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 analysis of roflumilast/tiotropium therapy versus tiotropium monotherapy for treating severe-to-very severe COPD

Abstract

Objective:

To conduct a cost-effectiveness analysis comparing roflumilast/tiotropium therapy vs tiotropium monotherapy in patients with severe-to-very severe COPD.

Methods:

The economic evaluation applied a disease-based Markov cohort model with five health states: (1) severe COPD, (2) severe COPD with a history of severe exacerbation, (3) very severe COPD, (4) very severe COPD with a history of severe exacerbation, and (5) death. Within a given health state, a patient may have a mild/moderate or severe exacerbation or die. Data from roflumilast clinical trials and published literature were used to populate model parameters. The model calculated health outcomes and costs for roflumilast/tiotropium therapy vs tiotropium monotherapy over a 5-year horizon. Incremental cost and benefits were then calculated as cost-effectiveness ratios, including cost per exacerbation avoided and cost per quality adjusted life year ($/QALY).

Results:

Over a 5-year horizon, the estimated incremental costs per exacerbation and per severe exacerbation avoided were $589 and $5869, respectively, and the incremental cost per QALY was $15,815. One-way sensitivity analyses varying key parameters produced an incremental cost per QALY ranging from $1963–$32,773.

Limitations:

A number of key parameters used in the model were obtained from studies in the literature that were conducted under different contexts. Specifically, the relative risk estimate for severe COPD patients originates from a small trial not designed to demonstrate the impact of roflumilast on frequency of exacerbations. In addition, the model extrapolates the relative risk estimates over periods of 5–30 years, even though the estimates were only observed in trials that spanned less than a year.

Conclusions:

The addition of roflumilast to tiotropium is cost-effective for the treatment of severe to very severe COPD patients.     

Economic evaluation of ezetimibe treatment in combination with statin therapy in the United States

Aims: This study assessed the cost-effectiveness of ezetimibe with statin therapy vs statin monotherapy from a US payer perspective, assuming the impending patent expiration of ezetimibe.

Methods: A Markov-like economic model consisting of 28 distinct health states was used. Model population data were obtained from US linked claims and electronic medical records, with inclusion criteria based on diagnostic guidelines. Inputs came from recent clinical trials, meta-analyses, and cost-effectiveness analyses. The base-case scenario was used to evaluate the cost-effectiveness of adding ezetimibe 10?mg to statin in patients aged 35–74 years with a history of coronary heart disease (CHD) and/or stroke, and with low-density lipoprotein cholesterol (LDL-C) levels ≥70?mg/dL over a lifetime horizon, assuming a 90% price reduction of ezetimibe after 1 year to take into account the impending patent expiration in the second quarter of 2017. Sub-group analyses included patients with LDL-C levels ≥100?mg/dL and patients with diabetes with LDL-C levels ≥70?mg/dL.

Results: The lifetime discounted incremental cost-effectiveness ratio (ICER) for ezetimibe added to statin was $9,149 per quality-adjusted life year (QALY) for the base-case scenario. For patients with LDL-C levels ≥100?mg/dL, the ICER was $839/QALY; for those with diabetes and LDL-C levels ≥70?mg/dL, it was $560/QALY. One-way sensitivity analyses showed that the model was sensitive to changes in cost of ezetimibe, rate reduction of non-fatal CHD, and utility weight for non-fatal CHD in the base-case and sub-group analyses.

Limitations: Indirect costs or treatment discontinuation estimation were not included.

Conclusions: Compared with statin monotherapy, ezetimibe with statin therapy was cost-effective for secondary prevention of CHD and stroke and for primary prevention of these conditions in patients whose LDL-C levels are ≥100?mg/dL and in patients with diabetes, taking into account a 90% cost reduction for ezetimibe.     

Cost effectiveness of rosuvastatin in patients at risk of cardiovascular disease based on findings from the JUPITER trial

Abstract

Objective:

This study assessed the long-term cost effectiveness of rosuvastatin therapy compared with placebo in reducing the incidence of major cardiovascular (CVD) events and mortality.

Methods:

A probabilistic Monte Carlo simulation model estimated long-term cost effectiveness of rosuvastatin therapy (20?mg daily) for the prevention of CVD mortality and morbidity. The model included three stages: (1) CVD prevention simulating the 4 years of the JUPITER trial, (2) initial CVD prevention beyond the trial, and (3) subsequent CVD event prevention. A US payer perspective was assessed reflecting direct medical costs, and up to a lifetime horizon. Sensitivity analyses tested the robustness of the model estimates.

Results:

For a hypothetical cohort of 100,000 patients at moderate and high risk of CVD events based on Framingham risk of ≥10%, estimated quality-adjusted life-years (QALYs) gained with rosuvastatin therapy compared with placebo was 33,480 over a lifetime horizon, and 25,380 and 9916 over 20-year and 10-year horizons, respectively. Approximately 12,073 events were avoided over the lifetime; 6,146 non-fatal MIs, 2905 non-fatal strokes, and 4030 CVD deaths avoided. Estimated incremental cost-effectiveness ratio (ICER) for cost per QALY was $7062 (lifetime), $10,743 (20-year horizon), and $44,466 (10-year horizon). For a hypothetical cohort similar to the overall JUPITER population, the cost per QALY ICER was $11,025 for the lifetime and $60,112 for a 10-year horizon.

Limitations:

The cost-effectiveness comparison of rosuvastatin 20?mg was against no active treatment (as opposed to an alternative statin) due to lack of comparative cardiovascular morbidity and mortality risk reduction data for other statins in a population similar to the JUPITER trial population. The analysis was conducted from the payer perspective and lack of inclusion of indirect costs limit interpretability of results from a societal perspective.

Conclusions:

Treatment with rosuvastatin 20?mg daily, is a cost-effective treatment alternative to no treatment in patients at a higher risk (Framingham risk ≥10%) of CVD.     

Cost-effectiveness of hydrophilic-coated intermittent catheters compared with uncoated catheters in Canada: a public payer perspective

Study design: A Markov model was used to analyze cost-effectiveness over a lifetime horizon.

Objective: To investigate the cost-effectiveness of hydrophilic-coated intermittent catheters (HCICs) compared with uncoated catheters (UCs) among individuals with neurogenic bladder dysfunction (NB) due to spinal cord injury (SCI).

Setting: A Canadian public payer perspective based on data from Ontario; including a scenario analysis from the societal perspective.

Methods: A previously published Markov decision model was modified to compare the lifetime costs and quality-adjusted life years (QALYs) for the two interventions. Three renal function and three urinary tract infection (UTI) health states as well as other catheter-related events were included. Scenario analyses, including utility gain from compact catheter and phthalate free catheter use, were performed. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness of the model.

Results: The model predicted that a 50-year-old patient with SCI would gain an additional 0.72 QALYs if HCICs were used instead of UCs at an incremental cost of $48,016, leading to an incremental cost-effectiveness ratio (ICER) of $66,634/QALY. Moreover, using HCICs could reduce the lifetime number of UTI events by 11%. From the societal perspective, HCICs cost less than UCs, while providing superior outcomes in terms of QALYs, life years gained (LYG), and UTIs. The cost per QALY further decreased when health-related quality-of-life (HRQoL) gains associated with compact HCICs or catheters not containing phthalates were included.

Conclusion: In general, ICERs in the range of CAD$50–100,000 could be considered cost-effective. The ICERs for the base case and sensitivity analyses suggest that HCICs could be cost-effective. From the societal perspective, HCICs were associated with potential cost savings in our model. The results suggest that reimbursement of HCICs should be considered in these settings.     

Febuxostat in the management of gout: a cost-effectiveness analysis

Objective:

To determine the cost-effectiveness of febuxostat vs allopurinol for the management of gout.

Methods:

A stochastic microsimulation cost-effectiveness model with a US private-payer perspective and 5-year time horizon was developed. Model flow based on guideline and real-world treatment paradigms incorporated gout flare, serum uric acid (sUA) testing, treatment titration, discontinuation, and adverse events, chronic kidney disease (CKD) incidence and progression, and type 2 diabetes mellitus (T2DM) incidence. Outcomes were estimated for the general gout population and for gout patients with CKD stages 3/4. Modeled treatment interventions were daily oral febuxostat 40–80?mg and allopurinol 100–300?mg. Baseline patient characteristics were taken from epidemiologic studies, efficacy data from randomized controlled trials, adverse event rates from package inserts, and costs from the literature, government sources, and expert opinion. Eight clinically-relevant incremental cost-effectiveness ratios were estimated: per patient reaching target sUA, per flare avoided, per CKD incidence, progression, stages 3/4 progression, and stage 5 progression avoided, per incident T2DM avoided, and per death avoided.

Results:

Five-year incremental cost-effectiveness ratios for the general gout population were $5377 per patient reaching target sUA, $1773 per flare avoided, $221,795 per incident CKD avoided, $29,063 per CKD progression avoided, $36,018 per progression to CKD 3/4 avoided, $71,426 per progression to CKD 5 avoided, $214,277 per incident T2DM avoided, and $217,971 per death avoided. In patients with CKD 3/4, febuxostat dominated allopurinol for all cost-effectiveness outcome measures.

Conclusions:

Febuxostat may be a cost-effective alternative to allopurinol, especially for patients with CKD stages 3 or 4.     

Cost-effectiveness of delayed-release dimethyl fumarate for the treatment of relapsing forms of multiple sclerosis in the United States

Objective:

To assess the cost-effectiveness of delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF), an effective therapy for relapsing forms of multiple sclerosis (MS), compared with glatiramer acetate and fingolimod, commonly used treatments in the US.

Methods:

A Markov model was developed comparing delayed-release DMF to glatiramer acetate and fingolimod using a US payer perspective and 20-year time horizon. A cohort of patients, mean age 38 years, with relapsing-remitting MS and Kurtzke Expanded Disability Status Scale (EDSS) scores between 0–6 entered the model. Efficacy and safety were estimated by mixed-treatment comparison of data from the DEFINE and CONFIRM trials and clinical trials of other disease-modifying therapies. Data from published studies were used to derive resource use, cost, and utility inputs. Key outcomes included costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Alternative scenarios tested in a sensitivity analysis included drug efficacy, EDSS-related or relapse-related costs, alternative perspectives, drug acquisition costs, and utility.

Results:

Base-case results with a 20-year time horizon indicated that delayed-release DMF increased QALYs +0.450 or +0.359 compared with glatiramer acetate or fingolimod, respectively. Reductions in 20-year costs with delayed-release DMF were ?$70,644 compared with once-daily glatiramer acetate and ?$32,958 compared with fingolimod. In an analysis comparing delayed-release DMF to three-times-weekly glatiramer acetate and assuming similar efficacy and safety to the once-daily formulation, 20-year costs with delayed-release DMF were increased by $15,806 and cost per QALY gained was $35,142. The differences in costs were most sensitive to acquisition cost and inclusion of informal care costs and productivity losses. The differences in QALYs were most sensitive to the impact of delayed-release DMF on disease progression and the EDSS utility weights.

Conclusion:

Delayed-release DMF is likely to increase QALYs for patients with relapsing forms of MS and be cost-effective compared with fingolimod and glatiramer acetate.     

Cost-effectiveness of second-line atezolizumab in Canada for advanced non-small cell lung cancer (NSCLC)

Aim: To assess the cost-effectiveness in Canada of atezolizumab compared with docetaxel or nivolumab for the treatment of advanced NSCLC after first-line platinum-doublet chemotherapy.

Materials and methods: A three-state partitioned-survival model was developed. Clinical inputs were obtained from the phase III OAK trial comparing atezolizumab with docetaxel in patients with advanced NSCLC who progressed after first-line platinum-doublet chemotherapy. Overall survival (OS) and progression-free survival (PFS) were extrapolated beyond the trial period using parametric models. A cure model assuming a 1% cure fraction was fitted to the OS data for atezolizumab. Outcomes for nivolumab were informed by a network meta-analysis (NMA) vs atezolizumab. Resource use and costs were informed by clinical expert opinion and published Canadian sources. Utility values were obtained from the OAK trial. The perspective of the analysis was that of the Canadian publicly-funded healthcare system. The base case time horizon was 10?years, and the discount rate was 1.5% annually for both costs and effects. Scenario analyses were performed to test the robustness of the results and all analyses were performed probabilistically.

Results: Atezolizumab demonstrated a quality-adjusted life-year (QALY) gain of 0.60 compared with docetaxel at an incremental cost of $85,073, resulting in an incremental cost-effectiveness ratio (ICER) of $142,074/QALY. Atezolizumab dominated nivolumab (regardless of dosing regimen), based on modest differences in both QALYs and costs. Docetaxel was most likely to be cost effective at willingness-to-pay (WTP) thresholds below $125,000/QALY gained, while atezolizumab was most likely to be cost effective beyond this WTP threshold. In most scenario analyses, the results remained robust to changes in parameters. A reduced time horizon and alternative approaches to the NMA had the greatest impact on cost-effectiveness results.

Conclusion: Atezolizumab represents a cost-effective therapeutic option in Canada for the treatment of patients with advanced NSCLC who progress after first-line platinum doublet chemotherapy.     

Cost-effectiveness of pembrolizumab for the adjuvant treatment of resected high-risk stage III melanoma in the United States

Abstract

Aims: To evaluate the cost-effectiveness of adjuvant pembrolizumab relative to observation alone following complete resection of high-risk stage III melanoma with lymph node involvement, from a US health system perspective.

Materials and methods: A Markov cohort model with four health states (recurrence-free, locoregional recurrence, distant metastases, and death) was developed to estimate costs, life-years, and quality-adjusted life-years (QALYs) associated with pembrolizumab vs observation over a lifetime (46-year) horizon. Using a parametric multi-state modeling approach, transition probabilities starting from recurrence-free were estimated based on patient-level data from KEYNOTE-054 (NCT02362594), a direct head-to-head phase 3 trial. Post-recurrence transition probabilities were informed by real-world retrospective data and clinical trials in advanced melanoma. Health state utilities and adverse event-related disutility were derived from KEYNOTE-054 trial data and published literature. Costs of drug acquisition and administration, adverse events, disease management, and terminal care were estimated in 2018?US dollars. Deterministic and probabilistic sensitivity analyses were conducted to assess robustness.

Results: Over a lifetime horizon, adjuvant pembrolizumab and observation were associated with total QALYs of 9.24 and 5.95, total life-years of 10.54 and 7.15, and total costs of $489,820 and $440,431, respectively. The resulting incremental cost-effectiveness ratios (ICERs) for pembrolizumab vs observation were $15,009/QALY and $14,550/life-year. Across the range of input values and assumptions tested in deterministic sensitivity analyses, pembrolizumab ranged from being a dominant strategy to having an ICER of $57,449/QALY vs observation. The ICER was below a willingness-to-pay threshold of $100,000/QALY in 90.2% of probabilistic simulations.

Limitations: Long-term extrapolation of outcomes was based on interim results from KEYNOTE-054, with a median follow-up of 15?months.

Conclusions: Based on common willingness-to-pay benchmarks, pembrolizumab is highly cost-effective compared with observation alone for the adjuvant treatment of completely resected stage III melanoma in the US.     

Economic analysis of bevacizumab,cetuximab, and panitumumab with fluoropyrimidine-based chemotherapy in the first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC)

Abstract

Objective:

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Canada (excluding non-melanoma skin cancers). Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds to human vascular endothelial growth factor. A sub-study confirmed its effectiveness in KRAS wild-type patients. Recent evidence has shown clinical benefit from anti-epidermal growth factor treatments cetuximab and panitumumab in these patients. The cost-effectiveness, to the Canadian healthcare system, of fluoropyrimidine-based chemotherapy (FBC) in combination with bevacizumab, cetuximab, or panitumumab was assessed for first-line treatment of KRAS wild-type mCRC patients.

Methods:

A Markov model was developed and calibrated to progression-free/overall survival, using separately reported trial survival and adverse event results for each comparator. Health-state resource utilization was derived from published data and oncologist input. Utilities and unit prices were obtained from published literature and standard Canadian sources.

Results:

Results per patient are over a lifetime horizon, to a maximum of 10 years, with 5% annual discounting. Comparators are ordered by total cost and the incremental cost-effectiveness ratio (ICER) of each is determined against the previous non-dominated therapy. Compared to FBC alone, bevacizumab?+?FBC has an ICER of $131,600 per QALY gained. Compared to bevacizumab?+?FBC, panitumumab?+?FBC is dominated and cetuximab?+?FBC has an ICER of $3.8 million per QALY. In probabilistic sensitivity analysis, bevacizumab?+?FBC had ～100%, ～100%, and 98.9% probabilities of being more cost-effective than both of the other combination treatments at thresholds of $50,000/QALY, $100,000/QALY, and $200,000/QALY, respectively.

Conclusion:

For first-line treatment of KRAS-WT mCRC, bevacizumab?+?FBC is associated with substantially lower costs as compared to panitumumab?+?FBC or cetuximab?+?FBC. Key limitations were that survival curves and adverse event rates were taken from separate clinical trials and that an indirect comparison was not included. Given these findings, bevacizumab is likely to offer the best value for money for this patient population.     

Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction

Background: Sacubitril/valsartan reduces cardiovascular death and hospitalizations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care.

Aims: To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective.

Methods: A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan vs enalapril for 66-year-old patients with HF over 10 years. Key health states included New York Heart Association classes I–IV and deaths; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Sacubitril/valsartan benefits were modeled by applying the hazard ratios (HRs) in PARADIGM-HF trial to baseline probabilities. Primary model outcomes were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for sacubitril/valsartan relative to enalapril

Results: Compared to enalapril, sacubitril/valsartan was associated with an ICER of SGD 74,592 (USD 55,198) per QALY gained. A major driver of cost-effectiveness was the cardiovascular mortality benefit of sacubitril/valsartan. The uncertainty of this treatment benefit in the Asian sub-group was tested in sensitivity analyses using a HR of 1 as an upper limit, where the ICERs ranged from SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained. Probabilistic sensitivity analyses showed the probability of sacubitril/valsartan being cost-effective was below 1%, 12%, and 71% at SGD 20,000, SGD 50,000, and SGD 100,000 per QALY gained, respectively.

Conclusions: At the current daily price sacubitril/valsartan may not represent good value for limited healthcare dollars compared to enalapril in reducing cardiovascular morbidity and mortality in HF in the Singapore healthcare setting. This study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering therapy.     

Nilotinib versus dasatinib as second-line therapy in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who are resistant or intolerant to imatinib: a cost-effectiveness analysis based on real-world data

Objective: To evaluate the cost-effectiveness of second-line nilotinib vs dasatinib among patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+?CML-CP) who are resistant or intolerant to imatinib, from a US third-party perspective.

Methods: A lifetime partitioned survival model was developed to compare the costs and effectiveness of nilotinib vs dasatinib, which included four health states: CP on treatment, CP post-discontinuation, progressive disease (accelerated phase [AP] or blast crisis [BC]), and death. Time on treatment, progression-free survival, and overall survival of nilotinib and dasatinib were estimated using real-world comparative effectiveness data. Parametric survival models were used to extrapolate outcomes beyond the study period. Drug treatment costs, medical costs, and adverse event costs were obtained from the literature and publicly available databases. Utilities of health states were derived from the literature. Incremental cost-effectiveness ratios, including incremental cost per life-year (LY) gained and incremental cost per quality-adjusted life-year (QALY) gained, were estimated comparing nilotinib and dasatinib. Deterministic sensitivity analyses were performed by varying patient characteristics, cost, and utility inputs.

Results: Over a lifetime horizon, nilotinib-treated patients were associated with 11.7 LYs, 9.1 QALYs, and a total cost of $1,409,466, while dasatinib-treated patients were associated with 9.5 LYs, 7.3 QALYs, and a total cost of $1,422,122. In comparison with dasatinib, nilotinib was associated with better health outcomes (by 2.2 LYs and 1.9 QALYs) and lower total costs (by $12,655). Deterministic sensitivity analysis results showed consistent findings in most scenarios.

Limitations: In the absence of long-term real-world data, the lifetime projection could not be validated.

Conclusions: Compared with dasatinib, second-line nilotinib was associated with better life expectancy, better quality-of-life, and lower costs among patients with Ph+?CML-CP who were resistant or intolerant to imatinib.     

Tumor treating fields and maintenance temozolomide for newly-diagnosed glioblastoma: a cost-effectiveness study

Abstract

Purpose: The EF-14 trial demonstrated that adding tumor treating fields (TTFields) to maintenance temozolomide (TMZ) significantly extends progression-free survival (PFS) and overall survival (OS) for newly-diagnosed glioblastoma (GBM) patients. This study assessed the cost-effectiveness of TTFields and TMZ for newly-diagnosed GBM from the US healthcare system perspective.

Methods and materials: Outcomes for newly-diagnosed GBM patients were estimated over a lifetime horizon using an area under the curve model with three states: stable disease, progressive disease, or death. The survival model integrated the 5-year EF-14 trial results with long-term GBM epidemiology data and US background mortality rates. Adverse event rates were derived from the EF-14 trial data. Utility values to determine quality-adjusted life-years, adverse event costs, and supportive care costs were obtained from published literature. A 3% discount rate was applied to future costs and outcomes. One-way and probabilistic sensitivity analyses were performed to assess result uncertainty due to parameter variability.

Results: Treatment with TTFields and TMZ was estimated to result in a mean increase in survival of 1.25 life years (95% credible range [CR]?=?0.89–1.67) and 0.96 quality-adjusted life years (QALYs) (95% CR = 0.67–1.30) compared to treatment with TMZ alone. The incremental total cost was $188,637 (95% CR = $145,324–$225,330). The incremental cost-effectiveness ratio (ICER) was $150,452 per life year gained and $197,336 per QALY gained. The model was most sensitive to changes in the cost of TTFields treatment.

Conclusions: Adding TTFields to maintenance TMZ resulted in a substantial increase in the estimated mean lifetime survival and quality-adjusted survival for newly-diagnosed GBM patients. Treatment with TTFields can be considered cost-effective within the reported range of willingness-to-pay thresholds in the US.     

Cost-effectiveness of percutaneous closure of a patent foramen ovale compared with medical management in patients with a cryptogenic stroke: from the US payer perspective

Abstract

Aims: To evaluate the cost-effectiveness of percutaneous patent foramen ovale (PFO) closure, from a US payer perspective. Lower rates of recurrent ischemic stroke have been documented following percutaneous PFO closure in properly selected patients. Stroke in patients aged <60?years is particularly interesting because this population is typically at peak economic productivity and vulnerable to prolonged disability.

Materials and methods: A Markov model comprising six health states (Stable after index stroke, Transient ischemic attack, Post-Transient Ischemic Attack, Clinical ischemic stroke, Post-clinical ischemic stroke, and Death) was constructed to evaluate the cost-effectiveness of PFO closure in combination with medical management versus medical management alone. The base-case model employed a 5-year time-horizon, with transition probabilities, clinical inputs, costs, and utility values ascertained from published and national costing sources. Incremental cost-effectiveness ratio (ICER) was evaluated per US guidelines, utilizing a discount rate of 3.0%.

Results: At 5?years, overall costs and quality-adjusted life-years (QALYs) obtained from PFO closure compared with medical management were $16,323 vs $7,670 and 4.18 vs 3.77, respectively. At 5?years, PFO closure achieved an ICER of $21,049, beneficially lower than the conventional threshold of $50,000. PFO closure reached cost-effectiveness at 2.3?years (ICER = $47,145). Applying discount rates of 0% and 6% had a negligible impact on base-case model findings. Furthermore, PFO closure was 95.4% likely to be cost-effective, with a willingness-to-pay (WTP) threshold of $50,000 and a 5-year time horizon.

Limitations: From a cost perspective, our economic model employed a US patient sub-population, so cost data may not extrapolate to other non-US stroke populations.

Conclusion: Percutaneous PFO closure plus medical management represents a cost-effective approach for lowering the risk of recurrent stroke compared with medical management alone.     

The cost-effectiveness of delayed-release dimethyl fumarate for the treatment of relapsing-remitting multiple sclerosis in Canada

Background: Multiple sclerosis (MS) causes significant disability and diminished quality-of-life. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is a new oral treatment for relapsing-remitting MS (RRMS) approved in the US, Australia, Canada, and Europe. Objectives: A cost-effectiveness model was developed to compare the health economic impact of DMF against other disease-modifying therapies (DMTs) as first-line RRMS treatment from a Canadian Ministry of Health perspective. Methods: A Markov cohort model was developed to simulate patients’ progression through health states based on the Kurtzke Expanded Disability Status Scale (EDSS) over a life-time horizon. Patients entered the model based on a distribution of baseline EDSS scores, from which they could progress to higher or regress to lower EDSS state, or remain in the same state. Relapses could occur at any EDSS score. Results from a mixed-treatment comparison were used to inform model inputs for disease progression and relapse rates per treatment. Costs included direct medical costs stratified by EDSS score. Utilities were accrued based on time spent in each EDSS state. Results: Compared with glatiramer acetate, DMF yielded 0.528 incremental quality-adjusted life-years (QALYs) at an incremental cost of $23 338 Canadian dollars (CAD), resulting in an incremental cost-effectiveness ratio (ICER) of CAD $44 118/QALY. The ICER for DMF compared with Rebif 44?mcg was CAD $10 672. Results were consistent across a wide range of one-way and probabilistic sensitivity analyses. Conclusions: Based on traditional cost-effectiveness thresholds in Canada (CAD $50 000–60 000), DMF can be considered a cost-effective option compared to other first-line DMTs.     

Cost effectiveness of transcatheter aortic valve replacement compared to medical management in inoperable patients with severe aortic stenosis: Canadian analysis based on the PARTNER Trial Cohort B findings

Abstract

Objective:

The only effective treatment for severe aortic stenosis (AS) is valve replacement. However, many patients with co-existing conditions are ineligible for surgical valve replacement, historically leaving medical management (MM) as the only option which has a poor prognosis. Transcatheter Aortic Valve Replacement (TAVR) is a less invasive replacement method. The objective was to estimate cost-effectiveness of TAVR via transfemoral access vs MM in surgically inoperable patients with severe AS from the Canadian public healthcare system perspective.

Methods:

A cost-effectiveness analysis of TAVR vs MM was conducted using a deterministic decision analytic model over a 3-year time horizon. The PARTNER randomized controlled trial results were used to estimate survival, utilities, and some resource utilization. Costs included the valve replacement procedure, complications, hospitalization, outpatient visits/tests, and home/nursing care. Resources were valued (2009 Canadian dollars) using costs from the Ontario Case Costing Initiative (OCCI), Ontario Ministry of Health and Long-Term Care and Ontario Drug Benefits Formulary, or were estimated using relative costs from a French economic evaluation or clinical experts. Costs and outcomes were discounted 5% annually. The effect of uncertainty in model parameters was explored in deterministic and probabilistic sensitivity analysis.

Results:

The incremental cost-effectiveness ratio (ICER) was $32,170 per quality-adjusted life year (QALY) gained for TAVR vs MM. When the time horizon was shortened to 24 and 12 months, the ICER increased to $52,848 and $157,429, respectively. All other sensitivity analysis returned an ICER of less than $50,000/QALY gained.

Limitations:

A limitation was lack of availability of Canadian-specific resource and cost data for all resources, leaving one to rely on clinical experts and data from France to inform certain parameters.

Conclusions:

Based on the results of this analysis, it can be concluded that TAVR is cost-effective compared to MM for the treatment of severe AS in surgically inoperable patients.     

Cost-effectiveness analysis of first-line pembrolizumab treatment for PD-L1 positive,non-small cell lung cancer in China

Purpose: Pembrolizumab was recently approved in several countries as a first-line treatment for patients with PD-L1 positive, non-small cell lung cancer (NSCLC). However, it is expensive. This study aimed to assess the cost-effectiveness of pembrolizumab in treating advanced NSCLC patients with PD-L1 positive cancer in China.

Methods: A Markov model was developed to compare the cost-effectiveness of pembrolizumab with chemotherapy for patients with PD-L1 expression on at least 50% of NSCLC tumor cells. Model inputs for transition probabilities and toxicity were derived from published clinical trial data, while health utilities were estimated from a literature review. Costs for drugs were updated to standard fee data from West China Hospital in 2017. Health outcomes were measured in quality-adjusted life years (QALYs), and cost-effectiveness was measured as the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were conducted to test the robustness of the model.

Results: Pembrolizumab gained 0.45 QALYs at an incremental cost of $46,362 compared to chemotherapy for an ICER of $103,128 per QALY gained. In most scenarios, the ICER exceeded three times the Chinese Gross Domestic Product per capita. Two-way sensitivity analysis showed that, when the utility of the progression-free status increased to the maximal value of 0.845 and the 1?mg dose price decreased to $10.50, the ICER reduced to $25,216/QALY.

Conclusions: Pembrolizumab is not likely to be cost-effective in the treatment of PD-L1 positive, NSCLC for Chinese patients. Less aggressive pricing may increase accessibility for patients in China.     

Cost-effectiveness of a chronic pain intervention for people living with HIV (PLWH)

Background: Chronic pain is a common, disabling, and costly comorbidity, particularly in people living with HIV (PLWH). This study developed and pilot tested a pain self-management intervention for chronic pain tailored to PLWH called Skills TO Manage Pain (STOMP).

Objectives: Given the additional resources needed to deliver STOMP in HIV clinical settings, an important objective of the pilot study was to assess not only STOMP’s preliminary efficacy, but also its cost-effectiveness.

Research design and subjects: The present study draws from a 44-participant, 2-arm randomized pilot trial of the STOMP intervention vs usual care among PLWH and at least moderate chronic pain (Clinicaltrials.gov: NCT02824562). Cost-effectiveness is presented as the incremental cost-effectiveness ratio (ICER). Costs were considered from the clinic perspective over a 1-year time horizon using real costs from the pilot trial. It was conservatively assumed there would be no costs savings. The Standard Gamble (SG) method was used to directly measure utilities.

Results: Thirty-six participants met inclusion criteria for the present analyses. Mean age was 52 years; 61% were female and 86% were black. The total cost of STOMP was $483.83 per person. Using the SG method, the change in QALYs was 0.15, corresponding to an ICER of $3,225.

Conclusions: STOMP’s cost/QALY is substantially lower than the $50,000 to $100,000/QALY benchmark often used to indicate cost-effectiveness. Although based on a pilot trial and, therefore, preliminary, these findings are promising, and suggest the importance of cost analyses in future STOMP trials.     

Economic evaluation for the US of nab-paclitaxel plus gemcitabine versus FOLFIRINOX versus gemcitabine in the treatment of metastatic pancreas cancer

Background: Nab-paclitaxel plus gemcitabine (NAB-P?+?GEM) and FOLFIRINOX have shown superior efficacy over gemcitabine (GEM) in the treatment of metastatic pancreatic ductal adenocarcinoma (mPDA). Although the incremental clinical benefits are modest, both treatments represent significant advances in the treatment of a high-mortality cancer. In this independent economic evaluation for the US, the aim was to estimate the comparative cost-utility and cost-effectiveness of these three regimens from the payer perspective.

Methods: In the absence of a direct treatment comparison in a single clinical trial, the Bucher indirect comparison method was used to estimate the comparative efficacy of each regimen. A Markov model evaluated life years (LY) and quality-adjusted life years (QALY) gained with NAB-P?+?GEM and FOLFIRINOX over GEM, expressed as incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR). All costs and outcomes were discounted at 3%/year. The impact of parameter uncertainty on the model was assessed by probabilistic sensitivity analyses.

Results: NAB-P?+?GEM was associated with differentials of +0.180 LY and +0.127 QALY gained over GEM at an incremental total cost of $25,965; yielding an ICER of $144,096/LY and ICUR of $204,369/QALY gained. FOLFIRINOX was associated with differentials of +0.368 LY and +0.249 QALY gained over GEM at an incremental total cost of $93,045; yielding an ICER of $253,162/LY and ICUR of $372,813/QALY gained. In indirect comparison, the overall survival hazard ratio (OS HR) for NAB-P?+?GEM vs FOLFIRINOX was 0.79 (95%CI?=?0.59–1.05), indicating no superiority in OS of either regimen. FOLFIRINOX had an ICER of $358,067/LY and an ICUR of $547,480/QALY gained over NAB-P?+?GEM. Tornado diagrams identified variation in the OS HR, but no other parameters, to impact the NAB-P?+?GEM and FOLFIRINOX ICURs.

Conclusions: In the absence of a statistically significant difference in OS between NAB-P?+?GEM and FOLFIRINOX, this US analysis indicates that the greater economic benefit in terms of cost-savings and incremental cost-effectiveness and cost-utility ratios favors NAB-P?+?GEM over FOLFIRINOX.