Alejandra Duenas

Multiple Criteria Decision Analysis for Health Technology Assessment

OBJECTIVES Multicriteria decision analysis (MCDA) has been suggested by some researchers as a method to capture the benefits beyond quality adjusted life-years in a transparent and consistent manner. The objectives of this article were to analyze the possible application of MCDA approaches in health technology assessment and to describe their relative advantages and disadvantages. METHODS This article begins with an introduction to the most common types of MCDA models and a critical review of state-of-the-art methods for incorporating multiple criteria in health technology assessment. An overview of MCDA is provided and is compared against the current UK National Institute for Health and Clinical Excellence health technology appraisal process. A generic MCDA modeling approach is described, and the different MCDA modeling approaches are applied to a hypothetical case study. RESULTS A comparison of the different MCDA approaches is provided, and the generic issues that need consideration before the application of MCDA in health technology assessment are examined. CONCLUSIONS There are general practical issues that might arise from using an MCDA approach, and it is suggested that appropriate care be taken to ensure the success of MCDA techniques in the appraisal process.

Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials

Objectives.  To study the evidence on the efficacy and safety of ezetimibe monotherapy for the treatment of primary (heterozygous familial and non‐familial) hypercholesterolaemia.

Factors associated with outcomes for looked-after children and young people: a correlates review of the literature.

In 2008, the Department of Health made a referral to the National Institute for Health and Clinical Excellence and the Social Care Institute for Excellence to develop joint public health guidance on improving the physical and emotional health and well-being of children and young people looked after by the local authority/state. To help inform the decision-making process by identifying potential research questions pertinent to the outcomes of looked-after children and young people (LACYP), a correlates review was undertaken. Iterative searches of health and social science databases were undertaken; searches of reference lists and citation searches were conducted and all included studies were critically appraised. The correlates review is a mapping review conducted using systematic and transparent methodology. Interventions and factors that are associated (or correlated) with outcomes for LACYP were identified and presented as conceptual maps. This review maps the breadth (rather than depth) of the evidence and represents an attempt to use the existing evidence base to map associations between potential risk factors, protective factors, interventions and outcomes for LACYP. Ninety-two studies were included: four systematic reviews, five non-systematic reviews, eight randomized controlled trials, 66 cohort studies and nine cross-sectional studies. The conceptual maps provide an overview of the key relationships addressed in the current literature, in particular, placement stability and emotional and behavioural factors in mediating outcomes. From the maps, there appear to be some key factors that are associated with a range of outcomes, in particular, number of placements, behavioural problems and age at first placement. Placement stability seems to be a key mediator of directional associations. The correlates review identified key areas where sufficient evidence to conduct a systematic review might exist. These were: transition support, training and support for carers and access to services.

The effectiveness of training and support for carers and other professionals on the physical and emotional health and well-being of looked-after children and young people: a systematic review

Looked-after children and young people (LACYP) are recognized as a high-risk group for behavioural and emotional problems, and additional specialist training for foster carers may reduce such problems. This systematic review aimed to identify and synthesize evidence on the effectiveness of additional training and support provided to approved carers, professionals and volunteers on the physical and emotional health and well-being of LACYP (including problem behaviours and placement stability). Searches of health and social science databases were conducted and records were screened for inclusion criteria. Citation and reference list searches were conducted on included studies. Included studies were synthesized and critically appraised. Six studies were included (five randomized controlled trials and one prospective cohort study), all of which focused on foster carers. Three studies reported a benefit of training and three reported no benefit but no detriment. Those reporting a benefit of training were conducted in the USA, and had longer-duration training, shorter follow-up assessment and recruited carers of younger children than studies that reported no benefit of training, which were conducted in the UK. Whether the difference in results is due to the type of training or to cultural or population differences is unclear. The findings suggest a mixed effect of training for foster carers on problem behaviours of LACYP. The evidence identified appears to suggest that longer-duration training programmes have a beneficial effect on the behaviour problems of LACYP, although future research should examine the impact of training durations and intensity on short-medium and longer-term outcomes of LACYP of different ages. Only training and support for foster carers was identified.

Cost-effectiveness analysis of different embryo transfer strategies in England

Objective  The objective of this study was to assess the cost‐effectiveness of different embryo transfer strategies for a single cycle when two embryos are available, and taking the NHS cost perspective.

Assessing the cost-effectiveness of type 1 diabetes interventions: the Sheffield type 1 diabetes policy model.

To build a flexible and comprehensive long‐term Type 1 diabetes mellitus model incorporating the most up‐to‐date methodologies to allow a number of cost‐effectiveness evaluations.

Estimating the health benefits and costs associated with ezetimibe coadministered with statin therapy compared with higher dose statin monotherapy in patients with established cardiovascular disease: results of a Markov model for UK costs using data registries.

BACKGROUND Ezetimibe has been reported to improve lipid control in patients with established cardiovascular disease (CVD). OBJECTIVE The aim of this study was to estimate the potential long-term impact on health status of prescribing ezetimibe in combination with statin therapy in patients with established CVD and evaluate its cost-effectiveness in a health economic model. METHODS A Markov model was used to compare ezetimibe and statin combination therapy with statin monotherapy. A published relationship linking changes in low-density lipoprotein cholesterol and cardiovascular events was used to estimate the cardiovascular events avoided through lipid-lowering therapies. The model was populated using results of extensive literature searches and a meta-analysis of clinical evidence. An adjustment was applied to model second-line lipid-lowering benefits. Conservative assumptions were used to extend the patient pathway beyond the clinical evidence. The analysis took the perspective of the UK Department of Health; therefore, only direct costs were included. Costs were calculated as year-2006 British pounds. RESULTS For a cohort of 1,000 hypothetical male patients aged 55 years, ezetimibe coadministered with current statin therapy was estimated to prevent a mean of 43 nonfatal myocardial infarctions, 7 nonfatal strokes, and 26 cardiovascular deaths over a lifetime, compared with doubling the current statin dose. The events avoided would provide a mean of 134 additional quality-adjusted life-years (QALYs). With a mean incremental cost of pound 3,693,000, the lifetime discounted cost per QALY gained would be pound 27,475 (95% CI, pound 27,331- pound 27,620) and would rise to pound 32,000 for men aged 75 years. CONCLUSIONS The results suggest that, in some instances, ezetimibe coadministration may be cost-effective compared with statin monotherapy, but there are several limitations with this model. The economic effects of ezetimibe must be revisited when long-term effectiveness and safety data become available.

Cost Effectiveness of Ezetimibe in Patients with Cardiovascular Disease and Statin Intolerance or Contraindications : A Markov Model

ObjectiveTo evaluate the cost effectiveness of long-term ezetimibe monotherapy in patients with established cardiovascular disease (CVD) who do not tolerate statins or in whom they are contraindicated.MethodsA Markov model was used to estimate the potential costs and benefits associated with ezetimibe monotherapy compared with no treatment. The benefits associated with ezetimibe treatment were informed by a systematic review of clinical evidence and a published relationship linking changes in low-density lipoprotein cholesterol (LDL-C) levels to cardiovascular events.ResultsIn the absence of data from clinical outcome trials, surrogate endpoints such as changes in lipid levels were used as indicators of clinical outcomes. A meta-analysis of seven placebo-controlled trials included in the review showed that ezetimibe was associated with a statistically significant mean reduction (from baseline to endpoint) in LDL-C of 18.56% (95% CI −19.68, −17.44; p < 0.00001) compared with placebo.Using 10 000 Monte Carlo simulations, it is estimated that ezetimibe monotherapy would prevent an average of 49 nonfatal myocardial infarctions, 11 nonfatal strokes, and 37 cardiovascular deaths in a cohort of 1000 patients aged 55 years with a baseline LDL-C concentration of 4.0 mmol/L. Events avoided provide an additional 211 quality-adjusted life-years (QALYs) over the 45 years modeled. With a mean incremental cost of £4 861 000 (year 2006 value), the discounted cost per QALY is £23 026 (Jackknife CI 22 979, 23 074). The model is reasonably robust to variations in key parameters. Incremental cost-effectiveness ratios fall below £20 000 per QALY for cohorts with baseline LDL-C values >4.5 mmol/L.ConclusionEzetimibe monotherapy compared with no treatment is a cost-effective alternative for individuals with a history of CVD and high LDL-C levels, who do not tolerate statins or in whom they are contraindicated.

Cost-effectiveness of a cardiovascular disease primary prevention programme in a primary health care setting. Results of the Polish part of the EUROACTION project

BACKGROUND Well designed cardiovascular disease (CVD) prevention programmes appear to be generally applicable and effective in reducing exposure to risk factors and the incidence of disease. However, introducing them broadly into clinical practice would have a significant impact on the healthcare budget, and requires careful consideration. AIM The purpose of this health economic analysis was to assess the potential cost-effectiveness of the model nurse-led, comprehensive CVD primary prevention programme which was prepared and introduced in the EUROACTION project, in high-risk patients in Poland. METHODS A Markov model was developed to assess the long-term costs of preventive intervention. The health states modelled were: event-free (all patients at the beginning of observation), stable angina first year, acute myocardial infarction, stable angina subsequent year, myocardial infarction subsequent year, CVD death, and other causes of death. Health benefits from the reduction in risk factors were estimated based on Framingham risk function assuming the probability of defined health states according to British registers. The time horizon of the analysis was ten years, and one Markov cycle length was one year. The analysis was prepared from the healthcare payers perspective. A willingness to pay threshold of three gross domestic product (GDP) per capita / quality-adjusted life years (QALY) was used. Univariate sensitivity analysis was conducted. Results were presented as an incremental cost-effectiveness ratio (ICER) expressed as an incremental cost per QALY. RESULTS In Poland, EUROACTION intervention resulted mainly in reductions in the prevalence of smoking (by 14%) and high blood pressure (by 7%). Intervention on other risk factors, including blood lipids, was found to be less effective. Estimated ICERs were 19,524 PLN for men and 82,262 PLN for women. The programme was even more cost-effective in smokers i.e. estimated ICERs were 12,377 PLN in men and 53,471 PLN in women. The results were most sensitive to variations in health states utilities and cost value range as well as the duration of treatment effect. CONCLUSIONS The model nurse-led, comprehensive CVD primary prevention programme developed in the EUROACTION project appears to be potentially highly cost-effective for high-risk male patients in Poland (below 1 GDP per capita per QALY). For women, the cost-effectiveness was less but still below the acceptable threshold (below three GDP per capita per QALY), although the sensitivity analysis showed that results were a subject of some uncertainty.

The cost-effectiveness of weight management programmes in a postnatal population

OBJECTIVES The aim of the study was to estimate the cost-effectiveness of a weight management programme including elements of physical exercise and dietary restriction which are designed to help women lose excess weight gained during pregnancy in the vulnerable postnatal period and inhibit the development of behaviours which could lead to future excess weight gain and obesity. STUDY DESIGN A mathematical model based on a regression equation predicting change in weight over a fifteen year postnatal period was developed. METHODS The model included programme effectiveness and resource data based on a randomized controlled trial of a weight management programme implemented in a postnatal population in the United States. Utility and mortality data based on body mass index categories were also included. The model adopted a National Health Service (NHS) and personal social services (PSS) perspective, a lifetime time horizon and estimated the cost effectiveness of a weight management programme against a no change comparator in terms of an incremental cost-effectiveness ratio (ICER). RESULTS The baseline results show that the difference in weight between women who received the weight management programme and women who received the control intervention was 3.02 kg at six months and 3.53 kg at fifteen years following childbirth. This results in an ICER of £7355 per quality adjusted life year (QALY) for women who were married at childbirth. CONCLUSION The estimated ICER would suggest that such a weight management programme is cost-effective at a NICE threshold of £20,000 per QALY. However significant structural and evidence based uncertainty is present in the analysis.