Network meta-analysis synthesizes direct and indirect evidence in a network of trials that compare multiple interventions and has the potential to rank the competing treatments according to the ...studied outcome. Despite its usefulness network meta-analysis is often criticized for its complexity and for being accessible only to researchers with strong statistical and computational skills. The evaluation of the underlying model assumptions, the statistical technicalities and presentation of the results in a concise and understandable way are all challenging aspects in the network meta-analysis methodology. In this paper we aim to make the methodology accessible to non-statisticians by presenting and explaining a series of graphical tools via worked examples. To this end, we provide a set of STATA routines that can be easily employed to present the evidence base, evaluate the assumptions, fit the network meta-analysis model and interpret its results.
Despite a major increase in the range and number of software offerings now available to help researchers produce evidence syntheses, there is currently no generic tool for producing figures to ...display and explore the risk‐of‐bias assessments that routinely take place as part of systematic review. However, tools such as the R programming environment and Shiny (an R package for building interactive web apps) have made it straightforward to produce new tools to help in producing evidence syntheses. We present a new tool, robvis (Risk‐Of‐Bias VISualization), available as an R package and web app, which facilitates rapid production of publication‐quality risk‐of‐bias assessment figures. We present a timeline of the tool's development and its key functionality.
Systematic reviews that collate data about the relative effects of multiple interventions via network meta-analysis are highly informative for decision-making purposes. A network meta-analysis ...provides two types of findings for a specific outcome: the relative treatment effect for all pairwise comparisons, and a ranking of the treatments. It is important to consider the confidence with which these two types of results can enable clinicians, policy makers and patients to make informed decisions. We propose an approach to determining confidence in the output of a network meta-analysis. Our proposed approach is based on methodology developed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group for pairwise meta-analyses. The suggested framework for evaluating a network meta-analysis acknowledges (i) the key role of indirect comparisons (ii) the contributions of each piece of direct evidence to the network meta-analysis estimates of effect size; (iii) the importance of the transitivity assumption to the validity of network meta-analysis; and (iv) the possibility of disagreement between direct evidence and indirect evidence. We apply our proposed strategy to a systematic review comparing topical antibiotics without steroids for chronically discharging ears with underlying eardrum perforations. The proposed framework can be used to determine confidence in the results from a network meta-analysis. Judgements about evidence from a network meta-analysis can be different from those made about evidence from pairwise meta-analyses.
The evaluation of the credibility of results from a meta-analysis has become an important part of the evidence synthesis process. We present a methodological framework to evaluate confidence in the ...results from network meta-analyses, Confidence in Network Meta-Analysis (CINeMA), when multiple interventions are compared.
CINeMA considers 6 domains: (i) within-study bias, (ii) reporting bias, (iii) indirectness, (iv) imprecision, (v) heterogeneity, and (vi) incoherence. Key to judgments about within-study bias and indirectness is the percentage contribution matrix, which shows how much information each study contributes to the results from network meta-analysis. The contribution matrix can easily be computed using a freely available web application. In evaluating imprecision, heterogeneity, and incoherence, we consider the impact of these components of variability in forming clinical decisions.
Via 3 examples, we show that CINeMA improves transparency and avoids the selective use of evidence when forming judgments, thus limiting subjectivity in the process. CINeMA is easy to apply even in large and complicated networks.
The increase in treatment options creates an urgent need for comparative effectiveness research. Randomized, controlled trials comparing several treatments are usually not feasible, so other ...methodological approaches are needed. Meta-analyses provide summary estimates of treatment effects by combining data from many studies. However, an important drawback is that standard meta-analyses can compare only 2 interventions at a time. A new meta-analytic technique, called network meta-analysis (or multiple treatments meta-analysis or mixed-treatment comparison), allows assessment of the relative effectiveness of several interventions, synthesizing evidence across a network of randomized trials. Despite the growing prevalence and influence of network meta-analysis in many fields of medicine, several issues need to be addressed when constructing one to avoid conclusions that are inaccurate, invalid, or not clearly justified. This article explores the scope and limitations of network meta-analysis and offers advice on dealing with heterogeneity, inconsistency, and potential sources of bias in the available evidence to increase awareness among physicians about some of the challenges in interpretation.
To synthesise evidence on the average bias and heterogeneity associated with reported methodological features of randomized trials.
Systematic review of meta-epidemiological studies.
We retrieved ...eligible studies included in a recent AHRQ-EPC review on this topic (latest search September 2012), and searched Ovid MEDLINE and Ovid EMBASE for studies indexed from Jan 2012-May 2015. Data were extracted by one author and verified by another. We combined estimates of average bias (e.g. ratio of odds ratios (ROR) or difference in standardised mean differences (dSMD)) in meta-analyses using the random-effects model. Analyses were stratified by type of outcome ("mortality" versus "other objective" versus "subjective"). Direction of effect was standardised so that ROR < 1 and dSMD < 0 denotes a larger intervention effect estimate in trials with an inadequate or unclear (versus adequate) characteristic.
We included 24 studies. The available evidence suggests that intervention effect estimates may be exaggerated in trials with inadequate/unclear (versus adequate) sequence generation (ROR 0.93, 95% CI 0.86 to 0.99; 7 studies) and allocation concealment (ROR 0.90, 95% CI 0.84 to 0.97; 7 studies). For these characteristics, the average bias appeared to be larger in trials of subjective outcomes compared with other objective outcomes. Also, intervention effects for subjective outcomes appear to be exaggerated in trials with lack of/unclear blinding of participants (versus blinding) (dSMD -0.37, 95% CI -0.77 to 0.04; 2 studies), lack of/unclear blinding of outcome assessors (ROR 0.64, 95% CI 0.43 to 0.96; 1 study) and lack of/unclear double blinding (ROR 0.77, 95% CI 0.61 to 0.93; 1 study). The influence of other characteristics (e.g. unblinded trial personnel, attrition) is unclear.
Certain characteristics of randomized trials may exaggerate intervention effect estimates. The average bias appears to be greatest in trials of subjective outcomes. More research on several characteristics, particularly attrition and selective reporting, is needed.
Narrative reviews of paediatric NAFLD quote prevalences in the general population that range from 9% to 37%; however, no systematic review of the prevalence of NAFLD in children/adolescents has been ...conducted. We aimed to estimate prevalence of non-alcoholic fatty liver disease (NAFLD) in young people and to determine whether this varies by BMI category, gender, age, diagnostic method, geographical region and study sample size.
We conducted a systematic review and meta-analysis of all studies reporting a prevalence of NAFLD based on any diagnostic method in participants 1-19 years old, regardless of whether assessing NAFLD prevalence was the main aim of the study.
The pooled mean prevalence of NAFLD in children from general population studies was 7.6% (95%CI: 5.5% to 10.3%) and 34.2% (95% CI: 27.8% to 41.2%) in studies based on child obesity clinics. In both populations there was marked heterogeneity between studies (I2 = 98%). There was evidence that prevalence was generally higher in males compared with females and increased incrementally with greater BMI. There was evidence for differences between regions in clinical population studies, with estimated prevalence being highest in Asia. There was no evidence that prevalence changed over time. Prevalence estimates in studies of children/adolescents attending obesity clinics and in obese children/adolescents from the general population were substantially lower when elevated alanine aminotransferase (ALT) was used to assess NAFLD compared with biopsies, ultrasound scan (USS) or magnetic resonance imaging (MRI).
Our review suggests the prevalence of NAFLD in young people is high, particularly in those who are obese and in males.
Abstract Healthcare providers are often looking for ways to objectively monitor and improve their patients' health and fitness, especially in between patient visits. Some insurance companies are ...using applications data as incentives to improve health and lower premiums. As more and more people start to use smartphones, they may provide a tool to help improve a patient's health and fitness. Specifically, fitness applications or “apps” on smartphones are programs that use data collected from a smartphone's inbuilt tools, such as the Global Positioning System, accelerometer, microphone, speaker, and camera, to measure health and fitness parameters. The apps then analyze these data and summarize them, as well as devise individualized plans based on users' goals, provide frequent feedback, personalized coaching, and additional motivation by allowing milestones to be shared on social media. This article introduces evidence that apps can better help patients reach their health and fitness goals. It then discusses what features to look for in an app, followed by an overview of popular health and fitness apps. Last, patient scenarios with app recommendations, limitations of apps, and future research are discussed.
Studies combined in a meta‐analysis often have differences in their design and conduct that can lead to heterogeneous results. A random‐effects model accounts for these differences in the underlying ...study effects, which includes a heterogeneity variance parameter. The DerSimonian‐Laird method is often used to estimate the heterogeneity variance, but simulation studies have found the method can be biased and other methods are available. This paper compares the properties of nine different heterogeneity variance estimators using simulated meta‐analysis data. Simulated scenarios include studies of equal size and of moderate and large differences in size. Results confirm that the DerSimonian‐Laird estimator is negatively biased in scenarios with small studies and in scenarios with a rare binary outcome. Results also show the Paule‐Mandel method has considerable positive bias in meta‐analyses with large differences in study size. We recommend the method of restricted maximum likelihood (REML) to estimate the heterogeneity variance over other methods. However, considering that meta‐analyses of health studies typically contain few studies, the heterogeneity variance estimate should not be used as a reliable gauge for the extent of heterogeneity in a meta‐analysis. The estimated summary effect of the meta‐analysis and its confidence interval derived from the Hartung‐Knapp‐Sidik‐Jonkman method are more robust to changes in the heterogeneity variance estimate and show minimal deviation from the nominal coverage of 95% under most of our simulated scenarios.
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