N-terminal pro-B-type Natriuretic Peptides’ Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds

2015 ◽  
Vol 123 (2) ◽  
pp. 264-271 ◽  
Author(s):  
Danielle Potgieter ◽  
Dale Simmers ◽  
Lisa Ryan ◽  
Bruce M. Biccard ◽  
Giovanna A. Lurati-Buse ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Individual Study ◽  
Entire Cohort ◽  
Individual Patient Level ◽  
Diagnostic Thresholds ◽  
Level Data ◽  
Prognostic Utility ◽  
The Individual ◽  
Meta Analyses ◽  
Post Hoc

Abstract Background: N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results. Methods: The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds. Results: The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds. Conclusions: Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.

The Orchard Plot: Cultivating a Forest Plot for Use in Ecology, Evolution and Beyond

2019 ◽  
Author(s):  
Shinichi Nakagawa ◽  
Malgorzata Lagisz ◽  
Rose E O'Dea ◽  
Joanna Rutkowska ◽  
Yefeng Yang ◽  
...  
Keyword(s):  
Meta Analysis ◽  
R Package ◽  
Effect Sizes ◽  
Forest Plot ◽  
Point Estimates ◽  
Aggregate Effect ◽  
The Individual ◽  
Meta Analyses ◽  
Heterogeneous Effect ◽  
Intuitive Interpretation

‘Classic’ forest plots show the effect sizes from individual studies and the aggregate effect from a meta-analysis. However, in ecology and evolution meta-analyses routinely contain over 100 effect sizes, making the classic forest plot of limited use. We surveyed 102 meta-analyses in ecology and evolution, finding that only 11% use the classic forest plot. Instead, most used a ‘forest-like plot’, showing point estimates (with 95% confidence intervals; CIs) from a series of subgroups or categories in a meta-regression. We propose a modification of the forest-like plot, which we name the ‘orchard plot’. Orchard plots, in addition to showing overall mean effects and CIs from meta-analyses/regressions, also includes 95% prediction intervals (PIs), and the individual effect sizes scaled by their precision. The PI allows the user and reader to see the range in which an effect size from a future study may be expected to fall. The PI, therefore, provides an intuitive interpretation of any heterogeneity in the data. Supplementing the PI, the inclusion of underlying effect sizes also allows the user to see any influential or outlying effect sizes. We showcase the orchard plot with example datasets from ecology and evolution, using the R package, orchard, including several functions for visualizing meta-analytic data using forest-plot derivatives. We consider the orchard plot as a variant on the classic forest plot, cultivated to the needs of meta-analysts in ecology and evolution. Hopefully, the orchard plot will prove fruitful for visualizing large collections of heterogeneous effect sizes regardless of the field of study.

Exploring the Morning Morality Effect in the context of moral utilitarianism: a post-hoc analysis

2021 ◽  
Author(s):  
Bastien Trémolière ◽  
Corentin J Gosling
Keyword(s):  
Effect Size ◽  
Autonomous Vehicles ◽  
Meta Analysis ◽  
Individual Study ◽  
Post Hoc Analysis ◽  
Cognitive Reflection ◽  
Confounding Variables ◽  
Small Effect Size ◽  
Large Heterogeneity ◽  
Post Hoc

Recent research has shown mixed evidence for the morning morality effect (i.e., the observation that individuals are less immoral in the morning than in the afternoon). In the present research, we target the morning morality effect in the context of moral utilitarianism, by reanalyzing observational data previously collected by our lab. These data include different tasks capturing moral utilitarianism (i.e., standard sacrificial dilemmas, an ecological utilitarian scale, and/or dilemmas involving the morality of autonomous vehicles). We report a meta-analysis of 6 studies which showed that participants became less utilitarian as the day goes on, but with a small effect size (r = -0.14) and a large heterogeneity. Exploration of this heterogeneity showed that such a conclusion was statistically significant for classic sacrificial dilemmas only. Notably, even when restricting the analysis to the classic sacrificial dilemmas, a moderate inconsistency remained. Post-hoc analysis of an individual study showed that this small effect did not survive the inclusion of potentially confounding variables, such as psychopathy trait and cognitive reflection. Implications and limitations are discussed.

Abstract 17059: Re-Use of Clinical Trial Data From the NHLBI Data Repository (BioLINCC) for Patient-Level Meta-Analyses of Cardiovascular Outcomes: Challenges and Opportunities

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Helena Sviglin ◽  
Gauri Dandi ◽  
Eileen Navarro Almario ◽  
Tejas Patel ◽  
Colin O Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Meta Analysis ◽  
Cardiovascular Outcomes ◽  
Data Repository ◽  
Common Data Elements ◽  
Patient Level Data ◽  
Patient Level ◽  
Level Data ◽  
Data Elements ◽  
Meta Analyses

Introduction: An objective of the Meta-AnalyTical Interagency Group (MATIG) is to conduct patient-level meta-analyses of cardiovascular outcomes using data from publicly available repositories. We describe challenges with data re-use from a seminal trial, provide a systematic approach to identify and curate data elements for hypothesis generation, and establish stackable trials to support these analyses. Methods: We used data from the ACCORD trial to assess risk factors and their gender specific differences for the event of hospitalization or death due to heart failure (hdHF), in patients with type 2 diabetes*. We identified the data elements needed to answer the research questions, reviewed the trial protocol to verify definitions, extracted patient-level data, performed quality assessment and statistical analysis. The results showed a gender difference in the effect of intensive vs. standard glucose-lowering therapy on hdHF. To validate the findings, we sought additional trials in BioLINCC to develop a compendium for meta-analysis, and repeated these steps for each trial. Results: Challenges for reusing the ACCORD trial included access to complete patient-level data and metadata. The compendium, developed to evaluate the stackability** of data across trials, identified differences in trial designs, patient populations, study interventions, and data elements that may impact the feasibility and interpretation of meta-analysis. An example of compendium components is shown in Table 1. Conclusion: High-quality metadata facilitate re-use of trial repository data. This compendium standardizes common data elements for gender, racial and age-group specific outcome assessment in major clinical trials. It provides the framework to assess the fitness of trials for patient-level meta-analyses. Efforts are underway by MATIG to expand the compendium to include risk factors and major cardiovascular outcomes across multiple large trials for meta-analysis.

scholarly journals The Effect of Bilingualism on Older Adults’ Inhibitory Control: A Meta-Analysis

2019 ◽  
Author(s):  
Bonnie A Armstrong ◽  
Natalie Ein ◽  
Brenda I Wong ◽  
Sara N Gallant ◽  
Lingqian Li
Keyword(s):  
Older Adults ◽  
Second Language Acquisition ◽  
Inhibitory Control ◽  
Language Proficiency ◽  
Meta Analysis ◽  
Individual Characteristics ◽  
Bilingual Advantage ◽  
The Individual ◽  
Meta Analyses ◽  
Design And Methods

AbstractBackground and ObjectivesThe effect bilingualism has on older adults’ inhibitory control has been extensively investigated, yet there is continued controversy regarding whether older adult bilinguals show superior inhibitory control compared with monolinguals. The objective of the current meta-analysis was to examine the reliability and magnitude of the bilingualism effect on older adults’ inhibitory control as measured by the Simon and Stroop tasks. In addition, we examined whether individual characteristics moderate the bilingual advantage in inhibition, including age (young–old vs old–old), age of second language acquisition, immigrant status, language proficiency, and frequency of language use.Research Design and MethodsA total of 22 samples for the Simon task and 14 samples for the Stroop task were derived from 28 published and unpublished articles (32 independent samples, with 4 of these samples using more than 1 task) and were analyzed in 2 separate meta-analyses.ResultsAnalyses revealed a reliable effect of bilingualism on older adults’ performance on the Simon (g = 0.60) and Stroop (g = 0.27) tasks. Interestingly, individual characteristics did not moderate the association between bilingualism and older adults’ inhibitory control.Discussion and ImplicationsThe results suggest there is a bilingual advantage in inhibitory control for older bilinguals compared with older monolinguals, regardless of the individual characteristics previously thought to moderate this effect. Based on these findings, bilingualism may protect inhibitory control from normal cognitive decline with age.

scholarly journals A Meta-Analysis of 46 Studies Identified by the FDA Demonstrates that Soy Protein Decreases Circulating LDL and Total Cholesterol Concentrations in Adults

2019 ◽  
Vol 149 (6) ◽  
pp. 968-981 ◽  
Author(s):  
Sonia Blanco Mejia ◽  
Mark Messina ◽  
Siying S Li ◽  
Effie Viguiliouk ◽  
Laura Chiavaroli ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Soy Protein ◽  
Ldl Cholesterol ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Heart Health ◽  
Health Claim ◽  
The Individual ◽  
Dose Response Effect ◽  
Meta Analyses

ABSTRACT Background Certain plant foods (nuts and soy protein) and food components (viscous fibers and plant sterols) have been permitted by the FDA to carry a heart health claim based on their cholesterol-lowering ability. The FDA is currently considering revoking the heart health claim for soy protein due to a perceived lack of consistent LDL cholesterol reduction in randomized controlled trials. Objective We performed a meta-analysis of the 46 controlled trials on which the FDA will base its decision to revoke the heart health claim for soy protein. Methods We included the 46 trials on adult men and women, with baseline circulating LDL cholesterol concentrations ranging from 110 to 201 mg/dL, as identified by the FDA, that studied the effects of soy protein on LDL cholesterol and total cholesterol (TC) compared with non-soy protein. Two independent reviewers extracted relevant data. Data were pooled by the generic inverse variance method with a random effects model and expressed as mean differences with 95% CI. Heterogeneity was assessed and quantified. Results Of the 46 trials identified by the FDA, 43 provided data for meta-analyses. Of these, 41 provided data for LDL cholesterol, and all 43 provided data for TC. Soy protein at a median dose of 25 g/d during a median follow-up of 6 wk decreased LDL cholesterol by 4.76 mg/dL (95% CI: −6.71, −2.80 mg/dL, P < 0.0001; I2 = 55%, P < 0.0001) and decreased TC by 6.41 mg/dL (95% CI: −9.30, −3.52 mg/dL, P < 0.0001; I2 = 74%, P < 0.0001) compared with non-soy protein controls. There was no dose–response effect or evidence of publication bias for either outcome. Inspection of the individual trial estimates indicated most trials (∼75%) showed a reduction in LDL cholesterol (range: −0.77 to −58.60 mg/dL), although only a minority of these were individually statistically significant. Conclusions Soy protein significantly reduced LDL cholesterol by approximately 3–4% in adults. Our data support the advice given to the general public internationally to increase plant protein intake. This trial was registered at clinicaltrials.gov as NCT03468127.

scholarly journals Forced vital capacity and cross-domain late-onset Pompe disease outcomes: an individual patient-level data meta-analysis

2019 ◽  
Vol 266 (9) ◽  
pp. 2312-2321
Author(s):  
Kenneth I. Berger ◽  
Steve Kanters ◽  
Jeroen P. Jansen ◽  
Andrew Stewart ◽  
Susan Sparks ◽  
...  
Keyword(s):  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Late Onset ◽  
Meta Analysis ◽  
Patient Level Data ◽  
Individual Patient Level ◽  
Patient Level ◽  
Cross Domain ◽  
Disease Outcomes ◽  
Level Data

scholarly journals Updating insights into rosiglitazone and cardiovascular risk through shared data: individual patient and summary level meta-analyses

BMJ ◽  
2020 ◽  
pp. l7078 ◽  
Author(s):  
Joshua D Wallach ◽  
Kun Wang ◽  
Audrey D Zhang ◽  
Deanna Cheng ◽  
Holly K Grossetta Nardini ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Systematic Review ◽  
Cardiovascular Risk ◽  
Meta Analysis ◽  
Odds Ratios ◽  
Level Data ◽  
Increased Risk ◽  
Meta Analyses ◽  
Analytical Approaches

AbstractObjectivesTo conduct a systematic review and meta-analysis of the effects of rosiglitazone treatment on cardiovascular risk and mortality using multiple data sources and varying analytical approaches with three aims in mind: to clarify uncertainties about the cardiovascular risk of rosiglitazone; to determine whether different analytical approaches are likely to alter the conclusions of adverse event meta-analyses; and to inform efforts to promote clinical trial transparency and data sharing.DesignSystematic review and meta-analysis of randomized controlled trials.Data sourcesGlaxoSmithKline’s (GSK’s) ClinicalStudyDataRequest.com for individual patient level data (IPD) and GSK’s Study Register platforms, MEDLINE, PubMed, Embase, Web of Science, Cochrane Central Registry of Controlled Trials, Scopus, and ClinicalTrials.gov from inception to January 2019 for summary level data.Eligibility criteria for selecting studiesRandomized, controlled, phase II-IV clinical trials that compared rosiglitazone with any control for at least 24 weeks in adults.Data extraction and synthesisFor analyses of trials for which IPD were available, a composite outcome of acute myocardial infarction, heart failure, cardiovascular related death, and non-cardiovascular related death was examined. These four events were examined independently as secondary analyses. For analyses including trials for which IPD were not available, myocardial infarction and cardiovascular related death were examined, which were determined from summary level data. Multiple meta-analyses were conducted that accounted for trials with zero events in one or both arms with two different continuity corrections (0.5 constant and treatment arm) to calculate odds ratios and risk ratios with 95% confidence intervals.Results33 eligible trials were identified from ClinicalStudyDataRequest.com for which IPD were available (21 156 patients). Additionally, 103 trials for which IPD were not available were included in the meta-analyses for myocardial infarction (23 683 patients), and 103 trials for which IPD were not available contributed to the meta-analyses for cardiovascular related death (22 772 patients). Among 29 trials for which IPD were available and that were included in previous meta-analyses using GSK’s summary level data, more myocardial infarction events were identified by using IPD instead of summary level data for 26 trials, and fewer cardiovascular related deaths for five trials. When analyses were limited to trials for which IPD were available, and a constant continuity correction of 0.5 and a random effects model were used to account for trials with zero events in only one arm, patients treated with rosiglitazone had a 33% increased risk of a composite event compared with controls (odds ratio 1.33, 95% confidence interval 1.09 to 1.61; rosiglitazone population: 274 events among 11 837 patients; control population: 219 events among 9319 patients). The odds ratios for myocardial infarction, heart failure, cardiovascular related death, and non-cardiovascular related death were 1.17 (0.92 to 1.51), 1.54 (1.14 to 2.09), 1.15 (0.55 to 2.41), and 1.18 (0.60 to 2.30), respectively. For analyses including trials for which IPD were not available, odds ratios for myocardial infarction and cardiovascular related death were attenuated (1.09, 0.88 to 1.35, and 1.12, 0.72 to 1.74, respectively). Results were broadly consistent when analyses were repeated using trials with zero events across both arms and either of the two continuity corrections was used.ConclusionsThe results suggest that rosiglitazone is associated with an increased cardiovascular risk, especially for heart failure events. Although increased risk of myocardial infarction was observed across analyses, the strength of the evidence varied and effect estimates were attenuated when summary level data were used in addition to IPD. Because more myocardial infarctions and fewer cardiovascular related deaths were reported in the IPD than in the summary level data, sharing IPD might be necessary when performing meta-analyses focused on safety.Systematic review registrationOSF Home https://osf.io/4yvp2/.

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