scholarly journals Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study

BMJ ◽  
2020 ◽  
pp. l6802 ◽  
Author(s):  
Helene Moustgaard ◽  
Gemma L Clayton ◽  
Hayley E Jones ◽  
Isabelle Boutron ◽  
Lars Jørgensen ◽  
...  
Keyword(s):  
Epidemiological Study ◽  
Systematic Reviews ◽  
Treatment Effects ◽  
Healthcare Providers ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Cochrane Database ◽  
Patient Reported ◽  
Meta Analyses ◽  
The Impact

Abstract Objectives To study the impact of blinding on estimated treatment effects, and their variation between trials; differentiating between blinding of patients, healthcare providers, and observers; detection bias and performance bias; and types of outcome (the MetaBLIND study). Design Meta-epidemiological study. Data source Cochrane Database of Systematic Reviews (2013-14). Eligibility criteria for selecting studies Meta-analyses with both blinded and non-blinded trials on any topic. Review methods Blinding status was retrieved from trial publications and authors, and results retrieved automatically from the Cochrane Database of Systematic Reviews. Bayesian hierarchical models estimated the average ratio of odds ratios (ROR), and estimated the increases in heterogeneity between trials, for non-blinded trials (or of unclear status) versus blinded trials. Secondary analyses adjusted for adequacy of concealment of allocation, attrition, and trial size, and explored the association between outcome subjectivity (high, moderate, low) and average bias. An ROR lower than 1 indicated exaggerated effect estimates in trials without blinding. Results The study included 142 meta-analyses (1153 trials). The ROR for lack of blinding of patients was 0.91 (95% credible interval 0.61 to 1.34) in 18 meta-analyses with patient reported outcomes, and 0.98 (0.69 to 1.39) in 14 meta-analyses with outcomes reported by blinded observers. The ROR for lack of blinding of healthcare providers was 1.01 (0.84 to 1.19) in 29 meta-analyses with healthcare provider decision outcomes (eg, readmissions), and 0.97 (0.64 to 1.45) in 13 meta-analyses with outcomes reported by blinded patients or observers. The ROR for lack of blinding of observers was 1.01 (0.86 to 1.18) in 46 meta-analyses with subjective observer reported outcomes, with no clear impact of degree of subjectivity. Information was insufficient to determine whether lack of blinding was associated with increased heterogeneity between trials. The ROR for trials not reported as double blind versus those that were double blind was 1.02 (0.90 to 1.13) in 74 meta-analyses. Conclusion No evidence was found for an average difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors. These results could reflect that blinding is less important than often believed or meta-epidemiological study limitations, such as residual confounding or imprecision. At this stage, replication of this study is suggested and blinding should remain a methodological safeguard in trials.

scholarly journals Systematic Reviews and Meta-Analysis in Spine Surgery—How Good Are They in Methodological Quality? A Systematic Review

2020 ◽  
pp. 219256822090681 ◽  
Author(s):  
Muthu Sathish ◽  
Ramakrishnan Eswar
Keyword(s):  
Systematic Review ◽  
Spine Surgery ◽  
Systematic Reviews ◽  
Methodological Quality ◽  
Meta Analysis ◽  
Eligibility Criteria ◽  
Cochrane Database ◽  
Critical Flaw ◽  
Meta Analyses

Study Design: Systematic review. Objectives: To assess the methodological quality of systematic reviews and meta-analyses in spine surgery over the past 2 decades. Materials and Methods: We conducted independent and in duplicate systematic review of the published systematic reviews and meta-analyses between 2000 and 2019 from PubMed Central and Cochrane Database pertaining to spine surgery involving surgical intervention. We searched bibliographies to identify additional relevant studies. Methodological quality was evaluated with AMSTAR score and graded with AMSTAR 2 criteria. Results: A total of 96 reviews met the eligibility criteria, with mean AMSTAR score of 7.51 (SD = 1.98). Based on AMSTAR 2 criteria, 13.5% (n = 13) and 18.7% (n = 18) of the studies had high and moderate level of confidence of results, respectively, without any critical flaws. A total of 29.1% (n = 28) of the studies had at least 1 critical flaw and 38.5% (n = 37) of the studies had more than 1 critical flaw, so that their results have low and critically low confidence, respectively. Failure to analyze the conflict of interest of authors of primary studies included in review and lack of list of excluded studies with justification were the most common critical flaw. Regression analysis demonstrated that studies with funding and studies published in recent years were significantly associated with higher methodological quality. Conclusion: Despite improvement in methodological quality of systematic reviews and meta-analyses in spine surgery in current decade, a substantial proportion continue to show critical flaws. With increasing number of review articles in spine surgery, stringent measures must be taken to adhere to methodological quality by following PRISMA and AMSTAR guidelines to attain higher standards of evidence in published literature.

scholarly journals Assessing treatment effects and publication bias across different specialties in medicine: a meta-epidemiological study

BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e045942
Author(s):  
Simon Schwab ◽  
Giuachin Kreiliger ◽  
Leonhard Held
Keyword(s):  
Epidemiological Study ◽  
Publication Bias ◽  
Treatment Effects ◽  
Meta Analysis ◽  
Small Study ◽  
Significant Treatment ◽  
Medical Specialties ◽  
Cochrane Database ◽  
Randomised Controlled ◽  
Meta Analyses

ObjectivesTo assess the prevalence of statistically significant treatment effects, adverse events and small-study effects (when small studies report more extreme results than large studies) and publication bias (over-reporting of statistically significant results) across medical specialties.DesignLarge meta-epidemiological study of treatment effects from the Cochrane Database of Systematic Reviews.MethodsWe investigated outcomes from 57 162 studies from 1922 to 2019, and overall 98 966 meta-analyses and 5534 large meta-analyses (≥10 studies). Egger’s and Harbord’s tests to detect small-study effects, limit meta-analysis and Copas selection models to bias-adjust effect estimates and generalised linear mixed models were used to analyse one of the largest collections of evidence in medicine.ResultsMedical specialties showed differences in the prevalence of statistically significant results of efficacy and safety outcomes. Treatment effects from primary studies published in high ranking journals were more likely to be statistically significant (OR=1.52; 95% CI 1.32 to 1.75) while randomised controlled trials were less likely to report a statistically significant effect (OR=0.90; 95% CI 0.86 to 0.94). Altogether 19% (95% CI 18% to 20%) of the large meta-analyses showed evidence for small-study effects, but only 3.9% (95% CI 3.4% to 4.4%) showed evidence for publication bias after further assessment of funnel plots. Adjusting treatment effects resulted in overall less evidence for efficacy.ConclusionsThese results suggest that reporting of large treatment effects from small studies may cause greater concern than publication bias. Incentives should be created so that studies of the highest quality become more visible than studies that report more extreme results.

scholarly journals Assessing treatment effects and publication bias across different specialties in medicine: a large empirical study of the Cochrane Database of Systematic Reviews

2020 ◽  
Author(s):  
Simon Schwab ◽  
Kreiliger Giuachin ◽  
Leonhard Held
Keyword(s):  
Publication Bias ◽  
Systematic Reviews ◽  
Treatment Effects ◽  
Evidence Based ◽  
Medical Specialties ◽  
Null Result ◽  
Cochrane Database ◽  
Funnel Plots ◽  
Meta Analyses ◽  
Based Medicine

Publication bias is a persisting problem in meta-analyses for evidence based medicine. As a consequence small studies with large treatment effects are more likely to be reported than studies with a null result which causes asymmetry. Here, we investigated treatment effects from 57,186 studies from 1922 to 2019, and overall 99,129 meta-analyses and 5,557 large meta-analyses from the Cochrane Database of Systematic Reviews. Altogether 19% (95%-CI from 18% to 20%) of the meta-analyses demonstrated evidence for asymmetry, but only 3.9% (95%-CI from 3.4% to 4.4%) showed evidence for publication bias after further assessment of funnel plots. Adjusting treatment effects resulted in overall less evidence for efficacy, and treatment effects in some medical specialties or published in prestigious journals were more likely to be statistically significant. These results suggest that asymmetry from exaggerated effects from small studies causes greater concern than publication bias.

scholarly journals Efficacy and safety of aliskiren combination therapy: a protocol for an umbrella review

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e043807
Author(s):  
Jiantong Shen ◽  
Wenming Feng ◽  
Yike Wang ◽  
Qiyuan Zhao ◽  
Billong Laura Flavorta ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Systematic Reviews ◽  
Cochrane Library ◽  
Umbrella Review ◽  
Quality Of Reporting ◽  
Ethical Approval ◽  
Registration Number ◽  
Third Person ◽  
Meta Analyses ◽  
The Impact

IntroductionEfficacy of aliskiren combination therapy with other antihypertensive has been evaluated in the treatment of patients with hypertension in recent systematic reviews. However, most previous reviews only focused on one single health outcome or one setting, none of them made a full summary that assessed the impact of aliskiren combination treatment comprehensively. As such, this umbrella review based on systematic reviews and meta-analyses is aimed to synthesise the evidences on efficacy, safety and tolerability of aliskiren-based therapy for hypertension and related comorbid patients.Methods and analysisA comprehensive search of PubMed, EMBASE, Cochrane Library, CNKI published from inception to August 2020 will be conducted. The selected articles are systematic reviews which evaluated efficacy, safety and tolerability of aliskiren combination therapy. Two reviewers will screen eligible articles, extract data and evaluate quality independently. Any disputes will be resolved by discussion or the arbitration of a third person. The quality of reporting evidence will be assessed using the Assessment of Multiple Systematic Reviews V.2 tool tool. We will take a mixed-methods approach to synthesising the review literatures, reporting summary of findings tables and iteratively mapping the results.Ethics and disseminationEthical approval is not required for the study, as we would only collect data from available published materials. This umbrella review will be also submitted to a peer-reviewed journal for publication after completion.PROSPERO registration numberCRD42020192131.

scholarly journals Consequences of the COVID-19 Syndemic for Nutritional Health: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1168
Author(s):  
Cristian Neira ◽  
Rejane Godinho ◽  
Fabio Rincón ◽  
Rodrigo Mardones ◽  
Janari Pedroso
Keyword(s):  
Systematic Review ◽  
Systematic Reviews ◽  
Preventive Measures ◽  
Physical Contact ◽  
Current Evidence ◽  
Study Objective ◽  
Eating Style ◽  
Healthy Nutrition ◽  
Meta Analyses ◽  
The Impact

Confinement at home, quarantine, and social distancing are some measures adopted worldwide to prevent the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2), which has been generating an important alteration in the routines and qualities of life of people. The impact on health is still being evaluated, and consequences in the nutritional field are not entirely clear. The study objective was to evaluate the current evidence about the impact that preventive measures of physical contact restriction causes in healthy nutrition. A systematic review was carried out according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” PRISMA Group and Cochrane method for rapid systematic reviews. Searching was performed in six electronic databases and evaluated articles published between 2010 and 2020, including among their participants adult subjects who had been exposed to the preventive measures of physical contact restriction. Seven studies met the selection criteria and reported an overall increase in food consumption, weight, Body Mass Index (BMI), and a change in eating style. Findings suggest that healthy nutrition is affected by preventive measures to restrict physical contact as a result of the COVID-19 syndemic.

scholarly journals Polyphenols and Cognition In Humans: An Overview of Current Evidence from Recent Systematic Reviews and Meta-Analyses

2020 ◽  
pp. 1-15
Author(s):  
Daniel Joseph Lamport ◽  
Claire Michelle Williams
Keyword(s):  
Systematic Reviews ◽  
Evidence Base ◽  
Epidemiological Studies ◽  
Cognitive Outcome ◽  
Current Evidence ◽  
Duration Of Treatment ◽  
Current Evidence Base ◽  
Cognitive Benefits ◽  
Meta Analyses ◽  
The Impact

There is increasing interest in the impact of dietary influences on the brain throughout the lifespan, ranging from improving cognitive development in children through to attenuating ageing related cognitive decline and reducing risk of neurodegenerative diseases. Polyphenols, phytochemicals naturally present in a host of fruits, vegetables, tea, cocoa and other foods, have received particular attention in this regard, and there is now a substantial body of evidence from experimental and epidemiological studies examining whether their consumption is associated with cognitive benefits. The purpose of this overview is to synthesise and evaluate the best available evidence from two sources, namely meta-analyses and systematic reviews, in order to give an accurate reflection of the current evidence base for an association between polyphenols and cognitive benefits. Four meta-analyses and thirteen systematic reviews published between 2017–2020 were included, and were categorised according to whether they reviewed specific polyphenol-rich foods and classes or all polyphenols. A requirement for inclusion was assessment of a behavioural cognitive outcome in humans. A clear and consistent theme emerged that whilst there is support for an association between polyphenol consumption and cognitive benefits, this conclusion is tentative, and by no means definitive. Considerable methodological heterogeneity was repeatedly highlighted as problematic such that the current evidence base does not support reliable conclusions relating to efficacy of specific doses, duration of treatment, or sensitivity in specific populations or certain cognitive domains. The complexity of multiple interactions between a range of direct and indirect mechanisms of action is discussed. Further research is required to strengthen the reliability of the evidence base.

scholarly journals Efficacy and safety of instantaneous wave-free ratio in patients undergoing coronary revascularisation: protocol for a systematic review

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e017868
Author(s):  
Joey S.W. Kwong ◽  
Sheyu Li ◽  
Wan-Jie Gu ◽  
Hao Chen ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Systematic Reviews ◽  
Meta Analysis ◽  
Adverse Outcomes ◽  
Coronary Revascularisation ◽  
Eligibility Criteria ◽  
Registration Number ◽  
Collection Form ◽  
Randomised Controlled ◽  
Meta Analyses

IntroductionEffective selection of coronary lesions for revascularisation is pivotal in the management of symptoms and adverse outcomes in patients with coronary artery disease. Recently, instantaneous ‘wave-free’ ratio (iFR) has been proposed as a new diagnostic index for assessing the severity of coronary stenoses without the need of pharmacological vasodilation. Evidence of the effectiveness of iFR-guided revascularisation is emerging and a systematic review is warranted.Methods and analysisThis is a protocol for a systematic review of randomised controlled trials and controlled observational studies. Electronic sources including MEDLINE via Ovid, Embase, Cochrane databases and ClinicalTrials.gov will be searched for potentially eligible studies investigating the effects of iFR-guided strategy in patients undergoing coronary revascularisation. Studies will be selected against transparent eligibility criteria and data will be extracted using a prestandardised data collection form by two independent authors. Risk of bias in included studies and overall quality of evidence will be assessed using validated methodological tools. Meta-analysis will be performed using the Review Manager software. Our systematic review will be performed according to the guidance from the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Ethics and disseminationEthics approval is not required. Results of the systematic review will be disseminated as conference proceedings and peer-reviewed journal publication.Trial registration numberThis protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42017065460.

scholarly journals Programme frequency, type, time and duration do not explain the effects of balance exercise in older adults: a systematic review with a meta-regression analysis

2018 ◽  
Vol 53 (16) ◽  
pp. 996-1002 ◽  
Author(s):  
Melanie K Farlie ◽  
Lauren Robins ◽  
Romi Haas ◽  
Jennifer L Keating ◽  
Elizabeth Molloy ◽  
...  
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Systematic Reviews ◽  
Centre Of Mass ◽  
Randomised Trials ◽  
Eligibility Criteria ◽  
Exercise Interventions ◽  
Balance Exercise ◽  
Control Centre ◽  
Meta Analyses

ObjectiveThe objective of this systematic review was to examine the effects of different balance exercise interventions compared with non-balance exercise controls on balance task performance in older adults.DesignSystematic review.Data sourcesMedline, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Scopus and Cochrane Database of Systematic Reviews were searched until July 2017.Eligibility criteria for selecting studiesSystematic reviews and meta-analyses of randomised trials of balance exercise interventions for older adults were identified for extraction of eligible randomised trials. Eligibility criteria for inclusion of randomised trials in meta-analyses were comparison of a balance exercise intervention with a control group that did not perform balance exercises, report of at least one end-intervention balance outcome measurement that was consistent with the five subgroups of balance exercise identified, and full-text article available in English.ResultsNinety-five trials were included in meta-analyses and 80 in meta-regressions. For four balance exercise types (control centre of mass, multidimensional, mobility and reaching), significant effects for balance exercise interventions were found in meta-analyses (standardised mean difference (SMD) 0.31–0.50), however with considerable heterogeneity in observed effects (I2: 50.4%–80.6%). Risk of bias assessments (Physiotherapy Evidence Database score and funnel plots) did not explain heterogeneity. One significant relationship identified in the meta-regressions of SMD and balance exercise frequency, time and duration explained 2.1% of variance for the control centre of mass subgroup.ConclusionLimitations to this study included the variability in design of balance interventions, incomplete reporting of data and statistical heterogeneity. The design of balance exercise programmes provides inadequate explanation of the observed benefits of these interventions.

AdvanTIG-302: Anti-TIGIT monoclonal antibody (mAb) ociperlimab (OCI) plus tislelizumab (TIS) versus pembrolizumab (PEM) in programmed death ligand-1 (PD-L1) selected, previously untreated, locally advanced, unresectable or metastatic non-small cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9128-TPS9128
Author(s):  
Mark A. Socinski ◽  
Alexander I. Spira ◽  
Luis G. Paz-Ares ◽  
Martin Reck ◽  
Shun Lu ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Cell Activation ◽  
Immune Cell ◽  
Locally Advanced ◽  
Double Blind Study ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Secondary Resistance ◽  
Programmed Death ◽  
Patient Reported

TPS9128 Background: Monotherapy with programmed death 1 (PD-1)/PD-L1 antibodies has improved clinical outcomes for patients (pts) with non-oncogenic driven NSCLC but clinical responses are limited by primary and secondary resistance, and improvements in durability of response are required. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) is a co-inhibitory, immune checkpoint receptor upregulated on T-cells and natural killer cells in multiple solid tumors, which can inhibit anticancer immune responses. OCI (BGB-A1217) is a novel, humanized mAb that binds to TIGIT with high affinity and specificity, which has demonstrated competent binding with C1q and all Fcγ receptors while inducing antibody-dependent cellular cytotoxicity. Preclinical and clinical studies suggest that dual targeting with anti-TIGIT and anti-PD-1 antibodies produces synergistic immune cell activation and enhanced antitumor activity. Methods: AdvanTIG-302 is a Phase 3, multicenter, international, randomized, double-blind study (NCT04746924) investigating OCI in combination with TIS compared with PEM in adult pts (≥ 18 years of age) with PD-L1 selected, previously untreated, locally advanced, unresectable or metastatic NSCLC without oncogenic EGFR or ALK mutation. Approximately 605 pts will be randomized 5:5:1 to receive: OCI 900 mg intravenously (IV) plus TIS 200 mg IV every three weeks (Q3W; Arm A), PEM 200 mg IV plus placebo IV Q3W (Arm B) or TIS 200 mg IV plus placebo IV Q3W (Arm C). Pts will be treated until disease progression, loss of clinical benefit, intolerable toxicity or withdrawal of consent. Stratification factors include histology (squamous vs non-squamous) and region (Asian vs non-Asian). Cross-over is not permitted. Key eligibility criteria include histologically confirmed disease, PD-L1 expression ≥ 50%, no known EGFR or ALK mutations and no prior checkpoint inhibitor therapy. Dual primary endpoints are investigator-assessed progression-free survival (PFS; RECIST v1.1) and overall survival (Arms A and B) in the Intention-to-Treat population. Secondary endpoints include PFS (assessed by Blinded Independent Review Committee), investigator-assessed overall response rate and duration of response, safety and tolerability, and patient-reported health-related quality of life (EORTC-QLQ-C30, QLQ-LC13 and EQ-5D-5L; Arms A and B). Exploratory endpoints include disease control rate, clinical benefit rate and time to response. This study will also evaluate the association between biomarkers and response or resistance. Study enrollment has begun and recruitment is ongoing. Clinical trial information: NCT04746924.

scholarly journals Management of haemorrhoids: protocol of an umbrella review of systematic reviews and meta-analyses

BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e035287
Author(s):  
Min Chen ◽  
Tai-Chun Tang ◽  
Tao-Hong He ◽  
Yong-Jun Du ◽  
Di Qin ◽  
...  
Keyword(s):  
Systematic Reviews ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Current Evidence ◽  
Cochrane Library ◽  
Final Report ◽  
Umbrella Review ◽  
Effect Model ◽  
Meta Analyses ◽  
The Impact

IntroductionThe prevalence of haemorrhoidal diseases was high in general population, and many treatments are proposed for the management of haemorrhoids. The treatments include conservative and surgical interventions; the credibility and strength of current evidence of their effectiveness are not comprehensively evaluated. We aim to evaluate the credibility of systematic reviews and meta-analyses that assess the effectiveness of the treatments for haemorrhoidal diseases through an umbrella review.Methods and analysisWe will search Ovid Medline, Embase, Cochrane library and Web of Science from inception to March 2020 without any language restriction. We will include meta-analyses that examine the effectiveness of treatments in the management of haemorrhoids. Two reviewers will independently screen the titles and abstracts of retrieved articles, and they will extract data from the included meta-analyses. For each meta-analysis, we will estimate the effect size of a treatment through the random-effect model and the fixed-effect model, and we will evaluate between-study heterogeneity (Cochrane’s Q and I2statistics) and small-study effect (Egger’s test); we will also estimate the evidence of excess significance bias. Evidence of each treatment will be graded according to prespecified criteria. Methodological quality of each meta-analysis will be evaluated by using Assessment of Multiple Systematic Reviews 2. The corrected cover area method will be used to assess the impact of overlap in reviews on the findings of the umbrella review.Ethics and disseminationWe will present the results of the umbrella review at conferences and publish the final report in a peer-reviewed journal. The umbrella review does not require ethical approval.PROSPERO registration numberCRD42019140702.

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