Economic evaluation of the use of enoxaparin for thromboprophylaxis in acutely ill medical patients

SUMMARY

The objective of this study was to assess the cost-effectiveness of prophylaxis for venous thromboembolism (VTE) in acutely ill medical patients using 40 mg enoxaparin od compared with unfractionated heparin (UFH) and placebo. An established decision tree model based on epidemiological data, clinical trials, and a recent meta-analysis was used to evaluate costs and consequences of alternative means of thromboprophylaxis in medical patients. Primary outcome measures were episodes of VTE (deep vein thrombosis or pulmonary embolism) and major bleeding. Secondary effectiveness measures included estimated mortality. In-hospital drug costs and administration time, in conjunction with long-term VTE complications up to 15 years and major bleeding, were considered. Results were estimated for a hypothetical cohort of 100 patients. The expected cost per 100 patients was £9,992 with enoxaparin 40 mg od, £9,972 with UFH 5000 IU bd and £8,781 with no prophylaxis. The expected number of episodes of VTE per 100 patients was 1.2 with enoxaparin 40 mg od, 1.4 with UFH 5000 IU bd and 3.2 with no prophylaxis. The expected number of episodes of major bleeding per 100 patients was 1.7 with enoxaparin 40 mg od, 3.5 with UFH 5000 IU bd and 1.1 with no prophylaxis. The cost-effectiveness ratios for enoxaparin compared to no prophylaxis were £796 per VTE event avoided (taking into account the small increase in bleeding). In acutely ill medical patients, enoxaparin 40 mg od was found to be cost-effective compared with no thromboprophylaxis. Compared to UFH prophylaxis, enoxaparin was found to be cost neutral.     

Effectiveness and safety of betrixaban extended prophylaxis for venous thromboembolism compared with standard-duration prophylaxis intervention in acute medically ill patients: a systematic literature review and network meta-analysis

Abstract

Aims: To determine the clinical effectiveness and safety of venous thromboembolism (VTE) prophylaxis using US- and Europe-approved anticoagulants relative to extended-duration VTE prophylaxis with betrixaban. Low molecular weight heparins (LMWHs), unfractionated heparin (UFH), fondaparinux sodium and placebo were each compared to betrixaban, as standard-duration VTE prophylaxis for hospitalized, non-surgical patients with acute medical illness at risk of VTE.

Materials and methods: A systematic literature review was conducted up to June 2019 to identify randomized controlled trials (RCTs) of VTE prophylaxis in hospitalized, non-surgical patients with acute medical illness at risk of VTE. Studies that reported the occurrence of VTE events (including death) and, where possible, major bleeding, from treatment initiation to 20–50?days thereafter were retrieved and extracted. A Bayesian fixed effect network meta-analysis was used to estimate efficacy and safety of betrixaban compared with standard-duration VTE prophylaxis.

Results: Seven RCTs were analyzed which compared betrixaban, LMWHs, UFH, fondaparinux sodium, or placebo. There were significantly higher odds (median odds [95% credible interval]) of VTE with LMWHs (1.38 [1.12–1.70]), UFH (1.60 [1.05–2.46]), and placebo (2.37 [1.55–3.66]) compared with betrixaban. There were significantly higher odds of VTE-related death with placebo (7.76 [2.14–34.40]) compared with betrixaban. No significant differences were observed for the odds of major bleeding with all comparators, VTE-related death with any active standard-duration VTE prophylaxis, or of VTE with fondaparinux sodium, compared with betrixaban.

Limitations and conclusions: In this indirect comparison, betrixaban was shown to be an effective regimen with relative benefits compared with LMWHs and UFH. This indicates that betrixaban could reduce the burden of VTE in at-risk hospitalized patients with acute medical illness who need extended prophylaxis, though without direct comparative evidence, stronger conclusions cannot be drawn.     

Economic evaluation of the use of Innohep® in the treatment of acute pulmonary embolism

Summary

This article reports the cost implications of using Innohep® (tinzaparin), a low-molecular-weight heparin (LMWH), instead of intravenous (iv) unfractionated heparin (UFH) in the treatment of acute pulmonary embolism (PE). The expected cost per patient, including initial treatment costs and the cost of managing adverse outcomes (but excluding costs common to both regimes) was found to be £191.81 for patients treated with UFH and £186.64 for patients treated with Innohep® (costs estimated as of end 1997). Therefore, the use of Innohep® reduces the expected cost per patient by £5.17 or 3%. When the costs of managing adverse outcomes occurring after cessation of UFH/Innohep® therapy are excluded, expected costs per patient for UFH and Innohep® treatment are £136.70 and £120.22, respectively. Therefore, when outcomes not directly attributable to the choice between UFH and Innohep® treatment are reduced, the use of Innohep® reduces the expected cost per patient by £16.48 or 12%.

Innohep® reduces costs through greater ease of administration, by removing the need for extensive laboratory monitoring and by saving staff time. These results are generally robust to variations in key assumptions. Sensitivity analysis demonstrates that if patients treated with Innohep® can be discharged from hospital earlier, with their treatment continuing at home, substantial cost savings may result.     

An indirect comparison,via enoxaparin,of rivaroxaban with dabigatran in the prevention of venous thromboembolism after hip or knee replacement

Abstract

Objective:

To compare the efficacy, in the prevention of venous thromboembolism (VTE), and safety, of rivaroxaban and dabigatran relative to the common comparator enoxaparin.

Methods:

Two randomized clinical trials of dabigatran, one after total hip replacement (THR), RE-NOVATE, and one after total knee replacement (TKR), RE-MODEL, were identified as using the same enoxaparin regimen (40?mg once daily given the evening before surgery) and being of comparable duration to two rivaroxaban trials, RECORD1 and RECORD3. Indirect comparisons were performed on both efficacy and safety endpoints. To enable comparisons, symptomatic VTE results were based on the total study duration period, i.e. including the follow-up period. Major bleeding included surgical-site bleeding events.

Results:

After THR, rivaroxaban 10?mg once daily significantly reduced total VTE and symptomatic VTE relative to dabigatran 220?mg once daily (relative risk 0.34 and 0.19, respectively). After TKR, rivaroxaban significantly reduced total VTE versus dabigatran (relative risk 0.53); symptomatic VTE was not different between dabigatran and rivaroxaban. There was no significant difference in the rates of major bleeding for patients receiving rivaroxaban or dabigatran.

Conclusions:

Based on the indirect comparisons, rivaroxaban was estimated to be more efficacious than dabigatran in the prevention of total VTE after THR and TKR. Our analysis relied upon published data for dabigatran and did not have the advantages of more detailed comparative data obtained directly from a randomized trial, as was the case with rivaroxaban. Further comparative research may be of value, but until available our conclusions represent the best available evidence.     

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

Abstract

Objective:

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

Methods:

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

Results:

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

Limitations:

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

Conclusions:

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

Cost-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.     

Length of stay and economic consequences with rivaroxaban vs enoxaparin/vitamin K antagonist in patients with DVT and PE: findings from the North American EINSTEIN clinical trial program

Objective:

Venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [(PE]) represents a substantial economic burden to the healthcare system. Using data from the randomized EINSTEIN DVT and PE trials, this North American sub-group analysis investigated the potential of rivaroxaban to reduce the length of initial hospitalization in patients with acute symptomatic DVT or PE.

Methods:

A post-hoc analysis of hospitalization and length-of-stay (LOS) data was conducted in the North American sub-set of patients from the randomized, open-label EINSTEIN trial program. Patients received either rivaroxaban (15?mg twice daily for 3 weeks followed by 20?mg once daily; n?=?405) or dose-adjusted subcutaneous enoxaparin overlapping with (guideline-recommended ‘bridging’ therapy) and followed by a vitamin K antagonist (VKA) (international normalized ratio?=?2.0–3.0; n?=?401). The open-label study design allowed for the comparison of LOS between treatment arms under conditions reflecting normal clinical practice. LOS was evaluated using investigator records of dates of admission and discharge. Analyses were carried out in the intention-to-treat population using parametric tests. Costs were applied to the LOS based on weighted mean cost per day for DVT and PE diagnoses obtained from the Healthcare Cost and Utilization Project dataset.

Results:

Of 382 patients hospitalized, 321 (84%), had acute symptomatic PE; few DVT patients required hospitalization. Similar rates of VTE patients were hospitalized in the rivaroxaban and enoxaparin/VKA treatment groups, 189/405 (47%) and 193/401 (48%), respectively. In hospitalized VTE patients, rivaroxaban treatment produced a 1.6-day mean reduction in LOS (median?=?1 day) compared with enoxaparin/VKA (mean?=?4.5 vs 6.1; median?=?3 vs 4), translating to total costs that were $3419 lower in rivaroxaban-treated patients.

Conclusion:

In hospitalized North American patients with VTE, treatment with rivaroxaban produced a statistically significant reduction in LOS. When treating DVT and PE patients, clinicians should consider newer anti-coagulants with less complex treatment regimens.     

Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism

Background:

Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin?+?VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin?+?VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin?+?VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE.

Methods:

A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin?+?VKA in adult patients treated for acute DVT or PE. All patients entered the model in the ‘on-treatment’ state upon commencement of oral rivaroxaban or enoxaparin?+?VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used.

Results:

Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin?+?VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model’s results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin?+?VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin?+?VKA approximately 76% of the time.

Limitations:

The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. ‘Real-world’ applicability is limited because data from the EINSTEIN trials were used in the model. Also, resource utilization and costs were based on the US healthcare system.

Conclusion:

Rivaroxaban is a cost-effective option for anticoagulation treatment of acute VTE patients.     

Cost-effectiveness of rivaroxaban versus apixaban for the initial treatment of venous thromboembolism and extended prevention of recurrences in the UK

Abstract

Aim: To evaluate the relative cost-effectiveness of using rivaroxaban vs apixaban for the initial treatment plus extended prevention of venous thromboembolism (VTE) in the UK. Extended prevention was assessed using a 10-mg rivaroxaban dose, as the 20-mg dose has already been evaluated.

Methods: A Markov model compared the health outcomes and costs of treating VTE patient cohorts with either rivaroxaban (15?mg twice daily for 3 weeks, followed by 20?mg once daily for 6 months, then extended prevention with 10?mg once daily) or apixaban (10?mg twice daily for 1 week, followed by 5?mg twice daily for 6 months, then extended prevention with 2.5?mg twice daily) over a lifetime horizon. The model included an initial acute treatment and prevention phase (0–6?months) and an extended prevention phase (6–18 months). Efficacy and safety data were derived from two network meta-analyses. Reference treatment comparators were derived from the EINSTEIN-Pooled study and EINSTEIN-CHOICE trial. Healthcare costs and utility data were derived from published literature.

Results: The rivaroxaban regimen was associated with increased quality-adjusted life years (QALYs) and slightly lower total costs compared with apixaban over a lifetime horizon. Deterministic and probabilistic sensitivity analyses demonstrated that rivaroxaban remained a cost-effective alternative to apixaban over a wide range of parameters. Incremental cost-effectiveness ratio estimates were below the £20,000 per QALY threshold in 74.1% of 2,000 model simulations. Scenario analyses further supported that rivaroxaban is a cost-effective alternative to apixaban.

Limitations: Clinical and safety inputs were derived from network meta-analysis, which are subject to inherent limitations whereby small differences between study designs may severely impact efficacy and safety outcomes. Furthermore, these inputs were based on data from clinical trials, which may not reflect real-world data.

Conclusions: Rivaroxaban was associated with a slightly lower total cost and increased QALYs compared with apixaban for VTE management in the UK over a lifetime horizon.     

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

Abstract

Objectives:

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

Methods:

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

Results:

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

Limitations:

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

Conclusions:

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

Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding. This study assessed the long-term clinical and economic benefits of extending treatment with apixaban when clinical equipoise exists compared to standard of care with enoxaparin/warfarin and other novel oral anti-coagulants (NOACs) for the treatment and prevention of recurrent VTE in Canada.

Methods A Markov model was developed to follow patients with VTE over their lifetimes. Efficacy and safety for apixaban and enoxaparin/warfarin were based on AMPLIFY and AMPLIFY-EXT, while relative efficacy to other NOACs was synthesized by network meta-analysis (NMA). Dosages for NOACs and enoxaparin/warfarin were based on their respective trials and were given up to 18 months and up to 6 months, followed by no treatment, respectively. Patient quality adjusted life years (QALYs) were based on published studies, and costs for resource utilization were from a Ministry of Health perspective, expressed as 2014 CAD ($).

Results Extended treatment with apixaban compared to enoxaparin/warfarin resulted in fewer recurrent VTEs, VTE-related deaths, and bleeding events, but at slightly increased cost. The incremental cost-effectiveness ratio was $4828 per QALY gained. Compared to other NOACs, apixaban had the fewest bleeding events, similar recurrent VTE events, and the lowest overall cost, which was driven by the strong bleeding profile. In scenario analyses of acute and lifetime treatments, apixaban was cost-effective against all strategies.

Conclusions Extended treatment with apixaban can offer substantial clinical benefits and is a cost-effective alternative to enoxaparin/warfarin and other NOACs.     

Cost-effectiveness analysis of exenatide once-weekly versus dulaglutide,liraglutide, and lixisenatide for the treatment of type 2 diabetes mellitus: an analysis from the UK NHS perspective

Objective: To assess the cost-effectiveness of exenatide 2?mg once-weekly (EQW) compared to dulaglutide 1.5?mg QW, liraglutide 1.2?mg and 1.8?mg once-daily (QD), and lixisenatide 20?μg QD for the treatment of adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on metformin.

Methods: The Cardiff Diabetes Model was applied to evaluate cost-effectiveness, with treatment effects sourced from a network meta-analysis. Quality-adjusted life years (QALYs) were calculated with health-state utilities applied to T2DM-related complications, weight changes, hypoglycemia, and nausea. Costs (GBP £) included drug treatment, T2DM-related complications, severe hypoglycemia, nausea, and treatment discontinuation due to adverse events. A 40-year time horizon was used.

Results: In all base-case comparisons, EQW was associated with a QALY gain per patient; 0.046 vs dulaglutide 1.5?mg; 0.102 vs liraglutide 1.2?mg; 0.043 vs liraglutide 1.8?mg; and 0.074 vs lixisenatide 20?μg. Cost per patient was lower for EQW than for liraglutide 1.8?mg (?£2,085); therefore, EQW dominated liraglutide 1.8?mg. The cost difference per patient between EQW and dulaglutide 1.5?mg, EQW and liraglutide 1.2?mg, and EQW and lixisenatide 20?μg was £27, £103, and £738, respectively. Cost per QALY gained with EQW vs dulaglutide 1.5?mg, EQW vs liraglutide 1.2?mg, and EQW vs lixisenatide 20?μg was £596, £1,004, and £10,002, respectively. In the probabilistic sensitivity analysis, the probability that EQW is cost-effective ranged from 76–99%.

Conclusion: Results suggest that exenatide 2?mg once-weekly is cost-effective over a lifetime horizon compared to dulaglutide 1.5?mg QW, liraglutide 1.2?mg QD, liraglutide 1.8?mg QD, and lixisenatide 20?μg QD for the treatment of T2DM in adults not adequately controlled on metformin alone.     

Costing anaesthetic practice: reconciling perspectives and approaches

Summary

In a previously published article by Broadway and Jones, the anaesthesia-related cost of a hernia repair operation was estimated to be £74.40, of which 21% was accounted for by anaesthetic agents and adjunct drugs. This result contrasts with our estimate of the total procedure cost for an inpatient hernia repair operation of £1,037.39, of which anaesthetic agents and adjunct drugs comprised less than 1%. In order to explain this difference, in this paper we compare and contrast our methodology for and perspective on costing resource use in anaesthesia with those used by Broadway et al. We conclude that these two apparently divergent results, once reconciled in terms of cost coverage and perspectives taken, are broadly equivalent (a reconciled cost of £78.21 compared with the £74.40 of Broadway and Jones.), and that the cost of anaesthetic agents and adjunct drugs constitute a small proportion of total procedure costs.     

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.     

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.     

Economic burden of venous thromboembolism: a systematic review

Abstract

Objective:

Deep vein thrombosis and pulmonary embolism – together referred to as venous thromboembolism (VTE) – result in a major burden on healthcare systems. However, to the authors’ knowledge no comprehensive review of the economic burden of VTE has so far been published.

Methods:

A literature search was carried out to identify references published in English since 1997 using Medline, the Cochrane Library and the Health Economic Evaluations Database. The primary outcomes of interest were ‘all-cause’ VTE and VTE after major orthopedic surgery.

Results:

A total of 1,037 full research articles and abstracts were screened for inclusion in the review. Of these, ten cost-of-illness studies were identified that met the inclusion criteria and are included in the current review. The results of large US database analyses vary, indicating costs of the initial VTE of approximately US$3,000–9,500. The total costs related to VTE over 3 months (US$5,000), 6 months (US$10,000) and 1 year (US$33,000) were considerable. Studies conducted in the European Union indicate lower additional inpatient costs after VTE of €1,800 after 3 months and €3,200 after 1 year, which still represent a considerable impact on healthcare systems. Complications after VTE can be very expensive, with estimates of the additional cost of treating the post-thrombotic syndrome ranging from $426 to $11,700 and heparin-induced thrombocytopenia from $3,118 to $41,133. A limitation of studies using older data is that recent changes in the treatment of VTE may affect the generalizability of these findings.

Conclusions:

Complications associated with VTE are frequent and costly. In particular, the cost of complications resulting from prophylaxis and treatment of VTE, such as post-thrombotic syndrome and heparin-induced thrombocytopenia, had a considerable economic impact.     

Retrospective database study to assess the economic impact of hip fracture in the United Kingdom

Objective:

Publications containing recent, real-world data on the economic impact of hip fractures in the UK are lacking. This retrospective electronic medical records database analysis assessed medication and healthcare resource use, direct healthcare costs, and factors predicting increased resource use and costs in adult UK hip fracture patients.

Methods:

Data were obtained from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics for adult patients hospitalized for their first hip fracture between January 1, 2006 and March 31, 2011 (index event); healthcare costs were calculated from the National Health Service perspective using 2011–2012 cost data.

Results:

Data from 8028 patients were analyzed. Resource use and costs were statistically significantly higher in the year following fracture (mean total [standard deviation (SD)] cost £7359 [£14,937]) compared with the year before fracture (mean total [SD] cost £3122 [£9435]; p?Conclusions:

Although we did not capture all pre- and post-index costs and healthcare utilization, this study provides important insights regarding the characteristics of patients with hip fracture, and information that will be useful in burden-of-illness and economic analyses.     

Cost-effectiveness of Viridal Duo compared to MUSE and Viagra in the treatment of erectile dysfunction in the UK - a preliminary model

Summary

This study estimated the cost-effectiveness of starting erectile dysfunction (ED) treatment with Viridal Duo relative to MUSE and Viagra over one year, from the perspective of the National Health Service. Decision analysis techniques were used to estimate the expected costs and consequences of managing ED, stratified by initial treatment. The model was based on estimates of clinical outcome and resource use obtained from published literature and a Delphi panel.

Viridal Duo is a registered trademark of Schwarz Pharma;

MUSE is a registered trademark of Astra Pharmaceuticals;

Viagra is a registered trademark of Pfizer Consumer Healthcare

Starting ED treatment with Viridal Duo instead of Viagra leads to an average 0.8 additional months during which a man can achieve successful erections (from 6.5 to 7.3 months) over one year, for an additional cost of £106 per patient (from £369 to £475). Starting ED treatment with Viagra instead of MUSE leads to an average 1.1 additional months during which a man can achieve successful erections (from 5.4 to 6.5 months) over one year and reduces the cost per patient by £85 (from £454 to £369).

Fifty-two percent of patients who start treatment with Viridal Duo continue successfully over one year. This compares to 38% and 18% of patients who start treatment with Viagra and MUSE respectively. Eighty-seven percent of the total success with Viridal Duo can be directly attributed to this treatment when used first-line. In contrast, 68% and 44% of the total success attributed to Viagra and MUSE respectively can be attributed to these treatments when chosen first-line. Moreover, an additional 44% and 27% of the expected total success with MUSE and Viagra is attributable to Viridal Duo.

Starting ED treatment with Viridal Duo rather than MUSE, when Viagra is either unavailable or contraindicated, increases the period during which a man can achieve successful erections by 1.8 months (from 5.5 to 7.3 months) for an additional cost of £14 per patient (from £460 to £474). Additionally, in patients who have previously failed Viagra, starting second-line treatment with Viridal Duo rather than MUSE leads to an average 1.6 additional months during which a man can achieve successful erections (from 4.0 to 5.6 months) over one year and reduces the cost per patient by £15 (from £493 to £478).

In conclusion, Viridal Duo is clinically more effective than Viagra and MUSE. Therefore, starting ED treatment with Viridal Duo instead of Viagra or MUSE increases the period during which a man can achieve successful erections, albeit for an additional cost. In patients who have previously failed first-line treatment with Viagra, starting second-line treatment with Viridal Duo instead of MUSE increases the period during which a man can achieve successful erections (by 40% at one year) and reduces healthcare costs (by £15 per patient).     

Impact of apixaban vs low molecular weight heparin/vitamin k antagonist on hospital resource use in patients with venous thromboembolism

Background: The clinical and economic benefits associated with apixaban treatment have been established in clinical trials and published economic evaluations. The benefits associated with apixaban could extend to improving hospital efficiencies, potentially influencing hospital resource use, and bed days. The objective of this study is to estimate the impact of 6-month treatment with apixaban vs low molecular weight heparin/vitamin k antagonist (LMWH/VKA) on hospital resource use among patients with venous thromboembolism (VTE).

Methods: A model was developed to assess the impact of apixaban vs LMWH/VKA for treatment of VTE and prevention of recurrences on hospital resource use and costs. Resource use items included total hospitalizations, length of stay (LOS), and emergency department (ED) visits, estimated for all incident VTE patients in the UK over a 5-year time horizon. Rates of hospitalizations, ED visits, and LOS associated with recurrent VTE, major, and clinically relevant non-major bleeding were obtained from the AMPLIFY trial; costs were obtained from UK published sources.

Results: Over a 5-year time horizon, the model predicted that, compared to 6 months of LMWH/VKA, 6 months of apixaban led to 3,954 fewer hospitalizations (consisting of 2,341 fewer new admissions and 1,613 fewer re-admissions) and 32,214 fewer bed days, among 332,607 incident VTE patients. ED visits were reduced by 1,582. The reduction in hospital resource use led to a cost saving of ～£4.5 million in a market of patients treated with apixaban as compared to a market treated with LMWH/VKA. Sensitivity analysis indicated these findings were robust over a wide range of inputs.

Conclusions: 6-month treatment with apixaban for treatment of VTE and prevention of recurrences on hospital resource use led to a reduction in hospitalizations and LOS in comparison to LMWH/VKA. These findings can help the efforts in reducing the growing burden of preventable re-admissions to hospitals.     

The cost-effectiveness of onabotulinumtoxinA for the prophylaxis of headache in adults with chronic migraine in the UK

Abstract

Background:

Although chronic migraine is associated with substantial disability and costs, few treatments have been shown to be effective. OnabotulinumtoxinA (Botox, Allergan Inc., Irvine, CA) is the first treatment to be licensed in the UK for the prophylaxis of headaches in adults with chronic migraine. This study aims to evaluate the cost-effectiveness of onabotulinumtoxinA in this indication in the UK.

Methods:

A state-transition (Markov) model was developed comparing onabotulinumtoxinA to placebo. Efficacy data and utility values were taken from the pooled Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trials program (n?=?1384). Estimates of resource utilisation were taken from the International Burden of Migraine Study (IBMS), and stopping rules were informed by published medical guidelines and clinical data. This study estimated 2-year discounted costs and quality-adjusted life years (QALYs) from the UK National Health Service perspective.

Results:

At 2 years, treatment with onabotulinumtoxinA was associated with an increase in costs of £1367 and an increase in QALYs of 0.1 compared to placebo, resulting in an incremental cost-effectiveness ratio (ICER) of £15,028. Treatment with onabotulinumtoxinA reduced headache days by an estimated 38 days per year at a cost of £18 per headache day avoided. Sensitivity analysis showed that utility values had the greatest influence on model results. The ICER remained cost-effective at a willingness to pay threshold of £20,000–£30,000/QALY in the majority of scenario analyses as well as in probabilistic sensitivity analysis, where onabotulinumtoxinA was cost-effective on 96% of occasions at a threshold of £20,000/QALY and 98% of occasions at £30,000/QALY.

Conclusion:

OnabotulinumtoxinA has been shown to reduce the frequency of headaches in patients with chronic migraine and can be considered a cost-effective use of resources in the UK National Health Service. The uncertainties in the model relate to the extrapolation of clinical data beyond the 56-week trial.