Symbicort: a pharmacoeconomic review

Abstract

Objective: This systematic review examines the published evidence on the pharmacoecomonics of Symbicort®. Symbicort is a combination inhaler used in asthma and chronic obstructive pulmonary disease (COPD) that contains budesonide and formoterol. In asthma, Symbicort can be used as fixed or adjustable dose maintenance therapy as well as for both maintenance and reliever therapy (SMART).

Method: A literature search of PubMed was carried out to find all publications on the pharmacoeconomics of Symbicort. Additional studies were searched for in the reference lists of the papers retrieved and by searching tables of contents of relevant journals. A total of 13 studies on Symbicort in asthma and 2 studies on Symbicort in COPD were found.

Results: Total costs were lower with Symbicort than with separate inhalers containing budesonide and formoterol. Adjustable dosing maintained control of asthma using less medication and was associated with lower treatment costs than fixed dosing with Symbicort or the combination of fluticasone/salmeterol. SMART improves asthma control, reduces exacerbations and reduces direct and indirect costs compared to fixed maintenance therapy with either Symbicort or fluticasone/salmeterol. In COPD, Symbicort offers clinical advantages over therapy with the monocomponents and these are achieved at little or no extra cost.     

Respiratory-related medical expenditure and inpatient utilisation among COPD patients receiving long-acting bronchodilator therapy

Abstract

Objective:

To evaluate chronic obstructive pulmonary disease (COPD)-related expenditure and hospitalisation in COPD patients treated with tiotropium versus alternative long-acting bronchodilators (LABDs).

Methods:

Data were from the Thomson Reuters MarketScan Research Databases. COPD patients ≥35 years with at least one LABD claim between July 1, 2004 and June 30, 2006 were classified into five cohorts based on index LABD: monotherapy with tiotropium, salmeterol/fluticasone propionate, formoterol fumarate, or salmeterol or combination therapy. Demographic and clinical characteristics were evaluated for a 6-month pre-period and COPD-related utilisation and total costs were evaluated for a 12-month follow-up period. LABD relationship to COPD-related costs and hospitalisations were estimated by multivariate generalised linear modelling (GLM) and multivariate logistic regression, respectively.

Results:

Of 52,274 patients, 53% (n?=?27,457) were male, 71% (n?=?37,271) were ≥65?years, and three LABD cohorts accounted for over 90% of the sample [53% (n?=?27,654) salmeterol/fluticasone propionate, 23% (n?=?11,762) tiotropium, and 15% (n?=?7755) combination therapy]. Patients treated with salmeterol/fluticasone propionate (p?<?0.001), formoterol fumarate (p?=?0.032), salmeterol (p?=?0.004), or with combination therapy (p?<?0.001) had higher COPD-related costs and a greater risk of inpatient admission (p?<?0.01 for all) versus tiotropium.

Limitations:

These data are based on administrative claims and as such do not include clinical information or information on risk factors, like smoking status, that are relevant to this population.

Conclusions:

Patients treated with tiotropim had lower COPD-related expenditures and risk of hospitalisation than patients treated with other LABDs     

Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal in Russian cities

Abstract

Objective:

To evaluate the cost-effectiveness of distributing naloxone to illicit opioid users for lay overdose reversal in Russian cities.

Method:

This study adapted an integrated Markov and decision analytic model to Russian cities. The model took a lifetime, societal perspective, relied on published literature, and was calibrated to epidemiologic findings.

Results:

For each 20% of heroin users reached with naloxone distribution, the model predicted a 13.4% reduction in overdose deaths in the first 5 years and 7.6% over a lifetime; on probabilistic analysis, one death would be prevented for every 89 naloxone kits distributed (95% CI?=?32–260). Naloxone distribution was cost-effective in all deterministic and probabilistic sensitivity analyses and cost-saving if resulting in a reduction in overdose events. Naloxone distribution increased costs by US$13 (95% CI?=?US$3–US$32) and QALYs by 0.137 (95% CI?=?0.022–0.389) for an incremental cost of US$94 per QALY gained (95% CI?=?US$40–US$325). In a worst-case scenario where overdose was rarely witnessed and naloxone was rarely used, minimally effective, and expensive, the incremental cost was US$1987 per QALY gained. If national expenditures on drug-related HIV, tuberculosis, and criminal justice were applied to heroin users, the incremental cost was US$928 per QALY gained.

Conclusions:

Naloxone distribution to heroin users for lay overdose reversal is highly likely to reduce overdose deaths in target communities and is robustly cost-effective, even within the constraints of this conservative model.     

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 a pentavalent human–bovine reassortant rotavirus vaccine for children ≤5 years of age in Taiwan

Abstract

Objective:

A Markov model was used to assess the impact of RV5, a pentavalent (G1, G2, G3, G4, P1A[8]) human bovine (WC3 strain) reassortant rotavirus vaccine, on reducing the healthcare burden and cost associated with rotavirus gastroenteritis (RGE) in Taiwan. Other cost-effectiveness analyses for rotavirus vaccination in industrialized countries have produced varying results depending on the input parameters assumed.

Methods:

Vaccination with RV5 is compared to no vaccination in a hypothetical cohort of Taiwanese children during their first 5 years of life to determine the per dose prices at which vaccination would be cost neutral or provide good value based on established standards from the healthcare (direct medical care costs only) and societal (all RGE-related costs) perspectives. The effects of vaccination on RGE healthcare utilization and days of parental work loss missed are based on results from the Rotavirus Efficacy and Safety Trial.

Results:

Without vaccination there would be 122,526 symptomatic episodes of RGE. Universal vaccination would reduce RGE-related deaths, hospitalizations, emergency department, and outpatient visits by 91.7%, 92.1%, 83.7%, and 73.4%, respectively. The price per dose at which vaccination would be cost-neutral is US$ 21.80 (688 NTD) and US$ 26.20 (827 NTD) from the healthcare and societal perspectives, respectively. At $25 per dose, the cost per QALY gained is US$ 2261 (71,335 NTD) from the healthcare perspective and cost saving from the societal perspective.

Key limitations:

The model only assesses the effect of RV5 on vaccinated children and does not account for herd immunity. However, given that high levels of coverage are anticipated in Taiwan, the effects of herd immunity are likely to be short-term.

Conclusion:

A pentavalent rotavirus vaccination program is likely to substantially reduce the healthcare burden associated with rotavirus gastroenteritis at a cost per QALY ratio within the range defined as cost-effective.     

Cost-effectiveness of omalizumab for uncontrolled allergic asthma in the Netherlands

Abstract

Background:

Omalizumab, licensed for patients with uncontrolled persistent allergic (IgE mediated) asthma, was found to be cost-effective based upon its clinical trial data. Observational studies have been undertaken to determine the real life outcomes of using omalizumab in the community.

Objective:

To determine the cost-effectiveness of omalizumab based upon observational data from the Netherlands and compare to its cost-effectiveness using clinical trial data.

Methods:

An observational study (eXpeRience) recruited allergic asthma patients eligible for Omalizumab therapy and followed them while on treatment. At 1 year, data from the Dutch patients enrolled in eXpeRience were examined to estimate the number of exacerbations and resource use while on omalizumab therapy compared to the year prior to omalizumab use. Observational data were used in a Markov model to calculate the lifetime cost-effectiveness ratios.

Results:

In the 1 year prior to omalizumab therapy the per-person rate of exacerbations was 3.39 compared to 1.07 in the year taking omalizumab. The discounted incremental lifetime additional costs for omalizumab were €55,865 for 1.46 additional quality-adjusted life years (QALY), resulting in €38,371/QALY. Using the INNOVATE clinical trial outcomes and current resource use, the prior ratio was €34,911/QALY, similar to the observational ratio. As in all observational studies, the main limitation is obtaining complete and accurate data. Patients with missing exacerbation or response data were excluded from this analysis.

Conclusion:

Non-clinical trial experience with omalizumab supported the finding of fewer exacerbations in the allergic asthma population while treated with omalizumab, and therapy was found to continue to have an attractive cost-effectiveness ratio.     

Direct medical costs associated with atopic diseases among young children in Thailand

Abstract

Objective:

Allergic diseases are the most common childhood illness in Thailand. Their prevalence has been rising over time, with several studies having revealed substantial economic burden. However, no such study had yet been conducted for Thailand. The aim of this study was to estimate direct medical costs associated with atopic diseases among children aged 0–5 years in Thailand.

Research design and methods:

A cost-of-illness model was constructed to estimate the total direct medical costs of atopic diseases comprising atopic dermatitis, chronic rhinitis, asthma (i.e., recurrent wheeze), and cow’s milk allergy. The model employed a prevalence-based approach, considering a total number of atopic cases in 2010. Direct medical costs were estimated using a bottom-up analysis with the estimation of the quantity of healthcare resource use and the unit costs. Epidemiological data were obtained from literature and Thai surveys, whereas treatment unit costs were from either a hospital database or Thai standard cost list. Expert opinion informed type, frequency, and quantity of medical resources utilized. Key limitations included lack of data-driven evidences on severity distribution for this particular age group, indirect costs, and medical resource use associated with each condition.

Results:

Total direct cost was estimated to be THB 27.8 billion (US$899 million). Treatments contributed largest to the total costs (46%), followed by inpatient care (37%), outpatient care (12%), and monitoring and labs (5%). Costs per treated patient were highest in cow’s milk allergy (THB 64,383; US$2077), followed by rhinitis (THB 12,669; US$409), asthma (THB 9633; US$312), and atopic dermatitis (THB 5432; US$175).

Conclusion:

Atopic diseases in young children are associated with substantial burden in direct medical costs to Thailand. These costs can be diminished through nutritional intervention recognized to effectively decrease the incidence of atopic diseases.     

Cost-effectiveness of a pentavalent rotavirus vaccine in Japan

Abstract

Objective:

To evaluate the impact of universal vaccination with a pentavalent rotavirus vaccine (RV5) on the healthcare burden and costs associated with rotavirus gastroenteritis (RGE) in Japan.

Methods:

The model included a hypothetical cohort of 1,091,156 children followed for their first 5 years of life. In the absence of universal vaccination, there were 19 deaths, 78,000 hospitalizations, and 678,000 outpatient visits due to RGE. The efficacy of RV5 is based on international clinical trial data, which was similar to the efficacy observed in clinical trials conducted in Japan. The primary outcome measure is the cost per quality-adjusted-life-year (QALY) gained. In the base case, the QALY loss per 1000 RGE episodes included 2.2 for children and 1.8 per parent.

Results:

Universal vaccination is projected to reduce hospitalizations by 92%, outpatient visits by 74%, and work-loss days by 73%. For the base case analysis, the total vaccination cost was ¥26 billion. The estimated reduction in medical costs was ¥16 billion. Of 2500 QALYs gained with the vaccination program, approximately half are directly attributed to the child. In the base case analysis, the incremental cost-effectiveness ratio (ICER) for vaccination vs no vaccination is ¥4 million and ¥2 million per quality-adjusted life year (QALY) gained from the healthcare payer and societal perspectives, respectively. The ICERs are ¥8 million and ¥4 million if parental disutilities are excluded.

Key limitation:

The QALY decrements for children and parents were evaluated using different instruments, and the QALY decrements do not vary based on episode severity. Given the interdependence between children and their parents, excluding parental disutilities may under-estimate the impact of RGE.

Conclusion:

Universal vaccination with RV5 in Japan is projected to have a substantial public health impact and may be cost-effective from both the payer and societal perspectives if parental disutilities are included in the cost-effectiveness ratios.     

Cost-effectiveness of add-on treatments to metformin in a Swedish setting: liraglutide vs sulphonylurea or sitagplitin

Objective:

To evaluate long-run cost-effectiveness in a Swedish setting for liraglutide compared with sulphonylureas (glimepiride) or sitagliptin, all as add-on to metformin for patients with type 2 diabetes insufficiently controlled with metformin in monotherapy.

Methods:

The IHE Cohort Model of Type 2 Diabetes was used to evaluate clinical and economic outcomes from a societal perspective. Model input data were obtained from two clinical trials, the Swedish National Diabetes Register and the literature. Cost data reflected year 2013 price level. The robustness of results was checked with one-way-sensitivity analysis and probability sensitivity analysis.

Results:

The cost per QALY gained for liraglutide (1.2?mg) compared to SU (glimepiride 4?mg), both as add-on to metformin, ranged from SEK 226,000 to SEK 255,000 in analyzed patient cohorts. The cost per QALY for liraglutide (1.2?mg) vs sitagliptin (100?mg) as second-line treatment was lower, ranging from SEK 149,000 to SEK 161,000. Costs of preventive treatment were driving costs, but there was also a cost offset from reduced costs of complications of ～20%. Notable cost differences were found for nephropathy, stroke, and heart failure. The predicted life expectancy with liraglutide increased the cost of net consumption for liraglutide.

Limitations:

The analysis was an ex-ante analysis using model input data from clinical trials which may not reflect effectiveness in real-world clinical practice in broader patient populations. This limitation was explored in the sensitivity analysis. The lack of specific data on loss of production due to diabetes complications implied that these costs may be under-estimated.

Conclusions:

Treatment strategies with liraglutide 1.2?mg improved the expected quality-of-life and increased costs when compared to SU and to sitagliptin for second-line add-on treatments. The cost per QALY for liraglutide was in the range considered medium by Swedish authorities.     

Cost-utility of pregabalin as add-on to usual care versus usual care alone in the management of peripheral neuropathic pain in Belgium

Abstract

Background and objectivess:

The cost effectiveness of pregabalin as an add-on to the standard treatment of Belgian patients with post-herpetic neuralgia (PHN) had been demonstrated in a previously published Markov model. The purpose of this study was to update that model with more recent cost data and clinical evidence, and reevaluate the cost effectiveness from the payer’s perspective of add-on pregabalin in a wider set of NeP conditions.

Methods:

The model, featuring 4-week cycles and a 1-year time horizon, consisted in four possible health states: mild, moderate or severe pain and withdrawn from therapy. Three versions of the model were developed, using transition probabilities derived from pain scores reported in three placebo-controlled studies. The two treatment arms were ‘usual care’ or ‘usual care?+?pregabalin’. Resource use and utility data were obtained from a chart review and unit costs from recent published data. The final outcome of the model was the incremental cost per quality-adjusted life-year (QALY) gained when adding pregabalin to standard care.

Results:

Based on 1000 simulations, two versions of the model showed that pregabalin was dominant respectively in 94.8% and 67.2% of the simulations, while the incremental cost per QALY was below €32,000/QALY in respectively 99.1% and 94.6% of the simulations. The third version did not show cost effectiveness, despite an incremental cost of only €300 after 1 year. However, in the corresponding study, patients seemed less responsive to GABA analogs, since 55% of them had failed to respond to gabapentin before study inclusion.

Limitations:

The studies upon which the model is based have a short follow-up time as compared to the model horizon. The endpoints of two studies were only provided at the aggregated level and do not necessarily reflect the real practice.

Conclusion:

Based on this analysis, it can be concluded that from a Belgium payer perspective pregabalin offers a slight increase in quality of life in the studied populations as compared to standard care. Pregabalin is cost effective in the majority of cases except in one published clinical study, despite a low incremental cost per year (€300).     

Bambuterol is a more cost-effective treatment strategy than salmeterol in asthmatic patients with nocturnal symptoms

Summary

We aimed to compare the cost-effectiveness of oral bambuterol (Bambec®) 20?mg once daily with that of salmeterol (Serevent®) via pressurised metered dose inhaler (pMDI) 50?µg twice daily for treatment of asthma patients with nocturnal symptoms. One hundred and twenty six patients aged 18-70 years and using inhaled corticosteroids at a constant daily dose and with forced expiratory volume in one second (FEV1) 40-85% of predicted normal value, were included in this double-blind, randomised, parallel-group study (two weeks' run-in, six weeks' treatment) in the United Kingdom, Italy and Norway. During run-in, they had to have a nocturnal awakening or early awakening due to asthma symptoms that required rescue medication at least once during a two-week run-in period, and a > 15% fall in overnight peak expiratory flow (PEF) on at least three out of the last seven days. Morning and evening PEF were measured and tremor was scored. The effectiveness variables in the cost-minimisation analysis were symptom-free days and number of nights with no awakenings. Costs for both study and rescue medication were calculated.

There were no statistically significant differences between bambuterol and salmeterol regarding morning and evening PEF (change from baseline), tremor, and the effectiveness variables. Mean number of symptom-free days was 25% vs. 20% and mean number of nights with no awakenings was 69% vs. 77% in the bambuterol and salmeterol groups, respectively. However treatment costs (study plus rescue medication) were lower during bambuterol treatment in all three countries. The per patient cost savings would be 47% in the UK, 27% in Italy and 40% in Norway if a patient changes from salmeterol to bambuterol. The conclusion is that the once-daily treatment with bambuterol is more cost-effective than the twice-daily treatment with salmeterol in asthma patients with nocturnal symptoms.     

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.     

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.     

A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America

Objective: A large, pivotal, phase 3 trial in patients with newly diagnosed multiple myeloma (MM) demonstrated that denosumab, compared with zoledronic acid, was non-inferior for the prevention of skeletal-related events (SREs), extended the observed median progression-free survival (PFS) by 10.7 months, and showed significantly less renal toxicity. The cost-effectiveness of denosumab vs zoledronic acid in MM in the US was assessed from societal and payer perspectives.

Methods: The XGEVA Global Economic Model was developed by integrating data from the phase 3 trial comparing the efficacy of denosumab with zoledronic acid for the prevention of SREs in MM. SRE rates were adjusted to reflect the real-world incidence. The model included utility decrements for SREs, administration, serious adverse events (SAEs), and disease progression. Drug, administration, SRE management, SAEs, and anti-MM treatment costs were based on data from published studies. For the societal perspective, the model additionally included SRE-related direct non-medical costs and indirect costs. The net monetary benefit (NMB) was calculated using a willingness-to-pay threshold of US$150,000. One-way deterministic and probabilistic sensitivity analyses were conducted.

Results: From a societal perspective, compared with zoledronic acid, the use of denosumab resulted in an incremental cost of US$26,329 and an incremental quality-adjusted life-year (QALY) of 0.2439, translating into a cost per QALY gained of US$107,939 and a NMB of US$10,259 in favor of denosumab. Results were sensitive to SRE rates and PFS parameters.

Limitations: Costs were estimated from multiple sources, which varied by tumor type, patient population, country, and other parameters. PFS and overall survival were extrapolated beyond the follow-up of the primary analysis using fitted parametric curves.

Conclusion: Denosumab’s efficacy in delaying or preventing SREs, potential to improve PFS, and lack of renal toxicity make it a cost-effective option for the prevention of SREs in MM compared with zoledronic acid.     

The real-world cost-effectiveness of adjuvant trastuzumab in HER-2/neu-positive early breast cancer in Taiwan

Background: Trastuzumab was considered a cost-effective adjuvant treatment for HER 2-positive early breast cancer. Since 2010, the Taiwanese National Health Insurance (NHI) has started to reimburse for 1-year adjuvant treatment. This study aims to provide an updated cost-effectiveness analysis from the NHI perspective, which explores assumptions about long-term cardiac toxicity and treatment benefit of 1-year adjuvant treatment sequentially after chemotherapy.

Methods: A Markov model was used to evaluate the cost-effectiveness of 1-year adjuvant trastuzumab for HER-2/neu positive early breast cancer over a 20-year life-time horizon. A probability sensitivity analysis using Monte Carlo simulation was performed to characterize uncertainties in the expected outcomes, which are expressed as an incremental costs effectiveness ratio (ICER, cost/QALY). A willingness-to-pay threshold of 3-times the per capita gross domestic product was adopted according to the WHO definition. The Taiwan per capita gross domestic product in 2015 was US$22,355; thus, a threshold was considered as NT$2,011,950 (US$67 065, 1USD?=30 NTD in 2015).

Results: The model showed that adjuvant trastuzumab treatment in HER-2/neu positive early breast cancer yielded 1.631 quality-adjusted life-years (QALY) compared with no trastuzumab treatment. The ICER was US $51,863 per QALY gained in the base-case scenario. The Monte Carlo simulation by varying all variables simultaneously demonstrated that the probability of cost-effectiveness at the willingness-to-pay threshold of US$67,065 was 50% for 1-year adjuvant trastuzumab.

Conclusions: From this real-world study, 1-year adjuvant trastuzumab treatment is likely to be a cost-effective therapy for patients with HER-2 positive breast cancer at the willingness-to-pay threshold of 3-times GDP per capita in Taiwan.     

Systematic review of models used in economic analyses in moderate-to-severe asthma and COPD

Background:

Respiratory diseases exert a substantial burden on society, with newer drugs increasingly adding to the burden. Economic models are often used, but seldom reviewed.

Purpose:

To summarize economic models used in economic analyses of drugs treating moderate-to-severe/very severe asthma or chronic obstructive pulmonary disease (COPD).

Methods:

This study searched Medline and Embase from inception to the end of February 2015 for cost-effectiveness/utility analyses that examined at least one drug against placebo, another drug, or other standard therapy in asthma or COPD. Two reviewers independently searched and extracted data with differences adjudicated via consensus discussion. Data extracted included model used and its qualities, validation methods, treatments compared, disease severity, analytic perspective, time horizon, data collection (pro- or retrospective), input rates and sources, costs and sources, planned sensitivity analyses, criteria for cost-effectiveness, reported outcomes, and sponsor.

Results:

This study analyzed 53 articles; 14 (25%) on asthma and 39 (75%) COPD. Markov models were commonly used for both asthma and COPD-related economic evaluations. Relatively few studies validated their model. For asthma-related studies, 10 examined inhaled corticosteroids and nine studied omalizumab. Placebo or standard therapy was the comparison in 11 studies and active drugs in the remainder.

Conclusions:

Few studies include validation of their models. Furthermore, controversy concerning some results was uncovered in this study, which needs to be avoided in the future.     

The cost-effectiveness of somatropin treatment for short children born small for gestational age (SGA) and children with growth hormone deficiency (GHD) in Sweden

Abstract

Objective: Reduction in health-related quality of life is common in children born small for gestational age (SGA) or children with growth hormone deficiency (GHD). Growth hormone treatment with somatropin in these children leads to normalisation of height. The aim of this study was to determine whether somatropin is a cost-effective treatment option for short children born SGA and GHD children in Sweden.

Methods: A Markov decision-tree model was used to calculate the relative costs and health benefits associated with somatropin treatment over the lifetime of SGA and GHD children, compared with no treatment. The analysis was undertaken from a Swedish Health Service perspective. As quality-adjusted life-year (QALY) data were not obtained directly in the clinical studies, a degree of uncertainty is related to these results. Sensitivity analyses assessed the degree of uncertainty surrounding central parameters.

Results: For short children born SGA, somatropin treatment was associated with an additional 3.29 QALYs at an incremental cost of 792,489 SEK (Swedish Krona), compared with no treatment. For GHD, somatropin treatment resulted in 3.25 additional QALYs at an incremental cost of 391,291 SEK. This equates to an incremental cost per QALY of 240,831 SEK and 120,494 SEK for SGA and GHD, respectively, below a cost-effectiveness threshold of 500,000–600,000 SEK/QALY.

Conclusions: Somatropin is a cost-effective treatment strategy in Sweden for children with GHD and SGA. To overcome present study limitations future clinical research should incorporate appropriate quality of life questionnaires.     

Cost effectiveness of tyrosine kinase inhibitor therapy in metastatic gastrointestinal stromal tumors

Abstract

Background:

Tyrosine kinase inhibitors (TKIs) such as imatinib mesylate have revolutionized the treatment of primary unresectable and/or metastatic gastrointestinal stromal tumors (GISTs), providing durable disease control and extended survival. Although most patients eventually progress on therapy, dose escalation has been shown to benefit some patients. Sunitinib, a multitargeted kinase inhibitor is effective against imatinib-resistant or intolerant GIST patients. Although the cost of TKI therapy in GIST is high, no other effective systemic treatment options exist.

Objective:

Review pharmacoeconomic studies to determine the cost effectiveness (CE) of 1st- and 2nd-line TKI therapies in GIST.

Methods:

A literature review using Medline and PubMed databases was conducted to identify published economic analyses of TKI therapy in GIST. Key results from these studies were analyzed.

Results:

Six pharmacoeconomic studies were identified, including three analyses of 1st-line imatinib and three analyses of 2nd-line sunitinib. These studies employed various time horizons and discount rates and modeled CE from a number of different perspectives. Most of the pharmacoeconomic studies reviewed used survival as their efficacy endpoint, projecting outcomes beyond available data to model CE. Analyses of 2nd-line sunitinib using survival additionally faced the challenge of adjusting for the effect of placebo crossover to active treatment in the pivotal phase III study. Most studies used Markov techniques with a range of transition probabilities.

Conclusions:

Published pharmacoeconomic studies of 1st- and 2nd-line TKI therapy for advanced GIST employ various time horizons, discount rates, and different CE models. Consequently, these differences make comparisons between studies difficult. Studies of 1st-line imatinib concluded that imatinib was cost effective in advanced, metastatic GIST. Likewise, based on data reviewed here, 2nd-line sunitinib appears to be cost effective in patients with advanced GIST who are intolerant/resistant to imatinib. Key limitations of this review included inconsistency among the studies evaluated with regard to methodologies, countries of origination (currency and healthcare systems), and patient demographics.     

Economic impact of using inhaled corticosteroids without prior exacerbation among elderly patients with chronic obstructive pulmonary disorder

Abstract

Objective:

To assess the economic impact of initiating inhaled corticosteroids (ICS) without evidence of prior exacerbation among elderly patients with chronic obstructive pulmonary disease (COPD) in the US.

Methods:

This retrospective study used administrative claims to identify newly diagnosed COPD patients between 1/1/2005 and 6/30/2006 who were dispensed ICS. The dispense date of the first ICS was set as the index date. Patients with prior diagnoses for asthma, cystic fibrosis, or lung cancer were excluded. Cohorts were constructed based on whether ICS therapy was concordant with recommended guidelines of having prior COPD exacerbation. Each COPD patient with prior exacerbation was matched to four patients without exacerbation based on age, gender, Charlson Comorbidity Index, and whether COPD diagnosis code was not elsewhere specified (i.e., 496). Multivariate regressions were estimated to assess the association between use of ICS therapy without prior exacerbation and total healthcare costs, controlling for demographics and clinical characteristics.

Results:

The study included 3650 patients: 730 with prior exacerbation and 2920 without prior exacerbation. Patients were 76 years of age and 54% were male. Those with prior exacerbation were more likely to have inpatient stays both prior to (74.4 vs. 44.1%, p?<?0.05) and following (37.0 vs. 33.1%, p?<?0.05) the index date. Controlling for patient characteristics, patients who were dispensed ICS without prior exacerbation had $1859 higher in total costs (p?<?0.05) compared to patients with prior exacerbation during the 12 months following ICS initiation.

Limitations:

The retrospective design of this study limits the interpretation of findings as association and not causality. This study is subject to selection bias due to unobservable confounders.

Conclusions:

Among COPD patients, initiation of ICS without prior exacerbation appears to be associated with increased healthcare costs. These findings suggest that ICS initiation without evidence of exacerbation as consistent with guidelines is associated with adverse economic consequences.