An economic evaluation of ramipril in the treatment of patients at high risk for cardiovascular events due to diabetes mellitus

SUMMARY

Cardiovascular disease (CVD) is a major cause of death and morbidity in the United Kingdom (UK) and carries with it a significant financial cost through health care resource use. More than one in three people die from CVD events, and the cost to the UK National Health Service (NHS) was £1.6 billion in 1996¹. The recently published MICRO-HOPE study evaluated the treatment of 3,577 patients at high risk for cardiovascular events from diabetes mellitus and demonstrated significant survival and morbidity benefits associated with ramipril.

The purpose of this paper is to assess whether the significant clinical benefits offered by ramipril can be translated into economic benefits, and to what extent it can reduce the economic burden of CVD to the UK NHS.

Applying the same analytical framework used in a previous economic analysis of the HOPE study, our base case estimate of cost-effectiveness for ramipril in the MICRO HOPE study is £2,396 per life-year saved (undiscounted) and £2,971 per life-year saved (discounted). A sensitivity analysis was performed which ranged from a best case of £1,954 per life-year saved (undiscounted) to a worst case of £2,964 per life-year saved (undiscounted). Our base case estimate of cost-effectiveness suggests that treating patients at high risk for CVD events with ramipril is likely to be a good investment of NHS resources.     

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.     

Use of opioid substitution therapies in the treatment of opioid use disorder: results of a UK cost-effectiveness modelling study

Aims: This study investigated the cost-effectiveness of buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT) vs no opioid substitution therapy (OST) for the treatment of opioid use disorder, from the UK National Health Service (NHS)/personal social services (PSS) and societal perspectives over 1 year.

Methods: Cost-effectiveness of OST vs no OST was evaluated by first replicating and then expanding an existing UK health technology assessment model. The expanded model included the impact of OST on infection rates of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection.

Results: Versus no OST, incremental cost-effectiveness ratios (ICERs) for BMT and MMT were £13,923 and £14,206 per quality-adjusted life year (QALY), respectively, from a NHS/PSS perspective. When total costs (NHS/PSS and societal) are considered, there are substantial savings associated with adopting OST; these savings are in excess of £14,032 for BMT vs no OST and £17,174 for MMT vs no OST over 1 year. This is primarily driven by a reduction in victim costs. OST treatment also impacted other aspects of criminality and healthcare resource use.

Limitations: The model’s 1-year timeframe means long-term costs and benefits, and the influence of changes over time are not captured.

Conclusions: OST can be considered cost-effective vs no OST from the UK NHS/PSS perspective, with a cost per QALY well below the UK’s willingness-to-pay threshold. There were only small differences between BMT and MMT. The availability of two or more cost-effective options is beneficial to retaining patients in OST programs. From a societal perspective, OST is estimated to save over £14,032 and £17,174 per year for BMT and MMT vs no OST, respectively, due to savings in victim costs. Further work is required to fully quantify the clinical and health economic impacts of different OST formulations and their societal impact over the long-term.     

Cost-effectiveness of insulin degludec compared with insulin glargine in a basal-bolus regimen in patients with type 1 diabetes mellitus in the UK

Abstract

Objective:

The aim of this study was to evaluate the cost-effectiveness of insulin degludec (IDeg) vs insulin glargine (IGlar) as part of a basal-bolus treatment regimen in adults with T1DM, using a short-term economic model.

Methods:

Data from two phase III clinical studies were used to populate a simple and transparent short-term model. The costs and effects of treatment with IDeg vs IGlar were calculated over a 12-month period. The analysis was conducted from the perspective of the UK National Health Service. Sensitivity analyses were conducted to assess the degree of uncertainty surrounding the results. The main outcome measure, the incremental cost-effectiveness ratio (ICER), was the cost per quality-adjusted life-year (QALY).

Results:

IDeg is a cost-effective treatment option vs IGlar in patients with T1DM on a basal-bolus regimen. The base case ICER was estimated at £16,895/QALY, which is below commonly accepted thresholds for cost-effectiveness in the UK. Sensitivity analyses demonstrated that the ICER was stable to variations in the majority of input parameters. The parameters that exerted the most influence on the ICER were hypoglycemia event rates, daily insulin dose, and disutility associated with non-severe nocturnal hypoglycemic events. However, even under extreme assumptions in the majority of analyses the ICERs remained below the commonly accepted threshold of £20,000–£30,000 per QALY gained.

Conclusions:

This short-term modeling approach accommodates the treat-to-target trial design required by regulatory bodies, and focuses on the impact of important aspects of insulin therapy such as hypoglycemia and dosing. For patients with T1DM who are treated with a basal-bolus insulin regimen, IDeg is a cost-effective treatment option compared with IGlar. IDeg may be particularly cost-effective for sub-groups of patients, such as those suffering from recurrent nocturnal hypoglycemia and those with impaired awareness of hypoglycemia.     

De-escalation from micafungin is a cost-effective alternative to traditional escalation from fluconazole in the treatment of patients with systemic Candida infections

Abstract

Background:

Systemic Candida infections (SCI) occur predominantly in intensive care unit patients and are a common cause of morbidity and mortality. Recently, changes in Candida epidemiology with an increasing prevalence of SCI caused by Candida non-albicans species have been reported. Resistance to fluconazole and azoles in general is not uncommon for non-albicans species. Despite guidelines recommending initial treatment with broad-spectrum antifungals such as echinocandins with subsequent switch to fluconazole if isolates are sensitive (de-escalation strategy), fluconazole is still the preferred first-line antifungal (escalation) in many clinical practice settings. After diagnosis of the pathogen, the initial therapy with fluconazole is switched to a broad-spectrum antifungal if a non-albicans is identified.

Methods:

The cost-effectiveness of initial treatment with micafungin (de-escalation) vs fluconazole (escalation) in patients with SCI was estimated using decision analysis based on clinical and microbiological data from pertinent studies. The model horizon was 42 days, and was extrapolated to cover a lifetime horizon. All costs were analyzed from the UK NHS perspective. Several assumptions were taken to address uncertainties; the limitations of these assumptions are discussed in the article.

Results:

In patients with fluconazole-resistant isolates, initial treatment with micafungin avoids 30% more deaths and successfully treats 23% more patients than initial treatment with fluconazole, with cost savings of £1621 per treated patient. In the overall SCI population, de-escalation results in 1.2% fewer deaths at a marginal cost of £740 per patient. Over a lifetime horizon, the incremental cost-effectiveness of de-escalation vs escalation was £15,522 per life-year and £25,673 per QALY.

Conclusions:

De-escalation from micafungin may improve clinical outcomes and overall survival, particularly among patients with fluconazole-resistant Candida strains. De-escalation from initial treatment with micafungin is a cost-effective alternative to escalation from a UK NHS perspective, with a differential cost per QALY below the ‘willingness-to-pay’ threshold of £30,000.     

Cost of NSAID adverse effects to the UK National Health Service

Summary

Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal problems, notably dyspepsia and bleeding. These adverse effects are costly both in terms of acute hospital admissions and in co-prescribing of gastroprotective agents. The costs of these interventions has been estimated for the National Health Service (NHS) in the UK on the basis of a typical Primary Care Group (PCG) of 100,000 people, the whole population, and for the average patient prescribed an NSAID. The annual burden of NSAID-related gastrointestinal adverse effects to the NHS is large. The middle estimate for an average PCG was £435,000 (range £290,000 to £633,000). The middle estimate for the UK was £251 million (range £166 million to £367 million). The middle cost per patient prescribed an NSAID was £48 (range £32 to £70). As much as half of all acid-suppressing prescribing in the UK may be for NSAID-related gastrointestinal effects.     

The cost-effectiveness of 5-FU-SA in the treatment of actinic keratoses of the face and scalp in the UK secondary care setting

Objective: The objective of this analysis was to estimate the relative cost-effectiveness of Actikerall¹ (5-FU-SA) vs cryotherapy in a secondary care setting in the UK, for lesion-directed treatment in patients with actinic keratoses (AK) of the face and scalp.

Methods: The model was a simple decision tree, with a 6-month time horizon. The perspective was that of the UK National Health Service (NHS). Modeled treatment effects included reported per-patient histological clearance and recurrence rates. Cost inputs comprised professional consultation time and cost of medication. Health-related utility estimation followed previously published methodology. Adverse events were not modeled. The key data and model structural assumptions followed expected UK practice. One-way and probabilistic sensitivity analyses were conducted to assess structural and parameter uncertainty.

Results: 5-FU-SA was found to be less costly (?£204) and more effective (+0.001 QALY) in base case and sensitivity analyses. In the probabilistic analysis there was 100% probability of being cost-effective over cryotherapy at £20,000 willingness to pay. Cost of professional time was a key driver of the model outcome. 5-FU-SA remained dominant across a range of scenario analyses, including exploration of assumptions around setting of care.

Limitations: The time horizon of the analysis was short and data were not extrapolated beyond the duration of the clinical trial; however, this approach is consistent with likely follow-up of an AK patient. The clinical outcomes observed in the trial were based on a large proportion of cryotherapy patients undergoing an additional cycle of treatment; this may not occur or be required in an experienced secondary care setting.

Conclusion: 5-FU-SA could be considered as a cost-effective choice for treatment of AK lesions of the face and scalp in secondary and mixed care settings in the UK. Use of 5-FU-SA in patients who would otherwise be managed with cryotherapy has the potential to result in cost savings.     

Cost effectiveness of rimonabant use in patients at increased cardiometabolic risk: estimates from a Markov model

Summary

Rimonabant, the first selective CB-1 receptor blocker, is expected to reduce cardiometabolic risk substantially. This study assesses the economics of such treatment in patients at elevated cardiometabolic risk.

A Markov model was developed using data from the Rimonabant in Obesity (RIO) trial, published risk equations, and UK cost and utility data. Patients begin either in a diabetic or a non-diabetic state and can transition to cardiovascular disease or to death (based on UK life tables). Transitions to diabetes and subsequent cardiovascular events are also counted. Resource use due to events and long-term management were translated to UK costs (2005 GBP). Tariffs for events and states were applied to age-dependent utilities. Extensive univariate and multivariate probabilistic sensitivity analyses were carried out.

Over 10 years, 8% will suffer a cardiovascular event with a loss of more than 1,000 quality-adjusted life years (QALYs) and a cost of more than £500,000 per 1,000 patients. Projecting risk for a lifetime, 1 year of rimonabant use is estimated to gain >65 QALYs at £8,574/QALY. In probabilistic sensitivity analysis, incremental cost-effectiveness ratios varied from £2,657 to £22,141/QALY.

Based on the metabolic effects seen in clinical trials, rimonabant should reduce cardiovascular risk in obese or overweight people at reasonable cost.     

Cost-effectiveness of combination chemotherapy (oxaliplatin or irinotecan in combination with 5-FU/FA) compared with 5-FU/FA alone

SUMMARY

Combination therapies of oxaliplatin with 5-fluorouracil (5-FU) and folinic acid (FA) and irinotecan with 5-FU/FA have been shown to offer comparable clinical improvements in advanced colorectal cancer and are becoming part of routine clinical practice in the UK. Using published key Phase III trials of these two combination therapies (oxaliplatin trial, 620 patients; irinotecan trial, 387 patients) we calculated incremental cost-effectiveness ratios for progression-free survival and response rates compared with each regimen's control arm. Average drug-acquisition costs were used.

The incremental cost to achieve an additional progression-free year is £26,665 for oxaliplatin in combination therapy and £30,171 for irinotecan in combination therapy. In terms of response rates, the costs incurred per year to achieve an additional responding patient are £31,065 for oxaliplatin in combination therapy and £46,343 for irinotecan combination therapy.

These analyses indicate that the two combination therapies offer comparable benefits in terms of efficacy and cost-effectiveness compared with 5-FU/FA alone. The two treatments differ in terms of their toxicity.     

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

SUMMARY

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

Copaxone is a registered trademark of Teva Pharmaceutical Industries, Israel     

Quality of life benefits and cost impact of prolonged release oxycodone/naloxone versus prolonged release oxycodone in patients with moderate-to-severe non-malignant pain and opioid-induced constipation: a UK cost-utility analysis

Abstract

Objective:

To compare the cost effectiveness of prolonged release oxycodone/naloxone (OXN) tablets (Targinact) and prolonged release oxycodone (OXY) tablets (OxyContin) in patients with moderate-to-severe non-malignant pain and opioid-induced constipation (OIC) from the perspective of the UK healthcare system.

Methods:

A cohort model used data from a phase III randomised, controlled trial (RCT). It calculated the cost difference between treatments by combining the cost of pain therapy with costs of laxatives and other resources used to manage constipated patients. SF-36 scores were converted into EQ-5D utility values to calculate the quality-adjusted life-year (QALY) gains. Deterministic and probabilistic sensitivity analyses were performed.

Results:

The incremental cost of OXN versus OXY was £159.68 for the average treatment duration of 301 days. OXN gave an incremental QALY gain of 0.0273. The estimated incremental cost-effectiveness ratio (ICER) was £5841.56 per QALY. Sensitivity analyses gave a maximum ICER of £10,347.03. In some scenarios, OXN dominated with a cost saving of up to £4254.70. Probabilistic sensitivity analysis showed that OXN had approximately 96.6% probability of cost effectiveness at the £20,000 threshold.

Limitations:

The model was conservative in predicting the probability of constipation beyond the 12-week RCT period. UK cost of constipation data were limited and based on primary care physician opinion.

Conclusions:

In the base case, direct treatment costs were slightly higher for patients treated with OXN than for those treated with OXY. However, patients treated with OXN experienced a quality of life gain, and had an ICER considerably below thresholds commonly applied in the UK. The model was most sensitive to the estimated cost of constipation with a number of realistic scenarios in the sensitivity analysis demonstrating a cost saving with OXN (OXN dominant). OXN is therefore estimated to be a cost-effective option for treating patients with severe non-malignant pain and OIC.     

Cost-effectiveness of targeted screening for the identification of patients with atrial fibrillation: evaluation of a machine learning risk prediction algorithm

Abstract

Aims: As many cases of atrial fibrillation (AF) are asymptomatic, patients often remain undiagnosed until complications (e.g. stroke) manifest. Risk-prediction algorithms may help to efficiently identify people with undiagnosed AF. However, the cost-effectiveness of targeted screening remains uncertain. This study aimed to assess the cost-effectiveness of targeted screening, informed by a machine learning (ML) risk prediction algorithm, to identify patients with AF.

Methods: Cost-effectiveness analyses were undertaken utilizing a hybrid screening decision tree and Markov disease progression model. Costs and outcomes associated with the detection of AF compared traditional systematic and opportunistic AF screening strategies to targeted screening informed by a ML risk prediction algorithm. Model analyses were based on adults ≥50?years and adopted the UK NHS perspective.

Results: Targeted screening using the ML risk prediction algorithm required fewer patients to be screened (61 per 1,000 patients, compared to 534 and 687 patients in the systematic and opportunistic strategies) and detected more AF cases (11 per 1,000 patients, compared to 6 and 8?AF cases in the systematic and opportunistic screening strategies). The targeted approach demonstrated cost-effectiveness under base case settings (cost per QALY gained of £4,847 and £5,544 against systematic and opportunistic screening respectively). The targeted screening strategy was predicted to provide an additional 3.40 and 2.05 QALYs per 1,000 patients screened versus systematic and opportunistic strategies. The targeted screening strategy remained cost-effective in all scenarios evaluated.

Limitations: The analysis relied on assumptions that include the extended period of patient life span and the lack of consideration for treatment discontinuations/switching, as well as the assumption that the ML risk-prediction algorithm will identify asymptomatic AF.

Conclusions: Targeted screening using a ML risk prediction algorithm has the potential to enhance the clinical and cost-effectiveness of AF screening, improving health outcomes through efficient use of limited healthcare resources.     

A cost–utility analysis of degarelix in the treatment of advanced hormone-dependent prostate cancer in the United Kingdom

Objective:

To determine the cost-effectiveness of the treatment of advanced hormone-dependent prostate cancer with degarelix compared to luteinizing hormone-releasing hormone (LHRH) agonists in the UK using the latest available evidence and the model submitted to AWMSG.

Methods:

A cost-effectiveness model was developed from the perspective of the UK National Health Service evaluating monthly injection of degarelix against 3-monthly leuprorelin therapy plus anti-androgen flare cover for the first-line treatment of patients with advanced (locally advanced or metastatic) hormone-dependent prostate cancer. A Markov process model was constructed using the patient population characteristics and efficacy information from the CS21 Phase III clinical trial and associated extension study (CS21A). The intention-to-treat (ITT) population and a high-risk sub-group with a PSA level >20?ng/mL were modeled.

Results:

In the base-case analysis using the patient access scheme (PAS) price, degarelix was dominant compared to leuprorelin with cost savings of £3633 in the ITT population and £4310 in the PSA?>?20?ng/mL sub-group. The chance of being cost-effective was 95% in the ITT population and 96% in the PSA?>?20?ng/mL sub-group at a threshold of £20,000 per quality-adjusted life-year (QALY). In addition, degarelix remained dominant when PSA progression was assumed equal and only the benefits of preventing testosterone flare were taken into account. Treatment with degarelix also remained dominant in both populations when the list price was used. The additional investment required to treat patients with degarelix could be offset in 19 months for the ITT population and 13 months for the PSA?>?20?ng/mL population. The model was most sensitive to the hazard ratio assumed for PSA progression between degarelix and leuprorelin and the quality-of-life (utility) of patients receiving palliative care.

Conclusion:

Degarelix is likely to be cost-effective compared to leuprorelin plus anti-androgen flare cover in the first-line treatment of advanced hormone-dependent prostate cancer.     

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 continuous subcutaneous apomorphine in the treatment of Parkinson’s disease in the UK and Germany

Abstract

Background:

Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting ～5.2 million people worldwide. Continuous subcutaneous apomorphine (CSAI) represents an alternative treatment option for advanced PD with motor fluctuation. The purpose of this analysis was to estimate the cost-effectiveness of CSAI compared with Levodopa/carbidopa intestinal gel (LCIG), Deep-Brain-Stimulation (DBS) and Standard-of-care (SOC).

Methods:

A multi-country Markov-Model to simulate the long-term consequences, disease progression (Hoehn & Yahr stages 3–5, percentage of waking-time in the OFF-state), complications, and adverse events was developed. Monte-Carlo simulation accounted for uncertainty. Probabilities were derived from RCT and open-label studies. Costs were estimated from the UK and German healthcare provider’s perspective. QALYs, life-years (LYs), and costs were projected over a life-time horizon.

Results:

UK lifetime costs associated with CSAI amounts to £78,251.49 and generates 2.85 QALYs and 6.28 LYs (€104,500.08, 2.92 QALYs and 6.49 LYs for Germany). Costs associated with LCIG are £130,011.34, achieves 3.06 QALYs and 6.93 LYs (€175,004.43, 3.18 QALYs and 7.18 LYs for Germany). The incremental-cost per QALY gained (ICER) was £244,684.69 (€272,914.58). Costs for DBS are £87,730.22, associated with 2.75 QALYs and 6.38 LYs (€105,737.08, 2.85 QALYs and 6.61 LYs for Germany). CSAI dominates DBS. SOC associated UK costs are £76,793.49; 2.62 QALYs and 5.76 LYs were reached (€90,011.91, 2.73 QALYs and 6 LYs for Germany).

Conclusions:

From a health economic perspective, CSAI is a cost-effective therapy and could be seen as an alternative treatment to LCIG or DBS for patients with advanced PD.     

EVEREST II high risk study based UK cost-effectiveness analysis of MitraClip® in patients with severe mitral regurgitation ineligible for conventional repair/replacement surgery

Abstract

Objectives:

To evaluate the cost-effectiveness of MitraClip, an interventional procedure for patients with chronic severe mitral regurgitation.

Methods:

A decision analytic model with a lifetime horizon was developed to assess the cost-effectiveness of MitraClip vs conventional medical management in patients with severe mitral regurgitation, ineligible for surgery. The analysis was performed from a UK NHS perspective and the estimates for mortality, adverse events, and cross-sectional NYHA class were obtained from the EVEREST II High Risk Study (HRS). Utility decrements were obtained from a heath technology assessment on Cardiac Resynchronization Therapy, while unit costs were obtained from national databases. The concept model was clinically validated. Costs (2011 £UK) and benefits were discounted at an annual rate of 3.5%.

Results:

Compared to medical management, over 2- and 10-year periods MitraClip had incremental Quality Adjusted Life Year (QALY) gains of 0.48 and 2.04, respectively. The Incremental Cost-Effectiveness Ratios for MitraClip at 2 and 10 years are £52,947 and £14,800 per QALY gained. Overall, the model was most sensitive to the choice of time horizon, the discount rate applied to benefits, the starting age of cohort, the utility decrement associated with NYHA II, and cost of the MitraClip procedure. The model was insensitive to changes in all other parameters. MitraClip was also found to be cost-effective, regardless of the modelling approach, and insensitive to the key assumptions of the procedure cost.

Study limitations:

The primary limitation of the analysis is the reliance on aggregate data from a modestly sized non-randomized study with a short-term follow-up period. Aligned to this was the need to extrapolate survival well beyond the study period in order to generate meaningful results. The impact of both of these limitations was explored via extensive sensitivity analyses.

Conclusion:

Compared to medical management, MitraClip is a cost-effective interventional procedure at conventional threshold values.     

Cost-effectiveness of TYRX absorbable antibacterial envelope for prevention of cardiovascular implantable electronic device infection

Aims: Infection is a major complication of cardiovascular implantable electronic device (CIED) therapy that usually requires device extraction and is associated with increased morbidity and mortality. The TYRX Antibacterial Envelope is a polypropylene mesh that stabilizes the CIED and elutes minocycline and rifampin to reduce the risk of post-operative infection.

Methods: A decision tree was developed to assess the cost-effectiveness of TYRX vs standard of care (SOC) following implantation of four CIED device types. The model was parameterized for a UK National Health Service perspective. Probabilities were derived from the literature. Resource use included drug acquisition and administration, hospitalization, adverse events, device extraction, and replacement. Incremental cost-effectiveness ratios (ICERs) were calculated from costs and quality-adjusted life-years (QALYs).

Results: Over a 12-month time horizon, TYRX was less costly and more effective than SOC when utilized in patients with an ICD or CRT-D. TYRX was associated with ICERs of £46,548 and £21,768 per QALY gained in patients with an IPG or CRT-P, respectively. TYRX was cost-effective at a £30,000 threshold at baseline probabilities of infection exceeding 1.65% (CRT-D), 1.95% (CRT-P), 1.87% (IPG), and 1.38% (ICD).

Limitations and conclusions: Device-specific infection rates for high-risk patients were not available in the literature and not used in this analysis, potentially under-estimating the impact of TYRX in certain devices. Nevertheless, TYRX is associated with a reduction in post-operative infection risk relative to SOC, resulting in reduced healthcare resource utilization at an initial cost. The ICERs are below the accepted willingness-to-pay thresholds used by UK decision-makers. TYRX, therefore, represents a cost-effective prevention option for CIED patients at high-risk of post-operative infection.     

When does economic model type become a decisive factor in health technology appraisals? Learning from the expanding treatment options for relapsing–remitting multiple sclerosis

Objectives: Specific economic model types often become de facto standard for health technology appraisal over time. Markov and discrete event simulation (DES) models were compared to investigate the impact of innovative modeling on the cost-effectiveness of disease-modifying therapies (DMTs) in relapsing–remitting multiple sclerosis (RRMS). Fingolimod was compared to dimethyl fumarate (DMF; in highly active [HA] RRMS), alemtuzumab (in HA RRMS) and natalizumab (in rapidly evolving severe RRMS). Comparator DMTs were chosen to reflect different dosing regimens.

Materials and methods: Markov and DES models used have been published previously. Inputs were aligned in all relevant respects, with differences in the modeling of event-triggered attributes, such as relapse-related retreatment, which is inherently difficult with a memoryless Markov approach. Outcomes were compared, with and without different attributes.

Results: All results used list prices. For fingolimod and DMF, incremental cost-effectiveness ratios (ICERs) were comparable (Markov: £4206/quality-adjusted life year [QALY] gained versus DES: £3910/QALY gained). Deviations were observed when long-term adverse events (AEs) were incorporated in the DES (Markov: £25,412 saved/QALY lost, versus DES: £34,209 saved/QALY lost, fingolimod versus natalizumab; higher ICERs indicate greater cost-effectiveness). For fingolimod versus alemtuzumab, when relapse-triggered retreatment was included in the DES, large cost differences were observed (difference between incremental cost is £35,410 and QALY is 0.10).

Limitations: UK payer perspective, therefore societal approach was not considered. Resource utilization and utilities for both models were not derived from the subpopulations; as the focus is on model type, input limitations that apply to both models are less relevant.

Conclusions: Whilst no model can fully represent a disease, a DES allows an opportunity to include features excluded in a Markov structure. A DES may be more suitable for modeling in RRMS for health technology assessment purposes given the complexity of some DMTs. This analysis highlights the capabilities of different model structures to model event-triggered attributes.     

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

Summary

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

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

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

The cost implications of the use of telmisartan or ramipril in patients at high risk for vascular events: the ONTARGET study

Abstract

Background:

The recently published ONTARGET trial found that telmisartan was non-inferior to ramipril in reducing CV death, MI, stroke, or heart failure in patients with vascular disease or high-risk diabetes. The cost implications of ramipril and telmisartan monotherapy use based on the ONTARGET study are reported here.

Methods and Results:

Only healthcare system costs were considered. Healthcare resource utilization was collected for each patient during the trial. The authors obtained country-specific unit costs to the different healthcare care resources consumed (i.e., hospitalizations events, procedures, non-study, and study drugs) for all enrolled patients. Purchasing power parities were used to convert country-specific costs into US dollars (US$ 2008). The total undiscounted costs of the study for the telmisartan group was $12,762 per patient and is higher than the ramipril group at $12,007 per patient, an un-discounted difference of $755 (95% confidence interval [CI], $218–$1292); The discounted costs for the telmisartan group was $11,722 compared with $11,019 for the ramipril group; a difference of $703 (95% CI, $209–$1197). The difference in costs is exclusively related to the acquisition cost of telmisartan over generic ramipril.

Limitations:

This analysis only considered direct healthcare system costs. Costs accrued outside the hospital were not collected. Combination therapy was excluded since it would likely be more expensive than ramipril alone, with no additional benefit and a risk of some harm.

Conclusions:

Based on these results, it is suggested that for the ONTARGET patients, the use of telmisartan instead of ramipril increases costs by 6.3%. These findings suggest that the choice to put patients on telmisartan should be justified based on the patient’s susceptibility to specific adverse events to minimize the cost implications.