Predicting time to full-time care in AD: a new model

Objective: To develop a model to predict the length of time before patients with Alzheimer's disease (AD) of varying severity require full-time care (FTC).

Methods: A predictive model (equation) of time to FTC (defined as being institutionalised or dependent) was developed based on the London and South-East Region (LASER–AD) epidemiological study using a discrete time representation of the Cox continuous time proportional hazards model and complementary log–log specification.

Results: Of the 117 pre-FTC patients, 68 (58.1%) patients progressed to FTC during the 54-month follow-up period. Analysis of potential predictors showed that baseline cognitive state, impairment of activities of daily living (ADL) and neuropsychiatric symptoms were strong predictors of time to FTC. In addition, the rate of cognitive and ADL decline predicted time to FTC. The final model predicted 88.2% of observations.

Conclusion: The model simulates and predicts progression of pre-FTC AD patients until the need for FTC based on assessments for cognitive, functional and behavioural domains. The main application of the model is to assess the cost effectiveness of AD therapies as potential adjuncts to a background AD treatment including disease-modifying treatments. The applicability of the predictive model to a specific setting should be carefully assessed, i.e. the patient population being examined should have similar characteristics as patients in the LASER–AD cohort.     

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.     

Addressing shortfalls in TIA care in the UK: an economic perspective

Abstract

Objective: To estimate the clinical outcomes and costs associated with reconfiguring the management of TIA in the UK to offer patients rapid access to outpatient clinics for specialist assessment and treatment.

Methods: An economic deterministic model was run comparing two pathways – one arm representing current clinical care based on national guidelines and clinical practice and patient referral to a weekly outpatient clinic, and a revised care pathway replicating phase 2 of the EXPRESS study with patient referral to a daily outpatient clinic. The outcomes of the model were measured in terms of recurrent strokes avoided and net budget impact to secondary care.

Results: Reconfiguring TIA care pathways in the UK could result in the avoidance of 8,164 recurrent stroke events. The model predicts savings of £25,573,279 for the UK healthcare system over 12 months. Annual net savings are predicted in England (£24,916,011), Scotland (£80,554) and Northern Ireland (£1,041,817). In Wales, increased costs of £450,435 are estimated.

Limitations: Using the data published from the EXPRESS study, it is not possible to model a stepwise approach to implementing the revised TIA care pathway. It is therefore assumed that it would be possible to implement the revised TIA care pathway as detailed in the EXPRESS study across the UK and achieve the reduction in recurrent stroke risk that was reported.

Conclusions: The model suggests that the reconfiguration of TIA care pathways in the UK to offer rapid access to treatment and assessment could prevent TIA-related future stroke events and potentially result in cost savings to the healthcare system.     

Economic evaluation of a 100% whey-based partially hydrolyzed infant formula in the prevention of atopic dermatitis among Swiss children

Abstract

Objective:

A pharmacoeconomic analysis was undertaken to determine costs, consequences, and cost-effectiveness of a partially hydrolyzed 100% whey-based infant formula, NAN-HA®, manufactured by Nestlé S.A, Switzerland (PHF-W), branded under BEBA HA® in Switzerland, in the prevention of atopic dermatitis (AD) in ‘at risk’ Swiss children when compared to standard cow’s milk formula (SF).

Methods:

Based on a 12-month time horizon including 6 months of formula consumption, an economic model was developed synthesizing treatment pathways, resource utilization, and costs associated with the treatment of AD in healthy ‘at risk’ Swiss newborns who could not be exclusively breastfed. Model inputs were retrieved from the literature, official formularies, and expert opinion. The treatment pathways considered a medical treatment approach, supplemented in some instances by a change of formula. The final outcome was the expected cost per avoided case of AD, yielding an incremental cost effectiveness ratio (ICER) for PHF-W vs SF. Outcomes were presented from three perspectives: the Swiss public healthcare system (MOH), the subject’s family, and society (SOC). A secondary analysis compared PHF-W to whey-based extensively hydrolyzed formula (EHF) in prevention.

Results:

The model yielded 1653 avoided AD cases by selecting PHF-W over SF in a birth cohort of 22,933 ‘at risk’ infants. The base case analyses generated an expected ICER of CHF 982 from the MOH perspective as well as savings of CHF 2202 and CHF 1220 from the family and SOC perspectives, respectively. PHF-W yielded CHF 11.4M savings against EHF when the latter was assumed to be used in prevention. One-way and probabilistic sensitivity analyses confirmed the robustness of the model.

Conclusion:

Under a range of assumptions, this analysis has established the dominance from the family and societal perspectives and cost-effectiveness from the MOH perspective of PHF-W vs SF in the prevention of AD among ‘at risk’ Swiss infants.     

The economic impact of galantamine vs placebo: An analysis based on functional capacity in a Swedish cohort study

Abstract

Objective:

To analyse the economic impact of galantamine, based on basic activities of daily living (ADL).

Methods:

Data were derived from Swedish patients enrolled in a 6-month placebo-controlled trial of galantamine (GAL-INT-1; n?=?80), and from the Kungsholmen–Nordanstig Project, a longitudinal study of 919 elderly persons in Sweden. Basic ADL were assessed using the Katz’ Index of Independence in Activities of Daily Living (ADL) (number of ADL lost [dependency in 0, 1–2, 3–4, or 5–6 ADL]). Costs were appraised based on regression analysis and on costs directly linked to ADL. Six-month costs for galantamine and placebo were calculated.

Results:

In the regression analyses, each increase in a Katz stage was associated with an annual cost increase of SEK 81,415–83,683 (～€8000). Results were similar using stage-specific costs. Overall, there was a small, non-significant numerical cost benefit for galantamine indicating cost neutrality.

Limitations:

The small number of Swedish patients in the GAL-INT-1 study, which was not powered for economic outcomes, limits the statistical power of the analysis. In addition, long-term outcomes are difficult to assess in persons with dementia because of practical and logistical problems.

Conclusions:

The benefits of galantamine in patients with AD can be achieved with no increase in cost. Combined with positive effects in terms of outcome, treatment with galantamine can be regarded as cost-effective using a cost–consequence approach.     

Modelling the clinical and economic implications of galantamine in the treatment of mild-to-moderate Alzheimer's disease in Germany

Abstract

Objective:

This analysis was to assess the long-term clinical and economic implications of galantamine in the treatment of mild-to-moderate Alzheimer's disease (AD) in Germany.

Methods:

An economic model was developed using discrete event simulation to predict the course of AD through changes in cognition, behavioural disturbance, and function over time. It compares the costs and benefits of galantamine versus no-drug treatment and ginkgo biloba. Clinical data were mainly derived from analyses of pooled data from clinical trials. Epidemiological and cost data were obtained from literature and public data sources. Costs (2009 euros) from the perspective of the German Statutory Health Insurance were used.

Results:

The mean survival time for the model population is about 3.44 years over 10 years of simulation. Galantamine delays average time to severe stage of the disease by 3.57 and 3.36 months, compared to no-drug treatment and ginkgo biloba, respectively. Galantamine reduces time spent in an institution by 2.34 and 2.21 months versus no-drug treatment and ginkgo biloba, respectively. The use of galantamine is projected to yield net savings of €3,978 and €3,972 per patient versus no-drug and ginkgo biloba treatments. These results, however, may be limited by lack of long-term comparative efficacy data as well as data on long-term care costs based on multiple outcome measures.

Conclusion:

Compared to no-drug treatment and ginkgo biloba, galantamine therapy provides clinical benefits and achieves savings in healthcare costs associated with care for patients with mild-to-moderate AD in Germany.     

Choice of angiotensin receptor blocker in moderate hypertension. A UK-based cost–benefit comparison of olmesartan- and candesartan-based regimens

Abstract

Introduction:

Selection of antihypertensive therapy hinges on an appropriate combination of efficacy, tolerability and compatibility with co-morbidities. Within a given class of antihypertensives, the choice of agent is often driven by cost, with the cheapest appropriate agent being chosen. Amongst the angiotensin receptor blockers (ARBs), this choice will often be losartan, as it is available in generic form. However, as the blood pressure lowering efficacy of losartan is modest, some patients will require an alternative ARB. In the UK this choice is often candesartan, although the agent with greatest BP lowering efficacy is olmesartan. The objective of this study was to use a cost-benefit model to compare the costs associated with target achievement using each of these two agents, in order to guide optimum use of prescribing budgets.

Method:

A probabilistic cost-benefit model was constructed for a cohort of patients with moderate hypertension, based on a standardised titration and maintenance algorithm using either olmesartan or candesartan, combined with thiazide and calcium channel blocker where required. Direct treatment costs were recorded, along with the proportion of patients achieving pre-defined treatment targets at each treatment level. Results were expressed as mean treatment cost per patient reaching target.

Results:

Based on the current QoF target of 150?mmHg systolic, 94.3% of patients on the olmesartan-based regimen reached target of 150?mmHg, compared with 89.0% of those on the candesartan-based regimen. 86% of olmesartan patients reached target on <3 drugs, compared with 74% of candesartan patients. The mean 12-month cost per patient reaching target was £171.36 for olmesartan versus £189.91 for candesartan. Ongoing annual maintenance costs for patients at target were £169.97 and £182.64, respectively. Similar results were obtained when considering alternative treatment targets

Limitations:

The study only compared two ARBs – candesartan and olmesartan and the results relate to prescribing costs only and do not include other healthcare costs. Additionally, the chosen outcome was blood pressure target achievement, rather than clinical endpoints. Given the stated objectives of the model, we do not believe these issues will have introduced bias in the direction of either comparator

Conclusion:

Although olmesartan has an apparently higher acquisition cost than candesartan, its superior BP lowering efficacy means that the overall cost per patient treated to target is actually lower. This result could have significant implications for making savings within primary care prescribing budgets in the UK.     

A cost-effectiveness analysis of levodopa/carbidopa intestinal gel compared to standard care in late stage Parkinson’s disease in the UK

Abstract

Objective:

Evaluation of cost-effectiveness of levodopa/carbidopa intestinal gel (LCIG), compared to standard care (SC) in patients with advanced Parkinson’s disease (aPD) in the UK.

Design:

Markov model to quantify costs and outcomes associated with LCIG versus SC in aPD patients at Hoehn and Yahr (H&Y) stages 3, 4 or 5 experiencing >50% OFF time per day. Time horizon was lifetime, LCIG treatment was assumed to last maximal 5 years after which patients revert to SC. Model comprised 12 aPD health states according to H&Y status and daily time spent in OFF state. Cost analyses are reported from a UK NHS and Personal Social Services perspective. Uncertainties were assessed through one-way sensitivity analyses.

Comparators:

LCIG, providing patients with continuous dopaminergic stimulation to maximise functional ON time during the day and SC, defined as medically determined best available oral medication.

Main outcome measures:

Cost-effectiveness, based on quality adjusted life years gained, presented as an incremental cost-effectiveness ratio.

Results:

Lifetime analysis yields an incremental cost per QALY of £36,024 for LCIG compared to SC (incremental cost £39,644, QALY gain 1.1). Results were sensitive to time on treatment, health state on treatment initiation, and estimates of long term benefit (OWSA results from £32,127 to £66,421 per QALY). Findings must be considered in the context of the study limitations which were mainly due to data availability constraints.

Conclusions:

LCIG is an effective treatment, reducing OFF time and improving quality of life in advanced PD. It provides value for money in levodopa-responsive aPD patients with severe motor fluctuations when no other treatment options are effective or suitable. Given LCIG is an orphan drug, it is reasonable to suggest that it may be considered cost-effective in the UK setting. However, further research is needed to complete current data gaps and increase robustness of the model.     

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.     

Economic evaluation of a 100% whey-based partially hydrolyzed infant formula in the prevention of atopic dermatitis among Danish children

Abstract

Objective:

A pharmacoeconomic analysis was undertaken to determine costs, consequences, and cost-effectiveness of a brand of partially hydrolyzed 100%-whey formula manufactured by Nestlé (PHF-W), in the prevention of atopic dermatitis (AD) in ‘at risk’ Danish children compared to extensively hydrolyzed formula (EHF-Whey or Casein).

Methods:

Given the non-significant differences between PHF-W and EHF, the base case analytic approach amounted to a cost-minimization analysis (CMA) reporting the difference in formula acquisition costs over the period of formula consumption for the population of interest. However, sensitivity analyses (SAs) were undertaken to explore applying the nominal efficacy of PHF-W and EHF, thus leading to a cost-effectiveness analysis (CEA). Hence, an economic model based on a 12-month time horizon was developed synthesizing treatment pathways, resource utilization, and costs associated with the treatment of AD in the population of interest. The final economic outcome of the SAs was the incremental cost per avoided case (ICER) defined as the expected cost per avoided case of AD for PHF-W vs EHF, determined from three perspectives: the Ministry of Health (MOH), the family of the subject, and society (SOC).

Results:

In the base case CMA, savings of DKK 9?M, DKK 20?M, and DKK 29?M were generated for PHF-W vs EHF from the MOH, family, and SOC perspectives. In the sensitivity CEA, PHF-W was dominant over EHF-Whey from all perspectives, while EHF-Casein displayed against PHF-W unattractive ICERs of DKK 315,930, DKK 408,407, and DKK 724,337 from the MOH, family, and SOC perspectives. Probabilistic SAs indicated that PHF-W was 86% likely to be dominant over EHF-Whey, whereas EHF-Casein had no likelihood of dominating PHF-W.

Conclusion:

Under a range of assumptions, this analysis demonstrated the attractiveness of PHF-W vs both types of EHF in the prevention of AD among ‘at risk’ Danish infants who are not or cannot be exclusively breastfed.     

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

Abstract

Objectives:

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

Methods:

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

Results:

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

Limitations:

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

Conclusions:

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

Cost of illness associated with Niemann-Pick disease type C in the UK

Abstract

Objective: Niemann-Pick disease type C (NP-C) is a rare and devastating genetic disorder characterised by a range of progressive neurological symptoms, which imposes a burden on patients, family members, the healthcare system and society overall. The objective of this study was to assess direct and indirect costs associated with NP-C in the UK.

Methods: This was a non-interventional, retrospective, cross-sectional cohort study based on responses from patients and/or their carers/guardians recruited from a UK NP-C database. Resource use and direct medical, direct non-medical and indirect costs were evaluated using data collected via postal survey in October 2007, which included a Medical Resource Use questionnaire. Total annual costs per patient were estimated.

Results: In total, 18 Medical Resource Use questionnaires (29% response rate) were received and analysed. The mean total annual cost (SD) of NP-C per patient was £39,168 (£50,315); 46% were direct medical costs, to which home visits and residential care contributed 68% and 15%, respectively. Direct non-medical costs accounted for 24% of the average annual cost per patient, mainly due to specialist education, and indirect costs 30%. If only direct medical costs were considered, the mean annual cost (SD) per patient was reduced to £18,012 (£46,536).

Conclusions: The direct annual per-patient cost of NP-C illness in 2007 appears moderate when compared with other rare and severely disabling diseases. However, cost estimates may be conservative, since findings are limited by a small sample size, low survey response rate and potential recall bias. As demonstrated by this study, a substantial proportion of the cost is shifted from the healthcare system to the patient, family and non-medical providers. These findings highlight the need for treatments that can slow or stop disease progression in NP-C.     

An assessment of the cost of percutaneous pulmonary valve implantation (PPVI) versus surgical pulmonary valve replacement (PVR) in patients with right ventricular outflow tract dysfunction

Abstract

Background:

Percutaneous pulmonary valve implantation (PPVI) using the Melody transcatheter pulmonary valve is a new procedure introduced in 2000 as a less invasive treatment for right ventricular outflow tract (RVOT) dysfunction. The aim of this new procedure is to restore pulmonary valve competence without the need of open-chest operation. By prolonging the conduit lifespan, it delays surgical pulmonary valve replacement (PVR) and it can therefore potentially reduce the number of open-chest interventions over a patient’s lifetime. PPVI has been shown to be feasible and safe and can be performed with a low complication rate.

Objectives and Methods:

The aim of this study is to assess the cost of PPVI and the cost of surgical pulmonary valve replacement (PVR) in patients with right ventricular outflow tract dysfunction using a cohort simulation model applied to the UK population.

Results:

The model resulted in an estimate of mean cost per patient of £5,791 when PPVI is unavailable as a treatment option and in an estimate of mean cost per patient of £8,734 when PPVI is available over the 25-year period of analysis. After sensitivity analysis was undertaken the results showed that the mean per patient cost difference in implementing PPVI over 25 years as compared to surgical PVR lies somewhere between £2,041 and £3,913.

Limitations:

Given the lack of long-term data on treatment progression, the cost estimates derived here are subject to considerable uncertainty, and extensive sensitivity analysis has been used to counter this. Consequently this study is merely indicative of the levels of cost which can be expected in a cohort of 1,000 patients faced with a choice of treatment with PPVI or surgery. It is not a cost-effectiveness study but it helps place current knowledge on short-term benefits into context.

Conclusions:

As this analysis shows PPVI is associated with a relatively small increase in treatment management costs over a long time period. It is left entirely to the reader to value whether this inferred increase in long-term cost is worthwhile given the known short-term benefits and any personal judgement formed over long-term benefit.     

Cost effectiveness of deferasirox compared to desferrioxamine in the treatment of iron overload in lower-risk,transfusion-dependent myelodysplastic syndrome patients

Abstract

Objective:

The study evaluated the cost effectiveness of deferasirox (Exjade) compared to non-proprietary desferrioxamine (DFO) for the control of transfusional iron overload in lower risk myelodysplastic syndromes (MDS) patients. A UK National Health Service perspective was adopted.

Methods:

Recent clinical evidence has demonstrated the efficacy and safety of deferasirox in transfusion-dependent MDS patients with elevated serum ferritin levels. An economic model was used to extrapolate the clinical benefits of iron chelation therapy (ICT) in a cohort of lower risk MDS patients. Costs for drug acquisition, drug administration and monitoring, and quality of life (utility) outcomes associated with mode of drug administration were derived from a variety of sources. The incremental cost per QALY gained for deferasirox was estimated. Costs and outcomes were discounted at 3.5% in line with UK standards.

Results:

The base-case cost effectiveness of deferasirox versus DFO was estimated to be £20,822 per QALY gained, the key driver being the additional quality of life benefits associated with a simpler mode of administration for deferasirox. A mean survival benefit for both forms of ICT of 4.5 years was estimated. The results were sensitive to drug dose, days of DFO administration, and patient weight.

Conclusions:

In the UK, a cost per QALY below £20,000–30,000 is considered cost effective. Hence, the results from this economic analysis suggest deferasirox is cost effective in lower risk, transfusion-dependent, MDS patients. Limitations with the analysis include a lack of comparative randomised controlled trial evidence, in particular to differentiate survival and clinical outcomes for deferasirox and DFO.     

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.     

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

Abstract

Background:

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

Methods:

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

Results:

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

Limitations:

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

Conclusions:

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

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.     

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.     

Cost effectiveness of teriparatide and PTH(1-84) in the treatment of postmenopausal osteoporosis

Abstract

Objectives:

The purpose was to assess the cost effectiveness from a societal perspective of the recombinant human parathyroid hormones: PTH(1-34) (teriparatide) and PTH(1-84) for patients with osteoporosis with similar characteristics to patients treated in normal clinical practice in Sweden.

Methods:

A Markov model of osteoporosis in postmenopausal women was developed using 6-month cycles and a lifetime horizon. The model was populated with patients similar to the Swedish cohort of the European Forsteo Observational Study (postmenopausal women; mean age: 70 years, total hip T-score: ?2.7 and 3.3 previous fractures). The cost effectiveness of both teriparatide and PTH(1-84) was estimated compared to no treatment and each other. Relative effectiveness assumptions were based on efficacy estimates from two phase III clinical trials.

Results:

The cost per QALY gained of teriparatide vs. no treatment was estimated at €43,473 and PTH(1-84) was estimated at €104,396. Teriparatide was indicated to be less costly and associated with more life-years and QALYs than PTH(1-84). When assuming no treatment effect on hip fractures the cost per QALY gained was €88,379. In the sensitivity analysis the cost effectiveness did not alter substantially with changes in the majority of the model parameters except for the residual effect of the treatment after stopping therapy.

Conclusions:

Based on the efficacy estimates from pivotal clinical trials and characteristics of patients treated in clinical practice in Sweden, teriparatide seems to be a more cost-effective option than PTH(1-84) when compared to no treatment. The relative efficacy between the two PTH compounds was based on an indirect comparison from two separate clinical trials which has to be considered when interpreting the results.