Historical clinical and economic consequences of anemia management in patients with end-stage renal disease on dialysis using erythropoietin stimulating agents versus routine blood transfusions: a retrospective cost-effectiveness analysis

Abstract

Objective:

To determine whether Medicare’s decision to cover routine administration of erythropoietin stimulating agents (ESAs) to treat anemia of end-stage renal disease (ESRD) has been a cost-effective policy relative to standard of care at the time.

Methods:

The authors used summary statistics from the actual cohort of ESRD patients receiving ESAs between 1995 and 2004 to create a simulated patient cohort, which was compared with a comparable simulated cohort assumed to rely solely on blood transfusions. Outcomes modeled from the Medicare perspective included estimated treatment costs, life-years gained, and quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated relative to the hypothetical reference case of no ESA use in the transfusion cohort. Sensitivity of the results to model assumptions was tested using one-way and probabilistic sensitivity analyses.

Results:

Estimated total costs incurred by the ESRD population were $155.47B for the cohort receiving ESAs and $155.22B for the cohort receiving routine blood transfusions. Estimated QALYs were 2.56M and 2.29M, respectively, for the two groups. The ICER of ESAs compared to routine blood transfusions was estimated as $873 per QALY gained. The model was sensitive to a number of parameters according to one-way and probabilistic sensitivity analyses.

Limitations:

This model was counter-factual as the actual comparison group, whose anemia was managed via transfusion and iron supplements, rapidly disappeared following introduction of ESAs. In addition, a large number of model parameters were obtained from observational studies due to the lack of randomized trial evidence in the literature.

Conclusions:

This study indicates that Medicare’s coverage of ESAs appears to have been cost effective based on commonly accepted levels of willingness-to-pay. The ESRD population achieved substantial clinical benefit at a reasonable cost to society.     

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.     

Cost-effectiveness of natalizumab versus fingolimod for the treatment of relapsing multiple sclerosis

Abstract

Background:

With the addition of new agents for the treatment of multiple sclerosis (MS) (e.g., fingolimod), there is a need to evaluate the relative value of newer therapies in terms of cost and effectiveness, given healthcare resource constraints in the United States.

Objective:

To assess the cost-effectiveness of natalizumab vs fingolimod in patients with relapsing MS.

Methods:

A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from a US managed care payer perspective. Two-year costs of treating patients with MS included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided (data from AFFIRM and FREEDOMS trials). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty.

Results:

Mean 2-year estimated treatment costs were $86,461 (natalizumab) and $98,748 (fingolimod). Patients receiving natalizumab had a mean of 0.74 relapses avoided per 2 years vs 0.59 for fingolimod. Natalizumab dominated fingolimod in the incremental cost-effectiveness analysis, as it was less costly and more effective in reducing relapses. One-way sensitivity analysis showed the results of the model were robust to changes in drug acquisition costs, administration costs, and costs of treating MS relapses. Probabilistic sensitivity analysis showed natalizumab was cost-effective 95.1% of the time, at a willingness-to-pay (WTP) threshold of $0 per relapse avoided, increasing to 96.3% of the time at a WTP threshold of $50,000 per relapse avoided.

Limitations:

Absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as primary model outcome, assumption of 100% adherence to MS treatment, and not capturing adverse event costs in the model.

Conclusions:

Natalizumab dominates fingolimod in terms of incremental cost per relapse avoided, as it is less costly and more effective.     

Cost-effectiveness of sofosbuvir plus ribavirin with or without pegylated interferon for the treatment of chronic hepatitis C in Italy

Abstract

Objective:

Across Italy up to 7.3% of the population is infected with hepatitis C virus (HCV), with long-term complications resulting in high medical costs and significant morbidity and mortality. Current treatment options have limitations due to side effects, interferon intolerability and ineligibility, long treatment durations and low sustained virological response (SVR) rates, especially for the most severe patients). Sofosbuvir is the first nucleotide polymerase inhibitor with pan-genotypic activity. Sofosbuvir, administered with ribavirin (RBV) and with or without pegylated interferon (PEG-INF), resulted in >90% SVR across treatment-naïve (TN) genotype (GT) 1–6 patients. It is also the first treatment option for patients that are unsuitable for interferon (UI). This analysis evaluates the cost – effectiveness of sofosbuvir for GTs 1–6 in Italy.     

Cost-effectiveness analysis of ferric carboxymaltose in iron-deficient patients with chronic heart failure in Sweden

Abstract

Objective:

Iron deficiency is a common but treatable comorbidity in chronic heart failure (CHF) that is associated with impaired health-related quality-of-life (HRQoL). This study evaluates the cost-effectiveness of the intravenous iron preparation ferric carboxymaltose (FCM) for the treatment of iron deficiency in CHF from a Swedish healthcare perspective.     

A review on cost-effectiveness analysis of agri-environmental measures related to the EU WFD: Key issues, methods, and applications

The European Water Framework Directive (WFD) explicitly integrates economics into water management and water policy in Europe. Specifically, Article 11 and Annex III of the Directive call for a cost-effectiveness analysis (CEA) of alternative mitigation measures as a requirement in formulating Programme of Measures (PoMs) to achieve ‘good ecological status’ for all waters in Europe. As agriculture is supposed to be the major contributor to diffuse water pollution, CEA of agri-environmental measures has been given paramount importance in establishing the PoMs. This paper summarises the status, significance, and methodological limitations of WFD-related CEA studies in Europe. Cases from the United Kingdom, countries surrounding the Baltic Sea and central and southern Europe were included in the review. Review results indicate that most WFD-related CEA studies: (1) were based on models of ‘representative’ farms without capturing the variability among real-world farms; (2) concentrate on a single ecological effect of measures or are based on cost estimates of the sectors directly involved in the pollutant-reduction programme (i.e., co-benefits, trade-offs, and external costs were not examined); and (3) did not incorporate uncertainties in both cost and effectiveness estimates. Based on the review results, the paper suggests policy implications and recommendations for future research in the field.     

Economic evaluation of a 100% whey-based partially hydrolyzed infant formula in the prevention of atopic dermatitis among Swiss children

Abstract

Objective:

A pharmacoeconomic analysis was undertaken to determine costs, consequences, and cost-effectiveness of a partially hydrolyzed 100% whey-based infant formula, NAN-HA®, manufactured by Nestlé S.A, Switzerland (PHF-W), branded under BEBA HA® in Switzerland, in the prevention of atopic dermatitis (AD) in ‘at risk’ Swiss children when compared to standard cow’s milk formula (SF).

Methods:

Based on a 12-month time horizon including 6 months of formula consumption, an economic model was developed synthesizing treatment pathways, resource utilization, and costs associated with the treatment of AD in healthy ‘at risk’ Swiss newborns who could not be exclusively breastfed. Model inputs were retrieved from the literature, official formularies, and expert opinion. The treatment pathways considered a medical treatment approach, supplemented in some instances by a change of formula. The final outcome was the expected cost per avoided case of AD, yielding an incremental cost effectiveness ratio (ICER) for PHF-W vs SF. Outcomes were presented from three perspectives: the Swiss public healthcare system (MOH), the subject’s family, and society (SOC). A secondary analysis compared PHF-W to whey-based extensively hydrolyzed formula (EHF) in prevention.

Results:

The model yielded 1653 avoided AD cases by selecting PHF-W over SF in a birth cohort of 22,933 ‘at risk’ infants. The base case analyses generated an expected ICER of CHF 982 from the MOH perspective as well as savings of CHF 2202 and CHF 1220 from the family and SOC perspectives, respectively. PHF-W yielded CHF 11.4M savings against EHF when the latter was assumed to be used in prevention. One-way and probabilistic sensitivity analyses confirmed the robustness of the model.

Conclusion:

Under a range of assumptions, this analysis has established the dominance from the family and societal perspectives and cost-effectiveness from the MOH perspective of PHF-W vs SF in the prevention of AD among ‘at risk’ Swiss infants.     

Economic evaluation of sevelamer for the treatment of hyperphosphatemia in chronic kidney disease patients not on dialysis in the United Kingdom

Abstract

Objectives:

To determine the cost effectiveness of sevelamer vs calcium carbonate in patients with chronic kidney disease and not on dialysis (CKD-ND) from the perspective of the National Health Service (NHS) in the UK.

Methods:

A Markov decision analytic model was developed to estimate (1) total life years (LYs), quality-adjusted life years (QALYs), and costs for patients treated with sevelamer or calcium carbonate; and (2) incremental costs per LY gained (LYG) and per QALY gained for sevelamer vs calcium carbonate. Data informing probability transitions to all-cause death and dialysis inception in CKD-ND patients were taken directly from the INDEPENDENT-CKD study and were extrapolated beyond the 3-year clinical trial using Weibull regression analysis. Estimates of health utility and costs (in £2011) were derived from the published literature.

Results:

Over a lifetime horizon, sevelamer treatment resulted in a gain of 2.05 LYs and 1.56 QALYs per patient, an increase of £37,282 in total costs per patient vs calcium carbonate (3.5% discount), and a per-patient cost of £18,193/LYG and £23,878/QALY gained. Results were robust to alternative assumptions in key parameters; results were most sensitive to alternative assumptions regarding the mean daily dose of sevelamer, impact of sevelamer on dialysis initiation, cost of dialysis, and health utility estimates. The probabilistic sensitivity analysis showed that sevelamer was cost-effective vs calcium carbonate in 93% of simulations at a willingness-to-pay threshold of £30,000/QALY gained.

Limitations:

While the model simulated a real-world clinical setting, this analysis was subject to limitations common to all decision analytic models, in that it used a mix of data sources and relied on several assumptions. Not all variables that impact real-world outcomes and costs were included in this model.

Conclusions:

Sevelamer is a cost-effective option compared to calcium carbonate for the first-line treatment of hyperphosphatemia in CKD-ND patients in the UK.     

Cost-effectiveness of partially-hydrolyzed formula for prevention of atopic dermatitis in Australia

Abstract

Objective:

To perform an economic evaluation of a specific brand of partially hydrolyzed infant formula (PHF-W) in the prevention of atopic dermatitis (AD) among Australian infants.

Methods:

A cost-effectiveness analysis was undertaken from the perspectives of the Department of Health and Aging (DHA), of the family of the affected subject and of society as a whole in Australia, based on a decision-analytic model following a hypothetical representative cohort of Australian newborns who are not exclusively breastfed and who have a familial history of allergic disease (i.e., are deemed ‘at risk’). Costs, consequences, and incremental cost-effectiveness ratios (ICER) were calculated for PHF-W vs standard cow’s milk based infant formula (SF), and, in a secondary analysis, vs extensively hydrolyzed infant formula (EHF-Whey), when the latter was used for the prevention of AD.

Results:

From a representative starting cohort of 87,724 ‘at risk’ newborns in Australia in 2009, the expected ICERs for PHF-W vs SF were AU$496 from the perspective of the DHA and savings of AUD1739 and AU$1243 from the family and societal perspectives, respectively. When compared to EHF-Whey, PHF-W was associated with savings for the cohort of AU$5,183,474 and AU$6,736,513 from the DHA and societal perspectives.

Limitations:

The generalizability and transferability of results to other settings, populations, or brands of infant formula should be made with caution. Whenever possible, a conservative approach directing bias against PHF-W rather than its comparators was applied in the base case analysis. Assumptions were verified in one-way and probabilistic sensitivity analyses, which confirmed the robustness of the model.

Conclusions:

PHF-W appears to be cost-effective when compared to SF from the DHA perspective, dominant over SF from the other perspectives, and dominant over EHF-Whey from all perspectives, in the prevention of AD in ‘at risk’ infants not exclusively breastfed, in Australia.     

A cost-effectiveness analysis of using azacitidine vs. decitabine in treating patients with myelodysplastic syndromes

Abstract

Objective:

Azacitidine and decitabine are used to treat patients with myelodysplastic syndromes (MDS) in the United States (US). This study sought to assess their relative cost-effectiveness.

Design and methods:

The authors developed a cost-effectiveness Markov model (1-month cycles) tracking hypothetical cohorts of MDS patients treated with azacitidine or decitabine over 2 years. The model used a US payer perspective and 2009 costs. Health states modeled included MDS with Transfusion Dependence, MDS with Transfusion Independence, Progression to Acute Myelogenous Leukemia (AML), and Death. Incremental cost-effectiveness outcomes included cost per quality-adjusted life year (QALY), cost per life year (LY), cost per patient-month of transfusion independence, and cost per case of AML progression avoided. One-way sensitivity analyses were performed on key model parameters.

Results:

Compared to decitabine, azacitidine was associated with better survival (1.512 LYs vs 1.292), more QALYs gained (1.041 vs 0.870), more patient-months with transfusion independence (8.328 vs 6.224), and a greater proportion of patients avoiding progression to AML (50.9% vs 28.5%). Total per-patient costs over 2 years for azacitidine were lower than for decitabine ($150,322 vs $166, 212).

Limitations:

To inform and update the model over time, it will be important that randomized or observational clinical studies be conducted to directly compare azacitidine and decitabine, provide new information on how these medicines are used, and on their relative clinical effectiveness.

Conclusion:

Results demonstrate that azacitidine provides greater clinical benefit and costs less than decitabine across all key outcomes. These results accentuate the positive role of azacitidine in providing cost-effective care for MDS.     

The cost-effectiveness of OM-85 in managing respiratory tract infections in China

Abstract

Objectives:

To demonstrate the health economic impact of OM-85, a bacterial lysates based immunostimulant, for its approved indications in China.

Methods:

A cost-effectiveness decision tree model was constructed comparing OM-85 with the best supportive care/placebo therapy for managing the acute exacerbation of chronic bronchitis and rhinosinusitis in the Chinese population. Clinical efficacy and adverse events (AE) data were included in the model based on a thorough literature review. All localized direct treatment costs, including drug cost, AE costs, and medical treatment costs for underlining diseases were included from a Chinese third party payer perspective. A Key Opinion Leaders (KOL) survey was conducted with 20 senior physicians specialized in respiratory, ENT, allergy, and immunology fields from tertiary hospitals in Beijing, Shanghai, Guangzhou, Hangzhou, Shenyang, and Wuhan to validate the local treatment costs. Incremental cost-effectiveness ratio (ICER) was calculated based on the above efficacy and cost information.

Results:

OM-85 is a cost-effective therapy when compared with placebo (standard care). OM-85 can treat/prevent one additional full episode exacerbation of chronic bronchitis and one additional full episode exacerbation of rhinosinusitis with only additional costs of RMB 653 and RMB 1182.84, respectively. In comparison, each acute exacerbation of chronic bronchitis will cost RMB 4510.10, and each acute exacerbation of rhinosinuisitis will cost RMB 1807.21 in a Chinese clinical management setting. One-way sensitivity analyses were performed and the ICER result was demonstrated to be consistent.

>Conclusions:

OM 85 reduces acute exacerbations among patients with chronic bronchitis and chronic rhinosinusitis when compared with Placebo (standard care). From a Chinese payer perspective, OM 85 is a cost-effective therapy in the clinical management of both chronic bronchitis and rhinosinusitis in the adult population.     

Cost-effectiveness of lurasidone vs aripiprazole among patients with schizophrenia who have previously failed on an atypical antipsychotic: an indirect comparison of outcomes from clinical trial data

Abstract

Objective:

Compare long-term costs and outcomes of lurasidone to aripiprazole among adults with schizophrenia in the US who previously failed ≥1 atypical antipsychotic (olanzapine, risperidone, quetiapine, or ziprasidone) based on an indirect comparison of outcomes data from clinical trials.

Methods:

A 5-year Markov cohort model was developed to compare long-term effectiveness of lurasidone to aripiprazole, including total discontinuations, relapse rates, and hospitalization rates. Cost inputs included pharmacy, mental health, and medical costs associated with cardiometabolic risks (diabetes and cardiovascular [CV] events). Effectiveness inputs were derived from an indirect comparison of aripiprazole and lurasidone using common comparators from CATIE. Cardiometabolic risks were derived from claims data analysis for diabetes, weight change and CV events, and Framingham body mass index (BMI) risk equation. Cost inputs were derived from published sources and Red Book. Costs and outcomes were discounted at 3% and tested with sensitivity analyses.

Results:

Over 5 years, total discounted costs for lurasidone and aripiprazole patients were $86,480 and $90,500, respectively. During this period, the number of relapses per patient, hospitalizations per patient, diabetes rates, and CV events per 1000 patients, respectively, were estimated to be lower for lurasidone (0.442, 0.245, 7.29%, and 37.3) than aripiprazole (0.478, 0.369, 7.36%, and 37.8). Results were sensitive to lurasidone and aripiprazole hospitalization rates. At a willingness-to-pay threshold of $50,000 per hospitalization avoided, lurasidone had a 100% probability of being more cost-effective than aripiprazole.

Limitations:

The model was based on results from various comparative clinical trials. Differences in patient population and study methods may change estimates from the model. The model does not account for patient heterogeneity.

Conclusions:

Based on this model, when switching from another atypical antipsychotic, lurasidone had fewer relapses and hospitalizations with a lower incidence of diabetes and CV events than aripiprazole. Additionally, lurasidone may be less costly than aripiprazole among adults with schizophrenia.     

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.