Claire McKenna

EOS 2D/3D X-ray Imaging System: A Systematic Review and Economic Evaluation

BACKGROUND EOS is a biplane X-ray imaging system manufactured by EOS Imaging (formerly Biospace Med, Paris, France). It uses slot-scanning technology to produce a high-quality image with less irradiation than standard imaging techniques. OBJECTIVE To determine the clinical effectiveness and cost-effectiveness of EOS two-dimensional (2D)/three-dimensional (3D) X-ray imaging system for the evaluation and monitoring of scoliosis and other relevant orthopaedic conditions. DATA SOURCES For the systematic review of EOS, electronic databases (MEDLINE, Allied and Complementary Medicine Database, BIOSIS Previews, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, EMBASE, Health Management Information Consortium, Inspec, ISI Science Citation Index and PASCAL), clinical trials registries and the manufacturers website were searched from 1993 to November 2010. REVIEW METHODS A systematic review of studies comparing EOS with standard X-ray [film, computed radiography (CR) or digital radiography] in any orthopaedic condition was performed. A narrative synthesis was undertaken. A decision-analytic model was developed to assess the cost-effectiveness of EOS in the relevant indications compared with standard X-ray and incorporated the clinical effectiveness of EOS and the adverse effects of radiation. The model incorporated a lifetime horizon to estimate outcomes in terms of quality-adjusted life-years (QALYs) and costs from the perspective of the NHS. RESULTS Three studies met the inclusion criteria for the review. Two studies compared EOS with film X-ray and one study compared EOS with CR. The three included studies were small and of limited quality. One study used an earlier version of the technology, the Charpak system. Both studies comparing EOS with film X-ray found image quality to be comparable or better with EOS overall. Radiation dose was considerably lower with EOS: ratio of means for posteroanterior spine was 5.2 (13.1 for the study using the Charpak system); ratio of means for the lateral spine was 6.2 (15.1 for the study using the Charpak system). The study comparing EOS with CR found image quality to be comparable or better with EOS. Radiation dose was considerably lower with EOS than CR; ratio of means for the centre of the back was 5.9 and for the proximal lateral point 8.8. The lowest ratio of means was at the nape of the neck, which was 2.9. No other outcomes were assessed in the included studies, such as implications for patient management from the nature and quality of the image. Patient throughput is the major determinant of the cost-effectiveness of EOS. The average cost per procedure of EOS decreases with utilisation. Using estimates of patient throughput at national level from Hospital Episode Statistics data suggests that EOS is not cost-effective for the indications considered. Throughput in the region of 15,100 to 26,500 (corresponding to a workload of 60 to 106 patient appointments per working day) for EOS compared with a throughput of only 7530 for CR (30 patient appointments per working day) is needed to achieve an incremental cost-effectiveness ratio of £30,000 per QALY. EOS can be shown to be cost-effective only when compared with CR if the utilisation for EOS is about double the utilisation of CR. LIMITATIONS The main limitation of the systematic review of the clinical effectiveness of EOS was the limited number and quality of the data available. In particular, there were no studies assessing the potential health benefits arising from the quality and nature of the image, over and above those associated with reduced radiation exposure. Uncertainty in the model inputs was not fully explored owing to a lack of reporting of standard deviations or confidence intervals in the published literature for most of the parameters. As a result, uncertainty in the cost-effectiveness results was not presented. CONCLUSIONS Radiation dose is considerably lower with EOS than standard X-ray, whereas image quality remains comparable or better with EOS. However, the long-term health benefits from reduced radiation exposure with EOS are very small and there was a lack of data on other potential patient health benefits. The implications of any changes in the quality and nature of the EOS image compared with standard X-ray, for patient health outcomes, needs to be assessed. Given the higher cost of an EOS machine, utilisation is the major determinant of cost-effectiveness. Estimates of patient throughput at national level suggest that EOS is not cost-effective. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Omalizumab for the treatment of severe persistent allergic asthma: a systematic review and economic evaluation

BACKGROUND Allergic asthma is a long-term disorder of the airways resulting from overexpression of immunoglobulin E (IgE) in response to environmental allergens. Patients with poorly controlled asthma are at high risk of exacerbations requiring additional treatment, including hospitalisations. Severe exacerbations are potentially life threatening. Guidelines identify five treatment steps for both adults and children. Omalizumab (Xolair(®)) is a recombinant DNA-derived humanised monoclonal antibody indicated as an add-on therapy in patients aged ≥ 6 years with severe persistent allergic asthma uncontrolled at treatment step 4 or 5. OBJECTIVE To determine the clinical effectiveness, safety and cost-effectiveness of omalizumab, as an add-on therapy to standard care, within its licensed indication, compared with standard therapy alone for the treatment of severe persistent allergic asthma in adults and adolescents aged ≥ 12 years and children aged 6-11 years. DATA SOURCES Eleven electronic databases (including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials) and additional sources including regulatory agency reports were searched from inception to October 2011. Additional data sources include: the manufacturers submission (MS); two previous National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) submissions; and existing reviews on the safety of omalizumab and oral corticosteroids (OCSs). REVIEW METHODS Systematic reviews of the clinical effectiveness and cost-effectiveness evidence for omalizumab were performed. The primary outcome was number of clinically significant (CS) exacerbations. Other outcomes included asthma symptoms, unscheduled health-care use, asthma-related mortality, OCS use and health-related quality of life (HRQoL). Because of methodological and clinical heterogeneity between trials, a narrative synthesis was applied. Pragmatic reviews with best evidence syntheses were used to assess adverse events of omalizumab and OCSs. The cost-effectiveness of omalizumab was assessed from the perspective of the UK NHS in the two separate populations: adults and adolescents, and children, using a cohort Markov model. Costs and outcomes were discounted at 3.5% per annum. Results are presented for additional subgroup populations: (1) hospitalised for asthma in the previous year, (2) adults and adolescents on maintenance OCSs and (3) three or more exacerbations in the previous year. RESULTS Eleven randomised controlled trials (RCTs) and 13 observational studies were identified, including four RCTs/subgroups in the adult licensed population and one subgroup in children. A minority of patients were on maintenance OCSs. No evidence comparing omalizumab with OCSs was identified. Omalizumab significantly reduced the incidence of CS exacerbations in both adults and children [adults: INvestigatioN of Omalizumab in seVere Asthma Trial (INNOVATE): rate ratio 0.74; 95% CI 0.55 to 1.00; children IA-05 EUP (the a priori subgroup of patients who met the European Medicines Agency license criteria) 0.66; 95% CI 0.44 to 1.00]. Significant benefits were observed for a range of other outcomes in adults. Subgroup evidence showed benefits in adults on maintenance OCSs. Evidence for an OCS-sparing effect of omalizumab was limited but consistent. Omalizumab is available as 75 mg and 150 mg prefilled syringes at prices of £128.07 and £256.15 respectively. The incremental cost-effectiveness ratio (ICER) for adults and adolescents is £83,822 per quality-adjusted life-year (QALY) gained, whereas the ICER for children is £78,009 per QALY gained. The results are similar for the subgroup population of ≥ 3 exacerbations in the previous year, whereas the ICER for the other subgroup populations are lower; £46,431 for the hospitalisation subgroup in adults and adolescents, £44,142 for the hospitalisation subgroup in children and £50,181 for the maintenance OCS subgroup. CONCLUSION Omalizumab reduces the incidence of CS exacerbations in adults and children, with benefits on other outcomes in adults. Limited, underpowered subgroup evidence exists that omalizumab reduces exacerbations and OCS requirements in adults on OCSs. Evidence in children is weaker and more uncertain. The ICERs are above conventional NHS thresholds of cost-effectiveness. The key drivers of cost-effectiveness are asthma-related mortality risk and, to a lesser extent, HRQoL improvement and OCS-related adverse effects. An adequately powered double-blind RCT in both adults and children on maintenance OCSs and an individual patient data meta-analysis of existing trials should be considered. A registry of all patients on omalizumab should be established. STUDY REGISTRATION The study was registered as PROSPERO CRD42011001625. FUNDING This report was commissioned by the National Institute for Health Research Health Technology Assessment programme on behalf of NICE as project number HTA 10/128/01.

Cost-effectiveness of radiofrequency catheter ablation for the treatment of atrial fibrillation in the United Kingdom

Objective: To assess the cost-effectiveness of radiofrequency catheter ablation (RFCA) compared with anti-arrhythmic drug (AAD) therapy for the treatment of atrial fibrillation (AF) from the perspective of the UK NHS. Design: Bayesian evidence synthesis and decision analytical model. Methods: A systematic review and meta-analysis was conducted and Bayesian statistical methods used to synthesise the effectiveness evidence from randomised control trials. A decision analytical model was developed to assess the costs and consequences associated with the primary outcome of the trials over a lifetime time horizon. Main outcome measure: Costs from a health service perspective and outcomes measured as quality-adjusted life years (QALYs). Results: The incremental cost-effectiveness ratio of RFCA varied between £7763 and £7910 for each additional QALY according to baseline risk of stroke, with a probability of being cost-effective from 0.98 to 0.99 for a cost-effectiveness threshold of £20 000. Results were sensitive to the duration of quality of life benefits from treatment. Conclusions: RFCA is potentially cost-effective for the treatment of paroxysmal AF in patients’ predominantly refractory to AAD therapy provided the quality-of-life benefits from treatment are maintained for more than 5 years. These findings remain subject to limitations in the existing evidence regarding the nature of life benefits and the prognostic importance of restoring normal sinus rhythm conferred using RFCA.

Cost-effectiveness of cardiovascular magnetic resonance in the diagnosis of coronary heart disease: an economic evaluation using data from the CE-MARC study

Objective To evaluate the cost-effectiveness of diagnostic strategies for coronary heart disease (CHD) derived from the CE-MARC study. Design Cost-effectiveness analysis using a decision analytic model to compare eight strategies for the diagnosis of CHD. Setting Secondary care out-patients (Cardiology Department). Patients Patients referred to cardiologists for the further evaluation of symptoms thought to be angina pectoris. Interventions Eight different strategies were considered, including different combinations of exercise treadmill testing (ETT), single-photon emission CT (SPECT), cardiovascular magnetic resonance (CMR) and coronary angiography (CA). Main outcome measures Costs expressed as UK sterling in 2010–2011 prices and health outcomes in quality-adjusted life-years (QALYs). The time horizon was 50 years. Results Based on the characteristics of patients in the CE-MARC study, only two strategies appear potentially cost-effective for diagnosis of CHD, both including CMR. The choice is between two strategies: one in which CMR follows a positive or inconclusive ETT, followed by CA if CMR is positive or inconclusive (Strategy 3 in the model); and the other where CMR is followed by CA if CMR is positive or inconclusive (Strategy 5 in the model). The more cost-effective of these two rests on the threshold cost per QALY gained below which health systems define an intervention as cost-effective. Strategy 3 appears cost-effective at the lower end of the threshold range used in the UK (£20 000 per QALY gained), while Strategy 5 appears cost-effective at the higher end of the threshold range (£30 000 per QALY). The results are robust to various sources of uncertainty although prior likelihood of CHD requiring revascularisation and the rate at which false negative patients are eventually appropriately identified do impact upon the results. Conclusions The CE-MARC study showed that CMR had superior diagnostic accuracy to SPECT and concluded that CMR should be more widely used in the investigation of patients with CHD. The economic evaluation results show that using CMR is also a cost-effective strategy and supports the wider adoption of this modality.

A systematic review of the clinical effectiveness of EOS 2D/3D X-ray imaging system

PurposeTo evaluate the available evidence for the clinical effectiveness of the EOS® 2D/3D X-ray imaging system for the evaluation and monitoring of scoliosis and other relevant orthopaedic conditions.MethodsA systematic review of studies of EOS®, compared with standard X-ray film, computed radiography or digital radiography, of patients with orthopaedic conditions was undertaken. Ten electronic databases were searched. The quality of the included studies was assessed and a narrative synthesis undertaken.ResultsThree small, limited quality studies, primarily of children with scoliosis, were identified. No patient health outcomes were reported. Spinal image quality was comparable or better overall with EOS®. Radiation dose was considerably lower with EOS® than X-ray film or computed radiography; the mean entrance surface dose was over five times lower with EOS® for the posteroanterior spine radiograph and over six times lower for the lateral spine radiograph.ConclusionsThe available clinical evidence for EOS® is limited to establishing its basic technical ability. The technical advancements associated with EOS® (the ability to generate a full body scan and to construct a three-dimensional model from synchronously acquired lateral and posteroanterior images) have not been evaluated in terms of their ability to improve patient outcomes. Whilst radiation dose is a concern for orthopaedic patients who require repeated imaging, it is difficult to quantify the reductions in radiation dose seen with EOS® in terms of patient health benefits. Clinical studies that investigate the impact of EOS® on patient management are required.

Omalizumab for the Treatment of Severe Persistent Allergic Asthma in Children Aged 6–11 Years

Following a licence extension to include those aged 6–11 years, the National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of omalizumab (Novartis Pharmaceuticals UK) to submit evidence for the clinical and cost effectiveness of this drug for patients with severe persistent allergic asthma in this age bracket. NICE had previously considered the use of omalizumab in patients aged 12 years and over. The Centre for Reviews and Dissemination (CRD) and the Centre for Health Economics (CHE) at the University of York were commissioned as the Evidence Review Group (ERG) to critically appraise the evidence presented by the manufacturer. This article summarizes that review of the evidence, the deliberations of the NICE Appraisal Committee and the resulting NICE guidance.The ERG critically reviewed the evidence presented in the manufacturer’s submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. The relevant patient population was patients aged 6–11 years of age with severe persistent allergic immunoglobulin E-mediated asthma whose condition remained uncontrolled despite best standard care with high-dose inhaled corticosteroids and a long-acting inhaled β2-agonist. The main clinical effectiveness data were derived from a pre-planned subgroup analysis of a single randomized controlled trial comparing omalizumab plus standard therapy against standard therapy alone. At a 52-week follow-up, the only outcome to show a statistically significant benefit of omalizumab compared with placebo was the number of exacerbations defined as ‘clinically significant’ [CS] (relative risk [RR] 0.504; 95% CI 0.350, 0.725; p<0.001). At the ERG’s request, the manufacturer provided analyses stratified by baseline exacerbation rate, which indicated the effect of omalizumab on CS exacerbations was statistically significant only for those children with ≥3 exacerbations as baseline. The ERG identified a number of issues relating to the clinical effectiveness results: it was unclear whether the pre-planned subgroup analysis had sufficient power; the definition of CS exacerbation was less severe than that used in UK clinical practice; and the method for imputing exacerbations for those who withdrew from treatment may have underestimated the exacerbation rate.The incremental cost-effectiveness ratio based on the manufacturer’s results was considerably above the threshold range stated in the NICE Guide to the Methods of Technology Appraisal. The ERG identified numerous issues relating to the cost-effectiveness results, which included the following: the 10-year time horizon for treatment may exceed that in clinical practice; the assumption of constant exacerbation rates over a lifetime given that adolescence is expected to impact on the severity of asthma; and whether it is appropriate to use health-related quality-of-life data collected in adults for children.The ERG concluded that omalizumab appears to reduce CS exacerbations but there was no evidence of improvement in daily symptoms, CS severe (CSS) exacerbations or hospitalization rates. The main driver of cost effectiveness was the reduction in asthma-related mortality associated with a reduction in CSS exacerbations. As the number of CSS exacerbations avoided was low, as is asthma-related mortality in children, the potential small gain in QALYs associated with omalizumab was not sufficient to compensate for the high treatment cost even under the most favourable scenario analyses. The Appraisal Committee recommended that omalizumab should not be routinely provided for the treatment of severe persistent allergic asthma in children aged 6–11 years.

Addressing adoption and research design decisions simultaneously: the role of value of sample information analysis.

Methods to estimate the cost-effectiveness of technologies are well developed with increasing experience of their application to inform adoption decisions in a timely way. However, the experience of using similarly explicit methods to inform the associated research decisions is less well developed despite appropriate methods being available with an increasing number of applications in health. The authors demonstrate that evaluation of both adoption and research decisions is feasible within typical time and resource constraints relevant to policy decisions, even in situations in which data are sparse and formal elicitation is required. In addition to demonstrating the application of expected value of sample information (EVSI) in these circumstances, the authors examine and carefully distinguish the impact that the research decision is expected to have on patients while enrolled in the trial, those not enrolled, and once the trial reports. In doing so, the authors are able to account for the range of opportunity cost associated with research and evaluate a number of research designs including length of follow-up and sample size. The authors also explore the implications for research design of conducting research while the technology is approved for widespread use and whether approval should be withheld until research reports. In doing so, the authors highlight the impact of irrecoverable opportunity costs when the initial costs of a technology are compensated only by later gains in health outcome.

Dronedarone for the Treatment of Atrial Fibrillation

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dronedarone (Multaq®, Sanofi-Aventis Limited, UK) to submit evidence on the clinical and cost effectiveness of the anti-arrhythmic drug (AAD) for the treatment of atrial fibrillation (AF) and atrial flutter, as part of the Institute’s single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics, both at the University of York, were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE’s subsequent decisions regarding the use of dronedarone within the UK NHS.The ERG review comprised a critique of the submitted evidence on the clinical effectiveness and cost effectiveness of dronedarone. The ERG examined the search strategy used to obtain relevant evidence, the selection of studies included in the assessment, outcome measures chosen and statistical methods employed. The ERG also validated the manufacturer’s decision analytic model and used it to explore the robustness of the cost-effectiveness results to key assumptions.The main clinical effectiveness evidence supporting the use of dronedarone as a treatment for AF came from four randomized controlled trials. These trials were compared with a broader set of trials examining the effectiveness of other AADs for AF: amiodarone, sotalol and class 1c agents (flecainide and propafenone). The evidence suggested that all AADs decreased the recurrence of AF but dronedarone had the smallest effect. A mixed treatment comparison analysis of the trials showed that dronedarone was associated with a lower risk of all-cause mortality than other AADs, but this was highly uncertain. There was limited evidence to assess the effect of dronedarone on stroke, and no statistically significant differences between dronedarone and other AADs were found for treatment discontinuation.From the evidence presented by the manufacturer, dronedarone appeared highly cost effective in each of the population groups examined compared with using standard baseline therapy alone as first-line treatment, or compared with sotalol or amiodarone as first-line AAD, with incremental cost-effectiveness ratios (ICERs) well below £20 000 per QALY gained. The ICER for dronedarone relative to class 1c agents was around £19000 per QALY. Although the evidence presented by the manufacturer indicated that dronedarone was cost effective, the estimates of treatment effect relative to other AADs and safety in the longer term were highly uncertain. The NICE Appraisal Committee in its preliminary guidance did not recommend the use of dronedarone for AF. However, following the response from a large number of consultees and commentators, NICE revised its preliminary guidance to allow the use of the drug in a specific subgroup of AF patients with additional cardiovascular risk factors.

Enhanced external counterpulsation for the treatment of stable angina and heart failure: a systematic review and economic analysis.

OBJECTIVES To determine the clinical effectiveness and cost-effectiveness of enhanced external counterpulsation (EECP) compared with usual care and placebo for refractory stable angina and heart failure, and to undertake analyses of the expected value of information to assess the potential value of future research on EECP. DATA SOURCES Major electronic databases were searched between November 2007 and March 2008. REVIEW METHODS A systematic review of the literature was undertaken and a decision model developed to compare EECP treatment with no treatment in adults with chronic stable angina. RESULTS Five studies were included in the review. In the Multicenter Study of Enhanced External Counterpulsation (MUST-EECP), time to greater than or equal to 1-mm ST segment depression (exercise-induced ischaemia) was statistically significantly improved in the EECP group compared with the control group (sham EECP), mean difference (MD) 41 seconds [95% confidence interval (CI) 9.10-73.90]. However, there was no statistically significant difference between the EECP and control groups in the change in exercise duration from baseline to end of treatment, self-reported angina episodes or daily nitroglycerin use, and the clinical significance of the limited benefits was unclear. There was also a lack of data on long-term outcomes. There were more withdrawals due to adverse events in the EECP group than in the control group, as well as a greater proportion of patients with adverse events [relative risk (RR) 2.13, 95% CI 1.35-3.38]. The three non-randomised studies compared EECP with elective percutaneous coronary intervention (PCI) and usual care. There was a high risk of selection bias in all three studies and the results should be treated with considerable caution. The study comparing an EECP registry with a PCI registry reported similar 1-year all-cause mortality in both groups. In the Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) trial, patients with heart failure were randomised to EECP or to usual care (pharmacotherapy only). At 6 months post treatment, the proportion of patients achieving at least a 60-second increase in exercise duration was higher in the EECP group (RR 1.39, 95% CI 0.89-2.16), but the proportion with an improvement in peak VO2 was similar in both groups. The clinical significance of this is unclear. The proportion of patients in the EECP group with an improvement in New York Heart Association classification was higher (RR 2.25, 95% CI 1.25-4.06) at 6 months, as was mean exercise duration, MD 34.6 (95% CI -4.86 to 74.06). There were more withdrawals in the EECP group than in the control group as a result of adverse events (RR 1.05, 95% CI 0.67-1.66). There were limitations in the generalisability of results of the trial and, again, a lack of data on long-term outcomes. The review of cost-effectiveness evidence found only one unpublished study but demonstrated that the long-term maintenance of quality of life benefits of EECP is central to the estimate of its cost-effectiveness. The incremental cost-effectiveness ratio of EECP was 18,643 pounds for each additional quality-adjusted life-year (QALY), with a probability of being cost-effective of 0.44 and 0.70 at cost-effectiveness thresholds of 20,000 pounds and 30,000 pounds per QALY gained respectively. Results were sensitive to the duration of health-related quality of life (HRQoL) benefits from treatment. CONCLUSIONS The results from a single randomised controlled trial (MUST-EECP) do not provide firm evidence of the clinical effectiveness of EECP in refractory stable angina or in heart failure. High-quality studies are required to investigate the benefits of EECP, whether these outweigh the common adverse effects and its long-term cost-effectiveness in terms of quality of life benefits.

Rimonabant for the treatment of overweight and obese people.

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of rimonabant for the treatment of obese or overweight patients based upon a review of the manufacturers submission to the National Centre for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submissions main evidence came from four randomised controlled trials. Rimonabant resulted in a significantly greater benefit than placebo for all primary weight loss outcomes. At 1 year, rimonabant had a statistically significant beneficial effect on systolic blood pressure, high-density lipoprotein cholesterol, triglycerides and fasting plasma glucose in diabetics and non-diabetics, and glycosylated haemoglobin in diabetics. Improvements were maintained over 2 years with rimonabant; withdrawal of rimonabant at 1 year resulted in a reduction in weight loss until there was no difference from placebo at 2 years. Psychiatric adverse events were experienced by 26% and 14% of rimonabant and placebo patients respectively; figures for symptoms of depression were 9% and 5% respectively. Pairwise comparisons of orlistat, sibutramine and rimonabant showed beneficial effects of rimonabant over orlistat and sibutramine for weight loss outcomes; however, response hurdles imposed on orlistat or sibutramine in clinical practice may not have been applied in the orlistat and sibutramine trials. The manufacturers Markov cohort model evaluated rimonabant versus orlistat, sibutramine and diet and exercise alone for three base-case populations. The incremental cost-effectiveness ratio (ICER) of rimonabant varied from 10,534 pounds to 13,236 pounds per quality-adjusted life-year (QALY) versus diet and exercise, to 8977 pounds to 12,138 pounds per QALY versus orlistat, to 1463 pounds to 3908 pounds per QALY versus sibutramine. In subgroup analysis there was a wider variation in the ICER estimates although none exceeded 20,000 pounds per QALY. The ICER of rimonabant remained under 20,000 pounds per QALY in reanalyses by the manufacturer and the ERG, with the results sensitive to the source of health-related quality of life (HRQoL) benefits in the model. Four treatment strategies were modelled in comparisons of rimonabant versus diet and exercise alone and orlistat and sibutramine in which rimonabant was continued only in patients achieving 5% weight loss at 3, 6, 9 or 12 months. In pairwise comparisons rimonabant remained below a threshold of 30,000 pounds per QALY in 70% of the comparisons reported. The results were most sensitive to the decrement applied to depression and the costs of screening for depression. In conclusion, areas of uncertainty remain in relation to the clinical effectiveness and cost-effectiveness of rimonabant, for example lack of evidence on long-term outcomes and the effect of rimonabant on cardiovascular events, developing diabetes and mortality, and lack of data on the HRQoL benefits associated with rimonabant. The lack of response hurdles applied to sibutramine and orlistat means that the comparator strategies were not considered by the ERG to reflect their respective product licenses or current NHS use. The NICE guidance issued as a result of the STA states that rimonabant is recommended as an adjunct to diet and exercise for adults who are obese or overweight and who have had an inadequate response to, are intolerant of or are contraindicated to orlistat and sibutramine.