Dilemmas in the interpretation of diagnostic accuracy studies on presurgical workup for epilepsy surgery.

We conducted a systematic review to determine which noninvasive technologies should be used in the workup for epilepsy surgery to identify structural or functional abnormalities to help locate the site of seizure onset. The review focused on patients where there was insufficient confidence, in either the decision to go to surgery or the site at which surgery should be conducted, after the initial clinical examination. The majority of the studies identified were single-gate diagnostic accuracy studies; none were randomized controlled trials, and only one reported the effect of the test results on the decision making process. It became apparent that the data derived from diagnostic accuracy studies could not be used to answer the review question. This article focuses on the methods used to extract data from the diagnostic accuracy studies, the difficulties interpreting the resulting data, why such studies are not an appropriate study design in this setting, and how the evidence-base can be improved.

Cost-effectiveness of aldosterone antagonists for the treatment of post-myocardial infarction heart failure.

OBJECTIVE: To assess the cost-effectiveness of eplerenone versus spironolactone as an adjunctive therapy to standard care in patients with heart failure (HF) following a myocardial infarction (post-MI) from the perspective of the National Health Service in the United Kingdom. METHODS: A systematic review was conducted, and a Bayesian meta-regression approach was used to establish the relative effectiveness of eplerenone and spironolactone by using evidence from randomized controlled trials. A decision analytic model was developed to assess the costs and consequences associated with the primary outcome of the trials over a lifetime time horizon. RESULTS: The incremental cost-effectiveness ratio of eplerenone compared with that of standard care alone was £ 4457 and £ 7893 for each additional quality-adjusted life-year when 2-year and lifetime treatment duration was assumed, respectively. In both scenarios, spironolactone did not appear cost-effective compared with eplerenone. The results were sensitive to the higher relative effectiveness estimated for eplerenone compared with spironolactone from the meta-regression. When a class effect was assumed for the effect on mortality and hospitalizations, spironolactone emerged as the most cost-effective treatment. CONCLUSIONS: Eplerenone appears more cost-effective than spironolactone for the treatment of post-MI HF. These findings, however, remain subject to important uncertainties regarding the effects of treatment on major clinical events. An adequately powered, well-conducted randomized controlled trial that directly compares spironolactone and eplerenone may be required to provide more robust evidence on the optimal management of post-MI HF. Despite these uncertainties, the use of an aldosterone antagonist was consistently demonstrated to be a highly cost-effective strategy for the management of post-MI HF in the National Health Service.

Measuring expectations of benefit from treatment in acupuncture trials: a systematic review.

OBJECTIVES: We conducted a systematic review that aimed to document and describe how (1) expectation of benefit from treatment (response expectancies) were measured and reported in acupuncture trials, and (2) examine any effect on outcomes. DESIGN: We searched MEDLINE, EMBASE, AMED, CIHAHL, CENTRAL and Science and Technology Proceedings up to November 2007 for randomised (RCT) and quasi-randomised (CCT) controlled trials and prospective controlled cohorts of acupuncture as treatment for a medical or psychological condition in adults. An update citation search was conducted in April 2010. We included studies that mentioned soliciting response expectancies. RESULTS: We found 58 RCTs that fulfilled our inclusion criteria. Around half referenced one of five published instruments, most of which were designed to measure sham credibility and included one question on response expectancy. A wide range of question phrasing and response scales was used. There was some evidence that response scales may influence the measurement of expectations. Eight trials analysed the association between pre-randomisation expectations for assigned treatment and outcomes, and six the effect of pre-randomisation expectations across all patients independent of treatment allocation. Some showed associations but others did not. CONCLUSIONS: There is some evidence that response expectancies interact with outcomes in acupuncture trials however the variety of question phrasing and analysis methods precludes drawing a firm conclusion about for whom and under which circumstance. To further our understanding of expectations, more methodological work is needed to standardise the questions and response scales that are used.

The use of measures of obesity in childhood for predicting obesity and the development of obesity-related diseases in adulthood: a systematic review and meta-analysis.

BACKGROUND: It is uncertain which simple measures of childhood obesity are best for predicting future obesity-related health problems and the persistence of obesity into adolescence and adulthood. OBJECTIVES: To investigate the ability of simple measures, such as body mass index (BMI), to predict the persistence of obesity from childhood into adulthood and to predict obesity-related adult morbidities. To investigate how accurately simple measures diagnose obesity in children, and how acceptable these measures are to children, carers and health professionals. DATA SOURCES: Multiple sources including MEDLINE, EMBASE and The Cochrane Library were searched from 2008 to 2013. METHODS: Systematic reviews and a meta-analysis were carried out of large cohort studies on the association between childhood obesity and adult obesity; the association between childhood obesity and obesity-related morbidities in adulthood; and the diagnostic accuracy of simple childhood obesity measures. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and a modified version of the Quality in Prognosis Studies (QUIPS) tool. A systematic review and an elicitation exercise were conducted on the acceptability of the simple measures. RESULTS: Thirty-seven studies (22 cohorts) were included in the review of prediction of adult morbidities. Twenty-three studies (16 cohorts) were included in the tracking review. All studies included BMI. There were very few studies of other measures. There was a strong positive association between high childhood BMI and adult obesity [odds ratio 5.21, 95% confidence interval (CI) 4.50 to 6.02]. A positive association was found between high childhood BMI and adult coronary heart disease, diabetes and a range of cancers, but not stroke or breast cancer. The predictive accuracy of childhood BMI to predict any adult morbidity was very low, with most morbidities occurring in adults who were of healthy weight in childhood. Predictive accuracy of childhood obesity was moderate for predicting adult obesity, with a sensitivity of 30% and a specificity of 98%. Persistence of obesity from adolescence to adulthood was high. Thirty-four studies were included in the diagnostic accuracy review. Most of the studies used the least reliable reference standard (dual-energy X-ray absorptiometry); only 24% of studies were of high quality. The sensitivity of BMI for diagnosing obesity and overweight varied considerably; specificity was less variable. Pooled sensitivity of BMI was 74% (95% CI 64.2% to 81.8%) and pooled specificity was 95% (95% CI 92.2% to 96.4%). The acceptability to children and their carers of BMI or other common simple measures was generally good. LIMITATIONS: Little evidence was available regarding childhood measures other than BMI. No individual-level analysis could be performed. CONCLUSIONS: Childhood BMI is not a good predictor of adult obesity or adult disease; the majority of obese adults were not obese as children and most obesity-related adult morbidity occurs in adults who had a healthy childhood weight. However, obesity (as measured using BMI) was found to persist from childhood to adulthood, with most obese adolescents also being obese in adulthood. BMI was found to be reasonably good for diagnosing obesity during childhood. There is no convincing evidence suggesting that any simple measure is better than BMI for diagnosing obesity in childhood or predicting adult obesity and morbidity. Further research on obesity measures other than BMI is needed to determine which is the best tool for diagnosing childhood obesity, and new cohort studies are needed to investigate the impact of contemporary childhood obesity on adult obesity and obesity-related morbidities. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005711. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Problems caused by heterogeneity in meta-analysis: a case study of acupuncture trials.

OBJECTIVES: To illustrate the pitfalls of using meta-analysis to combine estimates of effect in trials that are highly varied and have a high potential for bias. METHODS: We used a random-effects meta-analysis to pool the results of 51 sham-controlled acupuncture trials of chronic pain published in English before 2008 and explored the heterogeneity using meta-regression. We repeated the process on a subset of these trials that used a visually credible non-penetrating sham device as control (N = 12). RESULTS: In both analyses there were high levels of heterogeneity and many studies were at risk from potential bias. The heterogeneity was not explained by meta-regression. CONCLUSIONS: Trials of interventions that have high potential for bias, such as many in the acupuncture literature, do not meet the assumptions of the statistical procedure that underlie random-effects meta-analysis. Even in the absence of bias, heterogeneity in meta-analyses is not accounted for by the CIs around the pooled estimate.

The added clinical and economic value of diagnostic testing for epilepsy surgery.

The costs, benefits and risks associated with diagnostic imaging investigations for epilepsy surgery necessitate the identification of an optimal pathway in the pre-surgical workup. In order to assess the added value of additional investigations a full cost-effectiveness evaluation should be conducted, taking into account all of the life-time costs and benefits associated with undertaking additional investigations. This paper considers and applies the appropriate framework against which a full evaluation should be assessed. We conducted a systematic review to evaluate the progression of the literature through this framework, finding that only isolated elements of added value have been appropriately evaluated. The results from applying the full added value framework are also presented, identifying an optimal strategy for pre-surgical evaluation for temporal lobe epilepsy surgery. Our results suggest that additional FDG-PET and invasive EEG investigations after an initially discordant MRI and video-EEG appears cost-effective, and that the value of subsequent invasive-EEGs is closely linked to the maintenance of longer-term benefits after surgery. It is integral to the evaluation of imaging technologies in the work-up for epilepsy surgery that the impact of the use of these technologies on clinical decision-making, and on further treatment decisions, is considered fully when informing cost-effectiveness.

Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups.

BACKGROUND: There is currently no standard practice for the monitoring of patients receiving treatment for osteoporosis. Repeated dual-energy X-ray absorptiometry (DXA) is commonly used for monitoring treatment response, but it has its limitations. Bone turnover markers have advantages over DXA as they are non-invasive, relatively cheap and can detect changes in bone turnover rates earlier. However, they do have disadvantages, particularly high within- and between-patient variability. The ability of bone turnover markers to identify treatment non-responders and predict future fracture risk has yet to be established. OBJECTIVES: We aimed to determine the clinical effectiveness, test accuracy, reliability, reproducibility and cost-effectiveness of bone turnover markers for monitoring the response to osteoporosis treatment. DATA SOURCES: We searched 12 electronic databases (including MEDLINE, EMBASE, The Cochrane Library and trials registries) without language restrictions from inception to March 2012. We hand-searched three relevant journals for the 12 months prior to May 2012, and websites of five test manufacturers and the US Food and Drug Administration (FDA). Reference lists of included studies and relevant reviews were also searched. REVIEW METHODS: A systematic review of test accuracy, clinical utility, reliability and reproducibility, and cost-effectiveness of two formation and two resorption bone turnover markers, in patients being treated for osteoporosis with any of bisphosphonate [alendronate (Fosamax, MSD), risedronate (Actonel, Warner Chilcott Company), zolendronate (Zometa, Novartis)], raloxifene (Evista, Eli Lilly and Company Ltd), strontium ranelate (Protelos, Servier Laboratories Ltd), denosumab (Prolia, Amgen Ltd) or teriparatide (Forsteo, Eli Lilly and Company Ltd), was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Given the breadth of the review question, a range of study designs and outcome measures were eligible. The development of a decision model was planned to determine the cost-effectiveness of bone turnover markers for informing changes in patient management if clinical effectiveness could be established. RESULTS: Forty-two studies (70 publications) met the inclusion criteria; none evaluated cost-effectiveness. Only five were randomised controlled trials (RCTs); these assessed only the impact of bone marker monitoring on aspects of adherence. No RCTs evaluated the effectiveness of bone turnover marker monitoring on treatment management. One trial suggested that feedback of a good response decreased non-persistence [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53 to 0.95], and feedback of a poor response increased non-persistence (HR 2.22, 95% CI 1.27 to 3.89); it is not clear whether or not the trial recruited a population representative of that seen in clinical practice. Thirty-three studies reported results of some assessment of test accuracy, mostly correlations between changes in bone turnover and bone mineral density. Only four studies reported on intra- or interpatient reliability and reproducibility in treated patients. Overall, the results were inconsistent and inconclusive, owing to considerable clinical heterogeneity across the studies and the generally small sample sizes. As clinical effectiveness of bone turnover monitoring could not be established, a decision-analytic model was not developed. CONCLUSIONS: There was insufficient evidence to inform the choice of which bone turnover marker to use in routine clinical practice to monitor osteoporosis treatment response. The research priority is to identify the most promising treatment-test combinations for evaluation in subsequent, methodologically sound, RCTs. In order to determine whether or not bone turnover marker monitoring improves treatment management decisions, and ultimately impacts on patient outcomes in terms of reduced incidence of fracture, RCTs are required. Given the large number of potential patient population-treatment-test combinations, the most promising combinations would initially need to be identified in order to ensure that any RCTs focus on evaluating those strategies. As a result, the research priority is to identify these promising combinations, by either conducting small variability studies or initiating a patient registry to collect standardised data. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Controlling practitioner-patient relationships in acupuncture trials: a systematic review and meta-regression.

BACKGROUND: In trials, 'therapist intensive' complex interventions are typically delivered over time, during which a relationship between the practitioner and participant may develop. Such relationships are sometimes criticised as obscuring any 'true' treatment effect. Limiting interactions is one strategy that might be used to try to control for the effect of a therapeutic relationship. OBJECTIVES: We conducted systematic review into the rationale, methods and effects of constraining relationships in controlled trials and cohort studies of acupuncture, including studies published before 2008 with an update citation search in 2010. METHODS: We searched six databases without keyword restrictions. Meta-analysis and meta-regression were used to explore the effect of relationship constraint on pain outcomes. RESULTS: Eighty-one of 785 (10.3%) trials reported constraining relationships. Most did not state the reason for constraint, describe the nature of the limitation, provide information on how the constrained relationship was monitored or note protocol adherence. Where a reason was reported, this was primarily to maintain participant blinding, rarely was it stated that the constraint was to control the therapeutic relationship. We found no evidence of an effect of constraint on pain outcomes (percentage heterogeneity explained, p=0.89). These results were robust to variation in trial quality and design. CONCLUSIONS: Acupuncture trials appear to be constrained mostly to try to prevent participant unblinding to their allocated treatment, not to control the therapeutic relationship. The apparent lack of monitoring and negligible effects on pain outcomes of the included trials indicate the need for more high-quality randomised controlled trials investigating the effect of constraint.

Insufficient evidence to determine the impact of patient preferences on clinical outcomes in acupuncture trials: a systematic review.

OBJECTIVE: To review reporting of preferences in acupuncture studies and their effect on clinical outcomes. STUDY DESIGN AND SETTING: Systematic review of published randomized and quasi-randomized controlled trials of acupuncture reporting participant preferences for randomization or treatment or using a preference design. RESULTS: Of the 31 included trials, 5 reported on randomization preference, 18 on treatment preference, and 1 reported on both. Seven used a preference design. Four out of seven trials noted that the group with preferences had different baseline characteristics (less education, worse baseline measure score, and greater or fewer years with pain). There was a tendency for greater attrition in nonpreference arms at 6 months but not earlier. Around three-quarters of participants turned down randomization in favor of nontrial treatment, and preference for acupuncture was around 20% when offered multiple treatments. Questions used to elicit preferences varied across trials and were poorly reported. Ten trials reported the effects of preferences on outcomes; only one detected a statistically (but not clinically) significant difference. CONCLUSION: There is little evidence that preferences cause detectable effects on outcomes in acupuncture trials; however, trials use inconsistent methods and poorly report these data. Monitoring the level and effect of preferences in trials is recommended.

Dabigatran for the prevention of stroke and systemic embolism in atrial fibrillation: A NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dabigatran etexilate (Boehringer Ingelheim Ltd, UK) to submit evidence for the clinical and cost-effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) as part of the NICE single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group (ERG). This article presents a summary of the manufacturer's submission, the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service. Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen (DBG sequential), in which patients under 80 years are treated with dabigatran 150 mg twice daily (DBG150) and patients 80 years and over are given dabigatran 110 mg twice daily (DBG110). NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost-effective compared with warfarin or aspirin for patients with non-valvular AF and one or more risk factors. The RE-LY trial, a large multi-centre non-inferiority randomised clinical trial, was the primary source of clinical evidence. DBG150 was shown to be non-inferior, and subsequently superior to warfarin, for the primary outcome of all stroke/systemic embolism. DBG110 was found to be non-inferior to warfarin. Results were presented for a post hoc subgroup analysis for patients under and over 80 years of age, where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80 years of age. This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen. The economic evaluation compared the costs and outcomes of DBG110, DBG150 and DBG sequential against warfarin, aspirin, and aspirin plus clopidogrel. Across the three dosing regimens, dabigatran was associated with greater costs and better health outcomes than warfarin; however, DBG150 offered the most benefits and dominated DBG110 and DBG sequential (i.e. less costly and more effective). The cost-effectiveness of DBG150 was less favourable for patients well controlled on warfarin. In the first appraisal meeting, the committee issued a 'minded no' decision until additional analyses on the licensed DBG sequential regimen were presented by the manufacturer. These additional analyses indicated that the incremental cost-effectiveness ratio (ICER) of the DBG sequential regimen compared with warfarin ranged from £8,388 to £18,987 per quality-adjusted life year (QALY) gained depending on the level of monitoring costs assumed for warfarin. Patients on warfarin would need to be within therapeutic range 83-85 % of the time for the ICER to exceed £30,000 per additional QALY. Following consideration of the additional evidence and the responses from a large number of consultees and commentators, the committee recommended dabigatran as DBG sequential as an option for the prevention of stroke and systemic embolism in people with non-valvular AF with one or more risk factors for ischaemic stroke.

Omalizumab for the treatment of severe persistent allergic asthma in children aged 6-11 years: a NICE single technology appraisal.

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 ß2-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.

Prescription of anti-influenza drugs for healthy adults: a systematic review and meta-analysis.

In publicly funded health systems with finite resources, management decisions are based on assessments of clinical effectiveness and cost-effectiveness. The UK National Institute for Health and Clinical Excellence commissioned a systematic review to inform their 2009 update to guidance on the use of antiviral drugs for the treatment of influenza. We searched databases for studies of the use of neuraminidase inhibitors for the treatment of seasonal influenza. We present the results for healthy adults (ie, adults without known comorbidities) and people at-risk of influenza-related complications. There was an overall reduction in the median time to symptom alleviation in healthy adults by 0.57 days (95% CI -1.07 to -0.08; p=0.02; 2701 individuals) with zanamivir, and 0.55 days (95% CI -0.96 to -0.14; p=0.008; 1410 individuals) with oseltamivir. In those at risk, the median time to symptom alleviation was reduced by 0.98 days (95% CI -1.84 to -0.11; p=0.03; 1252 individuals) with zanamivir, and 0.74 days (95% CI -1.51 to 0.02; p=0.06; 1472 individuals) with oseltamivir. Little information was available on the incidence of complications. In view of the advantages and disadvantages of different management strategies for controlling seasonal influenza in healthy adults recommending the use of antiviral drugs for the treatment of people presenting with symptoms is unlikely to be the most appropriate course of action.

Duplex ultrasonography, magnetic resonance angiography, and computed tomography angiography for diagnosis and assessment of symptomatic, lower limb peripheral arterial disease: systematic review.

OBJECTIVES: To determine the diagnostic accuracy of duplex ultrasonography, magnetic resonance angiography, and computed tomography angiography, alone or in combination, for the assessment of lower limb peripheral arterial disease; to evaluate the impact of these assessment methods on management of patients and outcomes; and to evaluate the evidence regarding attitudes of patients to these technologies and summarise available data on adverse events. DESIGN: Systematic review. METHODS: Searches of 11 electronic databases (to April 2005), six journals, and reference lists of included papers for relevant studies. Two reviewers independently selected studies, extracted data, and assessed quality. Diagnostic accuracy studies were assessed for quality with the QUADAS checklist. RESULTS: 107 studies met the inclusion criteria; 58 studies provided data on diagnostic accuracy, one on outcomes in patients, four on attitudes of patients, and 44 on adverse events. Quality assessment highlighted limitations in the methods and quality of reporting. Most of the included studies reported results by arterial segment, rather than by limb or by patient, which does not account for the clustering of segments within patients, so specificities may be overstated. For the detection of stenosis of 50% or more in a lower limb vessel, contrast enhanced magnetic resonance angiography had the highest diagnostic accuracy with a median sensitivity of 95% (range 92-99.5%) and median specificity of 97% (64-99%). The results were 91% (89-99%) and 91% (83-97%) for computed tomography angiography and 88% (80-98%) and 96% (89-99%) for duplex ultrasonography. A controlled trial reported no significant differences in outcomes in patients after treatment plans based on duplex ultrasonography alone or conventional contrast angiography alone, though in 22% of patients supplementary contrast angiography was needed to form a treatment plan. The limited evidence available suggested that patients preferred magnetic resonance angiography (with or without contrast) to contrast angiography, with half expressing no preference between magnetic resonance angiography or duplex ultrasonography (among patients with no contraindications for magnetic resonance angiography, such as claustrophobia). Where data on adverse events were available, magnetic resonance angiography was associated with the highest proportion of adverse events, but these were mild. The most severe adverse events, although rare, were mainly associated with contrast angiography. CONCLUSIONS: Contrast enhanced magnetic resonance angiography seems to be more specific than computed tomography angiography (that is, better at ruling out stenosis over 50%) and more sensitive than duplex ultrasonography (that is, better at ruling in stenosis over 50%) and was generally preferred by patients over contrast angiography. Computed tomography angiography was also preferred by patients over contrast angiography; no data on patients' preference between duplex ultrasonography and contrast angiography were available. Where available, contrast enhanced magnetic resonance angiography might be a viable alternative to contrast angiography.