A UK analysis of the cost of switching renal transplant patients from an immediate-release to a prolonged-release formulation of tacrolimus based on differences in trough concentration variability

Background and aims:

Randomized controlled trials have shown that a once-daily prolonged-release (PR) tacrolimus formulation (PR tacrolimus; Advagraf), is non-inferior to a twice-daily immediate-release (IR) tacrolimus formulation (IR tacrolimus; Prograf) in terms of biopsy-proven acute rejection, graft failure and mortality in renal transplant recipients. However, relative to IR tacrolimus, PR tacrolimus exhibits reduced tacrolimus trough concentration variability, which has been associated with reduced graft failure. Based on these data, the present study evaluated the cost of switching UK renal transplant patients from IR tacrolimus to PR tacrolimus.

Methods:

UK-specific data on acute rejection, graft failure, and mortality were used to construct a budget impact model to assess the costs of switching from IR tacrolimus to PR tacrolimus on a 1:1?mg:mg basis. The model assumed that 3.1% of patients on PR tacrolimus had high tacrolimus trough concentration variability compared with 17.4% on IR tacrolimus, based on a study comparing PR tacrolimus and IR tacrolimus pharmacokinetics. A relative graft failure risk of 2.38 was applied to high variability patients based on data from a tacrolimus variability study in which 10/148 patients with low variability experienced graft failure, compared with 24/149 in the high variability group. Cost data were taken from the British National Formulary and 2012–2013 NHS tariff information.

Results:

The mean per-patient cost (including tacrolimus, concomitant immunosuppressive medications, dialysis after graft failure, and treatment for acute rejection) was GBP 26,941 (standard deviation [SD]?=?GBP 2765) with PR tacrolimus vs GBP 30,356 (SD?=?GBP 3085) for IR tacrolimus over a 5-year period, corresponding to a saving of GBP 3415 (SD?=?GBP 516) per patient or GBP 341,500 in a hypothetical 100-patient transplant center. Cost savings were driven primarily by lower dialysis costs resulting from the lower proportion of PR tacrolimus patients with high tacrolimus trough concentration variability (leading to lower graft failure risk).

Limitations:

The main limitation of the study was the use of heterogeneous data sources to capture the effect of within-patient variability on graft failure. The most important difference between the studies was the definition of the threshold between low and high within-patient variability. This was explored in sensitivity analyses in which the inter-arm difference in the inter-arm proportions of patients with high and low variability was abolished.

Conclusions:

Converting UK renal transplant recipients from IR tacrolimus to PR tacrolimus was associated with lower pharmacy and dialysis costs.     

Evaluating the economic implications of non-adherence and antibody-mediated rejection in renal transplant recipients: the role of once-daily tacrolimus in the UK

Abstract

Background and aims:

While short-term kidney graft survival has gradually improved over time, improvements in long-term graft survival have been more modest. One key clinical factor limiting improved longer-term outcomes is antibody-mediated rejection (AbMR), the incidence of which appears to be higher in patients who are non-adherent to immunosuppressants. Recent data show that adherence can be improved by reducing pill burden. The aim of the present study was to model the incidence and economic consequences of graft loss and AbMR in patients taking once- vs twice-daily tacrolimus in the UK.     

A cost-utility analysis of adjunctive treatment with newer antiepileptic drugs in the UK

Summary

A recent review found that economic assessment of epilepsy treatment relies largely on hypothetical modelling of outcomes and combining these with resource and cost data from different sources. Prospective evaluations combining cost studies with outcome assessments are lacking. However, such a prospective observational study has been carried out previously, but only partially reported. We present a comprehensive cost-utility analysis of adjunctive newer antiepileptic drugs (AEDs) based on observational data from that study, and assess the uncertainty of the results using bootstrapping.

A total of 125 patients with intractable epilepsy were recruited. Each patient was about to start treatment with a new adjunctive AED [clobazam, (non-proprietary) gabapentin (Neurontin®, Parke-Davis, UK), lamotrigine (Lamictal®, GlaxoSmithKline, UK), topiramate (Topamax®, Janssen-Cilag, UK), or vigabatrin (Sabril®, Aventis Pharma, UK)]. Patients completed semi-structured interviews on resource use, side effects, and the EuroQol EQ-5D. Patients were followed up for 6 months. Patient-specific cost and utility data were analysed separately for each AED on an intent-to-treat basis. Uncertainty in the estimated incremental cost-utility ratios was quantified using the non-parametric bootstrap method, and cost-effectiveness acceptability curves were calculated.

At 6 months, 78 patients were still on their prescribed drug. Only topiramate and vigabatrin patients showed an increase in EQ-5D scores, and therefore dominated

other AEDs. Topiramate had an incremental cost-effectiveness ratio of £7,869/QALY compared with vigabatrin, and had more than a 50% chance of being optimal if the ceiling ratio was above £10,000/QALY.

Observational studies provide a valuable source of information for the economic evaluation of AEDs. In this study non-parametric bootstrapping was used to confirm the cost-effectiveness of adjunctive topiramate for patients with refractory epilepsy.     

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.     

A discrete event simulation to model the cost-utility of fingolimod and natalizumab in rapidly evolving severe relapsing-remitting multiple sclerosis in the UK

Objective: Two disease-modifying therapies are licensed in the EU for use in rapidly-evolving severe (RES) relapsing-remitting multiple sclerosis (RRMS), fingolimod and natalizumab. Here a discrete event simulation (DES) model to analyze the cost-effectiveness of natalizumab and fingolimod in the RES population, from the perspective of the National Health Service (NHS) in the UK, is reported.

Methods: A DES model was developed to track individual RES patients, based on Expanded Disability Status Scale scores. Individual patient characteristics were taken from the RES sub-groups of the pivotal trials for fingolimod. Utility data were in line with previous models. Published costs were inflated to NHS cost year 2015. Owing to the confidential patient access scheme (PAS) discount applied to fingolimod in the UK, a range of discount levels were applied to the fingolimod list price, to capture the likelihood of natalizumab being cost-effective in a real-world setting.

Results: At the lower National Institute of Health and Care Excellence (NICE) threshold of £20,000/quality-adjusted life year (QALY), fingolimod only required a discount greater than 0.8% of list price to be cost-effective. At the upper threshold of £30,000/QALY employed by the NICE, fingolimod was cost-effective if the confidential discount is greater than 2.5%. Sensitivity analyses conducted using fingolimod list-price showed the model to be most sensitive to changes in the cost of each drug, particularly fingolimod.

Conclusions: The DES model shows that only a modest discount to the UK fingolimod list-price is required to make fingolimod a more cost-effective option than natalizumab in RES RRMS.     

A global economic model to assess the cost-effectiveness of new treatments for advanced breast cancer in Canada

Objective Considering the increasing number of treatment options for metastatic breast cancer (MBC), it is important to develop high-quality methods to assess the cost-effectiveness of new anti-cancer drugs. This study aims to develop a global economic model that could be used as a benchmark for the economic evaluation of new therapies for MBC.

Methods The Global Pharmacoeconomics of Metastatic Breast Cancer (GPMBC) model is a Markov model that was constructed to estimate the incremental cost per quality-adjusted life years (QALY) of new treatments for MBC from a Canadian healthcare system perspective over a lifetime horizon. Specific parameters included in the model are cost of drug treatment, survival outcomes, and incidence of treatment-related adverse events (AEs). Global parameters are patient characteristics, health states utilities, disutilities, and costs associated with treatment-related AEs, as well as costs associated with drug administration, medical follow-up, and end-of-life care. The GPMBC model was tested and validated in a specific context, by assessing the cost-effectiveness of lapatinib plus letrozole compared with other widely used first-line therapies for post-menopausal women with hormone receptor-positive (HR+) and epidermal growth factor receptor 2-positive (HER2+) MBC.

Results When tested, the GPMBC model led to incremental cost-utility ratios of CA$131 811 per QALY, CA$56 211 per QALY, and CA$102 477 per QALY for the comparison of lapatinib plus letrozole vs letrozole alone, trastuzumab plus anastrozole, and anastrozole alone, respectively. Results of the model testing were quite similar to those obtained by Delea et al., who also assessed the cost-effectiveness of lapatinib in combination with letrozole in HR+/HER2?+?MBC in Canada, thus suggesting that the GPMBC model can replicate results of well-conducted economic evaluations.

Conclusions The GPMBC model can be very valuable as it allows a quick and valid assessment of the cost-effectiveness of any new treatments for MBC in a Canadian context.     

Round the Houses: Homeownership and Failures of Asset-Based Welfare in the United Kingdom

This article explores the contingencies of financialisation and housing. More specifically, how the spatial and temporal dynamics of the UK housing market ensure that homeownership does not (and arguably cannot) deliver welfare provision in the way envisioned by asset-based welfare initiatives. The first section demonstrates the fundamental problem of conceptualising households as asset-holders; in particular, with regard to housing-based welfare strategies and as part of financialised growth strategies in the UK, more generally. We show that continuing to assume residential housing is a static and unchanging asset-class depoliticises how asset-based welfare intensifies household indebtedness. The second section demonstrates the temporal, spatial and social limits of homeownership in the UK. We argue that the financialisation of housing in the UK is a unique set of political and economic circumstances that cannot be repeated; therefore, current gains from residential housing are a one-off wealth windfall to particular (lucky) groups within society. The temporal and spatial limits of gains from residential housing mean that the same conditions cannot be repeated (often enough) in the way required for residential housing to provide a generalisable welfare function. Finally, the article concludes by suggesting the potential of new research that incorporates temporal, spatial and social contingencies of housing to demonstrate how financialisation materialises in everyday life.     

A prospective analysis of labour market status and self-rated health in the UK and Russia

Comparing prospective data from the UK and Russia, this paper analyzes whether the association of labour market status, and particularly unemployment, with subsequent health varies by the level of state protection provided to the unemployed. While the UK's unemployment welfare regime is classified as providing minimal protection, the Russian regime is sub-protective. Employing Cox duration analysis upon data from the Russian Longitudinal Monitoring Survey and the British Household Panel Survey for the period 2000–2007, this study finds that labour market status and economic circumstances independently predicted individual-level declines in self-rated health and, contrary to expectations, the associations of unemployment with health decline were similarly sized in the two countries.     

The behaviour of relative prices in the European Union: A sectoral analysis

Using multivariate unit root test methods, this paper investigates the Purchasing Power Parity (PPP) hypothesis at the sectoral level across six European countries over the last 17 years. Evidence of mean reversion towards PPP is found for the relative prices of some sectors and countries. Mean reversion in relative prices is explained by cross-country and cross-sectoral characteristics such as the distance between countries, nominal exchange rate volatility, differences in GDP per capita, non-tariff barriers, research and development, advertising, industrial concentration and tradeability of the products.     

Macroeconomic impacts of fiscal policy shocks in the UK: A DSGE analysis

This paper develops and estimates a new-Keynesian dynamic stochastic general equilibrium (DSGE) model for the analysis of fiscal policy in the UK. We find that government consumption and investment yield the highest GDP multipliers in the short-run, whereas capital income tax and public investment have dominating effect on GDP in the long-run. When nominal interest rate is at the zero lower bound, consumption taxes and public consumption and investment are found to be the most effective fiscal instruments throughout the analysed horizon, and capital and labour income taxes are established to be the least effective. The paper also shows that the effectiveness of fiscal policy decreases in a small open-economy scenario and that nominal rigidities improve effectiveness of public spending and consumption taxes, whereas decrease that of income taxes.     

A cost-benefit analysis of the random assignment UK Employment Retention and Advancement Demonstration

This article presents a cost-benefit analysis of Britain’s Employment Retention and Advancement (ERA) demonstration, which was evaluated through the first large-scale randomized control trial in the UK. ERA used a combination of job coaching and financial incentives in attempting to help long-term unemployed men and low-income lone parents sustain employment and progress in work once they were employed. Using both administrative and survey data, ERA’s effects on benefits and costs were estimated through impact analyses, which exploited the experimental design. The findings indicated that ERA was cost beneficial for long-term unemployed adult men, but not for lone parents. The key findings appear robust to sensitivity tests. Uncertainty, as implied by the SEs of the estimated impacts, was addressed through a Monte Carlo analysis, an approach seldom previously used in cost-benefit analyses of social programs.     

A multi-level analysis of sustainable mobility transitions: Niche development in the UK and Sweden

A wide range of intractable problems such as polluting emissions, noise, accidents, resource depletion, and inaccessibility of amenities are associated with the current transport regime. Given the slow movement towards a more sustainable mobility system, more radical, systemic innovation - a ‘transition’ - is required. Broadly speaking, this may be achieved via three routes: technological change, modal shift, and reduced travel demand. Drawing on concepts from the transitions literature (e.g., [Geels, F.W.: Technological Transitions and System Innovations: A Co-evolutionary and Socio-Technical Analysis, Edward Elgar, Cheltenham, 2005.]), we conceptualise each of these routes as a bundle of niche activities within an Area of Innovation, deviating to differing degrees from the current mobility ‘regime’. We present empirical evidence and indications of ongoing development of niches in these three areas within the UK and Sweden, and explore processes of co-evolution, divergence and tension within and between niches. Findings indicate recent market penetration of novel transport technologies, more advanced than modal shift or demand management activities; however, different transport technologies are more successful in each country. We also identify examples of a close relationship between development of radical vehicle/fuel technologies and provision of mobility services; and information technology as a driver in all three areas of innovation. We conclude that future innovation in transport depends on diversity, hybridisation, and co-evolution of niches. Finally, policy implications are discussed.     

A cost-utility study of the use of pregabalin added to usual care in refractory neuropathic pain patients in a Swedish setting

Abstract

Objectives:

Patients refractory to older therapies for neuropathic pain (NeP) have few remaining therapeutic options. This study evaluates the cost-utility of pregabalin in the treatment of patients with refractory neuropathic pain in Sweden, from a healthcare and a societal perspective.

Study limitations:

The use of non-randomized (observational) data to determine the effectiveness of treatments for NeP. The use of non-Swedish data for some input parameters in the model.

Methods:

A previously constructed discrete event simulation model was adapted to compare pregabalin combined with usual care to usual care alone in a Swedish setting. Pain profiles were generated using clinical data from five non-randomized pregabalin studies in refractory NeP patients. Utility data were generated from a UK survey of patients with NeP. Cost data were generated from the Swedish Dental and Pharmaceutical Benefits Board (TLV’s) product price database, a national NeP register, and a regional registry study. Indirect costs were estimated from published sources. One-way and probabilistic sensitivity analyses evaluated uncertainty in the model’s output.

Results:

The incremental cost-effectiveness ratio (ICER) for pregabalin plus usual care treatment compared to usual care was 51,616 SEK/€5364 and 123,993 SEK/€12,886 with and without indirect costs, respectively. One-way sensitivity analyses confirmed the clinical input data as the main driver of the model; even considerable changes to all other input parameters had only a modest effect on the ICER. The ICER remained well below a conservative threshold of 347,495 SEK /€36,113/£30,000 in all scenarios modelled.

Conclusions:

This study found pregabalin combined with usual care to be cost-effective compared to usual care in patients with refractory NeP from a Swedish Health Care perspective. Moreover, sensitivity analysis showed pregabalin’s cost-effectiveness to be robust in all scenarios modelled.     

A Canadian cost-effectiveness analysis of transcatheter mitral valve repair with the MitraClip system in high surgical risk patients with significant mitral regurgitation

Objective:

In patients with significant mitral regurgitation (MR) at high risk of mortality and morbidity from mitral valve surgery, transcatheter mitral valve repair with the MitraClip System is associated with a reduction in MR and improved quality-of-life and functional status compared with baseline. The objective was to evaluate the cost-effectiveness of MitraClip therapy compared with standard of care in patients with significant MR at high risk for mitral valve surgery from a Canadian payer perspective.

Methods:

A decision analytic model was developed to estimate the lifetime costs, life years, quality-adjusted life years (QALYs), and incremental cost per life year and QALY gained for patients receiving MitraClip therapy compared with standard of care. Treatment-specific overall survival, risk of clinical events, quality-of-life, and resource utilization were obtained from the Endovascular Valve Edge-to-Edge REpair High Risk Study (EVEREST II HRS). Health utility and unit costs (CAD $2013) were taken from the published literature. Sensitivity analyses were conducted to explore the impact of alternative assumptions and parameter uncertainty on results.

Results:

The base case incremental cost per QALY gained was $23,433. Results were most sensitive to alternative assumptions regarding overall survival, time horizon, and risk of hospitalization for congestive heart failure (CHF). Probabilistic sensitivity analysis showed MitraClip therapy to have a 92% chance of being cost-effective compared with standard of care at a willingness-to-pay threshold of $50,000 per QALY gained.

Study limitations:

Key limitations include the small number of patients included in the EVEREST II HRS which informed the analysis, the limited data available to inform clinical events and disease progression in the concurrent comparator group, and the lack of a comparator group from a randomized control trial.

Conclusion:

MitraClip therapy is likely a cost-effective option for the treatment of patients at high risk for mitral valve surgery with significant MR.     

美英公益企业发展的比较研究及其思考

本文从定义、历史背景、支撑环境三方面对美英公益企业的产生和发展进行了比较,指出由于路径依赖,美英公益企业演化的历史存在较大差异,即美国公益企业的发展主要受社会团体力量的驱动,而英国公益企业的发展主要受政府的推动。对中国公益企业的发展而言,采取政府主导和社会团体协助相结合的举措是比较可行的促进策略。     

A regional analysis of flows into and out of the UK national minimum wage

This article utilizes the panel element of the UK Labour Force Survey (LFS) to identify for individual regions total inflows and outflows and hazards for those individuals paid at or below the National Minimum Wage (NMW). In particular, it examines the extent and direction of the correlation between low-pay inflows and outflows and the economic cycle. Further, it examines the impact of regional variations in the bite of the NMW on regional flows into and out of the NMW.     

A real-world analysis of healthcare costs and relative risk of hyperprolactinemia associated with antipsychotic treatments in the United States

Abstract

Aims: Antipsychotic medications are associated with an increased risk of hyperprolactinemia, but differ in their propensity to cause this complication. This study aimed to assess the economic burden of hyperprolactinemia, and to compare its risk among adult patients using atypical antipsychotics (AAs) with a mechanism of action associated with no/low vs high/moderate prolactin elevation.

Methods: This retrospective cohort study was based on US Commercial and Medicaid claims databases. Healthcare costs were compared between matched hyperprolactinemia and hyperprolactinemia-free cohorts using a two-part model. Risk of hyperprolactinemia was compared between patients receiving AAs with a mechanism of action associated with no/low (no/low prolactin elevation cohort) vs high/moderate prolactin elevation (high/moderate prolactin cohort) using logistic regression.

Results: In the commercially insured sample, compared to the hyperprolactinemia-free cohort (n?=?499), the hyperprolactinemia cohort (n?=?499) was associated with incremental total healthcare costs of $5,732 ($20,081 vs $14,349; p?=?.004), and incremental medical costs of $3,861 ($13,218 vs $9,357; p?=?.040), mainly driven by hyperprolactinemia-related costs. In the Medicaid-insured sample, compared to the hyperprolactinemia-free cohort, the hyperprolactinemia cohort was associated with incremental total healthcare costs of $10,773 ($30,763 vs $19,990; p?=?.004), and incremental medical costs of $9,246 ($20,859 vs $11,613; p?=?.004), mainly driven by hyperprolactinemia-related and mental health-related costs. The odds of hyperprolactinemia in the no/low prolactin elevation cohort were 4–5-times lower than that in the high/moderate prolactin elevation cohort (odds ratio =0.21; p?<?.001).

Limitations: Hyperprolactinemia may be under-reported in claims data.

Conclusions: Hyperprolactinemia is associated with substantial healthcare costs. AAs associated with no/low prolactin elevation reduce the risk of hyperprolactinemia by 4–5-times compared to AAs associated with moderate/high prolactin elevation. Treatment options with minimal impact on prolactin levels may contribute to reducing hyperprolactinemia burden in AA-treated patients.     

A cost analysis of the management of attention-deficit/hyperactivity disorder (ADHD) in children in the UK

SUMMARY

A decision analysis was performed to model the effects and health economic differences of current UK management approaches to attention-deficit/hyperactivity disorder (ADHD) in children aged between 6 and 16 years. The approaches modelled were: medication using a standard immediate-release methylphenidate (MPH-IR) (once, twice or three times daily); medication using CONCERTA®XL (OROS®* methylphenidate; MPH), a long-acting once-daily formulation of methylphenidate; or behavioural therapy (BEH). Starting treatment with BEH alone resulted in the highest annual cost (UK£2,147), while the costs of starting treatment with MPH-IR alone (£1,332), or OROS®* MPH alone (£1,362) were comparable. Treatment switches to behavioural treatment or combined treatment (medication and behavioural) due to treatment failure occurred in 11.8% of OROS®* MPH and 24.2% of MPH-IR patients. Probabilistic sensitivity analyses showed that the results were sensitive towards treatment success and the proportion of patients with comorbidities, although conclusions were not altered. UK treatment costs over 1 year appear comparable regardless of whether patients were treated first with OROS®* MPH or MPH-IR. Treating patients first with BEH and then adding stimulant medication if needed resulted in higher overall annual treatment costs.

CONCERTA® XL and OROS® are trademarks of ALZA Corporation, USA.