-term AE decrements, it was found that fingolimod is cost-effective compared to alemtuzumab, assuming application of only a modest level of confidential PAS discount.     

The effectiveness of government spending on education and health care in developing and transition economies

Recent studies show that corruption is associated with higher military spending [Eur. J. Polit. Econ. 17 (2001) 794] and lower government spending on education and health care [J. Publ. Econ. 69 (1998) 263]. This suggests that policies aimed at reducing corruption may lead to changes in the composition of government outlays toward more productive spending. However, little empirical evidence has been presented to support the claim that public spending improves education and health indicators in developing and transition countries. This paper uses cross-sectional data for 50 such countries to show that increased public expenditure on education and health care is associated with improvements in both access to and attainment in schools, and reduces mortality rates for infants and children. The education regressions are robust to different specifications, but the relationship between health care spending and mortality rates is weaker.     

Cost-effectiveness analysis of rasburicase over standard of care for the prevention and treatment of tumor lysis syndrome in children with hematologic malignancies in China

Aims: To conduct a lifetime cost-effectiveness analysis (CEA) of rasburicase compared with standard of care (SOC) for tumor lysis syndrome (TLS) in children with hematologic malignancies from the Chinese healthcare system perspective.

Materials and methods: The CEA was performed using a decision tree model with a lifetime horizon. The model explores the cost-effectiveness of rasburicase vs SOC for both preventing TLS and treating established TLS among pediatric patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and non-Hodgkin’s lymphoma (NHL). Both the prophylaxis-use model and treatment-use model incorporate long-term health states of the diseases: survival without TLS and death. The efficacy data of rasburicase and SOC were obtained from published literature. Drug costs, healthcare resource utilization (HRU), and adverse event (AE) management costs were obtained via a published study with clinical experts. Costs in US dollar and quality-adjusted life year (QALY) are reported, and incremental cost-effectiveness ratios (ICERs) were also calculated. Uncertainties due to parameter fluctuations in the model were assessed through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA).

Results: During TLS prevention, compared with SOC, the ICER of rasburicase treatment in China are $17,580.04/QALY, $5,783.45/QALY, and $5,391.00/QALY for pediatric patients with AML, ALL, and NHL, respectively. For the established TLS treatment, compared with SOC, the ICERs of rasburicase treatment are $2,031.18/QALY, $1,142.93/QALY, and $990.37/QALY for pediatric patients with AML, ALL, and NHL, respectively.

Limitations: The clinical data for SOC are based on the published study in China, and the rasburicase prevention or treatment failure rate was either calculated based on the risk ratio or directly from the clinical study among non-Chinese pediatric patients. Another study limitation was the lack of utility data for pediatric patients with TLS and without TLS. Thus, the utility scores of pediatric cancer survivors were used as an alternative.

Conclusion: Rasburicase is estimated to be a cost-effective alternative to SOC in the prevention and treatment of TLS among Chinese pediatric patients with AML, ALL, and NHL.     

The cost-effectiveness of onabotulinumtoxinA for the prophylaxis of headache in adults with chronic migraine in the UK

Abstract

Background:

Although chronic migraine is associated with substantial disability and costs, few treatments have been shown to be effective. OnabotulinumtoxinA (Botox, Allergan Inc., Irvine, CA) is the first treatment to be licensed in the UK for the prophylaxis of headaches in adults with chronic migraine. This study aims to evaluate the cost-effectiveness of onabotulinumtoxinA in this indication in the UK.

Methods:

A state-transition (Markov) model was developed comparing onabotulinumtoxinA to placebo. Efficacy data and utility values were taken from the pooled Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trials program (n?=?1384). Estimates of resource utilisation were taken from the International Burden of Migraine Study (IBMS), and stopping rules were informed by published medical guidelines and clinical data. This study estimated 2-year discounted costs and quality-adjusted life years (QALYs) from the UK National Health Service perspective.

Results:

At 2 years, treatment with onabotulinumtoxinA was associated with an increase in costs of £1367 and an increase in QALYs of 0.1 compared to placebo, resulting in an incremental cost-effectiveness ratio (ICER) of £15,028. Treatment with onabotulinumtoxinA reduced headache days by an estimated 38 days per year at a cost of £18 per headache day avoided. Sensitivity analysis showed that utility values had the greatest influence on model results. The ICER remained cost-effective at a willingness to pay threshold of £20,000–£30,000/QALY in the majority of scenario analyses as well as in probabilistic sensitivity analysis, where onabotulinumtoxinA was cost-effective on 96% of occasions at a threshold of £20,000/QALY and 98% of occasions at £30,000/QALY.

Conclusion:

OnabotulinumtoxinA has been shown to reduce the frequency of headaches in patients with chronic migraine and can be considered a cost-effective use of resources in the UK National Health Service. The uncertainties in the model relate to the extrapolation of clinical data beyond the 56-week trial.     

Cost-effectiveness analysis in the Spanish setting of the PEAK trial of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer

Objective: To assess the cost-effectiveness of panitumumab in combination with mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) vs bevacizumab in combination with mFOLFOX6 as first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC) in Spain.

Methods: A semi-Markov model was developed including the following health states: Progression free; Progressive disease: Treat with best supportive care; Progressive disease: Treat with subsequent active therapy; Attempted resection of metastases; Disease free after metastases resection; Progressive disease: after resection and relapse; and Death. Parametric survival analyses of patient-level progression free survival and overall survival data from the PEAK Phase II clinical trial were used to estimate health state transitions. Additional data from the PEAK trial were considered for the dose and duration of therapy, the use of subsequent therapy, the occurrence of adverse events, and the incidence and probability of time to metastasis resection. Utility weightings were calculated from patient-level data from panitumumab trials evaluating first-, second-, and third-line treatments. The study was performed from the Spanish National Health System (NHS) perspective including only direct costs. A life-time horizon was applied. Probabilistic sensitivity analyses and scenario sensitivity analyses were performed to assess the robustness of the model.

Results: Based on the PEAK trial, which demonstrated greater efficacy of panitumumab vs bevacizumab, both in combination with mFOLFOX6 first-line in wild-type RAS mCRC patients, the estimated incremental cost per life-year gained was €16,567 and the estimated incremental cost per quality-adjusted life year gained was €22,794. The sensitivity analyses showed the model was robust to alternative parameters and assumptions.

Limitations: The analysis was based on a simulation model and, therefore, the results should be interpreted cautiously.

Conclusions: Based on the PEAK Phase II clinical trial and taking into account Spanish costs, the results of the analysis showed that first-line treatment of mCRC with panitumumab?+?mFOLFOX6 could be considered a cost-effective option compared with bevacizumab?+?mFOLFOX6 for the Spanish NHS.     

The cost-effectiveness of pregabalin in the treatment of fibromyalgia: US perspective

Abstract

Objective:

To evaluate the cost-effectiveness of pregabalin in the treatment of fibromyalgia in a US patient population.

Methods:

A decision-analytic model was developed comparing pregabalin 150?mg twice a day (BID) and pregabalin 225?mg BID to placebo, duloxetine, gabapentin, tramadol, milnacipran, and amitriptyline in patients with severe fibromyalgia (Fibromyalgia Impact Questionnaire score >59; pain score >6.5). The model estimated response rates for all treatments at 12 weeks based on three randomized trials with pregabalin and a systematic review of published randomized controlled trials. Response was categorized as ≥30% improvement in baseline pain score plus global impression of change rating of much improved or very much improved. After 12 weeks of treatment, responders to treatment entered a treatment Markov model in which response was maintained, lost, or treatment discontinued. The cost-effectiveness end-points were cost per responder at 12 weeks and 1 year. Resource use was estimated from published studies and costs were estimated from the societal perspective.

Results:

Over 12 weeks, total cost per patient was $229 higher with pregabalin 150?mg BID than placebo, whereas pregabalin 225?mg BID was $866 less costly than placebo. At 1 year, pregabalin was cost saving and more effective than placebo, duloxetine, tramadol, milnacipran, and gabapentin. Compared with amitriptyline, pregabalin was not cost-effective at both dosages, although when excluding old and methodologically weak studies of clinical effectiveness of amitriptyline, pregabalin 225?mg BID became cost saving and pregabalin 150?mg BID was cost-effective.

Limitations:

Comparisons between pregabalin and other active agents are based on indirect comparisons, not head-to-head trials, and so should be interpreted with caution. Limitations for comparators include an inability to access sub-group data, inconsistency of response definitions, inclusion of older trials, and absence of long-term studies.

Conclusions:

This model found pregabalin to be cost-effective in treating patients with severe fibromyalgia.