A Cost-effectiveness Analysis of Surgery, Endothermal Ablation, Ultrasound-guided Foam Sclerotherapy and Compression Stockings for Symptomatic Varicose Veins.

OBJECTIVE: The aim was to investigate the cost-effectiveness of interventional treatment for varicose veins (VV) in the UK NHS, and to inform the national clinical guideline on VV, published by the National Institute of Health and Care Excellence. DESIGN: An economic analysis was constructed to compare the cost-effectiveness of surgery, endothermal ablation (ETA), ultrasound-guided foam sclerotherapy (UGFS), and compression stockings (CS). The analysis was based on a Markov decision model, which was developed in consultation with members of the NICE guideline development group (GDG). METHODS: The model had a 5-year time horizon, and took the perspective of the UK National Health Service. Clinical inputs were based on a network meta-analysis (NMA), informed by a systematic review of the clinical literature. Outcomes were expressed as costs and quality-adjusted life years (QALYs). RESULTS: All interventional treatments were found to be cost-effective compared with CS at a cost-effectiveness threshold of £20,000 per QALY gained. ETA was found to be the most cost-effective strategy overall, with an incremental cost-effectiveness ratio of £3,161 per QALY gained compared with UGFS. Surgery and CS were dominated by ETA. CONCLUSIONS: Interventional treatment for VV is cost-effective in the UK NHS. Specifically, based on current data, ETA is the most cost-effective treatment in people for whom it is suitable. The results of this research were used to inform recommendations within the NICE guideline on VV.

Economic modelling of diagnostic and treatment pathways in National Institute for Health and Care Excellence clinical guidelines: the Modelling Algorithm Pathways in Guidelines (MAPGuide) project.

BACKGROUND: National Institute for Health and Care Excellence (NICE) clinical guidelines (CGs) make recommendations across large, complex care pathways for broad groups of patients. They rely on cost-effectiveness evidence from the literature and from new analyses for selected high-priority topics. An alternative approach would be to build a model of the full care pathway and to use this as a platform to evaluate the cost-effectiveness of multiple topics across the guideline recommendations. OBJECTIVES: In this project we aimed to test the feasibility of building full guideline models for NICE guidelines and to assess if, and how, such models can be used as a basis for cost-effectiveness analysis (CEA). DATA SOURCES: A 'best evidence' approach was used to inform the model parameters. Data were drawn from the guideline documentation, advice from clinical experts and rapid literature reviews on selected topics. Where possible we relied on good-quality, recent UK systematic reviews and meta-analyses. REVIEW METHODS: Two published NICE guidelines were used as case studies: prostate cancer and atrial fibrillation (AF). Discrete event simulation (DES) was used to model the recommended care pathways and to estimate consequent costs and outcomes. For each guideline, researchers not involved in model development collated a shortlist of topics suggested for updating. The modelling teams then attempted to evaluate options related to these topics. Cost-effectiveness results were compared with opinions about the importance of the topics elicited in a survey of stakeholders. RESULTS: The modelling teams developed simulations of the guideline pathways and disease processes. Development took longer and required more analytical time than anticipated. Estimates of cost-effectiveness were produced for six of the nine prostate cancer topics considered, and for five of eight AF topics. The other topics were not evaluated owing to lack of data or time constraints. The modelled results suggested 'economic priorities' for an update that differed from priorities expressed in the stakeholder survey. LIMITATIONS: We did not conduct systematic reviews to inform the model parameters, and so the results might not reflect all current evidence. Data limitations and time constraints restricted the number of analyses that we could conduct. We were also unable to obtain feedback from guideline stakeholders about the usefulness of the models within project time scales. CONCLUSIONS: Discrete event simulation can be used to model full guideline pathways for CEA, although this requires a substantial investment of clinical and analytic time and expertise. For some topics lack of data may limit the potential for modelling. There are also uncertainties over the accessibility and adaptability of full guideline models. However, full guideline modelling offers the potential to strengthen and extend the analytical basis of NICE's CGs. Further work is needed to extend the analysis of our case study models to estimate population-level budget and health impacts. The practical usefulness of our models to guideline developers and users should also be investigated, as should the feasibility and usefulness of whole guideline modelling alongside development of a new CG. FUNDING: This project was funded by the Medical Research Council and the National Institute for Health Research through the Methodology Research Programme [grant number G0901504] and will be published in full in Health Technology Assessment; Vol. 17, No. 58. See the NIHR Journals Library website for further project information.

Cost-effectiveness analysis: role and implications.

BACKGROUND: Cost-effectiveness analysis (CEA) is often misperceived to be a cost-cutting exercise. The intention of CEA is not to identify and implement cheap technologies, but rather those which offer maximum health gain, subject to available funds. Such analysis is crucial for decision making in health care, as tight budget constraints mean spending in one area of healthcare displaces spending elsewhere. Therefore in order to achieve the greatest health gain for the overall population, treatments must be selected which provide the greatest health gain within the available funds. SUMMARY: The relevance of CEA in health care systems is explained, using varicose vein treatment in the UK NHS as an example. Treatment for varicose veins is often not commissioned to at a local level, most likely because it is misperceived to be a cosmetic problem. However, this view does not take into account the impact of quality of life. CEA balances costs against a quantitative measure of health related quality of life, and could therefore be used to determine whether it is cost-effective to provide varicose vein treatment. The current literature on the cost-effectiveness of varicose vein treatment is reviewed, and an overview of cost-effectiveness principles is provided. Concepts such as economic modelling, incremental cost-effectiveness ratios (ICERs), net monetary benefit (NMB) and sensitivity analysis are explained, using examples relevant to varicose veins where appropriate. CONCLUSION: This article explains how, far from cutting costs and sacrificing patient health, CEA provides a useful tool to maximise the health of the population in the face of ever tightening budget constraints. CEA could be used to compare the cost-effectiveness of the various treatment options for varicose veins, and efficiencies realised.

Topical therapies for the treatment of localized plaque psoriasis in primary care: a cost-effectiveness analysis.

BACKGROUND: Topical therapies are a mainstay of psoriasis treatment, but they vary substantially in terms of cost. OBJECTIVES: To determine the cost-effectiveness and optimal treatment sequence for psoriasis of the trunk, limbs and scalp. METHODS: Probabilities of response from a network meta-analysis were used to determine the short-term efficacy of topical therapies. Longer-term outcomes, including relapse, were informed by published evidence and clinical opinion. Benefits of treatment were measured as quality-adjusted life years (QALYs). Direct costs included topical agents, primary and secondary care visits and second-line therapies for treatment failures. RESULTS: For the trunk and limbs, initial treatment with a two-compound formulation (TCF) product containing vitamin D and potent corticosteroid provided the most QALYs, followed by separate morning and evening application of vitamin D and potent corticosteroid [two-compound application, TCA (am/pm)], and then twice-daily potent corticosteroids. The use of twice-daily potent corticosteroids was the most cost-effective first-line strategy (incremental cost-effectiveness ratio £ 20,000 per QALY), followed by TCA (am/pm) (£ 22,658 per QALY) and TCF product (£ 179,439 per QALY). For scalp psoriasis, initial treatment with very potent corticosteroids generated the most QALYs, followed by TCF product and then potent corticosteroids. Very potent corticosteroids were the most cost-effective treatment but, if too aggressive, potent corticosteroids were optimal followed by TCF product (£ 219,846 per QALY). The cost-effectiveness of second- and third-line topical agents varied with the assumptions made. CONCLUSIONS: Potent corticosteroids, used alone or in combination with vitamin D, are the most cost-effective treatment for patients with psoriasis of the trunk and limbs. Potent or very potent corticosteroids are the most cost-effective treatment for patients with scalp psoriasis.

Topical therapies for the treatment of plaque psoriasis: systematic review and network meta-analyses.

The majority of people with psoriasis have localized disease, where topical therapy forms the cornerstone of treatment. We set out to summarize evidence on the relative efficacy, safety and tolerability of different topical treatments used in plaque psoriasis. We undertook a systematic review and meta-analyses of randomized trial data of U.K.-licensed topical therapies. The primary outcome was clear or nearly clear status stratified for (i) trunk and limbs; and (ii) scalp. Network meta-analyses allowed ranking of treatment efficacy. In total, 48 studies were available for trunk and limb psoriasis, and 17 for scalp psoriasis (22,028 patients in total); the majority included people with at least moderate severity psoriasis. Strategies containing potent corticosteroids (alone or in combination with a vitamin D analogue) or very potent corticosteroids dominated the treatment hierarchy at both sites (trunk and limbs, scalp); coal tar and retinoids were no better than placebo. No significant differences in achievement of clear or nearly clear status were observed between twice- and once-daily application of the same intervention or between any of the following: combined vitamin D analogue and potent corticosteroid (applied separately or in a single product), very potent corticosteroids, or potent corticosteroids (applied twice daily). Investigator and patient assessment of response differed significantly for some interventions (response rates to very potent corticosteroids: 78% and 39%, respectively). No significant differences were noted for tolerability or steroid atrophy, but data were limited. In conclusion, corticosteroids are highly effective in psoriasis when used continuously for up to 8 weeks and intermittently for up to 52 weeks. Coal tar and retinoids are of limited benefit. There is a lack of long-term efficacy and safety data available on topical interventions used for psoriasis.

Developing guidelines for venous thromboembolism for The National Institute for Clinical Excellence: involvement of the orthopaedic surgical panel.

Following the publication in 2007 of the guidelines from the National Institute for Health and Clinical Excellence (NICE) for prophylaxis against venous thromboembolism (VTE) for patients undergoing surgery, concerns were raised by British orthopaedic surgeons as to the appropriateness of the recommendations for their clinical practice. In order to address these concerns NICE and the British Orthopaedic Association agreed to engage a representative panel of orthopaedic surgeons in the process of developing expanded VTE guidelines applicable to all patients admitted to hospital. The functions of this panel were to review the evidence and to consider the applicability and implications in orthopaedic practice in order to advise the main Guideline Development Group in framing recommendations. The panel considered both direct and indirect evidence of the safety and efficacy, the cost-effectiveness of prophylaxis and its implication in clinical practice for orthopaedic patients. We describe the process of selection of the orthopaedic panel, the evidence considered and the contribution of the panel to the latest guidelines from NICE on the prophylaxis against VTE, published in January 2010.

Acupuncture of chronic headache disorders in primary care: randomised controlled trial and economic analysis.

OBJECTIVES: To determine the effects of a policy of using acupuncture, compared with a policy of avoiding acupuncture, on headache in primary care patients with chronic headache disorders. The effects of acupuncture on medication use, quality of life, resource use and days off sick in this population and the cost-effectiveness of acupuncture were also examined. DESIGN: Randomised, controlled trial. SETTING: General practices in England and Wales. PARTICIPANTS: The study included 401 patients with chronic headache disorder, predominantly migraine. INTERVENTIONS: Patients were randomly allocated to receive up to 12 acupuncture treatments over 3 months or to a control intervention offering usual care. MAIN OUTCOME MEASURES: Outcome measures included headache score; assessment of Short Form 36 (SF-36) health status and use of medication at baseline, 3 months and 12 months; assessment of use of resources every 3 months; and assessment of incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: Headache score at 12 months, the primary end-point, was lower in the acupuncture group than in controls. The adjusted difference between means was 4.6. This result was robust to sensitivity analysis incorporating imputation for missing data. Patients in the acupuncture group experienced the equivalent of 22 fewer days of headache per year. SF-36 data favoured acupuncture, although differences reached significance only for physical role functioning, energy and change in health. Compared with controls, patients randomised to acupuncture used 15% less medication, made 25% fewer visits to GPs and took 15% fewer days off sick. Total costs during the 1-year period of the study were on average higher for the acupuncture group than for controls because of the acupuncture practitioners' costs. The mean health gain from acupuncture during the year of the trial was 0.021 QALYs, leading to a base-case estimate of GBP9180 per QALY gained. This result was robust to sensitivity analysis. Cost per QALY dropped substantially when the analysis incorporated likely QALY differences for the years after the trial. CONCLUSIONS: The study suggests that acupuncture leads to persisting, clinically relevant benefits for primary care patients with chronic headache, particularly migraine. It is relatively cost-effective compared with a number of other interventions provided by the NHS. Further studies could examine the duration of acupuncture effects beyond 1 year and the relative benefit to patients with migraine with compared to tension-type headache. Trials are also warranted examining the effectiveness and cost-effectiveness of acupuncture in patients with headache receiving more aggressive pharmacological management.

A randomised comparison of UK genetic risk counselling services for familial cancer: psychosocial outcomes.

The aim of the study was to compare psychosocial outcomes for 50 new clinic attendees, referred for cancer genetic counselling to five UK centres. The centres represented England, Scotland and Wales, and were randomly selected from groups ranked by different levels of clinical activity in cancer genetics practice. Questionnaires assessed demographic data, risk perception, mental health and use of health services pre-consultation and at 1 and 12 months follow-up. Satisfaction was measured for attendees and referring doctors at follow-up. A total of 256 unaffected adults fulfilled the study criteria. The five centres varied widely with respect to service organisation and activity, but all had a greater proportion of unaffected attendees with a breast cancer risk (61-91%) than either a bowel cancer risk (0-33%) or ovarian cancer risk (3-25%). There were no significant differences in the psychosocial data between centres pre-counselling. No significant change over time occurred for any of the centres for risk perception or general psychological distress. There were significant differences between centres in reduction of cancer worry from baseline to 12 months and with the number of women who were recommended to have mammographic surveillance who had not received this. Overall, one-third of women for whom mammography had been recommended had not been screened within 1 year of follow-up. Subsequent attendance at the GP, but not at a hospital, was associated with risk level, but differences between centres could not be analysed. Satisfaction differed significantly between centres for 4 : 14 aspects of service provision and with 3 : 17 items concerning communication; satisfaction was high overall. Over 90% of referring doctors were moderately/very satisfied with the service, but 23% were dissatisfied with waiting times and 19% with access to preventive treatment. Results differed significantly between centres for doctor's satisfaction with the provision of referral criteria and prescribing information. In conclusion, there were relatively few significant differences in psychosocial outcomes between centres, considering the wide variation in service organisation and activity. These significant differences were not consistent across the centres, therefore, differences could not be linked to specific aspects of service provision.

A systematic review of the role of bisphosphonates in metastatic disease.

OBJECTIVES: To identify evidence for the role of bisphosphonates in malignancy for the treatment of hypercalcaemia, prevention of skeletal morbidity and use in the adjuvant setting. To perform an economic review of current literature and model the cost effectiveness of bisphosphonates in the treatment of hypercalcaemia and prevention of skeletal morbidity. DATA SOURCES: Electronic databases (1966-June 2001). Cochrane register. Pharmaceutical companies. Experts in the field. Handsearching of abstracts and leading oncology journals (1999-2001). REVIEW METHODS: Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. Overall event rates were pooled in a meta-analysis, odds ratios (OR) were given with 95% confidence intervals (CI). Where data could not be combined, studies were reported individually and proportions compared using chi-squared analysis. Cost and cost-effectiveness were assessed by a decision analytic model comparing different bisphosphonate regimens for the treatment of hypercalcaemia; Markov models were employed to evaluate the use of bisphosphonates to prevent skeletal-related events (SRE) in patients with breast cancer and multiple myeloma. RESULTS: For acute hypercalcaemia of malignancy, bisphosphonates normalised serum calcium in >70% of patients within 2-6 days. Pamidronate was more effective than control, etidronate, mithramycin and low-dose clodronate, but equal to high dose clodronate, in achieving normocalcaemia. Pamidronate prolongs (doubles) the median time to relapse compared with clodronate or etidronate. For prevention of skeletal morbidity, bisphosphonates compared with placebo, significantly reduced the OR for fractures (OR [95% CI], vertebral, 0.69 [0.57-0.84], non-vertebral, 0.65 [0.54-0.79], combined, 0.65 [0.55-0.78]) radiotherapy 0.67 [0.57-0.79] and hypercalcaemia 0.54 [0.36-0.81] but not orthopaedic surgery 0.70 [0.46-1.05] or spinal cord compression 0.71 [0.47-1.08]. However, reduction in orthopaedic surgery was significant in studies that lasted over a year 0.59 [0.39-0.88]. Bisphosphonates significantly increased the time to first SRE but did not affect survival. Subanalyses were performed for disease groups, drugs and route of administration. Most evidence supports the use of intravenous aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to patients with primary operable breast cancer and no metastatic disease, significantly reduced the number of patients developing bone metastases. This benefit was not maintained once regular administration had been discontinued. Two trials reported significant survival advantages in the treated groups. Bisphosphonates reduce the number of bone metastases in patients with both early and advanced breast cancer. Bisphosphonates are well tolerated with a low incidence of side-effects. Economic modelling showed that for acute hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were most cost-effective. Zoledronate 4 mg was the most costly, but most cost-effective treatment. For skeletal morbidity, Markov models estimated that the overall cost of bisphosphonate therapy to prevent an SRE was GBP250 and GBP1500 per event for patients with breast cancer and multiple myeloma, respectively. Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where fractures are prevented. CONCLUSIONS: High dose aminobisphosphonates are most effective for the treatment of acute hypercalcaemia and delay time to relapse. Bisphosphonates significantly reduce SREs and delay the time to first SRE in patients with bony metastatic disease but do not affect survival. Benefit is demonstrated after administration for at least 6-12 months. The greatest body of evidence supports the use of intravenous aminobisphosphonates. Further evidence is required to support use in the adjuvant setting.

A descriptive study of UK cancer genetics services: an emerging clinical response to the new genetics.

The objective was to describe NHS cancer genetic counselling services and compare UK regions. The study design was a cross-sectional study over 4 weeks and attendee survey. The setting was 22 of the 24 regional cancer genetics services in the UK NHS. Participants were individuals aged over 18 attending clinics at these services. Outcome measures were staff levels, referral rates, consultation rates, follow-up plans, waiting time. There were only 11 dedicated cancer geneticists across the 22 centres. Referrals were mainly concerned with breast (63%), bowel (18%) and ovarian (12%) cancers. Only 7% of referrals were for men and 3% were for individuals from ethnic minorities. Referral rates varied from 76 to 410 per million per annum across the regions. Median waiting time for an initial appointment was 19 weeks, ranging across regions from 4 to 53 weeks. Individuals at population-level genetic risk accounted for 27% of consultations (range 0%, 58%). Shortfalls in cancer genetics staff and in the provision of genetic testing and cancer surveillance have resulted in large regional variations in access to care. Initiatives to disseminate referral and management guidelines to cancer units and primary care should be adequately resourced so that clinical genetics teams can focus on the genetic testing and management of high-risk families.

A minimum income for healthy living

There is overwhelming evidence of the role of food and nutrition in the maintenance and promotion of good health, from the avoidance of classic deficiency diseases to the role of antioxidants in the prevention of coronary heart disease and cancer. Hopefully, the man will be active and enjoy a lot of walking, in comfortable shoes and away from traffic. Such exercise is rewarding in mental refreshment, in sociality, and weight regulation with its multiple short and long-term metabolic benefits. Society, including social welfare, has been slow in coming to terms with the new health knowledge.

Screening for hypercholesterolaemia versus case finding for familial hypercholesterolaemia: a systematic review and cost-effectiveness analysis.

BACKGROUND: In the majority of people with familial hypercholesterolaemia (FH) the disorder is caused by a mutation of the low-density lipoprotein receptor gene that impairs its proper function, resulting in very high levels of plasma cholesterol. Such levels result in early and severe atherosclerosis, and hence substantial excess mortality from coronary heart disease. Most people with FH are undiagnosed or only diagnosed after their first coronary event, but early detection and treatment with hydroxymethylglutaryl-coenzyme (HMG CoA) reductase inhibitors (statins) can reduce morbidity and mortality. The prevalence of FH in the UK population is estimated to be 1 in 500, which means that approximately 110,000 people are affected. OBJECTIVES: To evaluate whether screening for FH is appropriate. To determine which system of screening is most acceptable and cost-effective. To assess the deleterious psychosocial effects of genetic and clinical screening for an asymptomatic treatable inherited condition. To assess whether the risks of screening outweigh potential benefits. DATA SOURCES: Relevant papers were identified through a search of the electronic databases. Additional papers referenced in the search material were identified and collected. Known researchers in the field were contacted and asked to supply information on unpublished or ongoing studies. INCLUSION/EXCLUSION CRITERIA: SCREENING AND TREATMENT: The review included studies of the mortality and morbidity associated with FH, the effectiveness and cost of treatment (ignoring pre-statin therapies in adults), and of the effectiveness or cost of possible screening strategies for FH. PSYCHOSOCIAL EFFECTS OF SCREENING: The search for papers on the psychological and social effects of screening for a treatable inherited condition was limited to the last 5 years because recent developments in genetic testing have changed the nature and implications of such screening tests. Papers focusing on genetic testing for FH and breast cancer were included. Papers relating to the risk of coronary heart disease with similarly modifiable outcome (non-FH) were also included. DATA EXTRACTION AND ASSESSMENT OF VALIDITY: A data assessment tool was designed to assess the quality and validity of the papers which reported primary data for the social and psychological effects of screening. Available guidelines for systematically reviewing papers concentrated on quantitative methods, and were of limited relevance. An algorithm was developed which could be used for both the qualitative and quantitative literature. MODELLING METHODS: A model was constructed to investigate the relative cost and effectiveness of various forms of population screening (universal or opportunistic) and case-finding screening (screening relatives of known FH cases). All strategies involved a two-stage process: first, identifying those people with cholesterol levels sufficiently elevated to be compatible with a diagnosis of FH, and then either making the diagnosis based on clinical signs and a family history of coronary disease or carrying out genetic tests. Cost-effectiveness has been measured in terms of incremental cost per year of life gained. RESULTS: MODELLING COST-EFFECTIVENESS: FH is a life-threatening condition with a long presymptomatic state. Diagnostic tests are reasonably reliable and acceptable, and treatment with statins substantially improves prognosis. Therefore, it is appropriate to consider systematic screening for this condition. Case finding amongst relatives of FH cases was the most cost-effective strategy, and universal systematic screening the least cost-effective. However, when targeted at young people (16 year olds) universal screening was also cost-effective. Screening patients admitted to hospital with premature myocardial infarction was also relatively cost-effective. Screening is least cost-effective in men aged over 35 years, because the gains in life expectancy are small. (ABSTRACT TRUNCA

A minimum income for healthy living.

BACKGROUND: Half a century of research has provided consensual evidence of major personal requisites of adult health in nutrition, physical activity and psychosocial relations. Their minimal money costs, together with those of a home and other basic necessities, indicate disposable income that is now essential for health. METHODS: In a first application we identified such representative minimal costs for healthy, single, working men aged 18-30, in the UK. Costs were derived from ad hoc survey, relevant figures in the national Family Expenditure Survey, and by pragmatic decision for the few minor items where survey data were not available. RESULTS: Minimum costs were assessed at 131.86 pound sterling per week (UK April 1999 prices). Component costs, especially those of housing (which represents around 40% of this total), depend on region and on several assumptions. By varying these a range of totals from 106.47 pound sterling to 163.86 pound sterling per week was detailed. These figures compare, 1999, with the new UK national minimum wage, after statutory deductions, of pound 105.84 at 18-21 years and 121.12 pound sterling at 22+ years for a 38 hour working week. Corresponding basic social security rates are 40.70 pound sterling to 51.40 pound sterling per week. INTERPRETATION: Accumulating science means that absolute standards of living, "poverty", minimal official incomes and the like, can now be assessed by objective measurement of the personal capacity to meet the costs of major requisites of healthy living. A realistic assessment of these costs is presented as an impetus to public discussion. It is a historical role of public health as social medicine to lead in public advocacy of such a national agenda.

Constructing confidence intervals for cost-effectiveness ratios: an evaluation of parametric and non-parametric techniques using Monte Carlo simulation.

The statistic of interest in most health economic evaluations is the incremental cost-effectiveness ratio. Since the variance of a ratio estimator is intractable, the health economics literature has suggested a number of alternative approaches to estimating confidence intervals for the cost-effectiveness ratio. In this paper, Monte Carlo simulation techniques are employed to address the question of which of the proposed methods is most appropriate. By repeatedly sampling from a known distribution and applying the different methods of confidence interval estimation, it is possible to calculate the coverage properties of each method to see if these correspond to the chosen confidence level. As the results of a single Monte Carlo experiment would be valid only for that particular set of circumstances, a series of experiments was conducted in order to examine the performance of the different methods under a variety of conditions relating to the sample size, the coefficient of variation of the numerator and denominator of the ratio, and the covariance between costs and effects in the underlying data. Response surface analysis was used to analyse the results and substantial differences between the different methods of confidence interval estimation were identified. The methods, both parametric and non-parametric, which assume a normal sampling distribution performed poorly, as did the approach based on simply combining the separate intervals on costs and effects. The choice of method for confidence interval estimation can lead to large differences in the estimated confidence limits for cost-effectiveness ratios. The importance of such differences is an empirical question and will depend to a large extent on the role of hypothesis testing in economic appraisal. However, where it is suspected that the sampling distribution is skewed, normal approximation methods produce particularly poor results and should be avoided.

Pulling cost-effectiveness analysis up by its bootstraps: a non-parametric approach to confidence interval estimation.

The statistic of interest in the economic evaluation of health care interventions is the incremental cost effectiveness ratio (ICER), which is defined as the difference in cost between two treatment interventions over the difference in their effect. Where patient-specific data on costs and health outcomes are available, it is natural to attempt to quantify uncertainty in the estimated ICER using confidence intervals. Recent articles have focused on parametric methods for constructing confidence intervals. In this paper, we describe the construction of non-parametric bootstrap confidence intervals. The advantage of such intervals is that they do not depend on parametric assumptions of the sampling distribution of the ICER. We present a detailed description of the non-parametric bootstrap applied to data from a clinical trial, in order to demonstrate the strengths and weaknesses of the approach. By examining the bootstrap confidence limits successively as the number of bootstrap replications increases, we conclude that percentile bootstrap confidence interval methods provide a promising approach to estimating the uncertainty of ICER point estimates. However, successive bootstrap estimates of bias and standard error suggests that these may be unstable; accordingly, we strongly recommend a cautious interpretation of such estimates.

Costs and cost effectiveness of cardiovascular screening and intervention: the British family heart study.

OBJECTIVE: To measure costs and cost effectiveness of the British family heart study cardiovascular screening and intervention programme. DESIGN: Cost effectiveness analysis of randomised controlled trial. Clinical and resource use data taken from trial and unit cost data from external estimates. SETTING: 13 general practices across Britain. SUBJECTS: 4185 men aged 40-59 and their 2827 partners. INTERVENTION: Nurse led programme using a family centered approach, with follow up according to degree of risk. MAIN OUTCOME MEASURES: Cost of the programme it self; overall short term cost to NHS; cost per 1% reduction in coronary risk at one year. RESULTS: Estimated cost of putting the programme into practice for one year was 63 pounds per person (95% confidence interval 60 pounds to 65 pounds). The overall short term cost to the health service was 77 pounds per man (29 pounds to 124 pounds) but only 13 pounds per woman (-48 pounds to 74 pounds), owing to differences in utilisation of other health service resources. The cost per 1% reduction in risk was 5.08 pounds per man (5.92 pounds including broader health service costs) and 5.78 pounds per woman (1.28 pounds taking into account wider health service savings). CONCLUSIONS: The direct cost of the programme to a four partner practice of 7500 patients would be approximately 58,000 pounds. Annually, 8300 pounds would currently be paid to a practice of this size working to the maximum target on the health promotion bands, plus any additional reimbursement of practice staff salaries for which the practice qualified. The broader short term costs to the NHS may augment these costs for men but offset them considerably for women.

What can be concluded from the Oxcheck and British family heart studies: commentary on cost effectiveness analyses.

OBJECTIVES: To provide a commentary on the economic evaluations of the Oxcheck and British family heart studies: direct comparison of their relative effectiveness and cost effectiveness; comparisons with other interventions; and consideration of problems encountered. DESIGN: Modelling from cost and effectiveness data to estimate of cost per life year gained. SUBJECTS: Middle aged men and women. INTERVENTIONS: Screening for cardiovascular risk factors followed by appropriate lifestyle advice and drug intervention in general practice, and other primary coronary risk management strategies. MAIN OUTCOME MEASURES: Life years gained; cost per life year gained. RESULTS: Depending on the assumed duration of risk reduction, the programme cost per discounted life year gained ranged from 34,800 pounds for a 1 year duration to 1500 pounds for 20 years for the British family heart study and from 29,300 pounds to 900 pounds for Oxcheck. These figures exclude broader net clinical and cost effects and longer term clinical and cost effects other than coronary mortality. CONCLUSIONS: Despite differences in underlying methods, the estimates in the two economic analyses of the studies can be directly compared. Neither study was large enough to provide precise estimates of the overall net cost. Modelling to cost per life year gained provides more readily interpretable measures. These estimates emphasise the importance of the relatively weak evidence on duration effect. Only if the effect lasts at least five years is the Oxcheck programme likely to be cost effective. The effect must last for about 10 years to justify the extra cost associated with the British family heart study.