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.     

An analysis of the cost-effectiveness of switching from biphasic human insulin 30, insulin glargine,or neutral protamine Hagedorn to biphasic insulin aspart 30 in people with type 2 diabetes

Abstract

Aims:

The aim of this analysis was to assess the cost-effectiveness of switching from biphasic human insulin 30 (BHI), insulin glargine (IGlar), or neutral protamine Hagedorn (NPH) insulin (all?±?oral glucose-lowering drugs [OGLDs]) to biphasic insulin aspart 30 (BIAsp 30) in people with type 2 diabetes in India, Indonesia, and Saudi Arabia.

Methods:

The IMS CORE Diabetes Model was used to determine the clinical outcome, costs, and cost-effectiveness of switching from treatment with BHI, IGlar, or NPH to BIAsp 30 over a 30-year time horizon. A 1-year analysis was also performed based on quality-of-life data and treatment costs. Incremental cost-effectiveness ratios (ICERs) were expressed as a fraction of gross domestic product (GDP) per capita, and cost-effectiveness was defined as ICER <3-times GDP per capita.

Results:

Switching treatment from BHI, IGlar, or NPH to BIAsp 30 was associated with an increase in life expectancy of >0.7 years, reduction in all diabetes-related complications, and was considered as cost-effective or highly cost-effective in India, Indonesia, and Saudi Arabia (BHI to BIAsp 30, 0.26 in India, 1.25 in Indonesia, 0.01 in Saudi Arabia; IGlar to BIAsp 30, ?0.68 in India, ?0.21 in Saudi Arabia; NPH to BIAsp 30, 0.15 in India, ?0.07 in Saudi Arabia; GDP per head per annum/quality-adjusted life-year). Cost-effectiveness was maintained in the 1-year analyses.

Conclusions:

Switching from treatment with BHI, IGlar, or NPH to BIAsp 30 (all?±?OGLDs) was found to be cost-effective in India, Indonesia, and Saudi Arabia, both in the long and short term.     

Evaluation of the long-term cost-effectiveness of liraglutide therapy for patients with type 2 diabetes in France

Objectives:

The present study aimed to compare the projected long-term clinical and cost implications associated with liraglutide, sitagliptin and glimepiride in patients with type 2 diabetes mellitus failing to achieve glycemic control on metformin monotherapy in France.

Methods:

Clinical input data for the modeling analysis were taken from two randomized, controlled trials (LIRA-DPP4 and LEAD-2). Long-term (patient lifetime) projections of clinical outcomes and direct costs (2013 Euros; €) were made using a validated computer simulation model of type 2 diabetes. Costs were taken from published France-specific sources. Future costs and clinical benefits were discounted at 3% annually. Sensitivity analyses were performed.

Results:

Liraglutide was associated with an increase in quality-adjusted life expectancy of 0.25 quality-adjusted life years (QALYs) and an increase in mean direct healthcare costs of €2558 per patient compared with sitagliptin. In the comparison with glimepiride, liraglutide was associated with an increase in quality-adjusted life expectancy of 0.23 QALYs and an increase in direct costs of €4695. Based on these estimates, liraglutide was associated with an incremental cost-effectiveness ratio (ICER) of €10,275 per QALY gained vs sitagliptin and €20,709 per QALY gained vs glimepiride in France.

Conclusion:

Calculated ICERs for both comparisons fell below the commonly quoted willingness-to-pay threshold of €30,000 per QALY gained. Therefore, liraglutide is likely to be cost-effective vs sitagliptin and glimepiride from a healthcare payer perspective in France.     

Long-term cost-consequence analysis of exenatide once weekly vs sitagliptin or pioglitazone for the treatment of type 2 diabetes patients in the United States

Abstract

Objective:

Exenatide once-weekly (ExQW) is a GLP-1 receptor agonist shown to lower glucose and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the clinical benefits and associated economic benefits of treatment with ExQW compared with sitagliptin or pioglitazone in the US.

Methods:

The IMS CORE Diabetes Model, a validated computer simulation model, was used to project lifetime clinical outcomes and complication costs. The costs of glucose-lowering drugs were excluded as not all prices were available. Baseline patient characteristics (mean values: age, 52.5 years; diabetes duration, 6 years; HbA1_c, 8.51%; body mass index, 32.12?kg/m²) and clinical data were derived from a phase 3 clinical trial that compared ExQW with sitagliptin or pioglitazone in T2DM patients. At 6 months, patients treated with ExQW had greater improvements in HbA1_c and body weight than those treated with sitagliptin or pioglitazone. Complication costs were extracted from published sources. Health outcomes and costs were discounted at 3% per year. Sensitivity analyses were performed.

Results:

Over 35 years, and compared with sitagliptin or pioglitazone, ExQW increased life expectancy by, respectively, 0.28 (13.76?±?0.17 vs 13.48?±?0.18) and 0.17 years (13.76?±?0.17 vs 13.59?±?0.17), and quality-adjusted life years by, respectively, 0.28 (9.56?±?0.12 vs 9.28?±?0.12) and 0.24 years (9.56?±?0.12 vs 9.32?±?0.12). ExQW was associated with lower lifetime complication costs: compared with sitagliptin or pioglitazone, ExQW saved, respectively US$2215 (US$55,647?±?2039 vs US$57,862?±?2159) and US$933 (US$55,647?±?2039 vs US$56,580?±?2007) direct cost per patient. Cost-savings resulted mainly from a lower projected cumulative incidence of cardiovascular diseases and neuropathic complications.

Limitations:

Short-term changes in surrogate end-points were used to project lifetime effects on clinical outcomes. Pharmacy costs were excluded from the analyses.

Conclusions:

Over a patient’s lifetime, ExQW was projected to improve health and decrease diabetes-related complication costs compared with sitagliptin or pioglitazone.     

Long-term health economic benefits of sensor-augmented pump therapy vs continuous subcutaneous insulin infusion alone in type 1 diabetes: a UK perspective

Aims/hypothesis:

Continuous subcutaneous insulin infusion (CSII) is an important treatment option for type 1 diabetes patients unable to achieve adequate glycemic control with multiple daily injections (MDI). Combining CSII with continuous glucose monitoring (CGM) in sensor-augmented pump therapy (SAP) with a low glucose-suspend (LGS) feature may further improve glycemic control and reduce the frequency of hypoglycemia. A cost-effectiveness analysis of SAP?+?LGS vs CSII plus self-monitoring of blood glucose (SMBG) was performed to determine the health economic benefits of SAP?+?LGS in type 1 diabetes patients using CSII in the UK.

Methods:

Cost-effectiveness analysis was performed using the CORE diabetes model. Treatment effects were sourced from the literature, where SAP?+?LGS was associated with a projected HbA_1c reduction of ?1.49% vs ?0.62% for CSII, and a reduced frequency of severe hypoglycemia. The time horizon was that of patient lifetimes; future costs and clinical outcomes were discounted at 3.5% and 1.5% per annum, respectively.

Results:

Projected outcomes showed that SAP?+?LGS was associated with higher mean quality-adjusted life expectancy (17.9 vs 14.9 quality-adjusted life years [QALYs], SAP?+?LGS vs CSII), and higher life expectancy (23.8 vs 21.9 years), but higher mean lifetime direct costs (GBP 125,559 vs GBP 88,991), leading to an incremental cost-effectiveness ratio (ICER) of GBP 12,233 per QALY gained for SAP?+?LGS vs CSII. Findings of the base-case analysis remained robust in sensitivity analyses.

Conclusions/interpretation:

For UK-based type 1 diabetes patients with poor glycemic control, the use of SAP?+?LGS is likely to be cost-effective compared with CSII plus SMBG.     

A long-term analysis evaluating the cost-effectiveness of biphasic insulin lispro mix 75/25 and mix 50/50 versus long-acting basal insulin analogs in the United States

Abstract

Objective:

To evaluate the cost-effectiveness of biphasic insulin lispro mix 75/25 (LM75/25) and mix 50/50 (LM50/50) compared with a long-acting analog insulin (LAAI) regimen from the perspective of a US healthcare payer.

Methods:

A published computer simulation model of diabetes was used to evaluate the cost-effectiveness of LM75/25 and LM50/50 vs a LAAI (insulin glargine) from the perspective of a US healthcare payer. Treatment effects in terms of HbA1c benefits were taken from a recent meta-analysis. Direct medical costs including pharmacy, complication, and patient management costs were obtained from published sources. All costs were expressed in 2010 US dollars and future costs and clinical benefits were discounted at 3% per annum. Sensitivity analyses were performed.

Results:

LM75/25 and LM50/50 were associated with improvements in life expectancy of 0.08 and 0.09 years, improvements in quality-adjusted life expectancy of 0.07 quality-adjusted life years (QALYs) and 0.08 QALYs and increases in cost of US$ 1724 and US$ 1720, respectively, when compared with LAAI.

Limitations:

The base case analysis did not capture mild or serious hypoglycemia on the grounds that the hypoglycemia rate odds ratios failed to reach statistical significance in the meta-analysis. In addition, the baseline cohort characteristics were based on an insulin-naïve population, as opposed to the cohorts in the meta-analysis, which were heterogeneous with regard to insulin treatment history.

Conclusions:

Based on a recently published meta-analysis, biphasic analog insulins are likely to improve clinical outcomes and reduce costs vs LAAIs in the long-term treatment of type 2 diabetes patients in the US.     

Economic and health-related quality-of-life (HRQoL) comparison of lopinavir/ritonavir (LPV/r) and atazanavir plus ritonavir (ATV+RTV) based regimens for antiretroviral therapy (ART)-naïve and -experienced United Kingdom patients in 2011

Abstract

Background:

Using a United Kingdom (UK)-based National Health Services perspective for 2011 this study first estimated the cost-effectiveness and budget impact implications for lopinavir/ritonavir (LPV/r) vs atazanavir plus ritonavir (ATV+RTV) treatment of antiretroviral therapy (ART)-naïve patients and secondly examined the long-term health-related quality-of-life (HRQoL) and economic implications for LPV/r vs ATV+RTV treatment of ART-experienced patients.

Methods:

A previously published Markov model that integrates epidemiological data of human immunodeficiency virus (HIV) with predictors of coronary heart disease (CHD) was modified under a clearly specified set of assumptions to reflect viral load (VL) suppression profiles and other differences for these two regimens, applying results from the CASTLE study in ART-naïve patients and using data from BMS-045 in ART-experienced patients. ART costs were referenced to current (2011) pricing guidelines in the UK. Medical care costs reflected UK treatment patterns and relevant drug pricing. Costs and outcomes were discounted at 3.5% per year. Costs are expressed in British pounds (£) and life expectancy in quality-adjusted life years (QALYs).

Results:

In the ART-naïve subjects, the model predicted a marginal improved life expectancy of 0.031 QALYs (11 days) for the ATV+RTV regimen as a result of predicted CHD outcomes based on lower increases in cholesterol levels compared with the LPV/r regimen. The model demonstrated cost savings with the LPV/r regimen. The total lifetime cost savings was £4070 per patient for the LPV/r regimen. LPV/r saved £2133 and £3409 per patient at 5 and 10 years, respectively. Referenced to LPV/r, the incremental cost-effectiveness ratio (ICER) for ATV+RTV was £149,270/QALY. For ART-experienced patients VL suppression differences favored LPV/r, while CHD risk associated with elevated total cholesterol marginally favored ATV+RTV, resulting in a net improvement in life expectancy of 0.31 QALYs (106 days) for LPV/r. Five-year costs were £5538 per patient greater for ATV+RTV, with a discounted lifetime saving of £1445 per LPV/r patient. LPV/r was modestly dominant economically, producing better outcomes and cost savings.

Limitations:

The limitations of this study include uncertainty related to how well the model’s assumptions capture current practice, as well as the validity of the model parameters used. This study was limited to using aggregated data in the public domain from the two clinical trials. Thus, some of the model parameters may reflect limitations due to trial design and data aggregation bias. This study has attempted to illuminate the effect of these limitations by presenting the results of the comprehensive sensitivity analysis.

Conclusions:

Based on 2011 costs of HIV in the UK and the published efficacy data from the CASTLE and BMS-045 studies, ATV+RTV-based regimens are not expected to be a cost-effective use of resources for ART-naïve patients similar to patients in the CASTLE study, nor for ART-experienced patients based on the only published comparison of ATV+RTV and LPV/r.     

Cost-effectiveness of insulin detemir compared with neutral protamine Hagedorn insulin in patients with type 1 diabetes using a basal-bolus regimen in five European countries

Abstract

Objectives: The aim of this analysis was to evaluate the long-term clinical and economic outcomes associated with insulin detemir and neutral protamine Hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 1 diabetes in Belgian, French, German, Italian and Spanish settings.

Methods: The published and validated IMS CORE Diabetes Model was used to make long-term projections of life expectancy, quality-adjusted life expectancy and direct medical costs. The analysis was based on patient characteristics and treatment effects from a 2-year randomised controlled trial. Events were projected for a time horizon of 50 years. Potential uncertainty using a modelling approach was addressed.

Results: Basal-bolus therapy with insulin detemir was projected to improve quality-adjusted life expectancy by 0.45 years versus NPH in the German setting, with similar improvements in the other countries. Insulin detemir was associated with cost savings in Belgium, Germany and Spain. In France and Italy, lifetime costs were slightly higher in the detemir arm, leading to incremental cost-effectiveness ratios of €519 per QALY gained and €3,256 per QALY gained, respectively.

Conclusions: Compared to NPH, insulin detemir is likely to be a dominant treatment strategy in Belgium, Germany and Spain and highly cost-effective in France and Italy in patients with type 1 diabetes.     

Cost-effectiveness of continuous subcutaneous insulin infusion in people with type 2 diabetes in the Netherlands

Aims: Up to 30% of insulin-treated type 2 diabetes patients are unable to achieve HbA1c targets despite optimization of insulin multiple daily injections (MDI). For these patients the use of continuous subcutaneous insulin infusion (CSII) represents a useful but under-utilized alternative. The aim of the present analysis was to examine the cost-effectiveness of initiating CSII in type 2 diabetes patients failing to achieve good glycemic control on MDI in the Netherlands. Methods: Long-term projections were made using the IMS CORE Diabetes Model. Clinical input data were sourced from the OpT2mise trial. The analysis was performed over a lifetime time horizon. The discount rates applied to future costs and clinical outcomes were 4% and 1.5% per annum, respectively. Results: CSII was associated with improved quality-adjusted life expectancy compared with MDI (9.38 quality-adjusted life years [QALYs] vs 8.95 QALYs, respectively). The breakdown of costs indicated that ～50% of costs were attributable to diabetes-related complications. Higher acquisition costs of CSII vs MDI were partially offset by the reduction in complications. The ICER was estimated at EUR 62,895 per QALY gained and EUR 60,474 per QALY gained when indirect costs were included. Conclusions: In the Netherlands, CSII represents a cost-effective option in patients with type 2 diabetes who continue to have poorly-controlled HbA1c despite optimization of MDI. Since the ICER falls below the willingness-to-pay threshold of EUR 80,000 per QALY gained, CSII is likely to represent good-value for money in the treatment of poorly-controlled T2D patients compared with MDI.     

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.     

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

Abstract

Objectives:

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

Methods:

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

Results:

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

Limitations:

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

Conclusions:

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

Evaluation of the long-term cost-effectiveness of IDegLira versus liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the USA

Background and aims: IDegLira, a fixed ratio combination of insulin degludec and glucagon-like peptide-1 receptor agonist liraglutide, utilizes the complementary mechanisms of action of these two agents to improve glycemic control with low risk of hypoglycemia and avoidance of weight gain. The aim of the present analysis was to assess the long-term cost-effectiveness of IDegLira vs liraglutide added to basal insulin, for patients with type 2 diabetes not achieving glycemic control on basal insulin in the US setting.

Methods: Projections of lifetime costs and clinical outcomes were made using the IMS CORE Diabetes Model. Treatment effect data for patients receiving IDegLira and liraglutide added to basal insulin were modeled based on the outcomes of a published indirect comparison, as no head-to-head clinical trial data is currently available. Costs were accounted in 2015?US dollars ($) from a healthcare payer perspective.

Results: IDegLira was associated with small improvements in quality-adjusted life expectancy compared with liraglutide added to basal insulin (8.94 vs 8.91 discounted quality-adjusted life years [QALYs]). The key driver of improved clinical outcomes was the greater reduction in glycated hemoglobin associated with IDegLira. IDegLira was associated with mean costs savings of $17,687 over patient lifetimes vs liraglutide added to basal insulin, resulting from lower treatment costs and cost savings as a result of complications avoided.

Conclusions: The present long-term modeling analysis found that IDegLira was dominant vs liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the US, improving clinical outcomes and reducing direct costs.     

A cost-utility analysis of prolonged-release tacrolimus relative to immediate-release tacrolimus and ciclosporin in liver transplant recipients in the UK

Background: Calcineurin inhibitors (CNIs) represent the cornerstone of immunosuppressive therapy after liver transplantation. A recent network meta-analysis (NMA) evaluated the relative efficacy of CNIs ciclosporin, prolonged-release (PR) tacrolimus, and immediate-release (IR) tacrolimus in adult liver transplant recipients based on randomized and large observational trials published since 2000. Based on the NMA findings, the present study evaluated the cost-utility of PR tacrolimus relative to ciclosporin or IR tacrolimus in liver transplant recipients in the UK.

Methods: A Markov model was developed to evaluate the cost-utility of immunosuppressive regimens in liver transplant recipients, capturing costs associated with immunosuppression, retransplantation, acute rejection (AR), and cytomegalovirus infection. Mortality, graft loss, and AR odds ratios were derived from the NMA. Costs were taken from the British National Formulary and the NHS National Tariff and expressed in 2016 pounds sterling. Future costs and effects were discounted at 3.5% annually.

Results: Over 25 years, PR tacrolimus resulted in increased life expectancy and quality-adjusted life expectancy (QALE) relative to IR tacrolimus and ciclosporin. Relative to ciclosporin, QALE increased by 1.17 quality-adjusted life years (QALYs) with PR tacrolimus while costs increased by GBP £4645, yielding an incremental cost-effectiveness ratio (ICER) of £3962 per QALY gained. Relative to IR tacrolimus, QALE increased by 0.78 QALYs and costs by £1474, resulting in an ICER of £1889 per QALY gained. Sensitivity analysis showed the analysis to be most sensitive to dosing assumptions.

Conclusions: Based on a UK-specific analysis of the projected cost-utility of PR tacrolimus relative to IR tacrolimus and ciclosporin, PR tacrolimus was cost-effective, improving life expectancy and QALE relative to both IR tacrolimus and ciclosporin, yielding ICERs below £20 000 per QALY gained. The main limitations of the study were data source heterogeneity and omitting the economic and clinical effects of treating aspects of recurrent liver disease.     

Estimating the quality-of-life impact and cost-effectiveness of alpha-blocker and anti-muscarinic combination treatment in men with lower urinary tract symptoms related to benign prostatic hyperplasia and overactive bladder

Abstract

Objective:

A 12-week clinical trial (TIMES) demonstrated that therapy with tolterodine extended release (TOL)?+?tamsulosin (TAM) provides clinical benefits vs TOL or TAM monotherapy or placebo (PBO) in men with lower urinary tract symptoms (LUTS) including overactive bladder (OAB). The present analysis estimated the costs and quality-adjusted life-years (QALYs) associated with these therapies from the perspective of the UK healthcare system.

Methods:

TIMES cohorts receiving TOL, TAM, TOL?+?TAM, or PBO were followed from therapy initiation to 12 weeks. A decision-tree model was used to extrapolate the 12-week results to 1 year (including need for surgery owing to treatment failure at 12 weeks) and to track patients’ outcomes (symptoms, utility, and costs). Because TIMES did not include costs and QALYs, data from the EpiLUTS epidemiologic survey (12,796 males) were used to model a mathematical relationship between LUTS (daytime and nocturnal frequency, urgency episodes, urgency urinary incontinence episodes, and International Prostate Symptom Score [IPSS]), quality-of-life, and utility. This was used to convert improvements in TIMES patients’ LUTS into utility scores and QALYs. The model included drug and surgery procedure costs and hospital length of stay.

Results:

Incremental QALYs of TOL?+?TAM vs PBO, TAM, and TOL were 0.042, 0.021, and 0.013, and corresponding incremental costs were £189, £223, and ?£70, respectively, resulting in cost-utility ratios for TOL?+?TAM of £4508/QALY gained compared with PBO and £10,381/QALY gained compared with TAM. TOL?+?TAM combination therapy was both more effective and cost-saving compared with TOL. Univariate sensitivity analyses showed that patient utility was most responsive to changes in drug efficacy on IPSS and urgency episodes. Changing the percentage of patients undergoing surgery did not substantially affect model outcomes. The main limitation of the study was that the relation between LUTS and patient utility was based on an indirect association.

Conclusions:

TOL?+?TAM combination therapy appears to be cost-effective compared with TOL or TAM monotherapy or PBO in male patients with LUTS.     

Cost-effectiveness of tapentadol prolonged release compared with oxycodone controlled release in the UK in patients with severe non-malignant chronic pain who failed 1st line treatment with morphine

Abstract

Objectives:

The aim of this analysis was to assess the cost-effectiveness of tapentadol PR (prolonged release) compared with oxycodone CR (controlled release) in severe non-malignant chronic pain patients in whom controlled release morphine was ineffective or not tolerated.

Methods:

A Markov model was developed to assess costs and benefits over a 1-year time horizon from the National Health Service perspective in the UK. Patients could either continue on 2nd line therapy or switch to 3rd line opioid due to lack of efficacy or poor tolerability. Patients failing also 3rd line therapy entered the final absorbing health state (4th line). Data on tolerability, efficacy, and utilities for tapentadol and oxycodone were obtained from the three comparative phase III clinical trials. Costs of resource consumption associated with opioid treatment were derived from a retrospective database analysis of anonymized patient records.

Results:

The model results predicted that initiating 2nd line therapy with tapentadol leads to higher effectiveness and lower costs vs oxycodone. For the overall population included in the clinical trials, mean annual costs per patient when treated with tapentadol and oxycodone were £3543 and £3656, respectively. Treatment with tapentadol, while cheaper than oxycodone, was more effective (0.6371 vs 0.6237 quality-adjusted life years (QALYs) for tapentadol and oxycodone, respectively), meaning that tapentadol dominated oxycodone. For the sub-group of opioid-experienced patients with severe pain at baseline the ranking in terms of costs and QALYs remained unchanged. Extensive sensitivity analyses showed that conclusions about the cost-effectiveness are consistent.

Conclusions:

The cost-effectiveness study suggested that initiating 2nd line treatment in patients with severe non-malignant chronic pain in the UK with tapentadol instead of oxycodone improves patients’ quality-of-life and is less costly. Key limitations when interpreting the results are the use of different sources to populate the model and restricted generalizability due to data extrapolation.     

Cost-effectiveness of pembrolizumab in combination with chemotherapy in the 1st line treatment of non-squamous NSCLC in the US

Abstract

Aims: To describe cost-effectiveness of pembrolizumab plus platinum and pemetrexed chemotherapy in metastatic, non-squamous, NSCLC patients in the US.

Materials and methods: A model is developed utilizing partitioned survival analysis to estimate the cost-effectiveness of KEYNOTE-189 trial comparators pembrolizumab?+?chemotherapy (carboplatin/cisplatin?+?pemetrexed) vs chemotherapy alone. Clinical efficacy, treatment utilization, health utility, and safety data are derived from the trial and projected over 20 years. For extrapolating survival beyond the trial, a novel SEER population-data approach is applied (primary analysis), with separate estimation via traditional parametric extrapolation methods. Costs for drugs and non-drug disease management are also incorporated. Based on an indirect treatment comparison, cost-effectiveness of pembrolizumab?+?chemotherapy vs pembrolizumab monotherapy is evaluated for patients with programmed death-ligand 1 (PD-L1)?≥?50%.

Results: In the full non-squamous population, pembrolizumab?+?chemotherapy is projected to increase life expectancy by 2.04 years vs chemotherapy (3.96 vs 1.92), for an approximate doubling of life years. Resultant incremental cost-effectiveness ratios (ICERs) are $104,823/QALY and $87,242/life year. In patients with PD-L1?≥?50% and 1–49%, life expectancy is more than doubled (4.53 vs 1.88 years) and (4.87 vs 2.01 years), with a 32% (2.60 vs 1.97 years) increase in PD-L1?<?1% patients. Corresponding incremental costs/quality-adjusted life year (QALY) are $103,402, $66,837, and $183,529 for PD-L1?≥?50%, 1–49%, and <1% groups, respectively. Versus pembrolizumab monotherapy in PD-L1?≥?50% patients, representing current standard of care, pembrolizumab?+?chemotherapy increases life expectancy by 65% (4.53 vs 2.74 years) at an ICER of $147,365/QALY.

Limitations and conclusions: The addition of pembrolizumab to chemotherapy is projected to extend life expectancy to a point not previously seen in previously untreated metastatic non-squamous NSCLC. Although ICERs vary by sub-group and comparator, results suggest pembrolizumab?+?chemotherapy yields ICERs near, or in most cases, well below a 3-times US per capita GDP threshold of $180,000/QALY, and may be a cost-effective first-line treatment for metastatic non-squamous NSCLC patients.     

Long-term cost-effectiveness of insulin detemir versus NPH insulin in type 2 diabetes in Sweden

Abstract

Aim:

To evaluate the cost-effectiveness of insulin detemir vs. NPH insulin once daily, in patients with type 2 diabetes in the Swedish setting based on clinical data from a published randomized controlled trial.

Methods:

Projections of long-term outcomes were made using the IMS CORE Diabetes Model (CDM), based on clinical data from a 26-week randomized controlled trial that compared once daily insulin detemir and NPH insulin, when used to intensify insulin treatment in 271 patients with type 2 diabetes and body mass index (BMI) 25–40?kg/m². Trial results showed that insulin detemir was associated with a significantly lower incidence of hypoglycemic events and significantly less weight gain in comparison with NPH insulin. The analysis was conducted from a third party payer perspective and the base case analysis was performed over a time horizon of 40 years and future costs and clinical outcomes were discounted at a rate of 3% per year.

Results:

Insulin detemir was associated with higher mean (SD) quality-adjusted life expectancy (5.42 [0.10] vs. 5.31 [0.10] quality-adjusted life years [QALYs]) and lower overall costs (SEK 378,539 [10,372] vs. SEK 384,216 [11,230]; EUR 33,794 and EUR 34,300, respectively, where 1 EUR?=?11.2015 SEK) compared with NPH insulin. Sensitivity analysis showed that the principal driver of the benefits associated with insulin detemir was the lower rate of hypoglycemic events (major and minor events) vs. NPH insulin, suggesting that detemir might also be cost-saving over a shorter time horizon. Limitations of the analysis include the use of data from a trial outside Sweden in the Swedish setting.

Conclusions:

Based on clinical input data derived from a previously published randomized controlled trial, it is likely that in the Swedish setting insulin detemir would be cost-saving in comparison with NPH insulin for the treatment of patients with type 2 diabetes.     

Cost-effectiveness of a pentavalent rotavirus vaccine in Japan

Abstract

Objective:

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

Methods:

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

Results:

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

Key limitation:

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

Conclusion:

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

Cost-effectiveness of grass pollen subcutaneous immunotherapy (SCIT) compared to sublingual immunotherapy (SLIT) and symptomatic treatment in Austria,Spain, and Switzerland

Background: While specific immunotherapy (SIT) has been proven to be cost-effective for the treatment of allergic rhinitis compared to symptomatic treatment, there is a lack of European studies in which sublingual (SLIT) and subcutaneous (SCIT) immunotherapy were compared. The present analysis is focused on the cost-effectiveness of SCIT compared to SLIT and symptomatic treatment of grass pollen allergy in Austria, Spain, and Switzerland. It will address specific properties of the underlying healthcare systems.

Methods: The investigation is based on a previously published health economic model calculation. This was designed as a Markov model with pre-defined health stages and a duration of 9 years covering specific preparations for SCIT (Allergovit) and SLIT (Oralair). The effectiveness was assessed as symptom-score based quality-adjusted life years (QALYs). Additionally, total cost has been determined as well as the cost-effectiveness of SCIT. The robustness of model results was proved in further sensitivity analyses.

Results: With regard to the effectiveness of both SCIT and SLIT, preparations were dominant compared to pharmacological symptomatic therapy. Both strategies were associated with additional cost, but, combined with the results on effectiveness, both have to be regarded as cost-effective. A direct comparison of the SCIT (Allergovit) and SLIT (Oralair) showed lower total costs of SCIT vs SLIT for Austria, Spain, and Switzerland (€1,368 vs €2,012, €2,229 vs €2,547, and €1,901 vs €2,220) and superior effectiveness (SCIT =8.02 QALYs; SLIT =7.98 QALYs; and symptomatic therapy =7.90 QALYs).

Conclusion: In patients with allergic rhinitis, SIT offers cost-effective treatment options compared to symptomatic treatment. When comparing SCIT (Allergovit) and SLIT (Oralair), SCIT was dominant in terms of QALYs as well as costs, in particular due to a slightly higher patient compliance and lower drug costs.     

Incremental net monetary benefit of ocrelizumab relative to subcutaneous interferon β-1a

Aim: Disease-modifying therapies (DMTs) impact the natural history of relapsing forms of multiple sclerosis (RRMS) by reducing annual relapse rates and slowing disability progression. The effect of DMTs on indirect costs has not been consistently explored in cost-effectiveness studies thus far. The value to patients of an emerging DMT, ocrelizumab, was quantified in comparison to subcutaneous interferon beta-1a (IFNβSC) for the prevalent RRMS population with mild-to-moderate disability in the US, based on two Phase 3 trials, OPERA I and OPERA II, of ocrelizumab vs IFNβSC in RRMS.

Materials and methods: A Markov model was developed to compare disability progression as measured by Expanded Disability Status Scale (EDSS) and relapse outcomes over a 30-year horizon for ocrelizumab vs IFNβSC. Direct, indirect, and informal costs (2016?US dollars) and utilities for EDSS health states were obtained from the literature. Hazard ratios for disability progression and relapse rates were estimated from clinical trials. Value was assessed by calculating the net monetary benefit (NMB), defined as the monetary value of discounted quality-adjusted life years (QALYs) minus total costs, where the value of a QALY was $150,000. One-way sensitivity analyses were conducted.

Results: Ocrelizumab was associated with an incremental gain of 0.84 QALYs and cost savings of $287,713 relative to IFNβSC, resulting in an incremental NMB (INMB) of $413,611 per person over 30 years. The INMB increased by $151,763 for those initiating ocrelizumab at EDSS level 1 vs level 4. Influential parameters were QALY value, treatment costs, and disability progression; however, all sensitivity analyses indicated that the INMB for ocrelizumab relative to IFNβSC was ≥$300,000 per person.

Conclusions: Ocrelizumab provides greater value to RRMS patients compared with IFNβSC. Initiating ocrelizumab at lower EDSS levels leads to a greater cumulative value due to slower disability progression, which extends years with higher quality-of-life.