Cost-effectiveness of tapentadol prolonged release compared with oxycodone controlled release in the UK in patients with severe non-malignant chronic pain who failed 1st line treatment with morphine

Abstract

Objectives:

The aim of this analysis was to assess the cost-effectiveness of tapentadol PR (prolonged release) compared with oxycodone CR (controlled release) in severe non-malignant chronic pain patients in whom controlled release morphine was ineffective or not tolerated.

Methods:

A Markov model was developed to assess costs and benefits over a 1-year time horizon from the National Health Service perspective in the UK. Patients could either continue on 2nd line therapy or switch to 3rd line opioid due to lack of efficacy or poor tolerability. Patients failing also 3rd line therapy entered the final absorbing health state (4th line). Data on tolerability, efficacy, and utilities for tapentadol and oxycodone were obtained from the three comparative phase III clinical trials. Costs of resource consumption associated with opioid treatment were derived from a retrospective database analysis of anonymized patient records.

Results:

The model results predicted that initiating 2nd line therapy with tapentadol leads to higher effectiveness and lower costs vs oxycodone. For the overall population included in the clinical trials, mean annual costs per patient when treated with tapentadol and oxycodone were £3543 and £3656, respectively. Treatment with tapentadol, while cheaper than oxycodone, was more effective (0.6371 vs 0.6237 quality-adjusted life years (QALYs) for tapentadol and oxycodone, respectively), meaning that tapentadol dominated oxycodone. For the sub-group of opioid-experienced patients with severe pain at baseline the ranking in terms of costs and QALYs remained unchanged. Extensive sensitivity analyses showed that conclusions about the cost-effectiveness are consistent.

Conclusions:

The cost-effectiveness study suggested that initiating 2nd line treatment in patients with severe non-malignant chronic pain in the UK with tapentadol instead of oxycodone improves patients’ quality-of-life and is less costly. Key limitations when interpreting the results are the use of different sources to populate the model and restricted generalizability due to data extrapolation.     

Quality of life benefits and cost impact of prolonged release oxycodone/naloxone versus prolonged release oxycodone in patients with moderate-to-severe non-malignant pain and opioid-induced constipation: a UK cost-utility analysis

Abstract

Objective:

To compare the cost effectiveness of prolonged release oxycodone/naloxone (OXN) tablets (Targinact) and prolonged release oxycodone (OXY) tablets (OxyContin) in patients with moderate-to-severe non-malignant pain and opioid-induced constipation (OIC) from the perspective of the UK healthcare system.

Methods:

A cohort model used data from a phase III randomised, controlled trial (RCT). It calculated the cost difference between treatments by combining the cost of pain therapy with costs of laxatives and other resources used to manage constipated patients. SF-36 scores were converted into EQ-5D utility values to calculate the quality-adjusted life-year (QALY) gains. Deterministic and probabilistic sensitivity analyses were performed.

Results:

The incremental cost of OXN versus OXY was £159.68 for the average treatment duration of 301 days. OXN gave an incremental QALY gain of 0.0273. The estimated incremental cost-effectiveness ratio (ICER) was £5841.56 per QALY. Sensitivity analyses gave a maximum ICER of £10,347.03. In some scenarios, OXN dominated with a cost saving of up to £4254.70. Probabilistic sensitivity analysis showed that OXN had approximately 96.6% probability of cost effectiveness at the £20,000 threshold.

Limitations:

The model was conservative in predicting the probability of constipation beyond the 12-week RCT period. UK cost of constipation data were limited and based on primary care physician opinion.

Conclusions:

In the base case, direct treatment costs were slightly higher for patients treated with OXN than for those treated with OXY. However, patients treated with OXN experienced a quality of life gain, and had an ICER considerably below thresholds commonly applied in the UK. The model was most sensitive to the estimated cost of constipation with a number of realistic scenarios in the sensitivity analysis demonstrating a cost saving with OXN (OXN dominant). OXN is therefore estimated to be a cost-effective option for treating patients with severe non-malignant pain and OIC.     

Within trial cost-utility analysis of disease management program for patients hospitalized with atrial fibrillation: results from the SAFETY trial

Abstract

Background: The potential impact of disease management to optimize quality of care, health outcomes, and total healthcare costs across a range of cardiac disease states is unknown.

Methods: A trial-based cost-utility analysis was conducted alongside a randomized controlled trial of 335 patients with chronic, non-valvular AF (without heart failure; the SAFETY Trial) discharged to home from three tertiary referral hospitals in Australia. A home-based disease management intervention (the SAFETY intervention) that involved community-based AF care including home visits was compared to routine primary healthcare and hospital outpatient follow-up (standard management). Bootstrapped incremental cost-utility ratios were computed based on quality-adjusted life-years (QALYs) and total healthcare costs. Cost-effectiveness acceptability curves were constructed to explore the probability of the SAFETY intervention being cost-effective. Sub-group analyses were performed based on age and sex to determine differential cost-effectiveness.

Results: During median follow-up of 1.75?years, the SAFETY intervention was associated with a non-statistically significant increase in QALYs (0.02 per person) and lower total healthcare costs (–$4,375 per person). Although each of these findings were not statistically significant, the SAFETY intervention was found to be dominant (more effective and cost saving) in 58.8% of the bootstrapped iterations and cost-effective (more effective and gains in QALYs achieved at or below $50,000 per QALY gained) in 61.5% of the iterations. Males and those aged less than 78?years achieved greater gains in QALYs and savings in healthcare costs. The estimated value of perfect information in Australia (the monetized value of removing uncertainty in the cost-effectiveness results) was A$51 million, thus demonstrating the high potential gain from further research.

Conclusions: Compared with standard management, the SAFETY intervention is potentially a dominant strategy for those with chronic, non-valvular AF. However, there would be substantial value in reducing the uncertainty in these estimates from further research.

Trial registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12610000221055.     

Cost-utility of risperidone compared with standard conventional antipsychotics in chronic schizophrenia

SUMMARY

The high costs and the efficacy of risperidone warrant a systematic pharmacoeconomic evaluation in order to assess its relative cost-utility. The purpose of this study was to evaluate the costs and utilities of treatment in chronic schizophrenia. To achieve this, a cost-utility analysis, which compared risperidone to haloperidol and two depot antipsychotics: haloperidol decanoate and fluphenazine decanoate was conducted. A deterministic decision analysis was used to model chronic schizophrenia over one year. Probabilities were obtained from clinical trials for each medication that were combined using a random effects single arm meta-analysis. Utility values for different health states were obtained by patient interview. A government payer perspective was adopted for this analysis.

The study results demonstrate that risperidone is a dominant therapy in this baseline analysis since it is associated with the lowest overall cost and highest number of quality-adjusted life-years (QALYs). Compared with haloperidol, risperidone might save $6,510 (CAN$) per year while producing 0.04 more QALYs per average patient.     

Estimating the quality-of-life impact and cost-effectiveness of alpha-blocker and anti-muscarinic combination treatment in men with lower urinary tract symptoms related to benign prostatic hyperplasia and overactive bladder

Abstract

Objective:

A 12-week clinical trial (TIMES) demonstrated that therapy with tolterodine extended release (TOL)?+?tamsulosin (TAM) provides clinical benefits vs TOL or TAM monotherapy or placebo (PBO) in men with lower urinary tract symptoms (LUTS) including overactive bladder (OAB). The present analysis estimated the costs and quality-adjusted life-years (QALYs) associated with these therapies from the perspective of the UK healthcare system.

Methods:

TIMES cohorts receiving TOL, TAM, TOL?+?TAM, or PBO were followed from therapy initiation to 12 weeks. A decision-tree model was used to extrapolate the 12-week results to 1 year (including need for surgery owing to treatment failure at 12 weeks) and to track patients’ outcomes (symptoms, utility, and costs). Because TIMES did not include costs and QALYs, data from the EpiLUTS epidemiologic survey (12,796 males) were used to model a mathematical relationship between LUTS (daytime and nocturnal frequency, urgency episodes, urgency urinary incontinence episodes, and International Prostate Symptom Score [IPSS]), quality-of-life, and utility. This was used to convert improvements in TIMES patients’ LUTS into utility scores and QALYs. The model included drug and surgery procedure costs and hospital length of stay.

Results:

Incremental QALYs of TOL?+?TAM vs PBO, TAM, and TOL were 0.042, 0.021, and 0.013, and corresponding incremental costs were £189, £223, and ?£70, respectively, resulting in cost-utility ratios for TOL?+?TAM of £4508/QALY gained compared with PBO and £10,381/QALY gained compared with TAM. TOL?+?TAM combination therapy was both more effective and cost-saving compared with TOL. Univariate sensitivity analyses showed that patient utility was most responsive to changes in drug efficacy on IPSS and urgency episodes. Changing the percentage of patients undergoing surgery did not substantially affect model outcomes. The main limitation of the study was that the relation between LUTS and patient utility was based on an indirect association.

Conclusions:

TOL?+?TAM combination therapy appears to be cost-effective compared with TOL or TAM monotherapy or PBO in male patients with LUTS.     

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.     

Cost effectiveness analysis of immunotherapy in patients with grass pollen allergic rhinoconjunctivitis in Germany

Abstract

Objectives:

An economic evaluation was conducted to assess the outcomes and costs as well as cost-effectiveness of the following grass-pollen immunotherapies: OA (Oralair; Stallergenes S.A., Antony, France) vs GRZ (Grazax; ALK-Abelló, Hørsholm, Denmark), and ALD (Alk Depot SQ; ALK-Abelló) (immunotherapy agents alongside symptomatic medication) and symptomatic treatment alone for grass pollen allergic rhinoconjunctivitis.

Methods:

The costs and outcomes of 3-year treatment were assessed for a period of 9 years using a Markov model. Treatment efficacy was estimated using an indirect comparison of available clinical trials with placebo as a common comparator. Estimates for immunotherapy discontinuation, occurrence of asthma, health state utilities, drug costs, resource use, and healthcare costs were derived from published sources. The analysis was conducted from the insurant’s perspective including public and private health insurance payments and co-payments by insurants. Outcomes were reported as quality-adjusted life years (QALYs) and symptom-free days. The uncertainty around incremental model results was tested by means of extensive deterministic univariate and probabilistic multivariate sensitivity analyses.

Results:

In the base case analysis the model predicted a cost-utility ratio of OA vs symptomatic treatment of €14,728 per QALY; incremental costs were €1356 (95%CI: €1230; €1484) and incremental QALYs 0.092 (95%CI: 0.052; 0.140). OA was the dominant strategy compared to GRZ and ALD, with estimated incremental costs of ?€1142 (95%CI: ?€1255; ?€1038) and ?€54 (95%CI: ?€188; €85) and incremental QALYs of 0.015 (95%CI: ?0.025; 0.056) and 0.027 (95%CI: ?0.022; 0.075), respectively. At a willingness-to-pay threshold of €20,000, the probability of OA being the most cost-effective treatment was predicted to be 79%. Univariate sensitivity analyses show that incremental outcomes were moderately sensitive to changes in efficacy estimates. The main study limitation was the requirement of an indirect comparison involving several steps to assess relative treatment effects.

Conclusion:

The analysis suggests OA to be cost-effective compared to GRZ and ALD, and a symptomatic treatment. Sensitivity analyses showed that uncertainty surrounding treatment efficacy estimates affected the model outcomes.     

Cost-effectiveness analysis of standalone trabecular micro-bypass stents in patients with mild-to-moderate open-angle glaucoma in Canada

Objectives: To estimate the cost-utility of two trabecular micro-bypass stents (TBS) implantation vs standard of care (SOC) in patients with mild-to-moderate open-angle glaucoma (OAG) in the Canadian healthcare setting.

Methods: The deterioration in visual field (VF) defect over a 15-year time horizon was tracked using a Markov model with Hodapp-Parrish-Anderson stages of glaucoma (mild, moderate, advanced, severe/blind) and death as health states. Meta-analyses of randomized clinical trials were conducted to estimate the pooled reduction in intraocular pressure (IOP) and medication use due to TBS and SOC. The rate of decline in VF loss was adjusted by the extent of IOP reduction to estimate transition probabilities. Healthcare resource utilization, unit costs (2017 CAD), and progression-related utility scores were obtained by literature review, and medication costs with wastage were obtained from IMS Brogan PharmaStat. The impact of parameter and methodological uncertainty on costs and quality-adjusted life years (QALYs) was examined using probabilistic and 1-way sensitivity analyses.

Results: The meta-analysis showed an additional reduction of 1.13 medications/patient and an additional decrease in IOP of –1.10?mmHg at 36?months favoring TBS. TBS strongly dominated medication alone, due to higher improvement in quality-of-life (0.068 QALYs), fewer blind eyes (–0.0031), and a decrease in total healthcare costs of C$2,908.3 per patient over the time horizon (C$9,394.1 TBS vs C$12,302.4 medication alone). Sensitivity analyses showed that results were robust to the uncertainties in model inputs and assumptions. Time-to-dominance was 44?months (3.7?years).

Conclusions: The TBS procedure was cost-effective over SOC in a 15-year time horizon, with quality-of-life gains.     

Impact on health outcome and costs of influenza treatment with oseltamivir in elderly and high-risk patients

Summary

The main objective of this study was to evaluate health outcomes and costs to the healthcare payer of treating influenza with oseltamivir in a high-risk population. Data from published literature, clinical trials and public sources were used to develop a decision-analytic model simulating a high-risk population in the UK. The underlying clinical pathway predicts morbidity and mortality due to influenza, and its specified complications for the two influenza treatment strategies—oseltamivir and usual care. Health outcomes (quality-adjusted life years [QALYs], days to return to normal activity) and costs were estimated for events in the model. Robustness of the results was tested by probabilistic, univariate and multivariate sensitivity analyses.

Treatment with oseltamivir within 48 hours results in reduced morbidity, which translates into faster recovery and return to normal activity. Economic evaluation showed that treatment with oseltamivir in a high-risk population in the UK is a cost-effective strategy in all analysed scenarios with cost-utility ratios between £225 and £17,900 per QALY gained.

Treatment with oseltamivir is effective in terms of health outcome and cost for high-risk patients from the perspectives of the individual patient and healthcare payer.     

Evaluation of the long-term cost-effectiveness of liraglutide therapy for patients with type 2 diabetes in France

Objectives:

The present study aimed to compare the projected long-term clinical and cost implications associated with liraglutide, sitagliptin and glimepiride in patients with type 2 diabetes mellitus failing to achieve glycemic control on metformin monotherapy in France.

Methods:

Clinical input data for the modeling analysis were taken from two randomized, controlled trials (LIRA-DPP4 and LEAD-2). Long-term (patient lifetime) projections of clinical outcomes and direct costs (2013 Euros; €) were made using a validated computer simulation model of type 2 diabetes. Costs were taken from published France-specific sources. Future costs and clinical benefits were discounted at 3% annually. Sensitivity analyses were performed.

Results:

Liraglutide was associated with an increase in quality-adjusted life expectancy of 0.25 quality-adjusted life years (QALYs) and an increase in mean direct healthcare costs of €2558 per patient compared with sitagliptin. In the comparison with glimepiride, liraglutide was associated with an increase in quality-adjusted life expectancy of 0.23 QALYs and an increase in direct costs of €4695. Based on these estimates, liraglutide was associated with an incremental cost-effectiveness ratio (ICER) of €10,275 per QALY gained vs sitagliptin and €20,709 per QALY gained vs glimepiride in France.

Conclusion:

Calculated ICERs for both comparisons fell below the commonly quoted willingness-to-pay threshold of €30,000 per QALY gained. Therefore, liraglutide is likely to be cost-effective vs sitagliptin and glimepiride from a healthcare payer perspective in France.     

Cost-effectiveness of continuous subcutaneous apomorphine in the treatment of Parkinson’s disease in the UK and Germany

Abstract

Background:

Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting ～5.2 million people worldwide. Continuous subcutaneous apomorphine (CSAI) represents an alternative treatment option for advanced PD with motor fluctuation. The purpose of this analysis was to estimate the cost-effectiveness of CSAI compared with Levodopa/carbidopa intestinal gel (LCIG), Deep-Brain-Stimulation (DBS) and Standard-of-care (SOC).

Methods:

A multi-country Markov-Model to simulate the long-term consequences, disease progression (Hoehn & Yahr stages 3–5, percentage of waking-time in the OFF-state), complications, and adverse events was developed. Monte-Carlo simulation accounted for uncertainty. Probabilities were derived from RCT and open-label studies. Costs were estimated from the UK and German healthcare provider’s perspective. QALYs, life-years (LYs), and costs were projected over a life-time horizon.

Results:

UK lifetime costs associated with CSAI amounts to £78,251.49 and generates 2.85 QALYs and 6.28 LYs (€104,500.08, 2.92 QALYs and 6.49 LYs for Germany). Costs associated with LCIG are £130,011.34, achieves 3.06 QALYs and 6.93 LYs (€175,004.43, 3.18 QALYs and 7.18 LYs for Germany). The incremental-cost per QALY gained (ICER) was £244,684.69 (€272,914.58). Costs for DBS are £87,730.22, associated with 2.75 QALYs and 6.38 LYs (€105,737.08, 2.85 QALYs and 6.61 LYs for Germany). CSAI dominates DBS. SOC associated UK costs are £76,793.49; 2.62 QALYs and 5.76 LYs were reached (€90,011.91, 2.73 QALYs and 6 LYs for Germany).

Conclusions:

From a health economic perspective, CSAI is a cost-effective therapy and could be seen as an alternative treatment to LCIG or DBS for patients with advanced PD.     

Validation of the Bowel Function Index to detect clinically meaningful changes in opioid-induced constipation

Abstract

Objective: The Bowel Function Index (BFI) is a clinician-administered, patient-reported, 3-item questionnaire to evaluate opioid-induced constipation in cancer and non-cancer chronic pain patients. The objective of the present analysis was to evaluate the psychometric characteristics of the BFI using data from clinical studies of oral prolonged release (PR) oxycodone/naloxone.

Methods: OXN2401 was a multicenter, controlled, randomized, double-blind, parallel-group study including oral PR oxycodone combined with oral PR naloxone as well as oral PR oxycodone combined with corresponding naloxone placebo. OXN3401 and OXN3001 were 12-week multicenter, controlled, randomized, double-blind, parallel-group studies of a fixed combination of oral PR oxycodone/naloxone versus PR oxycodone. In addition, a placebo group was included in study OXN3401. BFI psychometric characteristics (reliability, reproducibility, convergent/known groups validity, and responsiveness) were evaluated.

Results: Demographic data (n=985) were comparable and analyses indicated a high degree of internal consistency (Cronbach's alpha >0.7). Change of less than 5 points in BFI was indicative of high reproducibility. Correlations between BFI item and total scores to stool frequency were statistically significant and in the low-to-moderate range (OXN2401 –0.23 to –0.29, p < 0.001; OXN3401 range –0.26 to –0.40, p < 0.001; OXN3001 –0.14 to –0.15, p < 0.05). Data indicate that a BFI score change of ≥12 points represents a clinically meaningful change in constipation.

Limitations: This publication for validation of BFI only includes data from three clinical trials. However, another publication of an additional specifically designed cross-sectional validation study is in preparation.

Conclusion: The BFI is a valid and reliable instrument for the assessment of opioid-induced constipation in chronic pain patients. Psychometric analyses from clinical trials support the BFI's psychometric properties.     

The cost-effectiveness of alectinib in anaplastic lymphoma kinase-positive (ALK+) advanced NSCLC previously treated with crizotinib

Introduction Anaplastic lymphoma kinase (ALK) targeting drugs provide an important option for advanced non-small cell lung cancer patients with this distinct tumor type; however, there is considerable uncertainty as to which drug provides the optimal value after crizotinib treatment. This study estimated the cost-utility of alectinib vs ceritinib from a US payer perspective.

Methods A cost-utility model was developed using partition survival methods and three health states: progression-free (PF), post-progression (PP), and death. Survival data were derived from the key clinical trials (alectinib: NP28761 &; NP28673, ceritinib: ASCEND I and II). Costs included drugs, adverse events, and supportive care. Utilities were based on trial data and the literature. One-way and probabilistic sensitivity analyses (PSA) were performed to assess parameter uncertainty.

Results Treatment with alectinib vs ceritinib resulted in increases of 2.55 months in the PF state, 0.44 quality adjusted life-years (QALYs), and $13,868, yielding a mean cost/QALY of $31,180. In the PSA, alectinib had a 96% probability of being cost-effective at a willingness-to-pay of $100,000/QALY. Drivers of model results were drug costs and utilities in the PF health state. The ICER ranged from $10,600–$65,000 per QALY in scenario analyses, including a sub-group analysis limited to patients with prior chemotherapy and crizotinib treatment.

Conclusions Treatment with alectinib in ALK?+?crizotinib-treated patients increased time progression-free and QALYs vs ceritinib. The marginal cost increase was driven by longer treatment durations with alectinib. This model demonstrates that alectinib may be considered a cost-effective treatment after progression on crizotinib.     

Evaluation of the cost-utility of insulin degludec vs insulin glargine in Sweden

Abstract

Objective:

To evaluate the annual cost-utility of insulin degludec compared with glargine in patients with: type 1 diabetes (T1D), type 2 diabetes receiving basal-only therapy (T2D-BOT), and type 2 diabetes receiving basal-bolus therapy (T2B-BB) in Sweden.

Methods:

A cost-utility model was programmed in Microsoft Excel to evaluate clinical and economic outcomes. The clinical trials were designed as treat-to-target, with insulin doses adjusted in order to achieve similar glycemic control between treatments, thus long-term modeling is not meaningful. Basal and bolus insulin doses, incidence of hypoglycemic events, frequency of self-monitoring of blood glucose, and possibility for flexibility in timing of dose administration were specified for each insulin in three diabetes populations, based on data collected in Swedish patients with diabetes and a meta-analysis of clinical trials with degludec. Using these characteristics, the model estimated costs from a societal perspective and quality-adjusted life years (QALYs) in the two scenarios.

Results:

Use of degludec was associated with a QALY gain compared with glargine in T1D (0.31 vs 0.26?QALYs), T2D-BOT (0.76 vs 0.69?QALYs), and T2D-BB (0.56 vs 0.47?QALYs), driven by reduced incidence of hypoglycemia and possibility for flexibility around timing of dose administration. Therapy regimens containing degludec were associated with increased costs compared to glargine-based regimens, driven by the increased pharmacy cost of basal insulin, but partially offset by other cost savings. Based on estimates of cost and clinical outcomes, degludec was associated with incremental cost-effectiveness ratios of SEK 19,766 per QALY gained, SEK 10,082 per QALY gained, and SEK 36,074 per QALY gained in T1D, T2-BOT, and T2-BB, respectively.

Limitations:

The hypoglycemic event rates in the base case analysis were derived from a questionnaire-based study that relied on patient interpretation and recall of hypoglycemic symptoms. The relative rates of hypoglycemia with degludec compared to glargine were derived from a meta-analysis of phase III trials, which may not reflect the relative rates observed in real-world clinical practice. Both of these key limitations were explored in one-way sensitivity analyses.

Conclusions:

Based on reduced incidence of hypoglycemia and possibility for flexibility around timing of dose administration, use of degludec is likely to be cost-effective compared to glargine from a societal perspective in T1D, T2-BOT, and T2-BB in Sweden over a 1-year time horizon.     

Cost-effectiveness of dabigatran etexilate in the prevention of stroke and systemic embolism in patients with atrial fibrillation in Belgium

Abstract

Objective:

To assess the cost-effectiveness of dabigatran etexilate (‘dabigatran’) vs vitamin K antagonists (VKAs) in the Belgian healthcare setting for the prevention of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (AF).

Research design and methods:

A Markov model was used to calculate the cost-effectiveness of dabigatran vs VKAs in Belgium, whereby warfarin was considered representative for the VKA class. Efficacy and safety data were taken from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial and a network meta-analysis. Local resource use and unit costs were included in the model. Effectiveness was expressed in Quality Adjusted Life-Years (QALYs). The model outcomes were total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). The level of International Normalized Ratio (INR) control and the use of other antithrombotic therapies observed in Belgian clinical practice were reflected in two scenario analyses.

Results:

In the base case analysis, total costs per patient were €13,333 for dabigatran and €12,454 for warfarin. Total QALYs per patient were 9.51 for dabigatran and 9.19 for warfarin. The corresponding ICER was €2807/QALY. The ICER of dabigatran was €970/QALY vs warfarin with real-world INR control and €5296/QALY vs a mix of warfarin, aspirin, and no treatment. Results were shown to be robust in one-way and probabilistic sensitivity analyses.

Limitations:

The analysis does not include long-term costs for clinical events, as these data were not available for Belgium. As in any economic model based on data from a randomized clinical trial, several assumptions had to be made when extrapolating results to routine clinical practice in Belgium.

Conclusion:

This analysis suggests that dabigatran, a novel oral anticoagulant, is a cost-effective treatment for the prevention of stroke and SE in patients with non-valvular AF in the Belgian healthcare setting.     

Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes

Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches.

Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs).

Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained).

Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost, outcomes, and incremental cost-utility.     

Cost-effective analysis of clopidogrel versus aspirin for high risk patients with established peripheral arterial disease in China

Abstract

Objective: To assess the cost-effectiveness of clopidogrel versus aspirin for high risk patients (pre-existing symptomatic atherosclerosis or multi-vascular territory involvement) with established peripheral arterial disease (PAD) for secondary prevention of atherothrombotic events in a Chinese setting.

Methods: A Markov model with a lifetime horizon was developed from the perspective of the national healthcare system in China. The primary outputs are quality adjusted life years (QALYs), direct medical costs, and the incremental cost-effectiveness ratios (ICERs). Clinical efficacy data were obtained from the CAPRIE trial. Drug acquisition cost, other direct medical costs, and utilities were from pricing records and the literature. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted to test the robustness of the model on all parameters.

Results: In patients with pre-existing atherosclerosis, 2 years of treatment with clopidogrel and aspirin would yield total QALYs of 8.776 and 8.576 at associated costs of ¥18,777 ($2,838) and ¥12,302 ($1,859), respectively, resulting in an ICER of ¥32,382 ($4,893) per QALY gained. In patients with PVD, secondary prevention with the same drugs would expect to lead to total QALYs of 8.836 and 8.632 at associated costs of ¥18,518 ($2,798) and ¥12,041 ($1,820), respectively, resulting in a corresponding ICER of ¥31,743 ($4,797) per QALY gained. The results were most sensitive to the discount rate for future outcomes and costs. The PSA indicated that the probability of clopidogrel being cost-effective was 100% at the willingness-to-pay threshold of 3-times GDP.

Conclusions: Secondary prevention with clopidogrel is an attractive cost-effective option compared with aspirin for high risk patients with established PAD from the perspective of the national healthcare system in Chinese settings.     

Cost-effectiveness of intravitreal aflibercept versus other treatments for wet age-related macular degeneration in Japan

Objective: This analysis estimated the cost-effectiveness of intravitreal aflibercept injection(s) (IAI) for wet age-related macular degeneration (wAMD) compared with other treatments in Japan.

Methods: This was a cost-utility analysis based on published data. A state-transition cohort model was constructed with six health states based on best-corrected visual acuity in the better-seeing eye. The cycle time was 4 weeks, and the time horizon was 12 years. The model compared IAI 2?mg every 8 weeks (2q8) for 2 years after three initial monthly injections, ranibizumab as needed, ranibizumab 0.5?mg every 4 weeks (0.5q4), pegaptanib sodium 0.3?mg every 6 weeks, verteporfin photodynamic therapy (PDT), and best supportive care, assumed to include medical management and monitoring, but no active therapy. Costs (expressed as Japanese yen [JPY]) and quality-adjusted life years (QALYs) gained were estimated for each treatment and discounted at 2.0%. Input data were obtained from clinical studies, the Japanese drug tariff and social insurance reimbursement schedule, and expert opinion. The analysis was conducted from the societal perspective, including medical costs as well as costs of blindness.

Results: IAI 2q8 was dominant (i.e. more effective in terms of QALYs and less costly) to all other comparators (ranibizumab as needed, ranibizumab 0.5q4, pegaptanib sodium, PDT, and best supportive care), as shown by the incremental cost-utility ratio (i.e. cost per QALY gained).

Limitations: The strengths of the analysis include the wide range of comparators evaluated and the use of Japanese-specific utility data. The limitations include the use of one eye, inclusion of published data up to 2 years only, and assumptions on disease course over 5 years.

Conclusions: IAI 2q8 was more effective in terms of QALYs and less costly compared with other treatments for wAMD in Japan.     

Clinical simulation model of long-acting opioids for treatment of chronic non-cancer pain in the United States

Abstract

Objective:

To evaluate costs and outcomes associated with initial tapentadol ER vs oxycodone CR for the treatment of chronic non-cancer pain (CNCP) in the US.