Magnetic Resonance Imaging of Cerebral Palsy in the Assessment of Time of Brain Insult.

The aim of this cross-sectional study was to find out the role of Magnetic resonance imaging (MRI) in the assessment of time of brain insult in cerebral palsy (CP). The study was conducted in the Department of Radiology & Imaging, Mymensingh Medical College Hospital, Mymensingh and a total number of 35 patients with were enrolled from January 2015 to December 2016. Maximum patients (57.2%) were under five years followed by 34.3% were of 5 to <8 years and 8.7% were of 8 to <12 years of age and mean age was 4.7 years. Majority of the patients were male 28(80%) and female were 7(20%). Among the patients 23(65.7%) came from poor, whereas 11(31.4%) came from middle class and only one (2.9%) from rich socioeconomic group. According to gestational age of the patients, 26(74.3%) were term (≥37weeks) at delivery and rest (25.7%) were preterm (<37 weeks). Delayed cry after birth were present in 32 (80%) patients. Regarding types of cerebral palsy spastic diplegia, spastic quadriplegia, hemiplegia and extrapyramidal were found 3(8.6%), 25(71.4%), 4(11.4%) and 3(8.6%) respectively. Abnormal MRI was reported in 94.2% patients and gave clues to time of insult in 79.9% (excluding the 14.3% miscellaneous findings). The findings were mal-developments (5.7%), periventricular white matter lesions (25.7%), cortical or deep grey matter lesions (48.6%), miscellaneous (14.3%) and normal (5.7%). Brain mal-developments were more seen in term than in preterm born children (5% vs. 0%). Periventricular white matter lesions were seen significantly more in preterm than in term born children (77.8% vs. 3.9%). Cortical or deep grey matter lesions occurred significantly more in term than in preterm born children (60% vs. 20%). Based on the study it can be concluded that Magnetic Resonance Imaging (MRI) can help in the assessment of time of insult to the developing brain in cerebral palsy (CP).

The cost-effectiveness of changes to the care pathway used to identify depression and provide treatment amongst people with diabetes in England: a model-based economic evaluation.

BACKGROUND: Diabetes is associated with premature death and a number of serious complications. The presence of comorbid depression makes these outcomes more likely and results in increased healthcare costs. The aim of this work was to assess the health economic outcomes associated with having both diabetes and depression, and assess the cost-effectiveness of potential policy changes to improve the care pathway: improved opportunistic screening for depression, collaborative care for depression treatment, and the combination of both. METHODS: A mathematical model of the care pathways experienced by people diagnosed with type-2 diabetes in England was developed. Both an NHS perspective and wider social benefits were considered. Evidence was taken from the published literature, identified via scoping and targeted searches. RESULTS: Compared with current practice, all three policies reduced both the time spent with depression and the number of diabetes-related complications experienced. The policies were associated with an improvement in quality of life, but with an increase in health care costs. In an incremental analysis, collaborative care dominated improved opportunistic screening. The incremental cost-effectiveness ratio (ICER) for collaborative care compared with current practice was £10,798 per QALY. Compared to collaborative care, the combined policy had an ICER of £68,017 per QALY. CONCLUSIONS: Policies targeted at identifying and treating depression early in patients with diabetes may lead to reductions in diabetes related complications and depression, which in turn increase life expectancy and improve health-related quality of life. Implementing collaborative care was cost-effective based on current national guidance in England.

What is the quality of economic evaluations of non-drug therapies? A systematic review and critical appraisal of economic evaluations of radiotherapy for cancer.

BACKGROUND: Breast, cervical and colorectal cancers are the three most frequent cancers in women, while lung, prostate and colorectal cancers are the most frequent in men. Much attention has been given to the economic evaluation of pharmaceuticals for treatment of cancer by the National Institute for Health and Care Excellence (NICE) in the UK and similar authorities internationally, while economic analysis developed for other types of anti-cancer interventions, including radiotherapy and surgery, are less common. OBJECTIVES: Our objective was to review methods used in published cost-effectiveness studies evaluating radiotherapy for breast, cervical, colorectal, head and neck and prostate cancer, and to compare the economic evaluation methods applied with those defined in the guidelines used by the NICE technology appraisal programme. METHODS: A systematic search of seven databases (MEDLINE, EMBASE, CDSR, NHSEED, HTA, DARE, EconLit) as well as research registers, the NICE website and conference proceedings was conducted in July 2012. Only economic evaluations of radiotherapy interventions in individuals diagnosed with cancer that included quality-adjusted life-years (QALYs) or life-years (LYs) were included. Included studies were appraised on the basis of satisfying essential, preferred and UK-specific methods requirements, building on the NICE Reference Case for economic evaluations and on other methods guidelines. RESULTS: A total of 29 studies satisfied the inclusion criteria (breast 14, colorectal 2, prostate 10, cervical 0, head and neck 3). Only two studies were conducted in the UK (13 in the USA). Among essential methods criteria, the main issue was that only three (10%) of the studies used clinical-effectiveness estimates identified through systematic review of the literature. Similarly, only eight (28%) studies sourced health-related quality-of-life data directly from patients with the condition of interest. Other essential criteria (e.g. clear description of comparators, patient group indication and appropriate time horizon) were generally fulfilled, while most of the UK-specific requirements were not met. CONCLUSION: Based on this review there is a dearth of up-to-date, robust evidence on the cost effectiveness of radiotherapy in cancer suitable to support decision making in the UK. Studies selected did not fully satisfy essential method standards currently recommended by NICE.

Echocardiographic assessment of cardiac involvement in systemic lupus erythematosus patients.

This study was designed to assess cardiac abnormalities in patients with systemic lupus erythematosus (SLE) by echocardiography. It was an analytic type of cross sectional study, conducted in lupus clinic, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2008 to June 2009. Fifty lupus patients, diagnosed on the basis of ACR criteria, without cardiovascular symptoms, were enrolled in the study and were evaluated by standard echocardiography with color Doppler. SLEDAI was applied for assessment of disease activity. Out of 50 patients 80% had abnormal echocardiographic findings. Pericardial thickening was found in 38% patients, pericardial effusion 20%, diastolic dysfunction 72%, hypokinesia of ventricular wall 8%, overall valvular abnormalities 20%, commonest being aortic regurgitation (12%), followed by mitral regurgitation (8%), and 6% had pulmonary hypertension. Males (100%) were more vulnerable to cardiac involvement than females (68.2%) and later age of disease onset (31-40 years) was associated with higher (87.5%) chance of echo abnormalities. The differences, however, were not statistically significant (p>0.05). There was significant relationship between disease duration and cardiac abnormalities (p<0.01). Active disease (80.08%) was associated with higher frequency of cardiac involvement than disease in remission (62.50%) but the result was not statistically significant (p=0.151). Cardiac abnormalities are very common in lupus patients even when clinically asymptomatic from cardiac aspect. Echocardiography is an excellent non-invasive tool for cardiac evaluation. These observations emphasize a need for further assessment of early intervention to reduce subsequent cardiac morbidity and mortality among the lupus patients.

What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review.

BACKGROUND: Obesity [defined as a body mass index (BMI) ≥ 30 kg/m(2)] represents a considerable public health problem and is associated with a significant range of comorbidities and an increased mortality risk. The primary aim of the management of obesity is to achieve weight reduction in the interests of health. For obese patients who cannot achieve or maintain a healthy weight by non-pharmacological means, drug therapy is recommended in combination with non-pharmacological interventions such as dietary modifications and exercise. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of three pharmacological interventions in obese patients. DATA SOURCES: Clinical effectiveness data used in the meta-analysis were sourced from articles identified in a systematic review of the literature. Data used to inform transitions to obesity-related comorbidities were derived from the General Practice Research Database (GPRD). The results of the meta-analysis and GPRD analyses informed the economic model supplemented by data from the Health Survey for England and other UK-specific data sourced from the literature. REVIEW METHODS: A systematic literature review was conducted of the clinical effectiveness and cost-effectiveness of orlistat, sibutramine and rimonabant within their licensed indications for the treatment of obese patients. Electronic bibliographic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in January 2009, and the reference lists of relevant articles were checked. Studies were included if they compared orlistat, sibutramine or rimonabant with lifestyle and/or exercise advice (standard care), placebo or metformin. RESULTS: Overall, 94 studies involving 24,808 individuals were included in the clinical meta-analysis. Eighty-three trials included data on weight change, 41 included data on BMI change and 45 and 36 studies reported on 5% and 10% body weight loss, respectively. Overall, the results show that the active drug interventions are all effective at reducing weight and BMI compared with placebo. In the case of sibutramine, the higher dose (15 mg) resulted in a greater reduction than the lower dose (10 mg). Generally, the data quality of the trials included was low with poor reporting of standard errors and standard deviations. Results from the BMI risk models derived from the GPRD showed consistent increases in risk with increasing BMI. Adjustments for key confounders, such as age, sex and smoking status, were found to be statistically significant at the 5% level, in all risk models. Applying linear models to estimate BMI trajectories, for the diabetic cohort, an average increase in BMI of 0.040 per year for both men and women was observed. The non-diabetic cohort model showed an increase in BMI of 0.175 per year for women and 0.145 per year for men. The results of the cost-effectiveness analyses suggest that sibutramine 15 mg dominates the other three active interventions and the net benefit analyses show that sibutramine 15 mg is the most cost-effective alternative for thresholds > £2000 per quality-adjusted life-year (QALY). However, both sibutramine and rimonabant have been withdrawn because of safety concerns relating to potential treatment-induced fatal adverse events. If the proportion of patients who experienced a fatal adverse event was > 1.8% (1.5%, 1.0%) for sibutramine 15 mg (sibutramine 10 mg, rimonabant) the treatment would not be considered cost-effective when using a threshold of £20,000 per QALY. LIMITATIONS: The clinical review did not include all possible lifestyle comparators, with the inclusion limited to only those trials included one of the active drug interventions. We also excluded all studies not reported in English. Although the clinical review included data from 94 studies, the quality of data was generally low, particularly in terms of the reporting of standard deviation. There was also inconsistency between the results of the mixed-treatment comparison (MTC) and the pair-wise analyses. CONCLUSION: The MTC of anti-obesity treatments shows that all the active treatments are effective at reducing weight and BMI. The economic results show that, compared with placebo, the treatments are all cost-effective when using a threshold of £20,000 per QALY, and, within the limitations of the data available, sibutramine 15 mg dominates the other three interventions. This work has highlighted many areas of methodological research that could be explored, including assessing inconsistencies within a network to determine differences between the results of pair-wise and MTC analyses; the use of meta-regression methods to look for effect modifiers; exploring the effect of local publication bias; and the use of joint models to analyse the repeated measures of BMI and the time-to-event processes simultaneously. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Prescribing high-dose lipid-lowering therapy early to avoid subsequent cardiovascular events: is this a cost-effective strategy?

BACKGROUND: While evidence shows high-dose statins reduce cardiovascular events compared with moderate doses in individuals with acute coronary syndrome (ACS), many primary care trusts (PCT) advocate the use of generic simvastatin 40 mg/day for these patients. METHODS AND RESULTS: Data from 28 RCTs were synthesized using a mixed treatment comparison model. A Markov model was used to evaluate the cost-effectiveness of treatments taking into account adherence and the likely reduction in cost for atorvastatin when the patent expires. There is a clear dose-response: rosuvastatin 40 mg/day produces the greatest reduction in low-density lipoprotein cholesterol (56%) followed by atorvastatin 80 mg/day (52%), and simvastatin 40 mg/day (37%). Using a threshold of £20,000 per QALY, if adherence levels in general practice are similar to those observed in RCTs, all three higher dose statins would be considered cost-effective compared to simvastatin 40 mg/day. Using the net benefits of the treatments, rosuvastatin 40 mg/day is estimated to be the most cost-effective alternative. If the cost of atorvastatin reduces in line with that observed for simvastatin, atorvastatin 80 mg/day is estimated to be the most cost-effective alternative. CONCLUSION: Our analyses show that current PCT policies intended to minimize primary care drug acquisition costs result in suboptimal care.

Early high-dose lipid-lowering therapy to avoid cardiac events: a systematic review and economic evaluation.

OBJECTIVE: To evaluate the cost-effectiveness of high-dose statins (atorvastatin 80 mg/day, rosuvastatin 40 mg/day and simvastatin 80 mg/day) versus simvastatin 40 mg/day in individuals with acute coronary syndrome (ACS). DATA SOURCES: Eleven bibliographic databases, including MEDLINE, CINAHL, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, DARE and NHS EED, were searched from inception to 2008. REVIEW METHODS: Data relating to study design, baseline patient characteristics, clinical or surrogate outcome, and adverse events were abstracted, and methodological quality was assessed according to standard methods. A synthesis of the available evidence was performed using a Bayesian mixed treatment meta-analysis using both direct and indirect evidence. An existing Markov model was modified to explore the costs and benefits associated with a lifetime of the differing treatment regimens. RESULTS: A total of 3345 titles and abstracts were screened for inclusion in the review of clinical effectiveness and 125 full papers retrieved and assessed in detail. Of these, 30 papers met the inclusion criteria for the review, describing 28 trials. The Bayesian mixed treatment meta-analysis demonstrated a clear dose-response relationship in terms of reductions in low-density lipoprotein cholesterol (LDL-c), with rosuvastatin 40 mg/day achieving the greatest percentage reduction (56%) from baseline, followed by atorvastatin 80 mg/day (52%), simvastatin 80 mg/day (45%) and simvastatin 40 mg/day (37%). Although serious adverse events with statins are rare, their incidence is likely to be greater with higher doses. Several clinical scenarios were used to explore the effect of adherence on the cost-effectiveness of the treatment regimens. Using a threshold of 20,000 pounds per quality-adjusted life-year (QALY) and assuming that the benefits and adherence rates observed in the clinical trials are generalisable to a clinical setting and that individuals who do not tolerate the higher-dose statins are prescribed simvastatin 40 mg/day, then simvastatin 80 mg/day, atorvastatin 80 mg/day and rosuvastatin 40 mg/day would be considered cost-effective compared with simvastatin 40 mg/day in individuals with ACS. Simvastatin 80 mg/day is not well tolerated because of the high incidence rates of less severe adverse events such as myopathy (26-fold higher than rates in those receiving simvastatin 20 mg/day), which are likely to affect adherence levels in clinical practice. The reference case shows that rosuvastatin is the optimal treatment for individuals with a recent history of ACS using a threshold of 20,000 pounds per QALY. However, this is based on the assumption that the additional incremental reductions in LDL-c observed in patients treated with rosuvastatin 40 mg/day compared with atorvastatin will transfer into corresponding changes in relative risks of cardiovascular events. CONCLUSIONS: Simvastatin 80 mg/day cannot be recommended because of the high incidence rates of adverse events. If the cost of atorvastatin decreases in line with that observed for simvastatin when the patent ends in 2011, atorvastatin 80 mg/day will be the most cost-effective treatment for all thresholds; if the cost reduces to 25% of the current value, atorvastatin 80 mg/day will be the most cost-effective treatment for thresholds between 5000 pounds and 30,000 pounds per QALY. Large long-term RCTs reporting effects in terms of clinical events are required to determine the optimum statin use for subgroups.

Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation.

OBJECTIVES: To review the clinical and cost-effectiveness of ezetimibe as a combination therapy or monotherapy for the treatment of primary hypercholesterolaemia in the UK. DATA SOURCES: Twelve electronic databases were searched from inception to June 2006. Searches were supplemented by hand-searching relevant articles, sponsor and other submissions of evidence to the National Institute of Health and Clinical Excellence and conference proceedings. REVIEW METHODS: A systematic review and meta-analysis (where appropriate) of the clinical efficacy evidence was undertaken following recommended guidelines. A Markov model was developed to explore the costs and health outcomes associated with ezetimibe treatment. RESULTS: No published clinical outcome trials (> 12 weeks) were identified. In the absence of clinical end-point data from trials, 13 (of which five were multi-arm) phase III multi-centre randomised controlled trials (RCTs) (of varying methodological quality) of short-term duration (12-48 weeks) with surrogate end-point data were included. For patients not adequately controlled with a statin alone, a meta-analysis of six studies showed that a fixed-dose combination of ezetimibe and statin treatment was associated with a statistically significant reduction in low-density lipoprotein cholesterol (LDL-c) and total cholesterol (Total-c) compared with statin alone (p < 0.00001). Four studies (not eligible for meta-analysis) that titrated (either forced or stepwise) the statin doses to LDL-c targets generally showed that the co-administration of ezetimibe and statin was significantly more effective in reducing plasma LDL-c concentrations than statin monotherapy (p < 0.05 for all studies). For patients where a statin is not considered appropriate, a meta-analysis of seven studies demonstrated that ezetimibe monotherapy significantly reduced LDL-c levels compared with placebo (p < 0.00001). There were no statistically significant differences in LDL-c-lowering effects across different subgroups. Ezetimibe therapy (either in combination with a statin or monotherapy) appeared to be well tolerated compared to statin monotherapy or placebo, respectively. No ezetimibe studies reported data on health-related quality of life (HRQoL). There was a wide range in the economic results depending on the treatment strategies evaluated. When comparing ezetimibe monotherapy with no treatment in individuals with baseline LDL-c values of 3.0-4.0 mmol/l, the results range from 21,000 pounds to 50,000 pounds per quality-adjusted life-year (QALY). Results for individuals with baseline LDL-c values over 5.0 mmol/l are below 30,000 pounds per QALY. When comparing the costs and benefits of adding ezetimibe to ongoing statin treatment compared with maintaining statin treatment at the current dose, the majority of results are above values generally considered to be cost-effective (range 19,000 pounds to 48,000 pounds per QALY). Based on the evidence available, when comparing the costs and benefits associated with adding ezetimibe to ongoing statin treatment compared with a switch to a more potent statin, the results are governed by the difference in the cost of the treatment regimens compared and results range from 1500 pounds to 116,000 pounds per QALY. CONCLUSIONS: The short-term RCT clinical evidence demonstrated that ezetimibe was effective in reducing LDL-c when administered as monotherapy or in combination with a statin. However, when used as a monotherapy, ezetimibe is less effective than statins in lowering LDL-c. Given the limitations in the effectiveness data, there is great uncertainty in the economic results. These suggest that ezetimibe could be a cost-effective treatment for individuals with high baseline LDL-c values, for patients with diabetes and for individuals with heterozygous familial hypercholesterolaemia. Long-term clinical outcome studies are needed to allow more precise cost-effectiveness estimates to be calculated.

The direct healthcare costs associated with ankylosing spondylitis patients attending a UK secondary care rheumatology unit.

OBJECTIVES: To explore the direct healthcare resources associated with ankylosing spondylitis (AS) in the UK. A secondary objective was to establish if resources, and thus healthcare costs, vary by disease severity. METHODS: Medical records of 147 sequential AS patients attending a UK secondary care rheumatology unit were examined to assess the direct healthcare resources used over the previous 12 months. Starting with a detailed inventory and measurement of resources consumed, unit cost multipliers were applied to the quantity of each type of resource consumed. The mean cost per patient was estimated using the total cost divided by the number of patients included. RESULTS: The mean (median) annual cost per patient was 1852 pounds sterling (892 pounds sterling). The distribution of cost data was skewed, with 11% of patients incurring 50% of the total costs. The three most relevant cost domains were physiotherapy, hospitalization and medication costs at 32, 21 and 20% of the total costs, respectively. Twenty percent of the patients received physiotherapy, 13% received inpatient care and almost all incurred medication costs. Thirty-four percent of patients were prescribed disease-modifying anti-rheumatic drugs and 85% non-steroidal anti-inflammatory drugs. Over 50% of patients had at least one comorbidity. CONCLUSION: Direct costs accelerate steeply with disease activity (Bath Ankylosing Spondylitis Disease Activity Index >6.0) and increasing loss of function (Bath Ankylosing Spondylitis Functional Index >6.0) in patients with AS. The most severely affected patients incur 50% of the total costs, and physiotherapy accounts for 32% of the total healthcare costs in the UK.

The cost-effectiveness of etanercept in patients with severe ankylosing spondylitis in the UK.

OBJECTIVES: To examine the costs and benefits associated with long-term etanercept (ETN) treatment in patients with severe ankylosing spondylitis (AS) in the UK in accordance with the BSR guidelines. METHODS: A mathematical model was constructed to estimate the costs and benefits associated with ETN plus non-steroidal anti-inflammatory drugs (NSAIDs) compared with NSAIDs alone. Individual patient data from Phase III RCTs was used to inform the proportion and magnitude of initial response to treatment and changes in health-related quality of life. A retrospective costing exercise on patients attending a UK secondary care rheumatology unit was used to inform disease costs. Published evidence on long-term disease progression was extrapolated over a 25-yr horizon. Uncertainty was examined using probabilistic sensitivity analyses. RESULTS: Over a 25-yr horizon, ETN plus NSAIDs gave 1.58 more QALYs at an additional cost of 35,978 pounds when compared with NSAID treatment alone. This equates to a central estimate of 22,700 pounds per QALY. The incremental cost per QALYs using shorter time periods were 27,600 pounds, 23,600 pounds and 22,600 pounds at 2, 5 and 15 yrs, respectively. Using a 25-yr horizon, 93% of results from the probabilistic analyses fall below a threshold of 25,000 pounds per QALY. CONCLUSIONS: This study demonstrates the potential cost-effectiveness of ETN plus NSAIDs compared with NSAIDs alone in patients with severe AS treated according to the BSR guidelines in the UK.

The cost-effectiveness of sibutramine in non-diabetic obese patients: evidence from four Western countries.

This paper aims to assess the cost-effectiveness of sibutramine in treating obese patients in the Western countries. The model estimates the costs and quality of life benefits directly associated with weight losses combined with the costs and benefits associated with the reduced incidence of coronary heart disease (CHD) and diabetes. The pivotal effectiveness evidence is derived from a German multicentre, double-blind, randomized clinical trial on obese (body mass index >/= 30 Euro kg m(-2)) patients. The incremental cost per quality-adjusted life year ranges from 10,734 Euro in Switzerland to 13,707 Euro in Germany. The total number of CHD events avoided ranges from 1.96 for the UK to 4.49 for Switzerland. The number of diabetes cases avoided is in the region of 3.0 (ranges from 2.58 for Germany to 3.28 for Switzerland). The majority of costs and benefits are accrued through sibutramine treatment and monitoring. Univariate sensitivity analyses show that results are sensitive to changes in the utility directly attributable to weight losses. The results demonstrate that the benefits associated with sibutramine-induced weight losses are obtained at a reasonable cost in each of the settings explored and suggest that sibutramine treatment could be considered as a viable option for pharmacotherapy treatment alongside diet and exercise.

A systematic review and economic evaluation of statins for the prevention of coronary events.

OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of statins for the primary and secondary prevention of cardiovascular events in adults with, or at risk of, coronary heart disease (CHD). DATA SOURCES: Electronic databases were searched between November 2003 and April 2004. REVIEW METHODS: A review was undertaken to identify and evaluate all literature relating to the clinical and cost effectiveness of statins in the primary and secondary prevention of CHD and cardiovascular disease (CVD) in the UK. A Markov model was developed to explore the costs and health outcomes associated with a lifetime of statin treatment using a UK NHS perspective. RESULTS: Thirty-one randomised studies were identified that compared a statin with placebo or with another statin, and reported clinical outcomes. Meta-analysis of the available data from the placebo-controlled studies indicates that, in patients with, or at risk of, CVD, statin therapy is associated with a reduced relative risk of all cause mortality, cardiovascular mortality, CHD mortality and fatal myocardial infarction (MI), but not of fatal stroke. It is also associated with a reduced relative risk of morbidity [non-fatal stroke, non-fatal MI, transient ischaemic attack (TIA), unstable angina] and of coronary revascularisation. It is hardly possible, on the evidence available from the placebo-controlled trials, to differentiate between the clinical efficacy of atorvastatin, fluvastatin, pravastatin and simvastatin. However, there is some evidence from direct comparisons between statins to suggest that atorvastatin may be more effective than pravastatin in patients with symptomatic CHD. There is limited evidence for the effectiveness of statins in different subgroups. Statins are generally considered to be well tolerated and to have a good safety profile. This view is generally supported both by the evidence of the trials included in this review and by postmarketing surveillance data. Increases in creatine kinase and myopathy have been reported, but rhabdomyolysis and hepatotoxicity are rare. However, some patients may receive lipid-lowering therapy for as long as 50 years, and long-term safety over such a timespan remains unknown. In secondary prevention of CHD, the incremental cost-effectiveness ratios (ICERs) increase with age varying between pound 10,000 and pound 17,000 per quality adjusted life year (QALY) for ages 45 and 85 respectively. Sensitivity analyses show these results are robust. In primary prevention of CHD there is substantial variation in ICERs by age and risk. The average ICERs weighted by risk range from pound 20,000 to pound 27,500 for men and from pound 21,000 to pound 57,000 for women. The results are sensitive to the cost of statins, discount rates and the modelling time frame. In the CVD analyses, which take into account the benefits of statins on reductions in stroke and TIA events, the average ICER weighted by risk level remains below pound 20,000 at CHD risk levels down to 0.5%. Limitations of the analyses include the requirement to extrapolate well beyond the timeframe of the trial period, and to extrapolate effectiveness results from higher risk primary prevention populations to the treatment of populations at much lower risk. Consequently, the results for the lower age bands and lower risks are subject to greater uncertainty and need to be treated with caution. CONCLUSIONS: There is evidence to suggest that statin therapy is associated with a statistically significant reduction in the risk of primary and secondary cardiovascular events. As the confidence intervals for each outcome in each prevention category overlap, it is not possible to differentiate, in terms of relative risk, between the effectiveness of statins in primary and secondary prevention. However, the absolute risk of CHD death/non-fatal MI is higher, and the number needed to treat to avoid such an event is consequently lower, in secondary than in primary prevention. The generalisability of these results is limited by the exclusion, in some studies, of patients who were hypersensitive to, intolerant of, or known to be unresponsive to, statins, or who were not adequately compliant with study medication during a placebo run-in phase. Consequently, the treatment effect may be reduced when statins are used in an unselected population. The results of the economic modelling show that statin therapy in secondary prevention is likely to be considered cost-effective. In primary prevention, the cost-effectiveness ratios are dependent on the level of CHD risk and age, but the results for the CVD analyses offer support for the more aggressive treatment recommendation issued by recent guidelines in UK. Evidence on clinical endpoints for rosuvastatin is awaited from on-going trials. The potential targeting of statins at low-risk populations is however associated with major uncertainties, particularly the likely uptake and long-term compliance to lifelong medication by asymptomatic younger patients. The targeting, assessment and monitoring of low-risk patients in primary care would be a major resource implication for the NHS. These areas require further research.

Estimating the cost and health status consequences of treatment with TNF antagonists in patients with psoriatic arthritis.

OBJECTIVES: Tumour necrosis factor (TNF) has been shown to improve the outcomes in patients with psoriatic arthritis (PsA). We estimate the long-term impact on health status of prescribing the TNF antagonist etanercept, and evaluate the cost-effectiveness in a health economic model. METHODS: The relationship between disability (Health Assessment Questionnaire) and health state utility was explored to estimate the quality-adjusted life years (QALYs) gained from the TNF antagonist etanercept. A model was then used to compare sequences of treatments for PsA after failure of two conventional disease modifying anti-rheumatic drugs (DMARDs). One arm commences on etanercept therapy and this is compared with a strategy commencing with combination therapy of methotrexate and ciclosporin and another commencing with leflunomide. Individual patient data from Phase III etanercept trials is used to populate the model supported by published evidence from extensive literature searches. By incorporating a life table specific for a PsA population, and using a number of evidence- and expert opinion-based assumptions for disease progression, the model was extended beyond the trial duration to a 10-yr time horizon. Cost offsets were produced by avoiding surgery through delayed progression; drug and monitoring costs were also modelled. RESULTS: Over the 10 yrs, modelled etanercept treatment gave 0.82 more QALYs when compared with combination therapy with methotrexate and ciclosporin, and 0.65 more QALYs in comparison with leflunomide. This equates to a central estimate for the cost per QALY of pound28 189 and pound28 189 for ciclosporin and leflunomide, respectively. Sensitivity analyses demonstrated this could vary by as much as +/-28%. CONCLUSIONS: With limited data currently available, the potential cost-effectiveness of etanercept in DMARD failures for adults with PsA appears encouraging. The result for other TNF antagonists will depend on how their relative efficacy and drug price compares with etanercept. A number of limitations are described and priorities for further research suggested.