Comparing olanzapine and ziprasidone in the treatment of schizophrenia: a case study in modeling

SUMMARY

When a new drug is introduced to the market, the availability of head-to-head data for comparisons of annual cost and health outcomes with other drugs already on the market is usually insufficient. When only limited head-to-head data are available, one alternative is to perform preliminary modeling using data from the best available studies. In this paper, we synthesise data from the most comparable available studies to create a model to compare the annual costs and health outcomes when initiating treatment for schizophrenia with one of two antipsychotic drugs: olanzapine, which was launched in the United States (US) market in September 1996, and ziprasidone, which was approved by the US Food and Drug Administration (FDA) in February 2001. Annual treatment costs were determined by response and relapse rates as well as acquisition costs. The results indicate similar annual treatment costs (US$48,676 for olanzapine; US$48,873 for ziprasidone), despite the lower drug acquisition cost for ziprasidone. Annual health outcomes differed between the olanzapine and ziprasidone groups with 23.5% and 25.2% relapsed, 36.7 and 37.4 hospital days, and 60.0 and 60.1 EPS days in the olanzapine and ziprasidone groups respectively. A head-to-head naturalistic trial is needed to validate the results of this modeling exercise.     

Pharmacoeconomic analysis of the treatment of schizophrenia with quetiapine,olanzapine, risperidone or haloperidol in Spain

Summary

The study objective was to compare the costs of the treatment of schizophrenia with quetiapine (QUE), olanzapine (OLA), risperidone (RIS) or haloperidol (HAL) and those of the secondary effects (SE) associated. A cost-effectiveness analysis, using a Markov process, was used.The time horizon was 12 months.The study population comprised Spanish adult schizophrenic patients.The NHS perspective was taken (direct costs).The costs of several SE of medication were analysed. Use of resources and costs were calculated following the recommendations of the Spanish Psychiatric Society and other sources.

The monthly rates of the onset of SE with each medicine were calculated using a meta-analysis and systematic review of the literature.

A simple univariate sensitivity analysis was performed. QUE is as efficacious as OLA and RIS, but apparently leading to fewer cases of extrapyramidal syndrome and sexual dysfunction, with lower costs. QUE is better tolerated than HAL, but with higher costs.     

Cost-effectiveness of amisulpride compared with risperidone in patients with schizophrenia

SUMMARY

Amisulpride is an atypical antipsychotic, which has demonstrated efficacy across the range of symptoms of schizophrenia. This study compares the treatment costs of amisulpride (including drug costs, hospital costs, and costs of clinician and nurse visits) with those of risperidone over a 6-month treatment period, from the perspective of the UK National Health Service. Resource utilisation data were collected alongside an international, multicentre clinical trial comparing amisulpride (400-1000 mg/day) with risperidone (4-10 mg/day) in 198 patients with schizophrenia. As this trial demonstrated that amisulpride had at least equivalent efficacy to risperidone, the present study was a cost-minimisation analysis. Unit cost data for the UK were obtained from published sources and applied to the clinical data to calculate direct treatment costs. Amisulpride was associated with lower drug acquisition costs and lower resource utilisation costs than risperidone, although the differences did not reach statistical significance. Overall, the average total cost per patient for 6 months of treatment with amisulpride (£12,673; 95% CI: 10,628,14,717) was £2,145 less than for risperidone (£14,818; 95% CI: 12,323,17,312). These findings are similar to those of a previous study that compared the treatment costs of amisulpride with those of haloperidol, and found that

amisulpride was associated with significantly lower direct treatment costs than haloperidol. Amisulpride is a valuable treatment option in patients with schizophrenia.     

Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States

Abstract

Objective:

Although the use of innovative drug delivery systems, like orally disintegrating antipsychotic tablets (ODT), may facilitate medication adherence and help reduce the risk of relapse and hospitalization, no information is available about the comparative cost-effectiveness of standard oral tablets (SOT) vs ODT formulations in the treatment of schizophrenia. This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of outpatients with schizophrenia from a US healthcare perspective. The study also compared olanzapine ODT with risperidone and aripiprazole, two other atypical antipsychotics available in both ODT and SOT formulations.

Methods:

Published medical literature and a clinical expert panel were used to populate a 1-year Monte Carlo Micro-simulation model. The model captures clinical and cost parameters including adherence levels, treatment discontinuation by reason, relapse with and without inpatient hospitalization, quality-adjusted life years (QALYs), treatment-emergent adverse events, healthcare resource utilization, and associated costs. Key outcomes were total annual direct cost per treatment, QALY, and incremental cost-effectiveness (ICER) per 1 QALY gained.

Results:

Based on model projections, olanzapine ODT therapy was more costly ($9808 vs $9533), but more effective in terms of a lower hospitalization rate (15% vs 16%) and better QALYs (0.747 vs 0.733) than olanzapine SOT therapy. Olanzapine ODT was more cost-effective than olanzapine SOT (ICER: $19,643), more cost-effective than risperidone SOT therapy (ICER: $39,966), and dominant (meaning less costly and more effective) than risperidone ODT and aripiprazole in ODT or SOT formulations.

Limitations:

Lack of head-to-head randomized studies comparing the three studied atypical antipsychotics required making input assumptions that need further study.

Conclusions:

This micro-simulation found that the utilization of olanzapine ODT for the treatment of schizophrenia is predicted to be more cost-effective than any other ODT or SOT formulations of the studied atypical antipsychotic medications.     

Cost-effectiveness analysis of glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis

SUMMARY

We have developed an economic model around the patient level data from the pivotal clinical trial for Copaxone® (glatiramer acetate), combined with published cost and natural history data, to demonstrate cost-effectiveness in relapsing-remitting multiple sclerosis (RRMS). Based upon analysis over 8 years, the cost per relapse avoided and cost per disability unit avoided was £11,000 and £8,862 respectively. To facilitate comparison with other therapies and across other disease areas we also calculated the cost per quality adjusted life year (QALY). Dependent upon the assumed utility loss associated with duration of relapse, the cost per QALY ranged between £22,586 and £64,636 over 8 years analysis. Given the nature of the disease and compared to accepted standards of cost-effectiveness in the UK, this analysis shows that glatiramer acetate is demonstrably cost-effective versus best supportive care alone.

Copaxone is a registered trademark of Teva Pharmaceutical Industries, Israel     

Cost-effectiveness analysis in the Spanish setting of the PEAK trial of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer

Objective: To assess the cost-effectiveness of panitumumab in combination with mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) vs bevacizumab in combination with mFOLFOX6 as first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC) in Spain.

Methods: A semi-Markov model was developed including the following health states: Progression free; Progressive disease: Treat with best supportive care; Progressive disease: Treat with subsequent active therapy; Attempted resection of metastases; Disease free after metastases resection; Progressive disease: after resection and relapse; and Death. Parametric survival analyses of patient-level progression free survival and overall survival data from the PEAK Phase II clinical trial were used to estimate health state transitions. Additional data from the PEAK trial were considered for the dose and duration of therapy, the use of subsequent therapy, the occurrence of adverse events, and the incidence and probability of time to metastasis resection. Utility weightings were calculated from patient-level data from panitumumab trials evaluating first-, second-, and third-line treatments. The study was performed from the Spanish National Health System (NHS) perspective including only direct costs. A life-time horizon was applied. Probabilistic sensitivity analyses and scenario sensitivity analyses were performed to assess the robustness of the model.

Results: Based on the PEAK trial, which demonstrated greater efficacy of panitumumab vs bevacizumab, both in combination with mFOLFOX6 first-line in wild-type RAS mCRC patients, the estimated incremental cost per life-year gained was €16,567 and the estimated incremental cost per quality-adjusted life year gained was €22,794. The sensitivity analyses showed the model was robust to alternative parameters and assumptions.

Limitations: The analysis was based on a simulation model and, therefore, the results should be interpreted cautiously.

Conclusions: Based on the PEAK Phase II clinical trial and taking into account Spanish costs, the results of the analysis showed that first-line treatment of mCRC with panitumumab?+?mFOLFOX6 could be considered a cost-effective option compared with bevacizumab?+?mFOLFOX6 for the Spanish NHS.     

A comparison of treatment patterns,healthcare resource utilization,and costs among young adult Medicaid beneficiaries with schizophrenia treated with paliperidone palmitate or oral atypical antipsychotics in the US

Abstract

Background: Much of the burden associated with schizophrenia is attributed to its early onset and chronic nature. Treatment with once monthly paliperidone palmitate (PP1M) is associated with lower healthcare utilization and better adherence as compared to oral atypical antipsychotics (OAAs). This study aimed to evaluate real-world effectiveness of PP1M and OAA therapies among US-based adult Medicaid patients with schizophrenia, overall and among young adults aged 18–35 years.

Methods: Adult patients with a diagnosis of schizophrenia and at least two claims for PP1M or OAA between January 1, 2010 and December 31, 2014 were selected from the IBM Watson Health MarketScan Medicaid Database. Treatment patterns and healthcare resource utilization and costs were compared between PP1M and OAA treatment groups following inverse probability of treatment (IPT) weighting to adjust for potential differences. Utilization and cost outcomes were estimated using OLS and weighted Poisson regression models.

Results: After IPT weighting, the young adult PP1M and OAA cohorts were comprised of 3,095 and 3,155 patients, respectively. PP1M patients had a higher duration of continuous treatment exposure (168.2 vs 132.5 days, p?=?.004) and better adherence on the index medication (proportion of days covered ≥80%: 19.0% vs 17.1%, p?<?.049). Young adults treated with PP1M were 37% less likely to have an all-cause inpatient admission (odds ratio [OR]?=?0.63, 95% confidence interval [CI]?=?0.53–0.74) and 33% less likely to have an ER visit (OR?=?0.67, 95% CI?=?0.55–0.81) compared to OAA young adult patients, but 27% more likely to have an all-cause outpatient office visit (OR?=?1.27, 95% CI?=?1.02–1.56). PP1M patients incurred significantly lower medical costs as compared to OAA patients.

Conclusions: Medicaid patients with schizophrenia treated with PP1M have higher medication adherence and have fewer hospitalizations as compared to patients treated with OAAs. PP1M may lead to reduced healthcare utilization and improved clinical outcomes.     

Cost-effectiveness analysis of rasburicase over standard of care for the prevention and treatment of tumor lysis syndrome in children with hematologic malignancies in China

Aims: To conduct a lifetime cost-effectiveness analysis (CEA) of rasburicase compared with standard of care (SOC) for tumor lysis syndrome (TLS) in children with hematologic malignancies from the Chinese healthcare system perspective.

Materials and methods: The CEA was performed using a decision tree model with a lifetime horizon. The model explores the cost-effectiveness of rasburicase vs SOC for both preventing TLS and treating established TLS among pediatric patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and non-Hodgkin’s lymphoma (NHL). Both the prophylaxis-use model and treatment-use model incorporate long-term health states of the diseases: survival without TLS and death. The efficacy data of rasburicase and SOC were obtained from published literature. Drug costs, healthcare resource utilization (HRU), and adverse event (AE) management costs were obtained via a published study with clinical experts. Costs in US dollar and quality-adjusted life year (QALY) are reported, and incremental cost-effectiveness ratios (ICERs) were also calculated. Uncertainties due to parameter fluctuations in the model were assessed through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA).

Results: During TLS prevention, compared with SOC, the ICER of rasburicase treatment in China are $17,580.04/QALY, $5,783.45/QALY, and $5,391.00/QALY for pediatric patients with AML, ALL, and NHL, respectively. For the established TLS treatment, compared with SOC, the ICERs of rasburicase treatment are $2,031.18/QALY, $1,142.93/QALY, and $990.37/QALY for pediatric patients with AML, ALL, and NHL, respectively.

Limitations: The clinical data for SOC are based on the published study in China, and the rasburicase prevention or treatment failure rate was either calculated based on the risk ratio or directly from the clinical study among non-Chinese pediatric patients. Another study limitation was the lack of utility data for pediatric patients with TLS and without TLS. Thus, the utility scores of pediatric cancer survivors were used as an alternative.

Conclusion: Rasburicase is estimated to be a cost-effective alternative to SOC in the prevention and treatment of TLS among Chinese pediatric patients with AML, ALL, and NHL.     

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 utidelone plus capecitabine for metastatic breast cancer in China

Abstract

Objective: To estimate the cost-effectiveness of utidelone plus capecitabine therapy compared to capecitabine alone in patients with metastatic breast cancer (MBC) resistant to anthracyclines and taxanes treatment in the Chinese context and provide a reference for the marketing of utidelone in China.

Methods: A Markov model was developed based on the NCT02253459 clinical trial to simulate the clinical course of patients with metastatic breast cancer who had received taxanes and anthracycline therapy. The quality-adjusted life years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) were then analyzed to evaluate the benefits. Two-parametric Weibull distribution was conducted to fit PFS and OS curves by using R. Sensitivity analyses were performed to evaluate the stability of the model designed.

Results: The addition of utidelone increased the cost and QALYs by $13,370.25 and 0.1961, respectively, resulting in an increased ICER of $68,180.78 per QALY. The most sensitive influential parameter on ICER was the price of utidelone. At the threshold of willingness-to-pay (WTP) of $24,380 (3 per capita GDP of China), the cost of utidelone per 30?mg of less than $18.5, $33.7, and greater than $48.8 resulted in a 100%, 50%, and 0% possibility of cost-effectiveness, respectively. The addition of utidelone was not cost-effective when it was $115.4 per 30?mg—the price of its analog paclitaxel. In consideration of varied economics levels across China, cost-effectiveness could be achieved with the price of utidelone ranging from $5.2 to $35.9.

Limitations: The survival curves extended beyond the follow-up time horizon, of which data were generated not from the real analyses but from our established two-parameter Weibull survival model.

Conclusion: It is recommended that the price of utidelone would be less than $18.5 per 30?mg in order to obtain cost-effectiveness for metastatic breast cancer patients resistant to anthracyclines and taxanes treatment in China.     

Cost-effectiveness implications of increased survival with anastrozole in the treatment of advanced breast cancer

Summary

Anastrozole (Arimidex*) has a survival benefit compared with megestrol acetate in postmenopausal women with advanced breast cancer who have failed on tamoxifen. It was felt appropriate that such a clinical finding should be subjected to economic evaluation.

A cost-effectiveness analysis was undertaken from the viewpoint of a third-party payer, of the data from a combined analysis of two clinical studies. The outcome measures were duration of drug treatment and life years gained. The incremental cost effectiveness ratio (ICER) of anastrozole was £1,608 per life year gained based on UK NHS drug prices in April 1998. Sensitivity analysis showed that the ICER could vary between £5 and £1,643, depending on relative drug costs in a number of countries, between £1,056 and £1,761, depending on the method used to calculate duration of treatment and survival, and could increase to £3,730, based on treatment provided during the extra period of survival.

Anastrozole is a highly cost-effective alternative to megestrol acetate for postmenopausal women with advanced breast cancer.     

Cost-effectiveness of quetiapine with lithium or divalproex for maintenance treatment of bipolar I disorder

Abstract

Background: Bipolar I disorder is a recurrent illness that affects 1% of the US population and constitutes a large economic burden. Few studies have investigated the cost-effectiveness of maintenance treatment options. The objective of this analysis was to assess the cost-effectiveness of quetiapine (QTP) in combination with lithium (Li) or divalproex (DVP) compared with that of Li or DVP alone for maintenance treatment of bipolar disorder.

Methods: The cost-effectiveness of maintenance treatment with QTP in combination with Li or DVP was compared with placebo (PBO) in combination with Li or DVP from a US direct costs perspective using a Markov model. The model simulated a cohort of 1,000 stabilized patients with bipolar I disorder and estimated the quarterly risk in three health states: euthymia, mania, and depression. Efficacy data were derived from two randomized, double-blind, placebo-controlled trials comparing QTP + Li/DVP with PBO + Li/DVP for up to 2 years. Resource data were obtained from published literature. Direct costs included drug costs, hospitalizations, and physician visits. Outcomes and costs were discounted at 3% and the price reference year was 2007. Endpoints included the number of acute mood episodes, hospitalizations due to an acute mood event, and costs per quality-adjusted life-years. A probabilistic sensitivity analysis (PSA) was conducted to evaluate uncertainty.

Results: In the base-case analysis, QTP + Li/DVP dominated PBO + Li/DVP. The PSA showed these results to be robust. In addition, treatment with QTP + Li/DVP was associated with reductions in acute manic episodes (46%), acute depressive episodes (41%), and related hospitalizations (44%) compared with PBO + Li/DVP.

Conclusions: These analyses, based on two randomized clinical trials, suggest that QTP + Li/DVP is a cost-effective maintenance treatment option for patients with bipolar I disorder compared with Li or DVP alone.     

Cost-effectiveness of cladribine tablets,alemtuzumab, and natalizumab in the treatment of relapsing-remitting multiple sclerosis with high disease activity in England

Aims: Cladribine tablets were the first oral short-course treatment approved for highly active relapsing multiple sclerosis (MS). The Association of British Neurologists guidelines currently recommend two infusion therapies, alemtuzumab and natalizumab, to treat high disease activity relapsing remitting MS (HDA-RRMS). This analysis assessed the cost-effectiveness of cladribine tablets in HDA-RRMS compared with alemtuzumab and natalizumab, from the perspective of the National Health Service (NHS) in England.

Materials and methods: A cohort-based Markov model with 11 health states (10 Expanded Disability Status Scale [EDSS] plus death) was developed. Transition matrices from the British Columbia registry were used to model the natural history of EDSS. The treatment effect on EDSS was modelled using hazard ratios for 6-month confirmed disability progression from an indirect treatment comparison (ITC). Relapses and drug-related adverse events were modeled via annualized relapse rates and event probabilities, with associated costs and quality-adjusted life year (QALY) losses. Utilities were derived from trials and the literature, and costs from NHS and literature sources. Uncertainty was assessed via probabilistic and deterministic sensitivity analyses.

Results: Cladribine tablets were dominant (i.e., less costly and more effective) vs alemtuzumab and natalizumab in pairwise comparisons, and the dominant strategy in fully incremental analyses. Incremental cost was driven largely by drug acquisition and administration costs, and incremental QALY gain largely by differences in delayed EDSS progression. Cladribine tablets had a 93% probability of being cost-effective at a threshold of GBP 30,000 per QALY gained, and remained dominant across the scenario analyses tested. The greatest influence on results was the treatment effect on disability progression derived from the ITC.

Limitations: Uncertainty over the efficacy of DMT beyond trial durations. In line with other comparative effectiveness analyses, the network meta-analysis informing this cost-effectiveness analysis was associated with a degree of uncertainty. No treatment switching analyses were undertaken.

Conclusions: Cladribine tablets are a cost-effective alternative to alemtuzumab and natalizumab in the treatment of HDA-RRMS from the perspective of the NHS in England.     

Cost-effectiveness analysis of clopidogrel versus aspirin in patients with atherothrombosis based on the CAPRIE trial

SUMMARY

Clopidogrel has been shown to reduce the secondary risk of ischaemic events in vascular disease compared to aspirin. This article compares the economics of the two drugs for this condition, by providing an incremental cost-effectiveness ratio (iCER) of clopidogrel versus aspirin, using Belgium as a case setting.

A 2 year Markov model, in which patients with vascular disease were assumed to receive either clopidogrel or aspirin, was developed from a healthcare payer's perspective. Survival data were based on the Saskatchewan Health database. Costs included treatment and adverse events. Cost-effectiveness was expressed as the cost per life year gained (LYG).

The iCER of clopidogrel versus aspirin was €13,390/LYG (95% CI: €6,990; €26,470). The robustness of these results was shown by univariate and probabilistic sensitivity analyses.

This analysis shows that clopidogrel is cost-effective for the secondary prevention of ischaemic events in the Belgian setting.     

Cost-effectiveness analysis of bariatric surgery for morbid obesity in Belgium

Aims: This study presents the cost-effectiveness analysis of bariatric surgery in Belgium from a third-party payer perspective for a lifetime and 10-year horizon.

Materials and methods: A decision analytic model incorporating Markov process was developed to compare the cost-effectiveness of gastric bypass, sleeve gastrectomy, and adjustable gastric banding against conventional medical management (CMM). In the model, patients could undergo surgery, or experience post-surgery complications, type 2 diabetes, cardiovascular diseases, or die. Transition probabilities, costs, and utilities were derived from the literature. The impact of different surgical methods on body mass index (BMI) level in the base-case analysis was informed by the Scandinavian Obesity Surgery Registry and the Swedish Obese Subject (SOS) study. Healthcare resource use and costs were obtained from Belgian sources. A base-case analysis was performed for the population, the characteristics of which were obtained from surgery candidates in Belgium.

Results: In the base-case analysis over a 10-year time horizon, the increment in quality-adjusted life-years (QALYs) gained from bariatric surgery vs CMM was 1.4 per patient, whereas the incremental cost was €3,788, leading to an incremental cost-effectiveness ratio (ICER) of €2,809 per QALY. Over a lifetime, bariatric surgery produced savings of €9,332, an additional 1.1 life years and 5.0 QALYs. Bariatric surgery was cost-effective at 10 years post-surgery and dominant over conventional management over a lifetime horizon.

Limitations: The model did not include the whole scope of obesity-related complications, and also did not account for variation in surgery outcomes for different populations of diabetic patients. Also, the data about management of patients after surgery was based on assumptions and the opinion of a clinical expert.

Conclusions: It was demonstrated that a current mix of bariatric surgery methods was cost-effective at 10 years post-surgery and cost-saving over the lifetime of the Belgian patient cohort considered in this analysis.     

Cost-effectiveness of sequential urate lowering therapies for the management of gout in Singapore

Abstract

Aims: Allopurinol is the most common urate lowering therapy (ULT) used to treat gout but may cause life-threatening severe cutaneous adverse reactions (SCAR) in a small number of patients. Risk of SCAR is increased for patients with the HLA-B*58:01 genotype. When alternative ULT is required, febuxostat or probenecid are recommended. The aim of this study was to conduct a cost-utility analysis of sequential ULT treatment strategies for gout, including strategies with and without HLA-B*58:01 genotyping prior to treatment initiation, with a view to inform optimal gout management in Singapore.

Materials and methods: A Markov model was developed from the Singapore healthcare payer perspective. Reflecting local practice, 12 different treatment strategies containing at least one ULT (allopurinol, febuxostat, probenecid) were evaluated in adults with gout. Response rates (SUA < 6mg/dL) were derived from an in-house network meta-analysis and from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated over a 30-year time horizon, with costs and benefits discounted at 3% per annum. Sensitivity analyses were conducted to explore uncertainties.

Results: Sequential treatment of allopurinol 300?mg/day-allopurinol 600?mg/day-probenecid (“standard of care”) was cost-effective compared to no ULT, with an ICER of SGD1,584/QALY. Allopurinol300-allopurinol600-probenecid-febuxostat sequence compared to allopurinol300-allopurinol600-probenecid had an ICER of SGD11,400/QALY. All other treatment strategies were dominated by preceding strategies. Treatment strategies incorporating HLA-B*58:01 genotyping before ULT use were dominated by the corresponding non-genotyping strategy.

Conclusions: Current standard of care (allopurinol300-allopurinol 600-probenecid) for gout is cost-effective compared with no ULT in the local context. Febuxostat is unlikely to be cost-effective in Singapore at current prices unless it is used last-line.     

Cost-effectiveness of desirudin in the prevention of the thromboembolic complications of surgery

Summary

New therapies reduce the risk of deep-vein thrombosis (DVT) following orthopaedic surgery, but may be more costly than low-molecular-weight heparin, the current standard treatment. Decision analysis and life-table methods were used to model the incremental cost-effectiveness of Revasc® (desirudin) compared with low-molecular-weight heparin (enoxaparin) in DVT prophylaxis following total hip replacement. A health-service perspective (payer, prescriber) was adopted and the principal endpoint was cost/life-year saved over 15 years. Costs were updated from published Swedish data to reflect 1998/9 UK prices and practices.

Prophylactic treatment with desirudin rather than enoxaparin for the prevention of thromboembolic complications of hip surgery should lead to an increase of 4.69 life-years/100 patients over 15 years, at an increased cost of £12,026/100 patients: the cost per life-year saved is therefore £2,566. This compares favourably with a range of commonly used alternative interventions. Desirudin is therefore a cost-effective method of preventing postoperative DVT in patients undergoing total hip replacement surgery.     

Cost-effectiveness of switching to biphasic insulin aspart from human premix insulin in a US setting

Objectives: To evaluate the cost-effectiveness of switching to biphasic insulin aspart (BIAsp 30) from human premix insulin for type 2 diabetes patients in the United States (US) setting.

Methods: The previously published and validated IMS Core Diabetes Model was used to project life expectancy, quality-adjusted life expectancy (QALE) and costs over 30 years. Patient characteristics and treatment effects were based on Canadian patients included the IMPROVE observational study (n = 311). Mean glycohaemoglobin (HbA_1c) was 8.4%, duration of diabetes 16 years and prevalence of complications high at baseline. Simulations were conducted from the perspective of a third-party payer, with costs accounted in 2008 US dollars ($).

Results: BIAsp 30 was projected to improve life expectancy by 0.202 years and QALE by 0.301 quality-adjusted life-years (QALYs), due to a reduced incidence of most diabetes-related complications. BIAsp 30 was associated with increased lifetime direct medical costs ($76,517 vs. 67,518) and an incremental cost-effectiveness ratio of $29,870 per QALY gained. Long-term outcomes were sensitive to the impact of BIAsp 30 on hypoglycaemia and changes in HbA_1c.

Conclusions: BIAsp 30 may represent a cost-effective treatment option in the US setting for advanced type 2 diabetes patients experiencing poor glycaemic control or hypoglycaemia on human premix insulin.

Limitations: The application of treatment effect data derived from a Canadian cohort to the US setting was a limitation of the cost-effectiveness analysis. The findings of this cost-effectiveness analysis are not applicable to insulin-naïve diabetes patients.     

Cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy for the treatment of follicular lymphoma patients who relapse after or are refractory to a rituximab-containing regimen in the US

Aims: Obinutuzumab (GA101, G) was approved in February 2016 by the US Food and Drug Administration to treat follicular lymphoma (FL) patients who relapsed after, or are refractory to (R/R), a rituximab-containing regimen (R/R-rituximab). In the GADOLIN trial, R/R-rituximab patients who received G plus bendamustine (B) followed by G-monotherapy (G?+?B) for up to 2 years had significantly improved progression-free survival and overall survival compared to patients receiving B-monotherapy. This study estimated the cost-effectiveness of G?+?B vs B-monotherapy for R/R-rituximab FL patients from a US payer perspective.

Materials and methods: Patient outcomes were simulated using a 3-state area under the curve model including progression-free survival, progressive disease, and death. This study used R/R-rituximab data from the National LymphoCare Study to extrapolate the GADOLIN trial’s refractory FL progression-free and overall survival data to a R/R-rituximab FL population. Drug utilization and adverse events were based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs in 2016. Utility estimates were derived from published literature. Post-progression treatment costs were based on observed post-progression therapies in GADOLIN. Sensitivity analyses were conducted to assess model uncertainty.

Results: G?+?B resulted in an increase in quality-adjusted life years relative to B-monotherapy of 1.24 (95% CR?=?0.61–1.87); the incremental total cost was $58,100 (95% CR?=?$54,500–$61,500). The incremental cost-effectiveness ratio was $47,000 per QALY gained, and, based on probabilistic simulations, there was a 98% probability that G?+?B was cost-effective at the $100,000 per QALY threshold.

Limitations and conclusions: This US-based analysis suggests that treatment with G?+?B compared to B-monotherapy is likely cost-effective in R/R-rituximab FL patients. Modeling a R/R-rituximab population based on a synthesis of GADOLIN and the National LymphoCare Study data introduces uncertainty in the analysis. However, the findings were robust to sensitivity analyses.