Evidence For Clinical Effectiveness Research Articles

Assessing the utility of an online registry for patients monitoring their own warfarin therapy

AimsTo evaluate the utility of an online self-report registry for patient self-monitoring and self-management (PSM) of warfarin therapy.MethodsA prospective observational study of UK-based patients undertaking PSM and recording their international...

PRM214 - Meta-Analysis to Support Technology Submissions to Health Technology Assessment Authorities: Criticisms By Nice And Evidence Review Groups in the Uk

The quality of evidence used in manufacturers’ submissions to health technology assessment (HTA) bodies is an important factor for the success of technology appraisals (TA). Indirect comparisons (IC) and network meta-analyses (NMA) are used in health policy decisions via the clinical effectiveness evidence in HTA submissions to the National Institute for Health and Care Excellence (NICE). The aim of this study was to: (i) assess the use of ICs and NMAs in HTA submissions to NICE; (ii) identify criticisms of ICs and NMAs in TAs generated by NICE and the Evidence Review Group (ERG); (iii) provide key insights and recommendations to minimise criticism of an IC or NMA in future HTA submissions. The NICE website was interrogated to identify both TAs and the associated ERG/final appraisal document reports published from January 2013 to June 2015 in any therapeutic setting. A large proportion of the TAs analysed included ICs or NMAs. Common criticisms were related to the identification of data and the study selection for inclusion, study heterogeneity and the inadequate reporting of methods and analyses. The majority of criticisms of evidence synthesis submitted to NICE were related to issues around the primary evidence included in the analyses rather than the statistical methods of the analyses. To avoid many of the criticisms identified in this study a transparent approach to the reporting of the ICs and NMAs (and systematic review) is recommended.

Lenalidomide for the Treatment of Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated with Deletion 5q Cytogenetic Abnormality: An Evidence Review of the NICE Submission from Celgene.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormality, as part of the Institute’s single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company’s submission, the ERG review, and the NICE’s subsequent decisions. The ERG reviewed the evidence for clinical and cost effectiveness of the technology, as submitted by the manufacturer to the NICE. The ERG searched for relevant additional evidence and validated the manufacturer’s decision analytic model to examine the robustness of the cost-effectiveness results. Clinical effectiveness was obtained from a three-arm, European, randomized, phase III trial among red blood cell (RBC) transfusion-dependent patients with low-/intermediate-1-risk del5q31 MDS. The primary endpoint was RBC independence for ≥26 weeks, and was reached by a higher proportion of patients in the lenalidomide 10 and 5 mg groups compared with placebo (56.1 and 42.6 vs 5.9 %, respectively; both p < 0.001). The option of dose adjustments after 16 weeks due to dose-limiting toxicities or lack of response made long-term effectiveness estimates unreliable, e.g. overall survival (OS). The de novo model of the manufacturer included a Markov state-transition cost-utility model implemented in Microsoft Excel. The base-case incremental cost-effectiveness ratio (ICER) of the manufacturer was £56,965. The ERG assessment indicated that the modeling structure represented the course of the disease; however, a few errors were identified and some of the input parameters were challenged. In response to the appraisal documentation, the company revised the economic model, which increased the ICER to £68,125 per quality-adjusted life-year. The NICE Appraisal Committee (AC) did not recommend lenalidomide as a cost-effective treatment. Subsequently, the manufacturer submitted a Patient Access Scheme (PAS) that provided lenalidomide free of charge for patients who remained on treatment after 26 cycles. This PAS improved the ICER to £25,300, although the AC considered the proportion of patients who received treatment beyond 26 cycles, and hence the ICER, to be uncertain. Nevertheless, the AC accepted a commitment from the manufacturer to publish, once available, data on the proportion of patients eligible for the PAS, and believed this provided reassurance that lenalidomide was a cost-effective treatment for low- or intermediate-1-risk MDS patients.

The Cost-Effectiveness of Low-Cost Essential Antihypertensive Medicines for Hypertension Control in China: A Modelling Study.

BackgroundHypertension is China’s leading cardiovascular disease risk factor. Improved hypertension control in China would result in result in enormous health gains in the world’s largest population. A computer simulation model projected the cost-effectiveness of hypertension treatment in Chinese adults, assuming a range of essential medicines list drug costs.Methods and FindingsThe Cardiovascular Disease Policy Model-China, a Markov-style computer simulation model, simulated hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring costs, disease-related costs, and quality-adjusted life years (QALYs) gained by preventing cardiovascular disease or lost because of drug side effects in untreated hypertensive adults aged 35–84 y over 2015–2025. Cost-effectiveness was assessed in cardiovascular disease patients (secondary prevention) and for two blood pressure ranges in primary prevention (stage one, 140–159/90–99 mm Hg; stage two, ≥160/≥100 mm Hg). Treatment of isolated systolic hypertension and combined systolic and diastolic hypertension were modeled as a reduction in systolic blood pressure; treatment of isolated diastolic hypertension was modeled as a reduction in diastolic blood pressure. One-way and probabilistic sensitivity analyses explored ranges of antihypertensive drug effectiveness and costs, monitoring frequency, medication adherence, side effect severity, background hypertension prevalence, antihypertensive medication treatment, case fatality, incidence and prevalence, and cardiovascular disease treatment costs. Median antihypertensive costs from Shanghai and Yunnan province were entered into the model in order to estimate the effects of very low and high drug prices. Incremental cost-effectiveness ratios less than the per capita gross domestic product of China (11,900 international dollars [Int$] in 2015) were considered cost-effective. Treating hypertensive adults with prior cardiovascular disease for secondary prevention was projected to be cost saving in the main simulation and 100% of probabilistic simulation results. Treating all hypertension for primary and secondary prevention would prevent about 800,000 cardiovascular disease events annually (95% uncertainty interval, 0.6 to 1.0 million) and was borderline cost-effective incremental to treating only cardiovascular disease and stage two patients (2015 Int$13,000 per QALY gained [95% uncertainty interval, Int$10,000 to Int$18,000]). Of all one-way sensitivity analyses, assuming adherence to taking medications as low as 25%, high Shanghai drug costs, or low medication efficacy led to the most unfavorable results (treating all hypertension, about Int$47,000, Int$37,000, and Int$27,000 per QALY were gained, respectively). The strengths of this study were the use of a recent Chinese national health survey, vital statistics, health care costs, and cohort study outcomes data as model inputs and reliance on clinical-trial-based estimates of coronary heart disease and stroke risk reduction due to antihypertensive medication treatment. The limitations of the study were the use of several sources of data, limited clinical trial evidence for medication effectiveness and harms in the youngest and oldest age groups, lack of information about geographic and ethnic subgroups, lack of specific information about indirect costs borne by patients, and uncertainty about the future epidemiology of cardiovascular diseases in China.ConclusionsExpanded hypertension treatment has the potential to prevent about 800,000 cardiovascular disease events annually and be borderline cost-effective in China, provided low-cost essential antihypertensive medicines programs can be implemented.

Fomepizole versus ethanol in the treatment of acute methanol poisoning: Comparison of clinical effectiveness in a mass poisoning outbreak

Context. Mass or cluster methanol poisonings are frequently reported from around the world. The comparative effectiveness of ethanol and fomepizole as antidotes for methanol poisoning is unknown due to the difficulty of performing a randomized controlled trial. Objective. During an outbreak of mass poisonings in the Czech Republic in 2012–2014, we compared the effects of antidotes on the frequency of health sequelae and mortality. Methods. The study was designed as a cross-sectional case series and quasi-case–control study. Patients with a diagnosis of methanol poisoning on admission to hospitals were identified for the study. Diagnosis was established when (i) a history of recent ingestion of illicit spirits was available and serum methanol was higher than 6.2 mmol/L (20 mg/dL), or (ii) there was a history/clinical suspicion of methanol poisoning, and serum methanol was above the limit of detection with at least two of the following: pH < 7.3, serum bicarbonate < 20 mmol/L, and anion gap or AG ≥ 20 mmol/L. Fomepizole was given as a bolus dose of 15 mg/kg i.v. diluted in isotonic saline, followed by 10 mg/kg every 12 h (every 4 h during hemodialysis); ethanol was administered both intravenously as a 10% solution in 5% glucose, and per os in boluses of 20% solution. Multivariate regression was applied to determine the effect of antidote on outcome. Additionally, for a retrospective quasi-case–control study, a control group of patients treated with ethanol, matched carefully on severity of poisoning and other key parameters, was selected. Results. Data were obtained from 100 hospitalized patients with confirmed poisoning: 25 patients treated with fomepizole were compared with 68 patients receiving ethanol (seven patients did not receive any antidote). More severely acidotic (p < 0.001) and late-presenting (>12 h; p = 0.028) patients received fomepizole more often than ethanol, as reflected in the higher number of fomepizole-treated patients being intubated (p = 0.009). No association was found between the type of antidote and the survival in either the case series (p = 0.205) or the quasi-control groups (p = 0.705) in which patients were very closely matched to minimize confounding by allocation. In the multivariate analysis, positive serum ethanol (odds ratio [OR], 10.8; 95% confidence interval [CI], 2.9–39.9) and arterial blood pH (OR, 3.7; 95% CI, 1.3–10.5) on admission were the only independent variables for the survival. The median intensive care unit length of stay was 6 (range, 2–22) days in the fomepizole group and 4 (range, 1–33) days in the ethanol group (p = 0.131). There were no differences in the use of elimination techniques between the two groups (neither in the full material (n = 100), nor the case–control groups (n = 50)). Conclusions. This study on antidotes for methanol poisoning did not show any evidence of different clinical effectiveness. Although ethanol is generally associated with a higher incidence of complications, this study suggests that both antidotes are similarly effective and that ethanol should not be avoided on grounds of effectiveness.

Developing a framework for estimating the potential impact of obesity interventions in a European city.

Obesity is a global challenge for healthy populations. It has given rise to a wide range of public health interventions, focusing on supportive environments and lifestyle change, including diet, physical activity and behavioural change initiatives. Impact is variable. However, more evidence is slowly becoming available and is being used to develop new interventions. In a period of austerity, momentum is building to review these initiatives and understand what they do, how they do it and how they fit together. Our project seeks to develop a relatively straight forward systematic framework using readily accessible data to map the complex web of initiatives at a policy, population, group and individual level aiming to promote healthy lifestyles, diet and physical activity levels or to reduce obesity through medical treatments in a city or municipality population. It produces a system for classifying different types of interventions into groupings which will enable commissioners to assess the scope and distribution of interventions and make a judgement about gaps in provision and the likely impact on mean body mass index (BMI) as a proxy measure for health. Estimated impact in each level or type of intervention is based upon a summary of the scientific evidence of clinical and/or cost effectiveness. Finally it seeks, where possible, to quantify the potential effects of different types of interventions on BMI and produce a cost per unit of BMI reduced. This approach is less sophisticated but identifies the areas where more sophisticated evaluation would add value.

Gap Between Evidence and Patient Access: Policy Implications for Bariatric and Metabolic Surgery in the Treatment of Obesity and its Complications.

Despite consistently supportive evidence of clinical effectiveness and economic advantages compared with currently available non-surgical obesity treatments, patient access to bariatric and metabolic surgery (BMS) is impeded. To address this gap and better understand the relationship between value and access, the objectives of this study were twofold: (i) identify the multidimensional barriers to adoption of BMS created by clinical guidelines, public policies, and health technology assessments; and, most importantly, (ii) develop recommendations for stakeholders to improve patient access to BMS. Updated public policies focused on treatment and clinical guidelines that reflect the demonstrated advantages of BMS, patient education on safety and effectiveness, updated reimbursement policies, and additional data on long-term BMS effectiveness are needed to improve patient access.

Assessment-Based Home Treatment for People with Severe Psychotic Disorders

Although there is growing evidence for clinical effectiveness of crisis resolution teams (also called Home Treatment Teams) for patients with severe psychotic disorders, a lot of studies suffer from poor model fidelity, which leads to an ignorance of specific effective factors. Here we present the implementation of an assessment-based Home Treatment in Germany. Assessment-derived therapeutic tasks are shared between team members by a manualized process. We visited 32 patients almost 600 times in 15 months. The median was 15.5 visits per patient. Adherence to Home Treatment intervention was significantly stronger (unplanned discharge 16 %) compared to prior hospitalization (unplanned discharge 50 %) (Chi-square test, p = 0.003). Applying this model, a detailed definition of specific tasks for team members leads to a high model fidelity and increases patients' compliance to therapy.

The prognostic utility of tests of platelet function for the detection of 'aspirin resistance' in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation.

The use of aspirin is well established for secondary prevention of cardiovascular disease. However, a proportion of patients suffer repeat cardiovascular events despite being prescribed aspirin treatment. It is uncertain whether or not this is due to an inherent inability of aspirin to sufficiently modify platelet activity. This report aims to investigate whether or not insufficient platelet function inhibition by aspirin ('aspirin resistance'), as defined using platelet function tests (PFTs), is linked to the occurrence of adverse clinical outcomes, and further, whether or not patients at risk of future adverse clinical events can be identified through PFTs. To review systematically the clinical effectiveness and cost-effectiveness evidence regarding the association between PFT designation of 'aspirin resistance' and the risk of adverse clinical outcome(s) in patients prescribed aspirin therapy. To undertake exploratory model-based cost-effectiveness analysis on the use of PFTs. Bibliographic databases (e.g. MEDLINE from inception and EMBASE from 1980), conference proceedings and ongoing trial registries up to April 2012. Standard systematic review methods were used for identifying clinical and cost studies. A risk-of-bias assessment tool was adapted from checklists for prognostic and diagnostic studies. (Un)adjusted odds and hazard ratios for the association between 'aspirin resistance', for different PFTs, and clinical outcomes are presented; however, heterogeneity between studies precluded pooling of results. A speculative economic model of a PFT and change of therapy strategy was developed. One hundred and eight relevant studies using a variety of PFTs, 58 in patients on aspirin monotherapy, were analysed in detail. Results indicated that some PFTs may have some prognostic utility, i.e. a trend for more clinical events to be associated with groups classified as 'aspirin resistant'. Methodological and clinical heterogeneity prevented a quantitative summary of prognostic effect. Study-level effect sizes were generally small and absolute outcome risk was not substantially different between 'aspirin resistant' and 'aspirin sensitive' designations. No studies on the cost-effectiveness of PFTs for 'aspirin resistance' were identified. Based on assumptions of PFTs being able to accurately identify patients at high risk of clinical events and such patients benefiting from treatment modification, the economic model found that a test-treat strategy was likely to be cost-effective. However, neither assumption is currently evidence based. Poor or incomplete reporting of studies suggests a potentially large volume of inaccessible data. Analyses were confined to studies on patients prescribed aspirin as sole antiplatelet therapy at the time of PFT. Clinical and methodological heterogeneity across studies precluded meta-analysis. Given the lack of robust data the economic modelling was speculative. Although evidence indicates that some PFTs may have some prognostic value, methodological and clinical heterogeneity between studies and different approaches to analyses create confusion and inconsistency in prognostic results, and prevented a quantitative summary of their prognostic effect. Protocol-driven and adequately powered primary studies are needed, using standardised methods of measurements to evaluate the prognostic ability of each test in the same population(s), and ideally presenting individual patient data. For any PFT to inform individual risk prediction, it will likely need to be considered in combination with other prognostic factors, within a prognostic model. This study is registered as PROSPERO 2012:CRD42012002151. The National Institute for Health Research Health Technology Assessment programme.

Paradigms, politics and pragmatics: psychotherapy in primary care in City and Hackney – a new model for the NHS

Whilst an earlier paper (Part 1) in this journal describes the historical, political and economic drivers behind the creation of the City and Hackney Primary Care Psychotherapy Consultation Service (PCPCS), this paper (Part 2) focuses on exploring the context within which the service functions. The paper provides an overview of its operational model and is organised into 10 sections. The first section outlines the service's clinical practice, whilst the second addresses the value of GP consultations as a core part of the PCPCS's provision. The third section addresses how the service, as departure from a more ‘pure’ psychoanalytic tradition of providing longer-term therapy, has managed its provision of brief treatments. There is a description of how the service manages its team of multi-disciplinary clinicians and their work in a variety of micro-cultures, conveying some of the challenges faced by the service and the team since its inception. Thereafter, the quantitative and qualitative evidence for the service's clinical and cost effectiveness is assessed, including outcome results and findings from a health economic evaluation. To illustrate some of the service's work in practice, some disguised clinical vignettes are presented. The paper also summarises the service's recent clinical innovations, as well as its contribution to the field of research, audit and training. Finally, the way forward for the service is considered in the context of current and emerging trends in psychological provision in primary care.

Assessment-based Home Treatment for People with Schizophrenia Spectrum Disorder

Introduction There is a growing evidence for clinical effectiveness of Home Treatment for patients with severe psychotic disorders . Here we present the development and implementation of a manualised assessment-based Home Treatment in Germany. Objectives We compared the 6-month effectiveness of an assessment-based Home Treatment in patients with schizophrenia spectrum disorder to standard care in a catchment area design. Aims The primary outcome criteria was the rehospitalisation rate. Secondary outcomes comprised improvement of symptoms, functioning, quality of life, medication adherence and satisfaction with care. Methods Assessments were carried out at baseline and at 3 and 6 month. Inpatient admission and treatment contacts were assessed from the hospital database. Results We visited 20 patients with severe psychotic disorder (ICD10: F2.x) almost 400 times in twelve months. The median was 15.5 visits per patient. The intervention resulted in a highly significant reduction of the rehospitalisation rate (−51%, P Conclusions Applying assessment-based Home Treatment for patients with severe psychotic disorders is an alternative treatment compared with standard care resulting in a significant lower rehospitalisation rate with an equivalent clinical outcome.

Interventions to treat premature ejaculation: a systematic review short report.

Premature ejaculation (PE) is commonly defined as ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the person wishes it. PE can be either lifelong and present since first sexual experiences (primary), or acquired (secondary), beginning later (Godpodinoff ML. Premature ejaculation: clinical subgroups and etiology. J Sex Marital Ther 1989;15:130-4). Treatments include behavioural and pharmacological interventions. To systematically review evidence for clinical effectiveness of behavioural, topical and systemic treatments for PE. The following databases were searched from inception to 6 August 2013 for published and unpublished research evidence: MEDLINE; EMBASE; Cumulative Index to Nursing and Allied Health Literature; The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects and the Health Technology Assessment database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science. The US Food and Drug Administration website and the European Medicines Agency (EMA) website were also searched. Randomised controlled trials (RCTs) in adult men with PE were eligible (or non-RCTs in the absence of RCTs). RCT data were extrapolated from review articles when available. The primary outcome was intravaginal ejaculatory latency time (IELT). Data were meta-analysed when possible. Other outcomes included sexual satisfaction, control over ejaculation, relationship satisfaction, self-esteem, quality of life, treatment acceptability and adverse events (AEs). A total of 103 studies (102 RCTs, 65 from reviews) were included. RCTs were available for all interventions except yoga. The following interventions demonstrated significant improvements (p < 0.05) in arithmetic mean difference in IELT compared with placebo: topical anaesthetics - eutectic mixture of local anaesthetics (EMLA(®), AstraZeneca), topical eutectic mixture for PE (Plethora Solutions Ltd) spray; selective serotonin reuptake inhibitors (SSRIs) - citalopram (Cipramil(®), Lundbeck), escitalopram (Cipralex(®), Lundbeck), fluoxetine, paroxetine, sertraline, dapoxetine (Priligy(®), Menarini), 30 mg or 60 mg; serotonin-noradrenaline reuptake inhibitors - duloxetine (Cymbalta(®), Eli Lilly & Co Ltd); tricyclic antidepressants - inhaled clomipramine 4 mg; phosphodiesterase-5 (PDE5) inhibitors - vardenafil (Levitra(®), Bayer), tadalafil (Cialis(®), Eli Lilly & Co Ltd); opioid analgesics - tramadol (Zydol SR(®), Grünenthal). Improvements in sexual satisfaction and other outcomes compared with placebo were evident for SSRIs, PDE5 inhibitors and tramadol. Outcomes for interventions not compared with placebo were as follows: behavioural therapies - improvements over wait list control in IELT and other outcomes, behavioural therapy plus pharmacotherapy better than either therapy alone; alpha blockers - terazosin (Hytrin(®), AMCO) not significantly different to antidepressants in ejaculation control; acupuncture - improvements over sham acupuncture in IELT, conflicting results for comparisons with SSRIs; Chinese medicine - improvements over treatment as usual; delay device - improvements in IELT when added to stop-start technique; yoga - improved IELT over baseline, fluoxetine better than yoga. Treatment-related AEs were evident with most pharmacological interventions. Although data extraction from reviews was optimised when more than one review reported data for the same RCT, the reliability of the data extraction within these reviews cannot be guaranteed by this assessment report. Several interventions significantly improved IELT. Many interventions also improved sexual satisfaction and other outcomes. However, assessment of longer-term safety and effectiveness is required to evaluate whether or not initial treatment effects are maintained long term, whether or not dose escalation is required, how soon treatment effects end following treatment cessation and whether or not treatments can be stopped and resumed at a later time. In addition, assessment of the AEs associated with long-term treatment and whether or not different doses have differing AE profiles is required. This study is registered as PROSPERO CRD42013005289. The National Institute for Health Research Health Technology Assessment programme.

Economic evaluations of contingency management in illicit drug misuse programmes: A systematic review.

UK clinical guidelines published in 2007 recommended contingency management (CM) as an adjunct to opiate substitution therapy. However, CM has not been adopted in the UK despite evidence of clinical effectiveness. Evidence for the cost-effectiveness of CM is less clear and will need to be explored if CM is to be adopted by national health systems in countries such as the UK. Systematic review and descriptive synthesis of published economic evaluations. The review identified nine published studies that could be classified as economic evaluations. These were all based within US treatment settings, and five were conducted by the same group of authors. All studies found that the addition of CM to usual care increased both costs and effects (commonly drug abstinence or medication adherence). This review confirms that the existing evidence base for cost-effectiveness has limited generalisability beyond the original research clinical settings and populations. The data were not sufficiently strong to make any conclusion about the cost-effectiveness of CM. More relevant and comprehensive evidence for cost-effectiveness than currently exists is needed.

Dispositivos interespinosos y hernia discal. Estudio morfogeométrico y clínico de 71 casos tratados con microdiscectomía L4-L5 asociada a colocación de espaciador

A controversial indication of interspinous spacers is their use as a complement to discectomy. At the present time, there is no solid clinical evidence of effectiveness of that association, which might result from variability in spacer positioning, restricting its correct biomechanical actions. In this study our goal was to identify and analyse the variability in the placement of an interspinous spacer, and to investigate its relationship with the clinical results. We performed a retrospective study on X-ray films from 71 patients suffering from disc herniation in L4-L5 who underwent surgery in our hospital, consisting of: microdiscectomy and biomed interspinous spacer implantation. The geomorphometric techniques used to analyse the data were procrustes superimposition and principal components analysis. We compared the clinical results (using the Herron and Turner scale), segmental lordosis and surgical distraction with the geomorphometric parameters. Significant morphological variability was found in the implant position showing cephalo-caudal translation and clockwise-counterclockwise rotations. This variability did not correlate with clinical results. A relationship with anatomical features (lordosis) and additional surgical distraction was identified. A different morphology of implant-segment configuration was identified in cases with recurrence of disc herniation. Geometric morphometrics allowed identifying high variability in the final placement of interspinous spacers. Nevertheless, it seems not to be related to the clinical outcome, depending rather on the degree of lordosis and distraction. Some differences in segment-implant morphology were identified in cases with recurrences. To assess the effectiveness of spacers, larger studies including morphological and clinical variables are required.

Efficacy and safety of pomegranate medicinal products for cancer.

Preclinical in vitro and in vivo studies demonstrate potent effects of pomegranate preparations in cancer cell lines and animal models with chemically induced cancers. We have carried out one systematic review of the effectiveness of pomegranate products in the treatment of cancer and another on their safety. The PubMed search provided 162 references for pomegranate and cancer and 122 references for pomegranate and safety/toxicity. We identified 4 clinical studies investigating 3 pomegranate products, of which one was inappropriate because of the low polyphenol content. The evidence of clinical effectiveness was poor because the quality of the studies was poor. Although there is no concern over safety with the doses used in the clinical studies, pomegranate preparations may be harmful by inducing synthetic drug metabolism through activation of liver enzymes. We have analysed various pomegranate products for their content of anthocyanins, punicalagin, and ellagic acid in order to compare them with the benchmark doses from published data. If the amount of coactive constituents is not declared, patients risk not benefiting from the putative pomegranate effects. Moreover, pomegranate end products are affected by many determinants. Their declaration should be incorporated into the regulatory guidance and controlled before pomegranate products enter the market.

The use of fenestrated and branched endovascular aneurysm repair for juxtarenal and thoracoabdominal aneurysms: a systematic review and cost-effectiveness analysis.

Patients with large abdominal aortic aneurysms (AAAs) are usually offered reparative treatment given the high mortality risk. There is uncertainty about how to treat juxtarenal AAAs (JRAAAs) or thoracoabdominal aortic aneurysms (TAAAs). Endovascular repair of an abdominal aortic aneurysm (EVAR) is often seen as safer and easier than open surgical repair (OSR). However, endovascular treatment of JRAAAs or TAAAs requires specially manufactured stent grafts, with openings to allow blood to reach branches of the aorta. Commissioners are receiving increasing requests for fenestrated EVAR (fEVAR) and branched EVAR (bEVAR), but it is unclear whether or not the extra cost of fEVAR or bEVAR is justified by advantages for patients. To assess the clinical effectiveness, safety and cost-effectiveness of fEVAR and bEVAR in comparison with conventional treatment (i.e. no surgery) or OSR for two populations: JRAAAs and TAAAs. Resources were searched from inception to October 2013, including MEDLINE (OvidSP), EMBASE (OvidSP) and the Cochrane Central Register of Controlled Trials (Wiley) and, additionally, for cost-effectiveness, NHS Economic Evaluation Database (NHS EED; Wiley) and EconLit (EBSCOhost). Conference abstracts were also searched. Studies were included based on an intervention of either fEVAR or bEVAR and a comparator of either OSR or no surgery. For clinical effectiveness, observational studies were excluded only if they were not comparative, i.e. explicitly selected on the basis of prognosis. For clinical effectiveness, searches retrieved 5253 records before deduplication. Owing to overlap between the databases, 1985 duplicate records were removed. Of the remaining 3268 records, based on titles and abstracts, 3244 records were excluded, leaving 24 publications to be ordered. All 24 studies were excluded as none of them satisfied the inclusion criteria. Sixteen studies were excluded on study design, six on intervention and two on comparator. Five out of 16 studies excluded on study design reported a comparison. However, all of the studies acknowledged that they had groups that were not comparable at baseline given that they had selectively assigned younger, fitter patients to OSR. Therefore, these studies were considered 'non-comparative'. For cost-effectiveness, searches identified 104 references before deduplication. Owing to overlap between the databases, 34 duplicate records were removed. Of the remaining 70 records, seven were included for the full assessment based on initial screening. After a full-text review, no studies were included. Because of the lack of clinical effectiveness evidence and difficulty in estimating costs given the rapidly changing and variable technology, a cost-effectiveness analysis (CEA) was not performed. Instead a detailed description of modelling methods was provided. Despite a thorough search, no studies could be found that met the inclusion criteria. All studies that compared either fEVAR or bEVAR with either OSR or no surgery explicitly selected patients based on prognosis, i.e. essentially the populations for each comparator were not the same. Despite not being able to conduct a CEA, we have provided detailed methods for the conduct if data becomes available. We recommend at least one clinical trial to provide an unbiased estimate of effect for fEVAR/bEVAR compared with OSR or no surgery. This trial should also collect data for a CEA. This study is registered as PROSPERO CRD42013006051. The National Institute for Health Research Health Technology Assessment programme.

Alteplase for the treatment of acute ischaemic stroke: a NICE single technology appraisal; an evidence review group perspective.

The National Institute for Health and Care Excellence (NICE) invited Boehringer Ingelheim GmbH, the manufacturer of alteplase, to submit evidence for the clinical and cost-effectiveness of alteplase for the prevention of strokes within a 0-4.5h window. The comparator was standard medical and supportive management that does not include alteplase. This paper provides a description of the company submission, the Evidence Review Group (ERG) review and NICE's subsequent decisions. Clinical effectiveness evidence for alteplase was derived from 5 trials. For the 3-4.5h treatment window, alteplase did not show a statistically significant treatment effect on death or dependency at three months follow-up. For the 0-4.5h treatment window data from a meta-analysis of 3 trials indicated that the reduction of death and dependency was statistically significant. In both cases there was a significant increase in symptomatic intracranial haemorrhage. The economic model described in the manufacturer's submission was considered by the ERG to meet the NICE reference case. The model structure was considered to be appropriate and the ERG has no major concerns regarding the selection of data used within the model. The incremental cost-effectiveness ratios (ICER) for all treatment windows were well below accepted willingness to pay thresholds. The ERG had no major concerns regarding the completeness of the submission or the robustness of the evidence presented. For all treatment windows considered, alteplase was found to be cost-effective compared with standard treatment.

Public engagement in priority-setting: Results from a pan-Canadian survey of decision-makers in cancer control

Decision-makers are challenged to incorporate public input into priority-setting decisions. We conducted a pan-Canadian survey of decision-makers in cancer control to investigate the types of evidence, especially evidence supplied by the public, that are utilized in health care priority-setting. We further examined how normative attitudes and contextual factors influence the use of public engagement as evidence at the committee level. Administered between November and December 2012, 67 respondents from 117 invited individuals participated in the survey. The results indicated that public engagement was infrequently utilized compared to clinical effectiveness evidence or cost evidence. General positive agreement between normative attitudes towards the use of evidence and the frequency of evidence utilization was observed, but absence of correlative agreement was found for the types of evidence that are supplied by the general public and for cost-effectiveness inputs. Regression analyses suggested that public engagement was unevenly utilized between jurisdictions and that educational background and barriers to implementing public input may decrease the odds of using public engagement as evidence. We recommend that institutions establish a link between committee members' normative attitudes for using public engagement and its real-world utilization.

What is the Clinical Effectiveness of Erythropoiesis Stimulating Agents for the Treatment of Cancer Treatment-Induced Anaemia?

Aim: Anaemia is a common side-effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions (RBCTs) to improve cancer treatment-induced anaemia (CIA). We aim to review the clinical-effectiveness evidence for ESAs for treating CIA. Methods: The clinical effectiveness review followed principles published by the NHS CRD. Electronic databases and grey literature sources were searched up to December 2013. Randomised controlled trials (RCTs) comparing ESAs in accordance with their EU licenses (based on start dose administered) with best supportive care, placebo, or other ESA in adults with CIAwere included. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL), and adverse events (AEs) were extracted from primary studies. Where appropriate, data were pooled using random-effects meta-analyses. Results: Twenty-three RCTs were included in the review. None of the RCTs were completely aligned with current EU licenses. Results suggest that there is clinical benefit from ESAs for anaemia-related outcomes. Sixty-three percent of participants who received ESAs achieved a haematological response compared with 18% of participants who did not receive ESAs, and there was a reduction in requirement for RBCT by an estimated 37% with ESAs. Data also suggest some improvement in HRQoL scores (FACT-F, FACT-G and FACT-An). The impact of ESAs on malignancy-related outcomes and AEs is uncertain. The overall survival (OS) results (HR 0.97, 95% CI 0.83, 1.13, I 2 of 42.4%) suggest no effect of ESAs on OS. Although all AEs were relatively rare (max. 6%), an increased risk for thromboembolic events, pruritus and hypertension was found. Post-hoc sensitivity analyses suggested that the effectiveness for some outcomes was improved when ESAs were evaluated ‘closer to licence’. Conclusions: Although results from the review suggest that ESAs may be beneficial when used closer to their licensed indications, this trend should be interpreted with caution due to high statistical heterogeneity, wide confidence intervals, multiple testing, and the licence interpretation. Disclosure: All authors have declared no conflicts of interest.

The reduced cost of providing a nationally recognised service for familial hypercholesterolaemia

ObjectiveFamilial hypercholesterolaemia (FH) affects 1 in 500 people in the UK population and is associated with premature morbidity and mortality from coronary heart disease. In 2008, National Institute for Health...