Cost effectiveness of posaconazole in the prophylaxis of invasive fungal infections in acute leukaemia patients for the French healthcare system

Abstract

Background:

Acute myeloblastic leukaemia (AML) patients are at high risk of suffering from invasive fungal infections (IFI). Posaconazole demonstrated higher efficacy than standard azole agents (SAA) in the prophylaxis of IFI in this population.

The authors estimated the cost effectiveness of posaconazole versus SAA in France.

Methods:

A decision-tree model was developed to compare posaconazole with SAA with the results of a published clinical trial. Clinical events were modelled with chance nodes reflecting probabilities of IFI, IFI-related death, and death from other causes. Medical resource consumption and costs were obtained from results of the clinical trial and from a dedicated survey on the costs of treating IFI using a retrospective chart review design.

Results:

IFI treatment costs were estimated using medical files from 50 AML patients from six French centres, with a proven and probable IFI, who had been followed-up for 298 days on average. Direct costs directly related to IFI were estimated at €51,033, including extra costs of index hospitalisation, costs of antifungal therapy and additional hospitalisations related to IFI treatment. The model indicated that the healthcare costs for the posaconazole strategy were €5,223 (€2,697 for prophylaxis and €2,526 for IFI management), which was €859 less than the €6,083 in costs with SAA (€469 for prophylaxis and €5614 for IFI management). A sensitivity analysis indicated that there was an 80% probability that prophylaxis using the posaconazole strategy would be superior.

Conclusion:

The findings from this analysis suggest that posaconazole use is a clinically and economically dominant strategy in the prophylaxis of IFI in AML patients, given the usual limits of economic models and the uncertainty of costs estimates.     

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.     

An update to the cost-effectiveness of posaconazole vs fluconazole or itraconazole in the prevention of invasive fungal disease among neutropenic patients in the United States

Abstract

Objectives:

Posaconazole has shown superior clinical efficacy in the prevention of invasive fungal disease (IFD) among neutropenic patients as well as cost-effectiveness in the US healthcare setting vs fluconazole or itraconazole (FLU/ITRA) based on oral suspension formulations of each therapy. This study aims to provide an update on the cost-effectiveness of posaconazole in the current US healthcare setting to reflect bioequivalent tablet formulations of posaconazole and fluconazole, as well as changes in healthcare and drug costs.     

Economic evaluation of dabigatran etexilate for the primary prevention of venous tromboembolic events following major orthopedic surgery in the Netherlands

Abstract

Objectives:

Dabigatran etexilate is a new oral direct thrombin inhibitor for prophylaxis of venous thromboembolism (VTE) in patients who have elective surgery for total hip replacement (THR) or total knee replacement (TKR). Among the advantages of dabigatran etexilate over subcutaneous prophylaxis with Low Molecular Weight Heparin (LMWH) are reduced resource uses for (i) teaching patients to self-inject; (ii) home-care visits for subcutaneous administration; and (iii) absence of heparin-induced thrombocytopenia (HIT). Based on the demonstrated non-inferiority, the aim of this study was to conduct a cost-minimization analysis of oral dabigatran etexilate vs subcutaneous low-molecular weight heparin (LMWH) and fondaparinux from the Dutch healthcare perspective.

Methods:

A retrospective cohort study was conducted to measure resource use associated with subcutaneous prophylaxis. Results of this study were used in the model to elucidate specific advantages of dabigatran etexilate, next to reduced needs for self-inject teaching and lack of Heparin-Induced Thrombocytopenia. Drug and other resource utilization data were combined with local unit costs. Probabilistic sensitivity analysis was performed to account for uncertainty around relevant parameters included.

Results:

Home-care visits for subcutaneous administration problems were needed in 9.9% (95% CI?=?6.4–13.4) and 9.6% (95% CI?=?5.8–13.4) of THR and TKR patients, respectively. Based on costs for 1000 patients treated with dabigatran etexilate vs LMWHs, per patient cost-savings with dabigatran etexilate were estimated at €30.68 (95% CI?=?2.01–65.52) and €23.19 (95% CI?=?0.69–48.48) for THR and TKR, respectively. The probability that dabigatran etexilate would be cost-saving was estimated at 98.3% and 97.9% for THR and TKR, respectively. These cost-savings were even higher when including fondaparinux in the analysis, with per patient cost-savings of €69.87 (43.42–106.10) and €18.33 (1.63–41.26) for THR and TKR, respectively. Separate calculations for dabigatran etexilate vs nadroparin and dalteparin in THR resulted in probabilities of achieving cost-savings with dabigatran etexilate of 36.2% and 100%, respectively. For TKR these probabilities were estimated at 54.3% and 100%, respectively.

Conclusions:

Thromboprophylaxis with dabigatran etexilate is cost-saving in patients undergoing THR and TKR from the Dutch healthcare perspective, compared to subcutaneous LMWHs.     

Association between drug tolerability and medical resource use in prophylaxis of invasive fungal infections after allogeneic hematopoietic stem cell transplant

Abstract

Objectives:

To conduct a retrospective analysis of the association between drug tolerability and potential economic impact measured by medical resource utilization (MRU) for prophylaxis of invasive antifungal infections (IFI) after allogeneic hematopoietic stem cell transplantation (alloHCT).

Methods:

An open-label, multi-center study (IMPROVIT) included patients (≥12-years old) who were randomized to receive oral voriconazole (VOR) or oral itraconazole (ITR) from the alloHCT day for at least 100 days and up to 180 days. Trial data on discontinuation and MRU for the first 100 days were analyzed.

Results:

Two hundred and twenty-four patients were in VOR and 241 in ITR, with similar demographic distributions (average age of 43 years, 58% male, 92% Caucasian). All-cause and study drug intolerance discontinuations were less frequent with VOR than ITR (50% vs 63%, p?=?0.0137; 7% vs 22%, p?<?0.0001). VOR patients had longer study drug exposure (median?=?96 vs 68 days, p?<?0.0001; mean?=?68 vs 60 days, p?=?0.0044). ITR patients were 2-times more likely (p?=?0.0110) to use other antifungals vs VOR patients. Controlling for treatment and key baseline variables, longer IFI prophylaxis was associated with fewer hospital days (p?<?0.0001) and less other antifungal use (p?<?0.0001). Patients who discontinued prophylaxis during the first 100 days incurred 10 more hospital days (p?<?0.0001) and 17 more other antifungal days (p?<?0.0001) compared to their counterparts. Eight more prophylaxis days were associated with ～1 less hospital day and 3.6 less other antifungal days (p?<?0.0001).

Key limitation:

MRU data collection was limited to the first 100 days post-transplant, which may not fully capture the real-world utilization and outcomes.

Conclusions:

Patients’ ability to tolerate and continue their antifungal prophylaxis after alloHCT is associated with less use of MRU such as other antifungals and hospital days. In the current resource-constrained healthcare environment, it is important to consider the potential economic impact of the tolerability of antifungal prophylaxis.     

Inverse probability weighting to control for censoring in a post hoc analysis of quality-adjusted survival data from a clinical trial of temsirolimus for renal cell carcinoma

Abstract

Objectives: The Belgian third-party payer wishes to set reimbursement tariffs at a level that reflects the costs of orthotic braces. This article aims to calculate production and distribution costs of a prefabricated hard neck and knee brace and to explore whether Belgian tariffs and actual retail prices correspond with estimated costs of these two braces.

Methods: The cost model considered manufacturing costs, general overheads, research and development costs, warehousing costs, profit and distribution margins. Data were gathered from manufacturers, a production site visit, desk research, a decomposition of finished products and stakeholder interviews. The price year was 2007.

Results: The cost model estimated a retail price of €55–€150 for the neck brace, depending on assumptions. The estimated retail price for the neck brace was lower than the reimbursement tariff of €194 and the actual retail price of €241. The estimated retail price of €331–€694 for the knee brace was lower than the actual retail price of €948.

Conclusions: Actual retail prices and reimbursement tariffs for a neck brace and a knee brace exceeded prices based on estimated costs. Therefore, there appears to be scope for reducing tariffs.     

Cost-effectiveness of de-escalation from micafungin versus escalation from fluconazole for invasive candidiasis in China

Aims: Guidelines on treating invasive candidiasis recommend initial treatment with a broad-spectrum echinocandin (e.g. micafungin), then switching to fluconazole if isolates prove sensitive (de-escalation strategy). This study aimed to evaluate the cost-effectiveness of de-escalation from micafungin vs escalation from fluconazole from a Chinese public payers perspective.

Materials and methods: Cost-effectiveness was estimated using a decision analytic model, in which patients begin treatment with fluconazole 400?mg/day (escalation) or micafungin 100?mg/day (de-escalation). From Day 3, when susceptibility results are available, patients are treated with either fluconazole (if isolates are fluconazole-sensitive/dose-dependent) or micafungin (if isolates are resistant). The total duration of (appropriate) treatment is 14 days. Model inputs are early (Day 3) and end-of-treatment mortality rates, treatment success rates, and health resource utilization. Model outputs are costs of health resource utilization over 42 days, incremental cost per life-year, and incremental cost per quality-adjusted life-year (QALY) over a lifetime horizon.

Results: In the base-case analysis, the de-escalation strategy was associated with longer survival and higher treatment success rates compared with escalation, at a lower overall cost (–¥1,154; –175 United States Dollars). Life-years and QALYs were also better with de-escalation. Thus, this strategy dominated the escalation strategy for all outcomes. In a probabilistic sensitivity analysis, 99% of 10,000 simulations were below the very cost-effective threshold (1?×?gross domestic product).

Limitations: The main limitation of the study was the lack of real-world input data for clinical outcomes on treatment with micafungin in China; data from other countries were included in the model.

Conclusion: A de-escalation strategy is cost-saving from the Chinese public health payer perspective compared with escalation. It improves outcomes and reduces costs to the health system by reducing hospitalization, due to an increase in the proportion of patients receiving appropriate treatment.     

Cost-effectiveness analysis of palivizumab among pre-term infant populations covered by Medicaid in the United States

Abstract

Objective:

Medicaid infants are at high risk of severe respiratory syncytial virus (RSV) disease. The study objective was to estimate the cost-effectiveness of palivizumab in a Medicaid population.

Methods:

A societal cost-utility analysis was conducted of prophylaxis with palivizumab vs no prophylaxis among four groups of premature infants: (1) <32 weeks gestational age (wGA) and ≤6 months chronologic age (CA); (2) 32–34 wGA, ≤3 months CA with 2009 American Academy of Pediatrics (AAP) risk factors (RF); (3) 32–35 wGA, ≤6 months CA with 2006 AAP RF; and (4) 32–35 wGA, ≤6 months CA with ≤1 RF. Full dosing of palivizumab was assumed throughout the RSV season (consistent with the FDA-approved label). All costs were in 2010 US dollars. The societal public payer spend for palivizumab was estimated using Medicaid reimbursement methodologies for the top 10 palivizumab-using states in 2010 minus mandatory manufacturer rebates. This study reports the incremental cost-effectiveness ratios (ICERs) in cost per quality-adjusted life-year (QALY) gained. Sensitivity and probabilistic analyses were also conducted.

Results:

Palivizumab saved costs and improved QALYs among infants <32 wGA. Palivizumab was cost-effective in infants 32–34 wGA with 2009 AAP RF ($16,037 per QALY) and in infants 32–35 wGA with 2006 AAP RF ($38,244 per QALY). The ICER for infants 32–35 wGA with ≤1 RF was $281,892 per QALY. Influential variables in the sensitivity analysis included the background rate of RSV hospitalization, the cost of palivizumab, and the efficacy of palivizumab.

Key limitations:

These results are not generalizable to commercially insured infants or infants outside of the US.

Conclusions:

This is the first cost-utility analysis of palivizumab in a Medicaid population. Palivizumab, when dosed consistent with the FDA-approved labeling, was either cost-saving or cost-effective among current guideline-eligible infants in the Medicaid population. Palivizumab did not demonstrate cost-effectiveness in 32–35 wGA infants with ≤1 RF.     

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 and outcomes associated with rivaroxaban vs enoxaparin for the prevention of postsurgical venous thromboembolism from a US payer’s perspective

Abstract

Objective:

The objective of this analysis was the evaluation of the outcomes and costs associated with rivaroxaban and enoxaparin for the prevention of postsurgical venous thromboembolism (VTE) in patients undergoing total hip replacement (THR) and total knee replacement (TKR) from the US payer perspective.

Methods:

VTE event rates have been reported in three Phase III clinical trials that compared rivaroxaban and enoxaparin for VTE prevention after orthopedic surgery during the prophylaxis (≤35 days for THR patients and 10–14 days for TKR patients) and post-prophylaxis periods (≤90 days following surgery). These data were used in this decision-analytic model to estimate and compare health outcomes and costs associated with rivaroxaban and enoxaparin. The base-case analysis considered the number and costs of symptomatic VTE events during the prophylaxis period only. A 90-day horizon was considered in the sensitivity analysis.

Results:

Following THR, when extended durations of prophylaxis (35 days) were compared, rivaroxaban was associated with lower costs than enoxaparin, with total saving costs of $695/patient. When an extended duration of rivaroxaban prophylaxis (35 days) was compared with a short duration (10–14 days) of enoxaparin prophylaxis, rivaroxaban was estimated to prevent 9.9 additional symptomatic VTE events per 1000 patients, while saving $244/patient (rate/1000 patients). In the TKR population, short duration of rivaroxaban prophylaxis was estimated to prevent 13.1 additional symptomatic VTE events per 1000 patients. It was also less costly than short duration enoxaparin prophylaxis, with a saving of $411/patient (rate/1000 patients).

Limitations:

Only statistically significant differences were captured in the base-case economic analysis, and, therefore, differences in pulmonary embolism (PE) and bleeding events were not captured.

Conclusions:

In this model, rivaroxaban reduced total treatment payer costs vs enoxaparin for the prevention of VTE in THR or TKR patients.     

Cost analysis: treatment of chemotherapy-induced anemia with erythropoiesis-stimulating agents in five European countries

Abstract

Objective:

Cost-analysis comparing darbepoetin-alfa (DARB), epoetin-alfa (EPO-A), and epoetin-beta (EPO-B) for treatment of chemotherapy-induced anemia in Belgium concluded that costs for DARB-treated patients were significantly lower than costs for EPO-A- or EPO-B-treated patients. The objective of the present study was to extend the Belgian analysis to Austria, France, Italy, Portugal, and Spain, estimating differences in costs between erythropoiesis-stimulating agents (ESAs) in each country.

Methods:

Differences in epidemiology and treatment patterns between countries were adjusted using data from Eurostat, national cancer registries, IMS sales data, and reimbursement and treatment guidelines. Belgian unit costs were replaced with country-specific costs. Costs were analyzed using a mixed-effects model stratifying for propensity score quintiles.

Results:

All populations were comparable to the Belgian population in terms of age, gender, ESA, and blood transfusions use. After adjusting for country-specific chemotherapy use and cancer incidence, total management costs per patient (Euro, 2010) were 19–26% (France, Spain) lower with DARB compared with EPO-A (p?<?0.0001) and 20–36% (Portugal, Austria) compared with EPO-B (p?<?0.01). Anemia-related costs with DARB were between 12% (Portugal; p?=?0.0235) and 38% (Italy; p?<?0.0001) lower compared with EPO-A (p?<?0.01; all remaining countries), and between 13% (Austria; p?=?0.064) and 19% (Portugal; p?=?0.0028) lower compared with EPO-B (p?<?0.05; all remaining countries except Italy; p?=?0.0935).

Limitations:

Not all differences could be accounted for by a lack of country-specific data; however, the potential under- and over-estimation of costs should be similar for all three ESAs.

Conclusions:

These findings are in line with the Belgian analysis. In all countries, total and anemia-related costs were lowest in patients receiving DARB vs EPO-A or EPO-B. This study demonstrates the feasibility of adapting real-life country-specific data to other settings, adjusting for differences in patients’ characteristics and treatment strategies. These findings should be valuable in healthcare decision-making in oncology patients treated in each of the countries studied.     

Cost-minimization analysis of fingolimod compared with natalizumab for the treatment of relapsing–remitting multiple sclerosis in Sweden

Abstract

Background:

Fingolimod and natalizumab have the same European Union licence for the treatment of relapsing multiple sclerosis, and are considered by the Committee for Medicinal Products for Human Use (CHMP) to have broadly similar efficacy.

Objective:

A cost-minimization analysis was performed to compare differences in treatment costs between fingolimod and natalizumab from a societal perspective in Sweden.

Methods:

This analysis included costs associated with initiating and following treatment (physician visits and monitoring), continuing therapy (drugs and administration), and lost patient productivity and leisure time. Unit costs (in Swedish krona [SEK]) were based on regional data (median prices for physician visits and monitoring sessions). Natalizumab infusion costs were obtained from the national cost-per-patient database. Drug costs for both therapies were 15,651 SEK/28 days.

Results:

After 3 years, fingolimod use was associated with savings of 124,823?SEK/patient compared with natalizumab (total cost/patient: 566,718 SEK vs 691,542 SEK). Cost savings with fingolimod were 40,402 SEK/patient after 1 year and 301,730 SEK/patient after 10 years. Treatment with natalizumab was 18% more expensive than fingolimod therapy after 1 year and 23% more expensive after 10 years.

Limitations:

Based on the CHMP assessment, it was assumed that fingolimod and natalizumab have similar efficacy. The analysis was conducted for Sweden, and caution is needed in extrapolating the results to other countries.

Conclusion:

Fingolimod is cost-saving compared with natalizumab for the treatment of relapsing–remitting multiple sclerosis in Sweden.     

Cost-minimization comparison of darunavir plus ritonavir and lopinavir/ritonavir in HIV-1 infected treatment-naïve women of childbearing age

Background:

Guidelines from the Department of Health and Human Services in the US recommend ritonavir-boosted lopinavir (LPV/r) as a preferred protease inhibitor (PI) for HIV-positive antiretroviral-na?ve pregnant women. These guidelines also cite ritonavir-boosted darunavir (DRV?+?RTV) as an alternative PI in this clinical scenario. The purpose of this analysis was to compare economic outcomes for regimens based on these two treatments.

Study design:

An existing discrete event simulation (DES) model was adapted to conduct a cost-minimization analysis comparing the two regimens in HIV-infected women of childbearing age (WOCBA), from the perspective of a healthcare payer in the US.

Methods:

The DES model was used to represent disease states, health events, healthcare encounters, pregnancy, and treatment choices in HIV-infected WOCBA starting treatment with regimens based on either LPV/r or DRV?+?RTV. It also incorporated parameters for individual patient characteristics, and for antiretroviral (ARV) treatment effectiveness, treatment sequencing, clinical progression, and resource use. Potential events included scheduled physician visits; viral suppression; viral rebound; AIDS-related complications; CHD events; treatment discontinuation and switching; ARV treatment side-effects (SE); and death. The primary outcomes were discounted 5-year and 10-year healthcare costs. Alternative scenarios considered different rates of switching from DRV?+?RTV to LPV/r upon conception.

Results:

Compared with DRV?+?RTV, LPV/r was associated with similar clinical outcomes while offering savings at the 5- and 10-year horizons (of $24,904 and $43,502 per patient, respectively), and in extensive sensitivity analyses. The main driver of the savings was the difference in cost between PIs.

Conclusions:

Starting HIV-infected ARV-treatment-na?ve WOCBA on an LPV/r-based regimen is cost-saving and provides similar patient outcomes compared to a DRV?+?RTV-based regimen.     

Cost-effectiveness of 3-year vs 1-year adjuvant therapy with imatinib in patients with high risk of gastrointestinal stromal tumour recurrence in the Netherlands; a modelling study alongside the SSGXVIII/AIO trial

Abstract

Background:

Surgical resection of gastrointestinal stromal tumour (GIST) is rarely curative in patients at high risk of tumour recurrence and therefore 1 year of post-surgery adjuvant imatinib therapy has been recommended in this sub-group. Recently, adjuvant imatinib therapy administered for 3 years has been demonstrated to further increase recurrence-free survival and overall survival. The goal of this study was to assess the economic value of extending the duration of adjuvant imatinib therapy in high-risk patients in the Netherlands.

Methods:

A multistate Markov model was developed to simulate how patients’ clinical status after GIST excision evolves over time until death. The model structure encompassed four primary health states: free of recurrence, first GIST recurrence, second GIST recurrence, and death. Transition probabilities between the health states, data on medical care costs, and quality-of-life were obtained from published sources and from expert opinion.

Results:

The expected number of life years (or quality-adjusted life years, QALYs) was higher in the 3-year group than in the 1-year group, 8.91 (6.55) and 7.04 (5.18) years, respectively. In the 3-year and 1-year group, the expected total costs amounted to €120,195 and €79,361, of which, €74,631 (62%) and €27,619 (35%) were adjuvant therapy drug costs, respectively. The difference in health benefits, that is 1.87 life years or 1.37 QALYs, and costs, €40,835, resulted in incremental cost-effectiveness ratios (ICER) of €21,865 per life year gained, and €29,872 per QALY gained.

Limitations:

A limitation of the study was inherently related to the uncertainty around the predictions of RFS. Scenario analyses were conducted to test the sensitivity of different RFS predictions on the results.

Conclusions:

Delayed recurrence due to treatment with longer-term adjuvant imatinib therapy represents a cost-effective treatment option with an ICER below the generally accepted threshold in the Netherlands.     

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.     

Use of a diagnosis-based risk adjustment model to estimate costs of indigent care in a community at Medicaid reimbursement rates

Objectives: This study used a diagnosis-based risk adjustment model to estimate the annual costs of uninsured patients in Austin, Texas, and describe the prevalence and costs of their chronic conditions. The data were supplied by the Indigent Care Collaboration, a partnership of local safety-net hospitals and clinics.

Methods: This study used the Diagnostic Cost Groups prospective Medicaid All-Encounters model, which uses diagnoses, age and gender to assign relative risk scores to patients. The relative risk scores were multiplied by the per capita Texas Medicaid expenditure to obtain estimated annual costs. Chronic diseases were described in terms of prevalence and total estimated annual cost.

Results: A total of 471,194 encounters were recorded for 163,729 patients meeting the study inclusion criteria between the 1st March 2004 and the 28th February 2005. The mean estimated patient yearly cost was US $1,307, and the total estimated yearly population cost was $228,909,529. The most common chronic conditions included hypertension, diabetes, depression, substance abuse, pregnancy, asthma, chronic obstructive pulmonary disease and congestive heart failure.

Conclusions: This study demonstrates how the unknown costs associated with caring for indigent uninsured patients in a community can be estimated at Medicaid reimbursement rates using the Diagnostic Cost Group model on aggregated patient encounter data.     

Cost-effectiveness of rivaroxaban in the prevention of venous thromboembolism: A Canadian analysis using the Ontario Ministry of Health Perspective

Abstract

Objectives:

A cost-effectiveness model for rivaroxaban evaluated the cost-effectiveness of prophylaxis with rivaroxaban (a once-daily, orally administered Factor Xa inhibitor) vs enoxaparin in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) and total knee replacement (TKR). This Canadian analysis was conducted using the Ontario Ministry of Health perspective over a 5-year time horizon. The model combined clinical data and builds upon existing economic models.

Methods:

The model included both acute VTE (represented as a decision tree) and long-term complications (represented as a Markov process with 1-year cycles) phases. The model allowed VTE event rates, quality-adjusted life expectancy and direct medical costs to be estimated over a 5-year time horizon, based on current approved practice patterns in Canada. A number of one-way sensitivity analyses were performed on the baseline assumptions, including a comparison of rivaroxaban with dalteparin, and probabilistic sensitivity analyses were performed to address any uncertainty concerning model inputs.

Results:

When comparing equal durations of therapy, rivaroxaban dominated enoxaparin in the prevention of VTE events in patients undergoing THR and TKR, providing more benefit at a lower cost. Rivaroxaban was cost-effective when comparing 35 days’ prophylaxis with 14 days’ prophylaxis with enoxaparin following THR. One-way and probabilistic sensitivity analyses demonstrated that the results of the economic analysis were robust to variations in key inputs. Rivaroxaban remained dominant during one-way sensitivity analyses comparing rivaroxaban with dalteparin after THR or TKR.

Limitations:

Although clinical trial data were used in the prophylaxis module, assumptions and values used in the post-prophylaxis and long-term complication (LTC) modules were based on several different literature sources; it was not always possible to source Canadian data.

Conclusions:

This economic analysis suggests that the use of rivaroxaban for the prophylaxis of VTE after THR or TKR in Canada was cost-effective.     

Cost minimization analysis of beta-blocker at the time of CT imaging for suspected of coronary heart disease in Japan

Objectives:

To conduct a cost-minimization analysis of landiolol for CT diagnosis of coronary heart diseases in patients with tachycardia in Japan.

Methods:

A decision-tree model was constructed to analyze costs from the healthcare payer’s perspective. Drug costs and diagnosis costs, computer tomography coronary angiography (CTCA), and coronary angiography (CAG), are adopted to the model. Landiolol is administered only to slow the heart rate to take CT images appropriately. Since some trials proved that there was no difference between landiolol and placebo in terms of efficacy and safety, this study conducted cost-minimization analysis. Of those suspected of coronary heart diseases, 22.5% are thought to be taking beta-blockers. The success rates for CT scanning for landiolol and placebo, derived from domestic trial data, were 81.4% (96/118, 77.8–84.9%) and 54.2% (64/118, 49.7–58.8%). Patients who failed to take a CT image were thought to take CAG. The healthcare cost was derived from a Japanese fee schedule. Costs of landiolol, CT imaging, and CAG are JPY2634 (USD1?=?JPY100, as of November 20, 2013), JPY38,116, and JPY101,322, respectively. The positive rate for CAG, derived from domestic trial data, was 37.1% (33/89, 32.0–42.2%). Various sensitivity analyses, both univariate and probabilistic ones, were conducted.

Results:

In the base case analysis, expected costs per patient for landiolol and placebo were JPY78,956 and JPY82,232, respectively. In budget impact analysis, 81,062 patients are eligible for landiolol and it can save JPY266million for whole patients. Sensitivity analyses suggested the robustness of the results.

Limitations:

This study did not consider any adverse effects in the decision-tree model. This model was developed especially for measuring the cost-saving effect of landiolol, through decreasing the number of patients who require CAG, due to imaging failure.

Conclusions:

Landiolol for CTCA diagnosis in patients suspected of coronary heart disease with tachycardia is thought to be cost saving.