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.     

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.     

Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema

Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME).

Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing ‘death’ state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec.

Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy).

Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy.     

Cost utility of allogeneic stem cell transplantation with matched unrelated donor versus treatment with imatinib for adult patients with newly diagnosed chronic myeloid leukaemia

Objective: To estimate, from the perspective of the German statutory health insurance, the cost utility of allogeneic stem cell transplantation with matched unrelated donor (MUD-SCT) in newly diagnosed, chronic-phase chronic myeloid leukaemia (CML) patients aged 40 years or younger, relative to the treatment with imatinib.

Methods: The incremental cost-effectiveness ratio (ICER) of the additional cost of imatinib versus MUD-SCT per quality-adjusted life year (QALY) gained was chosen as a target assessment. ICER was quantified using a Markov cohort modelling approach. The evaluation encompassed 5 years of treatment with either approach, and only direct medical costs (in €, year 2005) were considered.

Results: There were incremental costs of €77,410 for imatinib therapy per QALY gained versus MUD-SCT. No strategy was clearly dominant; on average, during 5 years, cost savings of €63,433 were obtained and 0.82 QALY lost by SCT compared to treatment with imatinib. QALYs gained in CML patients with either treatment resulted in considerable cost to the third-party payer in Germany. The results were particularly sensitive to the price of imatinib.

Conclusions: The analysis finds that imatinib is more costly but more effective (as measured in QALYs) over a 5-year time horizon. The resulting ICER of €77,410 per QALY is higher than commonly cited thresholds. The cost utility of MUD-SCT to treat CML in patients with a European Group for Blood and Marrow Transplantation score ≤ to 2 compares with that of the imatinib strategy.     

Cost-effectiveness of rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation in the Japanese healthcare setting

Abstract

Aims: This article aimed to examine the cost-effectiveness of rivaroxaban in comparison to warfarin for stroke prevention in Japanese patients with non-valvular atrial fibrillation (NVAF), from a public healthcare payer’s perspective.

Materials and methods: Baseline event risks were obtained from the J-ROCKET AF trial and the treatment effect data were taken from a network meta-analysis. The other model inputs were extracted from the literature and official Japanese sources. The outcomes included the number of ischaemic strokes, myocardial infarctions, systemic embolisms and bleedings avoided, life-years, quality-adjusted life-years (QALYs), incremental costs and incremental cost-effectiveness ratio (ICER). The scenario analysis considered treatment effect data from the same network meta-analysis.

Results: In comparison with warfarin, rivaroxaban was estimated to avoid 0.284 ischaemic strokes per patient, to increase the number of QALYs by 0.535 per patient and to decrease the total costs by ¥118,892 (€1,011.11) per patient (1 JPY = 0.00850638 EUR; XE.com, 7 October 2019). Consequently, rivaroxaban treatment was found to be dominant compared to warfarin. In the scenario analysis, the ICER of rivaroxaban versus warfarin was ¥2,873,499 (€24,446.42) per QALY.

Limitations: The various sources of data used resulted in the heterogeneity of the cost-effectiveness analysis results. Although, rivaroxaban was cost-effective in the majority of cases.

Conclusion: Rivaroxaban is cost-effective against warfarin for stroke prevention in Japanese patients with NVAF, giving the payer WTP of 5,000,000 JPY.     

Cost-effectiveness of insulin detemir versus insulin glargine for Thai type 2 diabetes from a payer’s perspective

Aims: An economic evidence is a vital tool that can inform the decision to use costly insulin analogs. This study aimed to evaluate long-term cost-effectiveness of insulin detemir (IDet) compared with insulin glargine (IGlar) in type 2 diabetes (T2DM) from the Thai payer’s perspective.

Methods: Long-term costs and outcomes were projected using a validated IMS CORE Diabetes Model, version 8.5. Cohort characteristics, baseline risk factors, and costs of diabetes complications were derived from Thai data sources. Relative risk was derived from a systematic review and meta-analysis study. Costs and outcomes were discounted at 3% per annum. Incremental cost-effectiveness ratio (ICER) was presented in 2015?US Dollars (USD). A series of one-way and probabilistic sensitivity analyses were performed.

Results: IDet yielded slightly greater quality-adjusted life years (QALYs) (8.921 vs 8.908), but incurred higher costs than IGlar (90,417.63 USD vs 66,674.03 USD), resulting in an ICER of ～1.7 million USD per QALY. The findings were very sensitive to the cost of IDet. With a 34% reduction in the IDet cost, treatment with IDet would become cost-effective according to the Thai threshold of 4,434.59 USD per QALY.

Conclusions: Treatment with IDet in patients with T2DM who had uncontrolled blood glucose with oral anti-diabetic agents was not a cost-effective strategy compared with IGlar treatment in the Thai context. These findings could be generalized to other countries with a similar socioeconomics level and healthcare systems.     

Cost-effectiveness of dipeptidyl peptidase-4 inhibitor monotherapy versus sulfonylurea monotherapy for people with type 2 diabetes and chronic kidney disease in Thailand

Objective: With a high prevalence of chronic kidney disease (CKD) in type 2 diabetes (T2DM) in Thailand, the appropriate treatment for the patients has become a major concern. This study aimed to evaluate long-term cost-effective of dipeptidyl peptidase-4 (DPP-4) inhibitor monothearpy vs sulfonylurea (SFU) monotherapy in people with T2DM and CKD.

Methods: A validated IMS CORE Diabetes Model was used to estimate the long-term costs and outcomes. The efficacy parameters were identified and synthesized using a systematic review and meta-analysis. Baseline characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. Costs were expressed in 2014?US Dollars. Outcomes were presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty.

Results: From a societal perspective, treatment with DPP-4 inhibitors yielded more quality-adjusted life years (QALYs) (0.024) at a higher cost (>66,000 Thai baht (THB) or >1,829.27 USD) per person than SFU, resulting in the ICER of >2.7 million THB/QALY (>74,833.70 USD/QALY). The cost-effectiveness results were mainly driven by differences in HbA1c reduction, hypoglycemic events, and drug acquisition cost of DPP-4 inhibitors. At the ceiling ratio of 160,000 THB/QALY (4,434.59 USD/QALY), the probability that DPP-4 inhibitors are cost-effective compared to SFU was less than 10%.

Conclusions: Compared to SFU, DPP-4 inhibitor monotherapy is not a cost-effective treatment for people with T2DM and CKD in Thailand.     

Cost-effectiveness analysis of intra-articular injections of a high molecular weight bioengineered hyaluronic acid for the treatment of osteoarthritis knee pain

Objective:

To determine the cost-effectiveness of bioengineered hyaluronic acid (BioHA, 1% sodium hyaluronate) intra-articular injections in treating osteoarthritis knee pain in poor responders to conventional care (CC) including non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics.

Methods:

Two decision analytic models compared BioHA treatment with either continuation of patient’s baseline CC with no assumption of disease progression (Model 1), or CC including escalating care costs due to disease progression (NSAIDs and analgesics, corticosteroid injections, and surgery; Model 2). Analyses were based on patients who received two courses of 3-weekly intra-articular BioHA (26-week FLEXX Trial?+?26-week Extension Study). BioHA group costs included fees for physician assessment and injection regimen, plus half of CC costs. Cost-effectiveness ratios were expressed as averages and incremental costs per QALY. One-way sensitivity analyses used the 95% confidence interval (CI) of QALYs gained in BioHA-treated patients, and ±20% of BioHA treatment and CC costs. Probabilistic sensitivity analyses were performed for Model 2.

Results:

For 214 BioHA patients, the average utility gain was 0.163 QALYs (95% CI?=??0.162 to 0.488) over 52 weeks. Model 1 treatment costs were $3469 and $4562 for the BioHA and CC groups, respectively; sensitivity analyses showed BioHA to be the dominant treatment strategy, except when at the lower end of the 95% CI. Model 2 annual treatment costs per QALY gained were $1446 and $516 for the BioHA and CC groups, respectively. Using CC as baseline strategy, the incremental cost-effectiveness ratio (ICER) of BioHA was $38,741/QALY gained, and was sensitive to response rates in either the BioHA or CC groups.

Conclusion:

BioHA is less costly and more effective than CC with NSAIDs and analgesics, and is the dominant treatment strategy. Compared with escalating CC, the $38,741/QALY ICER of BioHA remains within the $50,000 per QALY willingness-to-pay threshold to adopt a new technology.     

Cost-effectiveness analysis of first-line pembrolizumab treatment for PD-L1 positive,non-small cell lung cancer in China

Purpose: Pembrolizumab was recently approved in several countries as a first-line treatment for patients with PD-L1 positive, non-small cell lung cancer (NSCLC). However, it is expensive. This study aimed to assess the cost-effectiveness of pembrolizumab in treating advanced NSCLC patients with PD-L1 positive cancer in China.

Methods: A Markov model was developed to compare the cost-effectiveness of pembrolizumab with chemotherapy for patients with PD-L1 expression on at least 50% of NSCLC tumor cells. Model inputs for transition probabilities and toxicity were derived from published clinical trial data, while health utilities were estimated from a literature review. Costs for drugs were updated to standard fee data from West China Hospital in 2017. Health outcomes were measured in quality-adjusted life years (QALYs), and cost-effectiveness was measured as the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were conducted to test the robustness of the model.

Results: Pembrolizumab gained 0.45 QALYs at an incremental cost of $46,362 compared to chemotherapy for an ICER of $103,128 per QALY gained. In most scenarios, the ICER exceeded three times the Chinese Gross Domestic Product per capita. Two-way sensitivity analysis showed that, when the utility of the progression-free status increased to the maximal value of 0.845 and the 1?mg dose price decreased to $10.50, the ICER reduced to $25,216/QALY.

Conclusions: Pembrolizumab is not likely to be cost-effective in the treatment of PD-L1 positive, NSCLC for Chinese patients. Less aggressive pricing may increase accessibility for patients in China.     

Cost-effective analysis of clopidogrel versus aspirin for high risk patients with established peripheral arterial disease in China

Abstract

Objective: To assess the cost-effectiveness of clopidogrel versus aspirin for high risk patients (pre-existing symptomatic atherosclerosis or multi-vascular territory involvement) with established peripheral arterial disease (PAD) for secondary prevention of atherothrombotic events in a Chinese setting.

Methods: A Markov model with a lifetime horizon was developed from the perspective of the national healthcare system in China. The primary outputs are quality adjusted life years (QALYs), direct medical costs, and the incremental cost-effectiveness ratios (ICERs). Clinical efficacy data were obtained from the CAPRIE trial. Drug acquisition cost, other direct medical costs, and utilities were from pricing records and the literature. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted to test the robustness of the model on all parameters.

Results: In patients with pre-existing atherosclerosis, 2 years of treatment with clopidogrel and aspirin would yield total QALYs of 8.776 and 8.576 at associated costs of ¥18,777 ($2,838) and ¥12,302 ($1,859), respectively, resulting in an ICER of ¥32,382 ($4,893) per QALY gained. In patients with PVD, secondary prevention with the same drugs would expect to lead to total QALYs of 8.836 and 8.632 at associated costs of ¥18,518 ($2,798) and ¥12,041 ($1,820), respectively, resulting in a corresponding ICER of ¥31,743 ($4,797) per QALY gained. The results were most sensitive to the discount rate for future outcomes and costs. The PSA indicated that the probability of clopidogrel being cost-effective was 100% at the willingness-to-pay threshold of 3-times GDP.

Conclusions: Secondary prevention with clopidogrel is an attractive cost-effective option compared with aspirin for high risk patients with established PAD from the perspective of the national healthcare system in Chinese settings.     

Evaluation of the cost-utility of insulin degludec vs insulin glargine in Sweden

Abstract

Objective:

To evaluate the annual cost-utility of insulin degludec compared with glargine in patients with: type 1 diabetes (T1D), type 2 diabetes receiving basal-only therapy (T2D-BOT), and type 2 diabetes receiving basal-bolus therapy (T2B-BB) in Sweden.

Methods:

A cost-utility model was programmed in Microsoft Excel to evaluate clinical and economic outcomes. The clinical trials were designed as treat-to-target, with insulin doses adjusted in order to achieve similar glycemic control between treatments, thus long-term modeling is not meaningful. Basal and bolus insulin doses, incidence of hypoglycemic events, frequency of self-monitoring of blood glucose, and possibility for flexibility in timing of dose administration were specified for each insulin in three diabetes populations, based on data collected in Swedish patients with diabetes and a meta-analysis of clinical trials with degludec. Using these characteristics, the model estimated costs from a societal perspective and quality-adjusted life years (QALYs) in the two scenarios.

Results:

Use of degludec was associated with a QALY gain compared with glargine in T1D (0.31 vs 0.26?QALYs), T2D-BOT (0.76 vs 0.69?QALYs), and T2D-BB (0.56 vs 0.47?QALYs), driven by reduced incidence of hypoglycemia and possibility for flexibility around timing of dose administration. Therapy regimens containing degludec were associated with increased costs compared to glargine-based regimens, driven by the increased pharmacy cost of basal insulin, but partially offset by other cost savings. Based on estimates of cost and clinical outcomes, degludec was associated with incremental cost-effectiveness ratios of SEK 19,766 per QALY gained, SEK 10,082 per QALY gained, and SEK 36,074 per QALY gained in T1D, T2-BOT, and T2-BB, respectively.

Limitations:

The hypoglycemic event rates in the base case analysis were derived from a questionnaire-based study that relied on patient interpretation and recall of hypoglycemic symptoms. The relative rates of hypoglycemia with degludec compared to glargine were derived from a meta-analysis of phase III trials, which may not reflect the relative rates observed in real-world clinical practice. Both of these key limitations were explored in one-way sensitivity analyses.

Conclusions:

Based on reduced incidence of hypoglycemia and possibility for flexibility around timing of dose administration, use of degludec is likely to be cost-effective compared to glargine from a societal perspective in T1D, T2-BOT, and T2-BB in Sweden over a 1-year time horizon.     

Cost-effectiveness analysis of tissue plasminogen activator in acute ischemic stroke in Iran

Aims: Tissue plasminogen activator (tPA) is used to treat acute ischemic stroke up to 4.5?h after symptom onset. Its cost-effectiveness in developing countries is not specified yet. This study aimed to study cost-effectiveness of tPA in Iran.

Methods: This is a cost-effectiveness analysis from the perspective of the third party payer to compare IV tPA with no tPA of ischemic stroke. A Markov model with a lifetime horizon was used to analyze the costs and outcomes. Cost data were extracted from the 94 patients admitted in two hospitals in Iran. All costs were calculated based on US dollars in 2016. Quality-adjusted life years (QALY) were extracted from previously published literature. Cost-effectiveness was determined by calculating ICER by TreeAge Pro 2011 software.

Results: Lifetime costs of no tPA strategy were higher than tPA ($10,718 in the no tPA group compared with $8,796 in the tPA group). The tPA arm gained 0.20 QALY compared with no tPA. ICER was $8,471 per QALY. ICER value suggests that tPA is cost-effective compared with no tPA.

Limitations: The limitations of the present study are the reliance on calculated QALY value of other countries and difficulty in accessing patients treated with tPA.

Conclusions: The balance of hospitalization and rehabilitation costs and QALYs support the conclusion that treatment with intravenous tPA in the 4.5-h time window is cost-effective from the perspectives of the third party payer and inclusion of tPA in the insurance benefit package being reasonable.     

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.     

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

Abstract

Objective:

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

Research design and methods:

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

Main outcome measures:

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

Results:

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

Conclusions:

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

Cost-effectiveness of risk stratification for preventing type 2 diabetes using a multi-marker diabetes risk score

Abstract

Background:

Personalized medicine requires diagnostic tests that stratify patients into distinct groups that may differentially benefit from targeted treatment approaches. This study compared the costs and benefits of two approaches for identifying those at high risk of developing type 2 diabetes for entry into a diabetes prevention program. The first approach identified high risk patients using impaired fasting glucose (IFG). The second approach used the PreDx Diabetes Risk Score (DRS) to further stratify IFG patients into high-risk and moderate-risk groups.

Methods:

A Markov model was developed to simulate the incidence and disease progression of diabetes and consequent costs and quality-adjusted life expectancy (QALY), comparing alternative approaches for identifying high-risk patients. We modeled direct medical costs, including the costs of the stratification testing, over a 10-year time horizon from a US payer perspective.

Results:

Stratification of IFG patients by the DRS method leads to improved identification and prevention among those at highest risk. At 5 years, the number needed to treat (NNT) in the IFG-only approach was 39 patients to prevent one case of diabetes compared to an NNT of 15 in the IFG?+?DRS approach. When compared to IFG alone, the IFG?+?DRS approach results in an incremental cost-effectiveness ratio (ICER) of $17,100/QALY gained at 5 years and would become cost saving in 10 years. In contrast and as compared to no stratification, the IFG-only approach would produce an ICER of $235,500/QALY gained at 5 years and $94,600/QALY gained at 10 years. The study findings are limited by the generalizability of the DRS validation study and uncertainty regarding the long-term effectiveness of diabetes prevention.

Conclusions:

The analysis indicates that the cost-effectiveness of diabetes prevention can be improved by better identification of patients at highest risk for diabetes using the DRS.     

Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction

Background: Sacubitril/valsartan reduces cardiovascular death and hospitalizations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care.

Aims: To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective.

Methods: A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan vs enalapril for 66-year-old patients with HF over 10 years. Key health states included New York Heart Association classes I–IV and deaths; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Sacubitril/valsartan benefits were modeled by applying the hazard ratios (HRs) in PARADIGM-HF trial to baseline probabilities. Primary model outcomes were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for sacubitril/valsartan relative to enalapril

Results: Compared to enalapril, sacubitril/valsartan was associated with an ICER of SGD 74,592 (USD 55,198) per QALY gained. A major driver of cost-effectiveness was the cardiovascular mortality benefit of sacubitril/valsartan. The uncertainty of this treatment benefit in the Asian sub-group was tested in sensitivity analyses using a HR of 1 as an upper limit, where the ICERs ranged from SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained. Probabilistic sensitivity analyses showed the probability of sacubitril/valsartan being cost-effective was below 1%, 12%, and 71% at SGD 20,000, SGD 50,000, and SGD 100,000 per QALY gained, respectively.

Conclusions: At the current daily price sacubitril/valsartan may not represent good value for limited healthcare dollars compared to enalapril in reducing cardiovascular morbidity and mortality in HF in the Singapore healthcare setting. This study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering therapy.     

Tumor treating fields and maintenance temozolomide for newly-diagnosed glioblastoma: a cost-effectiveness study

Abstract

Purpose: The EF-14 trial demonstrated that adding tumor treating fields (TTFields) to maintenance temozolomide (TMZ) significantly extends progression-free survival (PFS) and overall survival (OS) for newly-diagnosed glioblastoma (GBM) patients. This study assessed the cost-effectiveness of TTFields and TMZ for newly-diagnosed GBM from the US healthcare system perspective.

Methods and materials: Outcomes for newly-diagnosed GBM patients were estimated over a lifetime horizon using an area under the curve model with three states: stable disease, progressive disease, or death. The survival model integrated the 5-year EF-14 trial results with long-term GBM epidemiology data and US background mortality rates. Adverse event rates were derived from the EF-14 trial data. Utility values to determine quality-adjusted life-years, adverse event costs, and supportive care costs were obtained from published literature. A 3% discount rate was applied to future costs and outcomes. One-way and probabilistic sensitivity analyses were performed to assess result uncertainty due to parameter variability.

Results: Treatment with TTFields and TMZ was estimated to result in a mean increase in survival of 1.25 life years (95% credible range [CR]?=?0.89–1.67) and 0.96 quality-adjusted life years (QALYs) (95% CR = 0.67–1.30) compared to treatment with TMZ alone. The incremental total cost was $188,637 (95% CR = $145,324–$225,330). The incremental cost-effectiveness ratio (ICER) was $150,452 per life year gained and $197,336 per QALY gained. The model was most sensitive to changes in the cost of TTFields treatment.

Conclusions: Adding TTFields to maintenance TMZ resulted in a substantial increase in the estimated mean lifetime survival and quality-adjusted survival for newly-diagnosed GBM patients. Treatment with TTFields can be considered cost-effective within the reported range of willingness-to-pay thresholds in the US.     

Cost-effectiveness of blinatumomab versus salvage chemotherapy in relapsed or refractory Philadelphia-chromosome-negative B-precursor acute lymphoblastic leukemia from a US payer perspective

Objective: To evaluate the cost-effectiveness of blinatumomab (Blincyto) vs standard of care (SOC) chemotherapy in adults with relapsed or refractory (R/R) Philadelphia-chromosome-negative (Ph?) B-precursor acute lymphoblastic leukemia (ALL) based on the results of the phase 3 TOWER study from a US healthcare payer perspective.

Methods: The Blincyto Global Economic Model (B-GEM), a partitioned survival model, was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab vs SOC. Response rates, event-free survival (EFS), overall survival (OS), numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from TOWER. EFS and OS were estimated by fitting parametric survival distributions to failure-time data from TOWER. Utility values were based on EORTC-8D derived from EORTC QLQ-C30 assessments in TOWER. A 50-year lifetime horizon and US payer perspective were employed. Costs and outcomes were discounted at 3% per year.

Results: The B-GEM projected blinatumomab to yield 1.92 additional life years and 1.64 additional quality-adjusted life years (QALYs) compared with SOC at an incremental cost of $180,642. The ICER for blinatumomab vs SOC was estimated to be $110,108/QALY gained in the base case. Cost-effectiveness was sensitive to the number and cost of inpatient days for administration of blinatumomab and SOC, and was more favorable in the sub-group of patients who had received no prior salvage therapy. At an ICER threshold of $150,000/QALY gained, the probability that blinatumomab is cost-effective was estimated to be 74%.

Limitations: The study does not explicitly consider the impact of adverse events of the treatment; no adjustments for long-term transplant rates were made.

Conclusions: Compared with SOC, blinatumomab is a cost-effective treatment option for adults with R/R Ph???B-precursor ALL from the US healthcare perspective at an ICER threshold of $150,000 per QALY gained. The value of blinatumomab is derived from its incremental survival and health-related quality-of-life (HRQoL) benefit over SOC.     

A short-term cost-utility analysis of insulin degludec versus insulin glargine U100 in patients with type 1 or type 2 diabetes in Denmark

Background and aims: Insulin degludec is an insulin analog with an ultra-long duration of action that exhibits less intra-patient variability in its glucose-lowering activity, and reduces nocturnal, overall, and severe hypoglycemia relative to insulin glargine. The aim of the present study was to evaluate the cost-effectiveness of insulin degludec relative to insulin glargine in patients with: type 1 diabetes (T1D), type 2 diabetes receiving basal-only therapy (T2DBOT), and type 2 diabetes receiving basal-bolus therapy (T2DBB) in Denmark.

Methods: A short-term (1 year) cost-utility model was developed to model insulin use, non-severe and severe hypoglycemia, and self-monitoring of blood glucose in patients using insulin degludec and insulin glargine from the perspective of a Danish healthcare payer. Where possible, data were derived from Danish patients with diabetes and meta-analyses of clinical trials comparing insulin degludec with insulin glargine. Using these characteristics, the model estimated costs and quality-adjusted life years (QALYs) gained for the two insulin regimens in each of the three diabetes populations.

Results: Insulin degludec dominated insulin glargine (i.e. reduced costs while improving quality-adjusted life expectancy) in patients with T1D and patients with type 2 diabetes using a basal-only insulin regimen. In the T2DBB cohort, insulin degludec was associated with an incremental cost-effectiveness ratio of DKK 221,063 per QALY gained, which would be considered cost-effective at a willingness-to-pay threshold of EUR 30,000 (～DKK 224,000) per QALY gained. Sensitivity analysis showed that results were most affected by changes in hypoglycemia rate ratio assumptions, but were broadly insensitive to changes in individual input parameters.

Conclusions: Insulin degludec reduces incidence of hypoglycemia and improves quality-of-life in patients with diabetes. Over a 1-year time horizon, insulin degludec resulted in cost savings relative to insulin glargine in T1D and T2DBOT cohorts, while being cost-effective in T2DBB.     

Cost-effectiveness of zoledronic acid vs clodronic acid for newly-diagnosed multiple myeloma from the United Kingdom healthcare system perspective

Abstract

Objective:

In the Medical Research Council Myeloma IX Study (MMIX), zoledronic acid (ZOL) 4?mg 3–4/week reduced the incidence of skeletal-related events (SREs), increased progression free survival (PFS), and prolonged overall survival (OS), compared with clodronic acid (CLO) 1600?mg daily, in 1970 patients with newly-diagnosed multiple myeloma (MM).

Methods:

An economic model was used to project PFS, OS, the incidence of SREs and adverse events and expected lifetime healthcare costs for patients with newly-diagnosed MM who are alternatively assumed to receive ZOL or CLO. The incremental cost-effectiveness ratio [ICER] of ZOL vs CLO was calculated as the ratio of the difference in cost to the difference in quality-adjusted life years (QALYs). Model inputs were based on results of MMIX and published sources.

Results:

Compared with CLO, treatment with ZOL increases QALYs by 0.30 at an additional cost of £1653, yielding an ICER of £5443 per QALY gained. If the threshold ICER is £20,000 per QALY, the estimated probability that ZOL is cost-effective is 90%.

Limitations:

The main limitation of this study is the lack of data on the effects of zoledronic acid on survival beyond the end of follow-up in the MMIX trial. However, cost-effectiveness was favourable even under the highly conservative scenario in which the timeframe of the model was limited to 5 years.

Conclusions:

Compared with clodronic acid, zoledronic acid represents a cost-effective treatment alternative in patients with multiple myeloma.