Ros Wade

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.

Systematic review and meta-analysis of the value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in children and young people with cancer

BackgroundFebrile neutropenia is a frequently occurring and occasionally life-threatening complication of treatment for childhood cancer. Many biomarkers have been proposed as predictors of adverse events. We aimed to undertake a systematic review and meta-analysis to summarize evidence on the discriminatory ability of initial serum biomarkers of febrile neutropenic episodes in children and young people.MethodsThis review was conducted in accordance with the Center for Reviews and Dissemination Methods, using three random effects models to undertake meta-analysis. It was registered with the HTA Registry of systematic reviews, CRD32009100485.ResultsWe found that 25 studies exploring 14 different biomarkers were assessed in 3,585 episodes of febrile neutropenia. C-reactive protein (CRP), pro-calcitonin (PCT), and interleukin-6 (IL6) were subject to quantitative meta-analysis, and revealed huge inconsistencies and heterogeneity in the studies included in this review. Only CRP has been evaluated in assessing its value over the predictive value of simple clinical decision rules.ConclusionsThe limited data available describing the predictive value of biomarkers in the setting of pediatric febrile neutropenia mean firm conclusions cannot yet be reached, although the use of IL6, IL8 and procalcitonin warrant further study.

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.

Systematic review and meta-analysis of the discriminatory performance of risk prediction rules in febrile neutropaenic episodes in children and young people

Introduction Febrile neutropaenia is a frequently occurring and occasionally life-threatening complication of treatment for childhood cancer, yet many children are aggressively over-treated. We aimed to undertake a systematic review and meta-analysis to summarise evidence on the discriminatory ability and predictive accuracy of clinical decision rules (CDR) of risk stratification in febrile neutropaenic episodes. Methods The review was conducted in accordance with Centre for Reviews and Dissemination methods, using random effects models to undertake meta-analysis. It was registered with the HTA Registry of systematic reviews, CRD32009100453. Results We found 20 studies describing 16 different CDR assessed in 8388 episodes of FNP. No study compared different approaches and only one CDR had been subject to testing across multiple datasets. This review cannot conclude that any system is more effective or reliable than any other. Conclusion To maximise the value of the information already collected by these and other cohorts of children with febrile neutropaenia, an individual-patient-data (IPD) meta-analysis is required to develop and test new and existing CDR to improve stratification and optimise therapy.

The EOS 2D/3D X-ray imaging system: a cost-effectiveness analysis quantifying the health benefits from reduced radiation exposure.

OBJECTIVES To evaluate the cost-effectiveness of the EOS(®) 2D/3D X-ray imaging system compared with standard X-ray for the diagnosis and monitoring of orthopaedic conditions. MATERIALS AND METHODS A decision analytic model was developed to quantify the long-term costs and health outcomes, expressed as quality-adjusted life years (QALYs) from the UK health service perspective. Input parameters were obtained from medical literature, previously developed cancer models and expert advice. Threshold analysis was used to quantify the additional health benefits required, over and above those associated with radiation-induced cancers, for EOS(®) to be considered cost-effective. RESULTS Standard X-ray is associated with a maximum health loss of 0.001 QALYs, approximately 0.4 of a day in full health, while the loss with EOS(®) is a maximum of 0.00015 QALYs, or 0.05 of a day in full health. On a per patient basis, EOS(®) is more expensive than standard X-ray by between £10.66 and £224.74 depending on the assumptions employed. The results suggest that EOS(®) is not cost-effective for any indication. Health benefits over and above those obtained from lower radiation would need to double for EOS to be considered cost-effective. CONCLUSION No evidence currently exists on whether there are health benefits associated with imaging improvements from the use of EOS(®). The health benefits from radiation dose reductions are very small. Unless EOS(®) can generate additional health benefits as a consequence of the nature and quality of the image, comparative patient throughput with X-ray will be the major determinant of cost-effectiveness.

Adjunctive colposcopy technologies for examination of the uterine cervix--DySIS, LuViva Advanced Cervical Scan and Niris Imaging System: a systematic review and economic evaluation.

BACKGROUND Women in England (aged 25-64 years) are invited for cervical screening every 3-5 years to assess for cervical intraepithelial neoplasia (CIN) or cancer. CIN is a term describing abnormal changes in the cells of the cervix, ranging from CIN1 to CIN3, which is precancerous. Colposcopy is used to visualise the cervix. Three adjunctive colposcopy technologies for examination of the cervix have been included in this assessment: Dynamic Spectral Imaging System (DySIS), the LuViva Advanced Cervical Scan and the Niris Imaging System. OBJECTIVE To determine the clinical effectiveness and cost-effectiveness of adjunctive colposcopy technologies for examination of the uterine cervix for patients referred for colposcopy through the NHS Cervical Screening Programme. DATA SOURCES Sixteen electronic databases [Allied and Complementary Medicine Database (AMED), BIOSIS Previews, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Database of Abstracts of Reviews of Effects (DARE), EMBASE, Health Management Information Consortium (HMIC), Health Technology Assessment (HTA) database; Inspec, Inside Conferences, MEDLINE, NHS Economic Evaluation Database (NHS EED), PASCAL, Science Citation Index Expanded (SCIE) and Science Citation Index (SCI) - Conference Proceedings], and two clinical trial registries [ClinicalTrials.gov and Current Controlled Trials (CCT)] were searched to September-October 2011. REVIEW METHODS Studies comparing DySIS, LuViva or Niris with conventional colposcopy were sought; a narrative synthesis was undertaken. A decision-analytic model was developed, which measured outcomes in terms of quality-adjusted life-years (QALYs) and costs were evaluated from the perspective of the NHS and Personal Social Services with a time horizon of 50 years. RESULTS Six studies were included: two studies of DySIS, one study of LuViva and three studies of Niris. The DySIS studies were well reported and had a low risk of bias; they found higher sensitivity with DySIS (both the DySISmap alone and in combination with colposcopy) than colposcopy alone for identifying CIN2+ disease, although specificity was lower with DySIS. The studies of LuViva and Niris were poorly reported and had limitations, which indicated that their results were subject to a high risk of bias; the results of these studies cannot be considered reliable. The base-case cost-effectiveness analysis suggests that both DySIS treatment options are less costly and more effective than colposcopy alone in the overall weighted population; these results were robust to the ranges tested in the sensitivity analysis. DySISmap alone was more costly and more effective in several of the referral groups but the incremental cost-effectiveness ratio (ICER) was never higher than £1687 per QALY. DySIS plus colposcopy was less costly and more effective in all reasons for referral. Only indicative analyses were carried out on Niris and LuViva and no conclusions could be made on their cost-effectiveness. LIMITATIONS The assessment is limited by the available evidence on the new technologies, natural history of the disease area and current treatment patterns. CONCLUSIONS DySIS, particularly in combination with colposcopy, has higher sensitivity than colposcopy alone. There is no reliable evidence on the clinical effectiveness of LuViva and Niris. DySIS plus colposcopy appears to be less costly and more effective than both the DySISmap alone and colposcopy alone; these results were robust to the sensitivity analyses undertaken. Given the lack of reliable evidence on LuViva and Niris, no conclusions on their potential cost-effectiveness can be drawn. There is some uncertainty about how generalisable these findings will be to the population of women referred for colposcopy in the future, owing to the introduction of the human papillomavirus (HPV) triage test and uptake of the HPV vaccine.

Systematic review and meta‐analysis of the value of clinical features to exclude radiographic pneumonia in febrile neutropenic episodes in children and young people

Introduction:  Children and young people who present with febrile neutropenia (FNP) secondary to malignancies or their treatment frequently do not undergo routine chest radiography. With shorter courses of antibiotic therapy, failure to recognise pneumonia and consequent under‐treatment could produce significant problems.

Graduated compression stockings for the prevention of deep-vein thrombosis in postoperative surgical patients: a systematic review and economic model with a value of information analysis.

BACKGROUND Deep-vein thrombosis (DVT) can occur in surgical patients. Routine prophylaxis can be pharmacological and/or mechanical [e.g. graduated compression stockings (GCSs)]. GCSs are available in knee length or thigh length. OBJECTIVE To establish the expected value of undertaking additional research addressing the relative effectiveness of thigh-length GCSs versus knee-length GCSs, in addition to pharmacoprophylaxis, for prevention of DVT in surgical patients. DESIGN Systematic review and economic model, including value of information (VOI) analysis. REVIEW METHODS Randomised controlled trials (RCTs) assessing thigh- or knee-length GCSs in surgical patients were eligible for inclusion. The primary outcome was incidence of DVT. DVT complications and GCSs adverse events were assessed. Random-effects meta-analysis was performed. To draw on a wider evidence base, a random-effects network meta-analysis (NMA) was undertaken for the outcome DVT. A review of trials and observational studies of patient adherence was also conducted. A decision-analytic model was developed to assess the cost-effectiveness of thigh- and knee-length GCSs and the VOI. RESULTS Twenty-three RCTs were included in the review of effectiveness. There was substantial variation between trials in terms of the patient characteristics, interventions and methods of outcome assessment. Five trials comparing knee-length with thigh-length GCSs with or without pharmacoprophylaxis were pooled; the summary estimate of effect indicated a non-significant trend favouring thigh-length GCSs [odds ratio (OR) 1.48, 95% confidence interval (CI) 0.80 to 2.73]. Thirteen trials were included in the NMA. In the base-case analysis, thigh-length GCSs with pharmacoprophylaxis were more effective than knee-length GCSs with pharmacoprophylaxis (knee vs. thigh OR 1.76, 95% credible interval 0.82 to 3.53). Overall, thigh-length stockings with pharmacoprophylaxis was the most effective treatment, with a 0.73 probability of being the most effective treatment in a new trial of all the treatments. Patient adherence was generally higher with knee-length GCSs, and patients preferred knee-length GCSs. Thigh-length GCSs were found to be cost-effective in all but the subgroup with the lowest baseline risk, although the absolute differences in costs and effects were relatively small. The expected value of perfect information ranged from £0.2M to £178.0M depending on the scenario and subgroup. The relative effect parameters had the highest expected value of partial perfect information and ranged from £2.0M to £39.4M. The value of further research was most evident in the high-risk subgroups. LIMITATIONS There was substantial variation across the included trials in terms of patient and intervention characteristics. Many of the included trials were old and poorly reported, which reduces the reliability of the results of the review. CONCLUSIONS Given that the results from both the standard meta-analysis and the NMA lacked precision (CIs were wide) owing to the heterogeneous evidence base, a new definitive trial in high-risk patients may be warranted. However, the efficiency of any further research (i.e. whether this represents value for money) is dependent on several factors, including the acquisition price of GCSs, expected compliance with thigh-length GCSs wear, and whether or not uncertainty can be resolved around possible effect modifiers, as well as the feasibility and actual cost of undertaking the proposed research. STUDY REGISTRATION This study is registered as PROSPERO CRD42014007202. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Quality assessment of comparative diagnostic accuracy studies: our experience using a modified version of the QUADAS-2 tool.

Assessing the quality of included studies is a vital step in undertaking a systematic review. The recently revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool (QUADAS-2), which is the only validated quality assessment tool for diagnostic accuracy studies, does not include specific criteria for assessing comparative studies. As part of an assessment that included comparative diagnostic accuracy studies, we used a modified version of QUADAS-2 to assess study quality. We modified QUADAS-2 by duplicating questions relating to the index test, to assess the relevant potential sources of bias for both the index test and comparator test. We also added review-specific questions. We have presented our modified version of QUADAS-2 and outlined some key issues for consideration when assessing the quality of comparative diagnostic accuracy studies, to help guide other systematic reviewers conducting comparative diagnostic reviews. Until QUADAS is updated to incorporate assessment of comparative studies, QUADAS-2 can be used, although modification and careful thought is required. It is important to reflect upon whether aspects of study design and methodology favour one of the tests over another.

Systematic review and meta-analysis of the value of clinical features to exclude radiographic pneumonia in febrile neutropenic episodes in children and young people.

Introduction:  Children and young people who present with febrile neutropenia (FNP) secondary to malignancies or their treatment frequently do not undergo routine chest radiography. With shorter courses of antibiotic therapy, failure to recognise pneumonia and consequent under‐treatment could produce significant problems.