Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer

Background: Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. Objectives: This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Methods: Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. Results: A piecewise model, in which the Kaplan–Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. Conclusion: In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses

Cost–effectiveness analysis for avelumab first-line maintenance treatment of advanced urothelial carcinoma in Scotland

Aim: The cost–effectiveness of avelumab first-line maintenance treatment for locally advanced or metastatic urothelial carcinoma in Scotland was assessed. Materials & methods: A partitioned survival model was developed comparing avelumab plus best supportive care (BSC) versus BSC alone, incorporating JAVELIN Bladder 100 trial data, costs from national databases and published literature and clinical expert validation of assumptions. Incremental cost–effectiveness ratio (ICER) was estimated using lifetime costs and quality-adjusted life-years (QALY). Results: Avelumab plus BSC had incremental costs of £9446 and a QALY gain of 0.63, leading to a base-case (deterministic) ICER of £15,046 per QALY gained, supported by robust sensitivity analyses. Conclusion: Avelumab first-line maintenance is likely to be a cost-effective treatment for locally advanced or metastatic urothelial carcinoma in Scotland

Automated Diabetic Retinopathy Image Assessment Software: Diagnostic Accuracy and Cost-Effectiveness Compared with Human Graders.

OBJECTIVE: With the increasing prevalence of diabetes, annual screening for diabetic retinopathy (DR) by expert human grading of retinal images is challenging. Automated DR image assessment systems (ARIAS) may provide clinically effective and cost-effective detection of retinopathy. We aimed to determine whether ARIAS can be safely introduced into DR screening pathways to replace human graders. DESIGN: Observational measurement comparison study of human graders following a national screening program for DR versus ARIAS. PARTICIPANTS: Retinal images from 20 258 consecutive patients attending routine annual diabetic eye screening between June 1, 2012, and November 4, 2013. METHODS: Retinal images were manually graded following a standard national protocol for DR screening and were processed by 3 ARIAS: iGradingM, Retmarker, and EyeArt. Discrepancies between manual grades and ARIAS results were sent to a reading center for arbitration. MAIN OUTCOME MEASURES: Screening performance (sensitivity, false-positive rate) and diagnostic accuracy (95% confidence intervals of screening-performance measures) were determined. Economic analysis estimated the cost per appropriate screening outcome. RESULTS: Sensitivity point estimates (95% confidence intervals) of the ARIAS were as follows: EyeArt 94.7% (94.2%-95.2%) for any retinopathy, 93.8% (92.9%-94.6%) for referable retinopathy (human graded as either ungradable, maculopathy, preproliferative, or proliferative), 99.6% (97.0%-99.9%) for proliferative retinopathy; Retmarker 73.0% (72.0 %-74.0%) for any retinopathy, 85.0% (83.6%-86.2%) for referable retinopathy, 97.9% (94.9%-99.1%) for proliferative retinopathy. iGradingM classified all images as either having disease or being ungradable. EyeArt and Retmarker saved costs compared with manual grading both as a replacement for initial human grading and as a filter prior to primary human grading, although the latter approach was less cost-effective. CONCLUSIONS: Retmarker and EyeArt systems achieved acceptable sensitivity for referable retinopathy when compared with that of human graders and had sufficient specificity to make them cost-effective alternatives to manual grading alone. ARIAS have the potential to reduce costs in developed-world health care economies and to aid delivery of DR screening in developing or remote health care settings

Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis.

Systematic review of published population based surveys to examine the relationship between primary open angle glaucoma (POAG) prevalence and demographic factors. A literature search identified population-based studies with quantitative estimates of POAG prevalence (to October 2014). Multilevel binomial logistic regression of log-odds of POAG was used to examine the effect of age and gender among populations of different geographical and ethnic origins, adjusting for study design factors. Eighty-one studies were included (37 countries, 216 214 participants, 5266 POAG cases). Black populations showed highest POAG prevalence, with 5.2% (95% credible interval (CrI) 3.7%, 7.2%) at 60 years, rising to 12.2% (95% CrI 8.9% to 16.6%) at 80 years. Increase in POAG prevalence per decade of age was greatest among Hispanics (2.31, 95% CrI 2.12, 2.52) and White populations (1.99, 95% CrI 1.86, 2.12), and lowest in East and South Asians (1.48, 95% CrI 1.39, 1.57; 1.56, 95% CrI 1.31, 1.88, respectively). Men were more likely to have POAG than women (1.30, 95% CrI 1.22, 1.41). Older studies had lower POAG prevalence, which was related to the inclusion of intraocular pressure in the glaucoma definition. Studies with visual field data on all participants had a higher POAG prevalence than those with visual field data on a subset. Globally 57.5 million people (95% CI 46.4 to 73.1 million) were affected by POAG in 2015, rising to 65.5 million (95% CrI 52.8, 83.2 million) by 2020. This systematic review provides the most precise estimates of POAG prevalence and shows omitting routine visual field assessment in population surveys may have affected case ascertainment. Our findings will be useful to future studies and healthcare planning

Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis: implications for aetiology and early prevention.

The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adjusting for study design factors. 143 published articles (42 countries, 374 349 subjects aged 1-18 years, 74 847 myopia cases) were included. Increase in myopia prevalence with age varied by ethnicity. East Asians showed the highest prevalence, reaching 69% (95% credible intervals (CrI) 61% to 77%) at 15 years of age (86% among Singaporean-Chinese). Blacks in Africa had the lowest prevalence; 5.5% at 15 years (95% CrI 3% to 9%). Time trends in myopia prevalence over the last decade were small in whites, increased by 23% in East Asians, with a weaker increase among South Asians. Children from urban environments have 2.6 times the odds of myopia compared with those from rural environments. In whites and East Asians sex differences emerge at about 9 years of age; by late adolescence girls are twice as likely as boys to be myopic. Marked ethnic differences in age-specific prevalence of myopia exist. Rapid increases in myopia prevalence over time, particularly in East Asians, combined with a universally higher risk of myopia in urban settings, suggest that environmental factors play an important role in myopia development, which may offer scope for prevention

Adiposity in early, middle and later adult life and cardiometabolic risk markers in later life; findings from the British regional heart study.

OBJECTIVES: This research investigates the associations between body mass index (BMI) at 21, 40-59, 60-79 years of age on cardiometabolic risk markers at 60-79 years. METHODS: A prospective study of 3464 British men with BMI measured at 40-59 and 60-79 years, when cardiometabolic risk was assessed. BMI at 21 years was ascertained from military records, or recalled from middle-age (adjusted for reporting bias); associations between BMI at different ages and later cardiometabolic risk markers were examined using linear regression. Sensitive period, accumulation and mobility life course models were devised for high BMI (defined as BMI≥75th centile) and compared with a saturated BMI trajectory model. RESULTS: At ages 21, 40-59 and 60-79 years, prevalences of overweight (BMI≥25 kg/m2) were 12%, 53%, 70%, and obesity (≥30 kg/m2) 1.6%, 6.6%, and 17.6%, respectively. BMI at 21 years was positively associated with serum insulin, blood glucose, and HbA1c at 60-79 years, with increases of 1.5% (95%CI 0.8,2.3%), 0.4% (0.1,0.6%), 0.3% (0.1,0.4%) per 1 kg/m2, respectively, but showed no associations with blood pressure or blood cholesterol. However, these associations were modest compared to those between BMI at 60-79 years and serum insulin, blood glucose and HbA1c at 60-79 years, with increases of 8.6% (8.0,9.2%), 0.7% (0.5,0.9%), and 0.5% (0.4,0.7%) per 1 kg/m2, respectively. BMI at 60-79 years was also associated with total cholesterol and blood pressure. Associations for BMI at 40-59 years were mainly consistent with those of BMI at 60-79 years. None of the life course models fitted the data as well as the saturated model for serum insulin. A sensitive period at 50 years for glucose and HbA1c and sensitive period at 70 years for blood pressure were identified. CONCLUSIONS: In this cohort of men who were thin compared to more contemporary cohorts, BMI in later life was the dominant influence on cardiovascular and diabetes risk. BMI in early adult life may have a small long-term effect on diabetes risk

Cost-effectiveness analysis for avelumab first-line maintenance treatment of advanced urothelial carcinoma in Scotland

Aim: The cost-effectiveness of avelumab first-line maintenance treatment for locally advanced or metastatic urothelial carcinoma in Scotland was assessed. Materials & methods: A partitioned survival model was developed comparing avelumab plus best supportive care (BSC) versus BSC alone, incorporating JAVELIN Bladder 100 trial data, costs from national databases and published literature and clinical expert validation of assumptions. Incremental cost-effectiveness ratio (ICER) was estimated using lifetime costs and quality-adjusted life-years (QALY). Results: Avelumab plus BSC had incremental costs of £9446 and a QALY gain of 0.63, leading to a base-case (deterministic) ICER of £15,046 per QALY gained, supported by robust sensitivity analyses. Conclusion: Avelumab first-line maintenance is likely to be a cost-effective treatment for locally advanced or metastatic urothelial carcinoma in Scotland

Will moving into East Village housing increase household physical activity levels? Evaluation of a natural experiment

Background: Although the built environment may be an important influence on physical activity (PA), formal evidence is weak. The 2012 London Olympic Games Athletes’ Village (renamed East Village) is being used to provide a combination of affordable (social, intermediate) and market-rent accommodation. It offers a unique opportunity to assess the health impact of moving to a built environment designed to encourage active living. Methods: A two-year controlled longitudinal study of 1200 households (including at least one adult) is being carried out to establish whether PA levels in households relocating to East Village show a sustained increase when compared to households living outside East Village. Those applying to live in East Village are being recruited on application. Participants are having assessments of objectively measured PA (using Actigraph monitors), and body composition in their current place of residence and will be reassessed two-years later, either in East Village (intervention group) or in their original place of residence (control group). GPS receivers are being worn to map patterns of use of the local environment (including indoor and outdoor activity). In addition, accurate GIS mapping is being used to establish whether health promoting environmental resources influence levels of active transport, including walking and cycling. Multilevel models will examine differences in PA change between intervention and control groups, adjusting for individual and household level factors, and other sociodemographic confounding factors collected using electronic questionnaires. Results: We are examining whether differences in PA amongst intervention and control groups relate to use of the local environment, and if so, which environmental components. With a 70% follow-up rate the study is powered to detect a 5% increase in the number of daily steps (and other activity/adiposity outcomes); this represents the lower limit of a potentially worthwhile increase in physical activity. To date, 1225 participants (from 833 households), have been recruited; 712 from social households, 486 and 27 from those seeking intermediate and market-rent accommodation. At least 4 days (>540 min) of PA data have been collected from 69%, 85%, and 85% respectively. Sub-group analysis shows three-quarters of Actigraph data matches GPS data. Baseline recruitment will be complete by Autumn-2015. Conclusions: This study offers an important opportunity for a natural experiment. This study seeks to identify factors that encourage active use of the local environment. While the opportunity is unique, the results may be generalisable to other urban building projects and should inform future evidence-based urban planning

A theological examination of the religious teaching on 'usury' within the three monotheistic traditions of Judaism, Christianity, and Islam and its relevance for the world today

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN025458 / BLDSC - British Library Document Supply CentreGBUnited Kingdo