De-escalation from micafungin is a cost-effective alternative to traditional escalation from fluconazole in the treatment of patients with systemic Candida infections

Abstract

Background:

Systemic Candida infections (SCI) occur predominantly in intensive care unit patients and are a common cause of morbidity and mortality. Recently, changes in Candida epidemiology with an increasing prevalence of SCI caused by Candida non-albicans species have been reported. Resistance to fluconazole and azoles in general is not uncommon for non-albicans species. Despite guidelines recommending initial treatment with broad-spectrum antifungals such as echinocandins with subsequent switch to fluconazole if isolates are sensitive (de-escalation strategy), fluconazole is still the preferred first-line antifungal (escalation) in many clinical practice settings. After diagnosis of the pathogen, the initial therapy with fluconazole is switched to a broad-spectrum antifungal if a non-albicans is identified.

Methods:

The cost-effectiveness of initial treatment with micafungin (de-escalation) vs fluconazole (escalation) in patients with SCI was estimated using decision analysis based on clinical and microbiological data from pertinent studies. The model horizon was 42 days, and was extrapolated to cover a lifetime horizon. All costs were analyzed from the UK NHS perspective. Several assumptions were taken to address uncertainties; the limitations of these assumptions are discussed in the article.

Results:

In patients with fluconazole-resistant isolates, initial treatment with micafungin avoids 30% more deaths and successfully treats 23% more patients than initial treatment with fluconazole, with cost savings of £1621 per treated patient. In the overall SCI population, de-escalation results in 1.2% fewer deaths at a marginal cost of £740 per patient. Over a lifetime horizon, the incremental cost-effectiveness of de-escalation vs escalation was £15,522 per life-year and £25,673 per QALY.

Conclusions:

De-escalation from micafungin may improve clinical outcomes and overall survival, particularly among patients with fluconazole-resistant Candida strains. De-escalation from initial treatment with micafungin is a cost-effective alternative to escalation from a UK NHS perspective, with a differential cost per QALY below the ‘willingness-to-pay’ threshold of £30,000.     

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.     

Cost effectiveness of paliperidone palmitate versus risperidone long-acting injectable and olanzapine pamoate for the treatment of patients with schizophrenia in Sweden

Abstract

Objective:

To model the cost effectiveness of paliperidone palmitate (paliperidone long-acting injectable; PLAI), a new once-monthly long-acting antipsychotic therapy, compared with risperidone long-acting injectable (RLAI) and olanzapine pamoate (OLAI), in multi-episode patients (two or more relapses) with schizophrenia in Sweden.

Methods:

A Markov decision analytic model was developed to simulate the history of a cohort of multi-episode patients transitioning through different health states on a monthly basis over a 5-year time horizon from the perspective of the Swedish healthcare system. Therapeutic strategies consisted of starting treatment with RLAI (mean dose 37.5?mg every 2 weeks), PLAI (mean dose 75?mg equivalent (eq.) every month) or OLAI (150?mg every 2 weeks or 300?mg every 4 weeks). Probability of relapse, level of adherence, side-effects (extrapyramidal symptoms, tardive dyskinesia, weight gain and diabetes) and treatment discontinuation (switch) were derived from long-term observational data when feasible. Incremental cost-effectiveness outcomes, discounted at 3% annually, included cost per quality-adjusted life-year (QALY) and cost per relapse avoided (expressed in 2009 Swedish Krona SEK).

Results:

Relative to RLAI and OLAI, PLAI is economically dominant: more effective (additional QALYs, less relapses) and less costly treatment option over a 5-year time horizon. The results were robust when tested in sensitivity analysis.

Limitations:

The impact of once-monthly treatment on adherence levels is not yet known, and not all variables that could impact on real-world outcomes and costs were included in this model.

Conclusion:

PLAI was cost saving from a Swedish payer perspective compared with RLAI and OLAI in the long-term treatment of multi-episode (two or more relapses) schizophrenia patients.     

Adapting a global cost-effectiveness model to local country requirements: posaconazole case study

Abstract

Background:

Many countries have various requirements for local economic analyses to assess the value of a new health technology and/or to secure reimbursement. This study presents a case study of an economic model developed to assess the cost-effectiveness of posaconazole vs standard azole therapy (fluconazole/itraconazole) to prevent invasive fungal infections (IFIs), which was adapted by at least 11 countries.

Methods:

Modeling techniques were used to assess the cost-effectiveness of posaconazole vs fluconazole/itraconazole as IFI prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndromes and chemotherapy-induced neutropenia. For the core model, the probabilities of experiencing an IFI, IFI-related death, and death from other causes were estimated from clinical trial data. Long-term mortality, drug costs, and IFI treatment costs were obtained from secondary sources. Locally changed parameters were probabilities of long-term death and survival, currency, drug costs, health utility, IFI treatment costs, and discount rate.

Results:

Locally adapted cost-effective modeling studies indicate that prophylaxis with posaconazole, compared with fluconazole/itraconazole, prolongs survival, and, in most countries, is cost-saving. In all countries, the model predicted that prophylaxis with posaconazole would be associated with an increase in life-years, with increases ranging from 0.016–0.1 life-year saved. In all countries, use of the model led to posaconazole being approved by the appropriate reimbursement authority.

Limitations:

The study did not have power to detect differences between posaconazole and fluconazole or itraconazole separately. The risk of death after 100 days was assumed to be equal for those who did and did not develop an IFI, and equal probabilities of IFI-related and other death during the trial period were used for both groups.

Conclusions:

A core economic model was successfully adapted locally by several countries. The model showed that posaconazole was cost-saving or cost-effective vs fluconazole/itraconazole and led to positive reimbursement listings.     

Posaconazole vs fluconazole/itraconazole in the prophylaxis of invasive fungal infections in immunocompromised patients: A cost-effectiveness analysis in Greece

Abstract

Background:

Invasive fungal infections (IFIs) present a major issue in clinical practice, due to their high morbidity and mortality rates. In a pivotal multi-centre, randomized clinical trial, posaconazole prophylaxis prevented IFIs more effectively than did either fluconazole or itraconazole, and improved overall survival.

Objective:

The aim of this study was to perform an economic evaluation of the aforementioned therapeutic strategies for IFI prophylaxis in neutropenic patients, in the Greek healthcare setting.

Method:

A decision analytic model was developed, which described the course of neutropenic patients under posaconazole or standard azole (fluconazole or itraconazole) treatment. Effectiveness data for each treatment regimen were derived from published results of a pivotal, multi-centre, randomized clinical trial. Cost and healthcare resources utilization data depict Greek clinical practice and are derived from official Greek sources, from a third party payer perspective.

Results:

Prophylaxis with posaconazole resulted in fewer IFIs (0.05 vs 0.11 per patient) compared to treatment with fluconazole or itraconazole, during the first 100 days from initiation of prophylaxis treatment. The cost per avoided IFI with posaconazole was €6455, while the incremental cost per life year gained (LYG) was estimated at €24,196. Extensive sensitivity analyses corroborated the base-case results. Possible limitations of the study are the exclusion of indirect and outpatient costs from the analysis and the inherent uncertainty with regards to the transferability of the clinical efficacy results of the clinical trial to the Greek healthcare setting.

Conclusions:

The utilization of posaconazole for prophylaxis of IFIs neutropenic patients is a therapeutic strategy that provides superior clinical efficacy, while being cost-effective compared to alternative therapies.     

Cost-effectiveness of primary antifungal prophylaxis with posaconazole versus itraconazole in allogeneic hematopoietic stem cell transplantation

Abstract

Purpose:

To evaluate the cost-effectiveness of posaconazole vs itraconazole in the prevention of invasive fungal infections (IFIs) in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods:

Total hospital-based costs from initial admission for allo-HSCT until day 100 after transplantation were evaluated for 49 patients in whom the clinical efficacy of antifungal prophylaxis with posaconazole vs itraconazole had been previously analyzed and reported. Clinical and economic data were used to determine the incremental costs per IFI avoided and per life-year gained for posaconazole compared with itraconazole. Confidence intervals for the incremental cost-effectiveness ratio (ICER) and a cost-effectiveness acceptability curve were estimated through bootstrapping with the bias-corrected percentile method.

Results:

According to our analysis, the total cost of allo-HSCT per patient during the 100-day fixed-treatment period was €46,562 in the posaconazole group (n?=?33) and €45,080 in the itraconazole group (n?=?16). However, the reduction in the incidence of IFI and the improved outcome with posaconazole resulted in a favorable ICER of €11,856 per IFI avoided and €5218 per life-year gained. With the outcomes of the bootstrap procedure, the cost-effectiveness acceptability curve was constructed. Assuming a threshold of €30,000 per life-year gained, the ICER based on life-years gained is acceptable with 75% certainty.

Limitations:

This evaluation is based on data from a single-center, non-randomized study. Preference weights or utilities were not available to calculate quality-adjusted life-years. Extra-mural costs were only partially evaluated from a hospital perspective. Indirect costs and economic consequences are not included.

Conclusions:

This economic evaluation compared direct medical costs associated with posaconazole or itraconazole treatment; the data suggest that posaconazole may be cost-effective as antifungal prophylaxis during the early high-risk neutropenic period and up to 100 days after allo-HSCT.     

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

Abstract

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

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

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

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

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

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.     

National and regional dose escalation and cost of tumor necrosis factor blocker therapy in biologic-naïve rheumatoid arthritis patients in US health plans

Objective:

This study examined the proportion and magnitude of dose escalation nationally and regionally among rheumatoid arthritis (RA) patients treated with TNF-blockers and estimated the costs of TNF-blocker therapy.

Methods:

This retrospective cohort study used claims data from US commercially-insured adult RA patients who initiated adalimumab, etanercept, or infliximab therapy between 2005–2009. Biologic-naïve patients enrolled in the health plan for ≥6 months before and ≥12 months after therapy initiation were followed for 12 months. Dose escalation was assessed using three methods: (1) average weekly dose?>?recommended label dose, (2) average ending dispensed dose?>?maintenance dose, and (3) average dose after maintenance dose?>?maintenance dose. Annual cost of therapy included costs for mean dose and drug administration fees.

Results:

Overall, 1420 etanercept, 874 adalimumab, and 454 infliximab patients were included. A significantly lower proportion of etanercept-treated patients had dose escalation using the average weekly dose (3.9% vs 21.4% adalimumab and 69.6% infliximab; p?p?p?Limitations:

Exclusion of patients not on continuous TNF-blocker therapy limits the generalizability; however, ～50% of patients were persistent on therapy for 12 months. The study population comprised RA patients in commercial health plans, thus the results may not be generalizable to Medicare or uninsured populations.

Conclusions:

In this retrospective study, etanercept patients had the lowest proportions and magnitudes of dose escalation across all methods compared to adalimumab and infliximab patients nationally and regionally. Mean annual cost was lowest for etanercept-treated patients.     

Hospital economic impact from hemostatic matrix usage in cardiac surgery

Objective:

Improved health outcomes can result in economic savings for hospitals and payers. While effectiveness of topical hemostatic agents in cardiac surgery has been demonstrated, evaluations of their economic benefit are limited. This study quantifies the cost consequences to hospitals, based on clinical outcomes, from using a flowable hemostatic matrix vs non-flowable topical hemostatic agents in cardiac surgery.

Research design and methods:

Applying clinical outcomes from a prospective randomized clinical trial, a cost consequence framework was utilized to model the economic impact of comparator groups. From that study, clinical outcomes were obtained and analyzed for a flowable hemostatic matrix (FLOSEAL, Baxter Healthcare Corporation) vs non-flowable topical hemostats (SURGICEL Nu-Knit, Ethicon–Johnson &; Johnson; GELFOAM, Pfizer). Costing analyses focused on the following outcomes: complications, blood transfusions, surgical revisions, and operating room (OR) time. Cardiac surgery costs were analyzed and expressed in 2012 US dollars based on available literature searches and US data. Comparator group variability in cost consequences (i.e., cost savings) was calculated based on annualized impact and scenario testing.

Results:

Results suggest that if a flowable hemostatic matrix (rather than a non-flowable hemostat) was utilized exclusively in 600 mixed cardiac surgeries annually, a hospital could improve patient outcomes by a reduction of 33 major complications, 76 minor complications, 54 surgical revisions, 194 transfusions, and 242?h of OR time. These outcomes correspond to a net annualized cost consequence savings of $5.38 million, with complication avoidance as the largest contributor.

Conclusions:

This cost consequence framework and supportive modeling was used to evaluate the hospital economic impact of outcomes resulting from the usage of various hemostatic agents. These analyses support that cost savings can be achieved from routine use of a flowable hemostatic matrix, rather than a non-flowable topical hemostat, in cardiac surgery.     

An economic evaluation of ramipril in the treatment of patients at high risk for cardiovascular events due to diabetes mellitus

SUMMARY

Cardiovascular disease (CVD) is a major cause of death and morbidity in the United Kingdom (UK) and carries with it a significant financial cost through health care resource use. More than one in three people die from CVD events, and the cost to the UK National Health Service (NHS) was £1.6 billion in 1996¹. The recently published MICRO-HOPE study evaluated the treatment of 3,577 patients at high risk for cardiovascular events from diabetes mellitus and demonstrated significant survival and morbidity benefits associated with ramipril.

The purpose of this paper is to assess whether the significant clinical benefits offered by ramipril can be translated into economic benefits, and to what extent it can reduce the economic burden of CVD to the UK NHS.

Applying the same analytical framework used in a previous economic analysis of the HOPE study, our base case estimate of cost-effectiveness for ramipril in the MICRO HOPE study is £2,396 per life-year saved (undiscounted) and £2,971 per life-year saved (discounted). A sensitivity analysis was performed which ranged from a best case of £1,954 per life-year saved (undiscounted) to a worst case of £2,964 per life-year saved (undiscounted). Our base case estimate of cost-effectiveness suggests that treating patients at high risk for CVD events with ramipril is likely to be a good investment of NHS resources.     

Trajectory analysis of healthcare costs for patients with major depressive disorder treated with high doses of duloxetine

Abstract

Objective:

To examine healthcare cost patterns prior to and following duloxetine initiation in patients with major depressive disorder (MDD), focusing on patients initiated at or titrated to high doses.

Research design and methods:

Retrospective analysis of 10,987 outpatients, aged 18–64 years, who were enrolled in health insurance for 6 months preceding and 12 months following duloxetine initiation.

Outcome measures:

Repeated measures and pre–post analyses were used to examine healthcare cost trajectories before and after initiation of low- (<60?mg/day), standard- (60?mg/day), and high-dose (>60?mg/day) duloxetine therapy. Decision tree analysis was used to identify patient characteristics that might explain heterogeneity in economic outcomes following titration to high-dose therapy.

Results:

Low-, standard-, and high-dose duloxetine were initiated for 29.6%, 60.9%, and 9.5% of patients, respectively. Within 6 months, 13.7% of patients had dose increases to >?60?mg/day. Regardless of dose, total costs increased prior to and decreased following initiation of treatment. The High Initial Dose Cohort had higher costs both prior to and throughout treatment compared to the other two cohorts. Following escalation to >?60?mg/day, higher medication costs were balanced by lower inpatient costs. Titration to high-dose therapy was cost-beneficial for patients with histories of a mental disorder in addition to MDD and higher prior medical costs.

Limitations:

Conclusions are limited by a lack of supporting clinical information and may not apply to patients who are not privately insured.

Conclusions:

In data taken from insured patients with MDD who were started on duloxetine in a clinical setting, healthcare costs increased prior to and decreased following initiation of therapy. Compared to patients initiated at low- and standard-doses, costs were greater prior to and following initiation for patients initiated at high doses. Increases in pharmacy costs associated with escalation to high-dose therapy were offset by reduced inpatient expenses.     

Cost-effectiveness of novel relapsed-refractory multiple myeloma therapies in Norway: lenalidomide plus dexamethasone vs bortezomib

Abstract

Objective:

To estimate the cost-effectiveness (cost per additional life-year [LY] and quality-adjusted life-year [QALY] gained) of lenalidomide plus dexamethasone (LEN/DEX) compared with bortezomib for the treatment of relapsed-refractory multiple myeloma (rrMM) in Norway.

Methods:

A discrete-event simulation model was developed to predict patients’ disease course using patient data, best response, and efficacy levels obtained from LEN/DEX MM-009/-010 trials and the bortezomib (APEX) published clinical trial. Predictive equations for time-to-progression (TTP) and post-progression survival (PPS) were developed by identifying the best fitting parametric survival distributions and selecting the most significant predictors. Disease and adverse event management was obtained via survey from Norwegian experts. Costs, derived from official Norwegian pricing data bases, included drug, administration, monitoring, and adverse event management costs.

Results:

Complete or partial responders were 65% for LEN/DEX compared to 43% for bortezomib. Derived median TTP was 11.45 months for LEN/DEX compared to 5.15 months for bortezomib. LYs and QALYs were higher for LEN/DEX (4.06 and 2.95, respectively) than for bortezomib (3.11 and 2.19, respectively). The incremental costs per QALY and LY gained from LEN/DEX were NOK 247,978 and NOK 198,714, respectively, compared to bortezomib. Multiple sensitivity analyses indicated the findings were stable. The parameters with the greatest impact were 4-year time horizon (NOK 441,457/QALY) and higher bound confidence intervals for PPS (NOK 118,392).

Limitations:

The model analyzed two therapies not compared in head-to-head trials, and predicted results using an equation incorporating patient-level characteristics. It is a limited estimation of the costs and outcomes in a Norwegian setting.

Conclusions:

The simulation model showed that treatment with LEN/DEX leads to greater LYs and QALYs when compared to bortezomib in the treatment of rrMM patients. The incremental cost-effectiveness ratio indicated treatment with LEN/DEX to be cost-effective and was the basis of the reimbursement approval of LEN/DEX in Norway.     

Cost-utility of exenatide once weekly compared with insulin glargine in patients with type 2 diabetes in the UK

Abstract

Objective:

To compare the cost-utility of exenatide once weekly (EQW) and insulin glargine in patients with type 2 diabetes in the United Kingdom (UK).

Research design and methods:

The IMS CORE Diabetes Model was used to project clinical and economic outcomes for patients with type 2 diabetes treated with EQW or insulin glargine. Treatment effects and patient baseline characteristics (mean age: 58 years, mean glycohaemoglobin: 8.3%) were taken from the DURATION-3 study. Unit costs and health state utility values were derived from published sources. As the price of EQW is not yet known, the prices of two currently available glucagon-like peptide-1 products were used as benchmarks. To reflect diabetes progression, patients started on EQW switched to insulin glargine after 5 years. The analysis was conducted from the perspective of the UK National Health Service over a time horizon of 50 years with costs and outcomes discounted at 3.5%. Sensitivity analyses explored the impact of changes in input data and assumptions and investigated the cost utility of EQW in specific body mass index (BMI) subgroups.

Main outcome measures:

Incremental cost-effectiveness ratio (ICER) for EQW compared with insulin glargine.

Results:

At a price equivalent to liraglutide 1.2?mg, EQW was more effective and more costly than insulin glargine, with a base case ICER of £10,597 per quality-adjusted life-year (QALY) gained. EQW was associated with an increased time to development of any diabetes-related complication of 0.21 years, compared with insulin glargine. Three BMI subgroups investigated (<30, 30–35 and >35?kg/m²) reported ICERs for EQW compared with insulin glargine ranging from £9425 to £12,956 per QALY gained.

Conclusions:

At the prices investigated, the cost per QALY gained for EQW when compared with insulin glargine in type 2 diabetes in the UK setting, was within the range normally considered cost effective by NICE. Cost effectiveness in practice will depend on the final price of EQW and the extent to which benefits observed in short-term randomised trials are replicated in long-term use.     

The cost implications of an early versus delayed invasive strategy in acute coronary syndromes: the TIMACS study

Background:

The Timing of Intervention in Acute Coronary Syndromes (TIMACS) trial demonstrated that early invasive intervention (within 24 hours) was similar to a delayed approach (after 36 hours) overall but improved outcomes were seen in patients at high risk. However, the cost implications of an early versus delayed invasive strategy are unknown.

Methods and results:

A third-party perspective of direct cost was chosen and United States Medicare costs were calculated using average diagnosis related grouping (DRG) units. Direct medical costs included those of the index hospitalization (including clinical, procedural and hospital stay costs) as well as major adverse cardiac events during 6 months of follow-up. Sensitivity and sub-group analyses were performed. The average total cost per patient in the early intervention group was lower compared with the delayed intervention group (?$1170; 95% CI ?$2542 to $202). From the bootstrap analysis (5000 replications), the early invasive approach was associated with both lower costs and better clinical outcomes regarding death/myocardial infarction (MI)/stroke in 95.1% of the cases (dominant strategy). In high-risk patients (GRACE score ≥141), the net reduction in cost was greatest (?$3720; 95% CI ?$6270 to ?$1170). Bootstrap analysis revealed 99.8% of cases were associated with both lower costs and better clinical outcomes (death/MI/stroke).

Limitations:

We were unable to evaluate the effect of community care and investigations without hospitalization (office visits, non-invasive testing, etc). Medication costs were not captured. Indirect costs such as loss of productivity and family care were not included.

Conclusions:

An early invasive management strategy is as effective as a delayed approach and is likely to be less costly in most patients with acute coronary syndromes.     

A review of international pharmacoeconomic models assessing the use of aspirin in primary prevention

Abstract

Purpose:

The aim of this narrative review was to summarise the cost analyses and supporting trial data for aspirin prophylaxis in primary prevention.

Methods:

A PubMed search using the term ‘aspirin and cost-effective and primary prevention’ was performed. Professional meetings (2009) were also searched for any relevant abstracts contacting the terms ‘aspirin’ and ‘cost effectiveness’. Where possible, outcomes were discussed in terms of cost implications (expressed as quality-adjusted life-year [QALY], disability-adjusted life-year or incremental cost-effectiveness ratio) in relation to the annual risk of cardiovascular disease. Aspirin was included in cost-effectiveness models that determined direct cost savings.

Results:

A total of 67 papers were identified using PubMed, and 17 cost-effectiveness studies, which assessed aspirin in primary prevention (largely based on the key primary prevention studies), and two abstracts were included in the review. These analyses showed that low-dose aspirin was cost effective in a variety of scenarios. In the UK, Germany, Spain, Italy and Japan, the mean 10-year direct cost saving (including follow-up costs and aspirin costs) per patient was €201, €281, €797, €427 and €889 with aspirin use in patients with an annual coronary heart disease risk of 1.5%. Cost-effectiveness analyses were affected by age, risk level for stroke and myocardial infarction (MI), risk of bleeds and adherence to aspirin. Underutilisation is a major limiting factor, as the appropriate use of aspirin in an eligible population (n?=?301,658) based on the NHANES database would prevent 1273 MIs, 2184 angina episodes and 565 ischaemic strokes in patients without previous events; this would result in a direct cost saving of $79.6?million (€54.7?million; 2010 values), which includes aspirin costs.

Conclusions:

Most analyses in primary prevention have shown that low-dose aspirin is a cost-effective option, and is likely to meet the willingness of a healthcare system to pay for any additional QALY gained in the majority of healthcare systems.     

Cost reduction from resolution/improvement of carcinoid syndrome symptoms following treatment with above-standard dose of octreotide LAR

Aims: To calculate the cost reduction associated with diarrhea/flushing symptom resolution/improvement following treatment with above-standard dose octreotide-LAR from the commercial payor’s perspective.

Materials and methods: Diarrhea and flushing are two major carcinoid syndrome symptoms of neuroendocrine tumor (NET). Previously, a study of NET patients from three US tertiary oncology centers (NET 3-Center Study) demonstrated that dose escalation of octreotide LAR to above-standard dose resolved/improved diarrhea/flushing in 79% of the patients within 1 year. Time course of diarrhea/flushing symptom data were collected from the NET 3-Center Study. Daily healthcare costs were calculated from a commercial claims database analysis. For the patient cohort experiencing any diarrhea/flushing symptom resolution/improvement, their observation period was divided into days of symptom resolution/improvement or no improvement, which were then multiplied by the respective daily healthcare cost and summed over 1 year to yield the blended mean annual cost per patient. For patients who experienced no diarrhea/flushing symptom improvement, mean annual daily healthcare cost of diarrhea/flushing over a 1-year period was calculated.

Results: The economic model found that 108 NET patients who experienced diarrhea/flushing symptom resolution/improvement within 1 year had statistically significantly lower mean annual healthcare cost/patient than patients with no symptom improvement, by $14,766 (p?=?.03). For the sub-set of 85 patients experiencing resolution/improvement of diarrhea, their cost reduction was more pronounced, at $18,740 (p?=?.01), statistically significantly lower than those with no improvement; outpatient costs accounted for 56% of the cost reduction (p?=?.02); inpatient costs, emergency department costs, and pharmacy costs accounted for the remaining 44%.

Limitations: The economic model relied on two different sources of data, with some heterogeneity in the prior treatment and disease status of patients.

Conclusions: Symptom resolution/improvement of diarrhea/flushing after treatment with an above-standard dose of octreotide-LAR in NET was associated with a statistically significant healthcare cost decrease compared to a scenario of no symptom improvement.     

Treatment of candidemia with echinocandins: data on hospital resource use from a real world setting

Abstract

Objective:

Real-world data on patients treated with echinocandins for candidemia are limited. This study examined the effect of three echinocandin-based treatment regimens on resource utilization in patients with Candida infection.

Research design and methods:

A retrospective cohort study of patients hospitalized between 2005 and 2010 with a blood culture positive for Candida. Length of stay (LOS) following AF initiation (post-AF LOS) and total days with AF treatment were compared in patients treated with three different echinocandin regimens: patients with echinocandin only, patients who received fluconazole prior to an echinocandin (fluconazole-echinocandin), and patients who received an echinocandin prior to fluconazole (echinocandin-fluconazole). Generalized linear models were used to adjust for confounders.

Results:

A total of 647 patients met inclusion criteria. Patients treated with echinocandin only were more acutely ill, having more organ dysfunction and sepsis. Unadjusted post-AF LOS was significantly greater in the groups that received both echinocandin and fluconazole (mean, 13.1 days for echinocandin-only vs 25.5 and 21.2 days for fluconazole-echinocandin and echinocandin-fluconazole groups, respectively, p?<?0.001). These groups also had a higher total number of days with AF orders. These differences remained after multivariate adjustment and in survivor-only analyses. Compared with echinocandin-only treatment, the average marginal effect of fluconazole-echinocandin and echinocandin-fluconazole regimens were associated with significantly longer adjusted post-AF LOS (by 7.2 days and 9.3 days, respectively, p?<?0.001) and significantly more adjusted total AF days (by 5.3 days for fluconazole-echinocandin and 6.5 days for echinocandin-fluconazole patients, p?<?0.001). Limitations included lack of visibility to specific reasons for therapy changes.

Conclusions:

Fluconazole before or after echinocandin was associated with significantly greater resource utilization than echinocandin use alone.     

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).