Some Problems with the Investigation of Noninferiority in Meta-analysis

2004 ◽  
Vol 43 (05) ◽  
pp. 470-474 ◽  
Author(s):  
N. Victor ◽  
S. Witte
Keyword(s):  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Intention To Treat ◽  
Protocol Population ◽  
Noninferiority Trials ◽  
Interval Approach ◽  
Bivariate Method ◽  
Full Analysis ◽  
Meta Regression ◽  
Meta Analyses

Summary Objectives: Noninferiority trials have become commonplace in recent years. Like individual clinical trials, meta-analyses can also investigate noninferiority. However, certain important topics have to be considered. Methods: The proposed methods in this paper have their origin in the framework of noninferiority trials and meta-analyses. This paper can therefore be seen as a combination of both fields. Two issues are highlighted in the paper; difficulties in the choice of delta for a noninferiority meta-analysis leading to different deltas and methods for meta-analyses with different analysis sets, based on the full-analysis set with the intention-to-treat principle or the per-protocol population. Analytical methods, sensitivity analyses, meta-regression, and a bivariate method are introduced. The proposed graphical presentations support the analytical results. Conclusion: The confidence interval approach using meta-regression or bivariate methods is appropriate using both analysis sets for meta-analyses investigating noninferiority.

Triclosan-Coated Sutures Reduce the Risk of Surgical Site Infections: A Systematic Review and Meta-analysis

2015 ◽  
Vol 36 (2) ◽  
pp. 169-179 ◽  
Author(s):  
Anucha Apisarnthanarak ◽  
Nalini Singh ◽  
Aila Nica Bandong ◽  
Gilbert Madriaga
Keyword(s):  
Systematic Review ◽  
Abdominal Surgery ◽  
Random Effects ◽  
Meta Analysis ◽  
Surgical Site Infections ◽  
Sensitivity Analyses ◽  
Publication Type ◽  
Random Effects Models ◽  
Meta Regression ◽  
Meta Analyses

OBJECTIVETo analyze available evidence on the effectiveness of triclosan-coated sutures (TCSs) in reducing the risk of surgical site infection (SSI).DESIGNSystematic review and meta-analysis.METHODSA systematic search of both randomized (RCTs) and nonrandomized (non-RCT) studies was performed on PubMed Medline, OVID, EMBASE, and SCOPUS, without restrictions in language and publication type. Random-effects models were utilized and pooled estimates were reported as the relative risk (RR) ratio with 95% confidence interval (CI). Tests for heterogeneity as well as meta-regression, subgroup, and sensitivity analyses were performed.RESULTSA total of 29 studies (22 RCTs, 7 non-RCTs) were included in the meta-analysis. The overall RR of acquiring an SSI was 0.65 (95% CI: 0.55–0.77; I2=42.4%, P=.01) in favor of TCS use. The pooled RR was particularly lower for the abdominal surgery group (RR: 0.56; 95% CI: 0.41–0.77) and was robust to sensitivity analysis. Meta-regression analysis revealed that study design, in part, may explain heterogeneity (P=.03). The pooled RR subgroup meta-analyses for randomized controlled trials (RCTs) and non-RCTs were 0.74 (95% CI: 0.61–0.89) and 0.53 (95% CI: 0.42–0.66), respectively, both of which favored the use of TCSs.CONCLUSIONThe random-effects meta-analysis based on RCTs suggests that TCSs reduced the risk of SSI by 26% among patients undergoing surgery. This effect was particularly evident among those who underwent abdominal surgery.Infect Control Hosp Epidemiol 2015;36(2): 1–11

How long is the interval between the onset and the initial management of bipolar disorder? A meta-analysis

2017 ◽  
Vol 41 (S1) ◽  
pp. S13-S13
Author(s):  
G. De Girolamo ◽  
G. Signorini ◽  
J. Dagani ◽  
F. Faustini
Keyword(s):  
Bipolar Disorder ◽  
Age Of Onset ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
First Episode ◽  
Initial Management ◽  
Study Heterogeneity ◽  
Meta Regression ◽  
Competing Interest ◽  
Meta Analyses

ObjectiveTo evaluate the length of the interval between the onset and the initial management of bipolar disorder (BD).MethodWe conducted a meta-analysis using the preferred reporting items for systematic reviews and meta-analyses guidelines. Systematic searches located studies reporting estimates of the age of onset (AOO) and indicators of the age at initial management of BD. We calculated a pooled estimate of the interval between AOO and age at management. Factors influencing between-study heterogeneity were investigated using sensitivity analyses, meta-regression, and multiple meta–regression.ResultsTwenty-seven studies, reporting 51 samples and a total of 9415 patients, met the inclusion criteria. The pooled estimate for the interval between the onset of BD and its management was 5–8 years (standardized difference, .53; 95% confidence interval, .45 to .62). There was very high between-sample heterogeneity (I2 ¼ 92.6; Q ¼ 672). A longer interval was found in studies that defined the onset according to the first episode (compared to onset of symptoms or illness) and defined management as age at diagnosis (rather than first treatment or first hospitalization). A longer interval was reported among more recently published studies, among studies that used a systematic method to establish the chronology of illness, among studies with a smaller proportion of bipolar I patients, and among studies with an earlier mean AOO.ConclusionsThere is currently little consistency in the way researchers report the AOO and initial management of BD. However, the large interval between onset and management of BD presents an opportunity for earlier intervention.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Metacognitive training for schizophrenia spectrum patients: a meta-analysis on outcome studies

2015 ◽  
Vol 46 (1) ◽  
pp. 47-57 ◽  
Author(s):  
B. van Oosterhout ◽  
F. Smit ◽  
L. Krabbendam ◽  
S. Castelein ◽  
A. B. P. Staring ◽  
...  
Keyword(s):  
Statistical Power ◽  
Meta Analysis ◽  
Data Gathering ◽  
Effect Sizes ◽  
Sensitivity Analyses ◽  
Positive Symptoms ◽  
Metacognitive Training ◽  
Intention To Treat ◽  
Schizophrenia Spectrum ◽  
Meta Analyses

Background.Metacognitive training (MCT) for schizophrenia spectrum is widely implemented. It is timely to systematically review the literature and to conduct a meta-analysis.Method.Eligible studies were selected from several sources (databases and expert suggestions). Criteria included comparative studies with a MCT condition measuring positive symptoms and/or delusions and/or data-gathering bias. Three meta-analyses were conducted on data gathering (three studies; 219 participants), delusions (seven studies; 500 participants) and positive symptoms (nine studies; 436 participants). Hedges’ g is reported as the effect size of interest. Statistical power was sufficient to detect small to moderate effects.Results.All analyses yielded small non-significant effect sizes (0.26 for positive symptoms; 0.22 for delusions; 0.31 for data-gathering bias). Corrections for publication bias further reduced the effect sizes to 0.21 for positive symptoms and to 0.03 for delusions. In blinded studies, the corrected effect sizes were 0.22 for positive symptoms and 0.03 for delusions. In studies using proper intention-to-treat statistics the effect sizes were 0.10 for positive symptoms and −0.02 for delusions. The moderate to high heterogeneity in most analyses suggests that processes other than MCT alone have an impact on the results.Conclusions.The studies so far do not support a positive effect for MCT on positive symptoms, delusions and data gathering. The methodology of most studies was poor and sensitivity analyses to control for methodological flaws reduced the effect sizes considerably. More rigorous research would be helpful in order to create enough statistical power to detect small effect sizes and to reduce heterogeneity. Limitations and strengths are discussed.

scholarly journals Comparative efficacy and safety of oral or transdermal opioids in the treatment of knee or hip osteoarthritis: a systematic review and Bayesian network meta-analysis protocol

BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e022142
Author(s):  
Jun Wang ◽  
Yin Wang ◽  
Hui Zhang ◽  
Ming Lu ◽  
Weilu Gao ◽  
...  
Keyword(s):  
Bayesian Network ◽  
Meta Analysis ◽  
Hip Osteoarthritis ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Meta Analyses ◽  
Transdermal Opioids ◽  
And Function

IntroductionOsteoarthritis is a common degenerative joint disease that eventually leads to disability and poor quality of life. The main symptoms are joint pain and mobility disorders. If the patient has severe pain or other analgesics are contraindicated, opioids may be a viable treatment option. To evaluate and compare the efficacy and safety of opioids in the treatment of knee or hip osteoarthritis, we will integrate direct and indirect evidence using a Bayesian network meta-analysis to establish hierarchies of these drugs.Methods and analysisWe will search the Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Web of Science and PsycINFO databases as well as published and unpublished research in international registries and regulatory agency websites for osteoarthritis reports published prior to 5 January 2018. There will be no restrictions on the language. Randomised clinical trials that compare oral or transdermal opioids with other various opioids, placebo or no treatment for patients with knee or hip osteoarthritis will be included. The primary outcomes of efficacy will be pain and function. We will use pain and function scales to evaluate the main outcomes. The secondary outcomes of safety will be defined as the proportion of patients who have stopped treatment due to side effects. Pairwise meta-analyses and Bayesian network meta-analyses will be performed for all related outcome measures. We will conduct subgroup analyses and sensitivity analyses to assess the robustness of our findings. The Grading of Recommendations, Assessment, Development and Evaluations framework will be used to assess the quality of the evidence contributing to each network assessment.Ethics and disseminationThis study does not require formal ethical approval because individual patient data will not be included. The findings will be disseminated through peer-reviewed publications or conference presentations.PROSPERO registration numberCRD42018085503.

Statistical and measurement pitfalls in the use of meta-regression in meta-analysis

2017 ◽  
Vol 22 (5) ◽  
pp. 469-476 ◽  
Author(s):  
Frank L. Schmidt
Keyword(s):  
Social Sciences ◽  
Organizational Behavior ◽  
Meta Analysis ◽  
Social Science Research ◽  
Science Research ◽  
Content Type ◽  
Marketing Social ◽  
Meta Regression ◽  
Meta Analyses ◽  
Almost All

Purpose Meta-regression is widely used and misused today in meta-analyses in psychology, organizational behavior, marketing, management, and other social sciences, as an approach to the identification and calibration of moderators, with most users being unaware of serious problems in its use. The purpose of this paper is to describe nine serious methodological problems that plague applications of meta-regression. Design/methodology/approach This paper is methodological in nature and is based on well-established principles of measurement and statistics. These principles are used to illuminate the potential pitfalls in typical applications of meta-regression. Findings The analysis in this paper demonstrates that many of the nine statistical and measurement pitfalls in the use of meta-regression are nearly universal in applications in the literature, leading to the conclusion that few meta-regressions in the literature today are trustworthy. A second conclusion is that in almost all cases, hierarchical subgrouping of studies is superior to meta-regression as a method of identifying and calibrating moderators. Finally, a third conclusion is that, contrary to popular belief among researchers, the process of accurately identifying and calibrating moderators, even with the best available methods, is complex, difficult, and data demanding. Practical implications This paper provides useful guidance to meta-analytic researchers that will improve the practice of moderator identification and calibration in social science research literatures. Social implications Today, many important decisions are made on the basis of the results of meta-analyses. These include decisions in medicine, pharmacology, applied psychology, management, marketing, social policy, and other social sciences. The guidance provided in this paper will improve the quality of such decisions by improving the accuracy and trustworthiness of meta-analytic results. Originality/value This paper is original and valuable in that there is no similar listing and discussion of the pitfalls in the use of meta-regression in the literature, and there is currently a widespread lack of knowledge of these problems among meta-analytic researchers in all disciplines.

scholarly journals Leishmanicidal effects of resveratrol and its derivatives: a systematic review and meta-Analysis

2020 ◽  
Author(s):  
Nasrin Amiri Dashatan ◽  
Marzieh Ashrafmansouri ◽  
Mehdi Koushki ◽  
Nayebali Ahmadi
Keyword(s):  
Systematic Review ◽  
Publication Bias ◽  
Data Extraction ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Protective Effects ◽  
Random Effects Models ◽  
Important Health ◽  
Mean Differences ◽  
Meta Analyses

Abstract Background Leishmaniasis is one of the most important health problems worldwide. The evidence has suggested that resveratrol and its derivatives have anti-leishmanial effects; however, the results are inconsistent and inconclusive. The aim of this study was to assess the effect of resveratrol and its derivatives on the Leishmania viability through a systematic review and meta-analysis of available relevant studies. Methods The electronic databases PubMed, ScienceDirect, Embase, Web of Science and Scopus were queried between October 2000 and April 2020 using a comprehensive search strategy. The eligible articles selected and data extraction conducted by two reviewers. Mean differences of IC50 (concentration leading to reduction of 50% of Leishmania) for each outcome was calculated using random-effects models. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity and the stability of the pooled results. Publication bias was evaluated using the Egger’s and Begg’s tests. We also followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for this review. Results Ten studies were included in the meta-analysis. We observed that RSV and its derivatives had significant reducing effects on Leishmania viability in promastigote [24.02 µg/ml; (95% CI 17.1, 30.8); P < 0.05; I2 = 99.8%; P heterogeneity = 0.00] and amastigote [18.3 µg/ml; (95% CI 13.5, 23.2); P < 0.05; I2 = 99.6%; P heterogeneity = 0.00] stages of Leishmania. A significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity. Subgroup analysis indicated that the pooled effects of leishmanicidal of resveratrol and its derivatives were affected by type of stilbenes and Leishmania species. Conclusions Our findings clearly suggest that the strategies for the treatment of leishmaniasis should be focused on natural products such as RSV and its derivatives. Further study is needed to identify the mechanisms mediating this protective effects of RSV and its derivatives in leishmaniasis.

scholarly journals Natriuretic peptide-guided treatment for heart failure: a systematic review and meta-analysis

2019 ◽  
Vol 25 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Julie McLellan ◽  
Clare R Bankhead ◽  
Jason L Oke ◽  
F D Richard Hobbs ◽  
Clare J Taylor ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Natriuretic Peptide ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Individual Outcomes ◽  
All Cause Mortality ◽  
Registration Number ◽  
Randomised Controlled ◽  
Meta Analyses

BackgroundGUIDE-IT, the largest trial to date, published in August 2017, evaluating the effectiveness of natriuretic peptide (NP)-guided treatment of heart failure (HF), was stopped early for futility on a composite outcome. However, the reported effect sizes on individual outcomes of all-cause mortality and HF admissions are potentially clinically relevant.ObjectiveThis systematic review and meta-analysis aims to combine all available trial level evidence to determine if NP-guided treatment of HF reduces all-cause mortality and HF admissions in patients with HF.Study selectionEight databases, no language restrictions, up to November 2017 were searched for all randomised controlled trials comparing NP-guided treatment versus clinical assessment alone in adult patients with HF. No language restrictions were applied. Publications were independently double screened and extracted. Fixed-effect meta-analyses were conducted.Findings89 papers were included, reporting 19 trials (4554 participants), average ages 62–80 years. Pooled risk ratio estimates for all-cause mortality (16 trials, 4063 participants) were 0.87, 95% CI 0.77 to 0.99 and 0.80, 95% CI 0.72 to 0.89 for HF admissions (11 trials, 2822 participants). Sensitivity analyses, restricted to low risk of bias, produced similar estimates, but were no longer statistically significant.ConclusionsConsidering all the evidence to date, the pooled effects suggest that NP-guided treatment is beneficial in reducing HF admissions and all-cause mortality. However, there is still insufficient high-quality evidence to make definitive recommendations on the use of NP-guided treatment in clinical practice.Trial registration numberSystematic Review Cochrane Database Number: CD008966.

scholarly journals Is Sensory Loss an Understudied Risk Factor for Frailty? A Systematic Review and Meta-analysis

2020 ◽  
Vol 75 (12) ◽  
pp. 2461-2470
Author(s):  
Benjamin Kye Jyn Tan ◽  
Ryan Eyn Kidd Man ◽  
Alfred Tau Liang Gan ◽  
Eva K Fenwick ◽  
Varshini Varadaraj ◽  
...  
Keyword(s):  
Systematic Review ◽  
Risk Factor ◽  
Longitudinal Studies ◽  
Meta Analysis ◽  
Sensory Loss ◽  
Cross Sectional ◽  
Sensory Impairments ◽  
Subgroup Analyses ◽  
Meta Regression ◽  
Meta Analyses

Abstract Background Age-related sensory loss and frailty are common conditions among older adults, but epidemiologic research on their possible links has been inconclusive. Clarifying this relationship is important because sensory loss may be a clinically relevant risk factor for frailty. Methods In this systematic review and meta-analysis, we searched 3 databases for observational studies investigating 4 sensory impairments—vision (VI), hearing (HI), smell (SI), and taste (TI)—and their relationships with frailty. We meta-analyzed the cross-sectional associations of VI/HI each with pre-frailty and frailty, investigated sources of heterogeneity using meta-regression and subgroup analyses, and assessed publication bias using Egger’s test. Results We included 17 cross-sectional and 7 longitudinal studies in our review (N = 34,085) from 766 records. Our cross-sectional meta-analyses found that HI and VI were, respectively, associated with 1.5- to 2-fold greater odds of pre-frailty and 2.5- to 3-fold greater odds of frailty. Our results remained largely unchanged after subgroup analyses and meta-regression, though the association between HI and pre-frailty was no longer significant in 2 subgroups which lacked sufficient studies. We did not detect publication bias. Longitudinal studies largely found positive associations between VI/HI and frailty progression from baseline robustness, though they were inconclusive about frailty progression from baseline pre-frailty. Sparse literature and heterogenous methods precluded meta-analyses and conclusions on the SI/TI–frailty relationships. Conclusions Our meta-analyses demonstrate significant cross-sectional associations between VI/HI with pre-frailty and frailty. Our review also highlights knowledge gaps on the directionality and modifiability of these relationships and the impact of SI/TI and multiple sensory impairments on frailty.

An individual patient data (IPD) meta-analysis of the impact of thrombocytosis (?plts) on overall survival (OS) whilst using an intermittent chemotherapy (iCTx) strategy in advanced colorectal cancer (aCRC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15044-e15044
Author(s):  
Richard Adams ◽  
Kaitlyn Goey ◽  
Benoist Chibaudel ◽  
Miriam Koopman ◽  
Cornelis J. A. Punt ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Sensitivity Analyses ◽  
First Line Therapy ◽  
Initial Regimen ◽  
Intermittent Chemotherapy ◽  
Baseline Factors ◽  
Central Database ◽  
Continuous Strategies ◽  
Meta Analyses ◽  
The Impact

e15044 Background: iCTx in pts with aCRC offers potential for improvement in QoL. The COIN trial is the largest study to compare iCTx v. continuous strategies in aCRC, a pre-specified subgroup analysis of 16 baseline factors was undertaken among pts with stable or responding disease after 3 mths of first-line therapy to see if the relative treatment effect differed by subgroup. Baseline ⇡plts alone identified a group of pts with significantly worse OS when an iCTx strategy was applied. Here we seek to validate this finding in other intermittent strategy trials. Methods: Published RCTs of iCTx in aCRC were identified via literature review. Eligible trials could allow one or more re-introductions of “full” initial regimen either upon progression or after a set period of time. Outcome and platelet data were requested and collated into a central database. The COIN trial was declared the discovery dataset and other eligible trials the validating datasets. Two co-primary hypotheses were agreed based upon the COIN trial results: Hypothesis 1: In pts with baseline ⇡plts, any planned complete stop of all therapyis detrimental to OS when compared to any maintenance strategy. Hypothesis 2: In pts with baseline ⇡plts, any planned stop of oxaliplatin(Ox) therapy is detrimental to OS when compared to any equivalent strategy where Ox is maintained. Unadjusted IPD meta-analysis was performed according to a pre-specified statistical plan. Results: All trials had broadly similar inclusion criteria . Incidence of ⇡plts range 17-32%. ⇡plts was a poor prognostic marker. Combining IPD from all trials, iCTx was not detrimental to OS. Hypothesis 1 included AIO-0207, CAIRO3, COIN B, OPTIMOX 2 and GISCAD with 1622 pts, HR for interaction of ⇡plts with treatment strategy 0.97 (0.66-1.40), p = 0.78. Hypothesis 2 included TTD MACRO, NORDIC VII and OPTIMOX I, with 1268 pts, HR for interaction 1.36 (0.71-2.62), p = 0.18. Conclusions: These IPD meta-analyses do not validate COIN trial findings that showed reduced OS in pts with baseline ⇡plts who are given a planned treatment break. Sensitivity analyses will be presented, including impact of RAS mut status.

scholarly journals Brain grey matter abnormalities in medication-free patients with major depressive disorder: a meta-analysis

2014 ◽  
Vol 44 (14) ◽  
pp. 2927-2937 ◽  
Author(s):  
Y.-J. Zhao ◽  
M.-Y. Du ◽  
X.-Q. Huang ◽  
S. Lui ◽  
Z.-Q. Chen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Anterior Cingulate Cortex ◽  
Grey Matter ◽  
Meta Analysis ◽  
Anterior Cingulate ◽  
Healthy Controls ◽  
Major Depressive ◽  
Meta Regression ◽  
Meta Analyses

BackgroundBecause cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment, inclusion of medicated patients may have biased previous meta-analyses of voxel-based morphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD patients should be able to distinguish the morphological features of the disease itself from those of treatment.MethodA systematic search was conducted for the relevant studies. Effect-size signed differential mapping was applied to analyse the grey matter differences between all medication-free MDD patients and healthy controls. Meta-regression was used to explore the effects of demographics and clinical characteristics.ResultsA total of 14 datasets comprising 400 medication-free MDD patients and 424 healthy controls met the inclusion criteria. The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey matter in prefrontal and limbic regions in MDD. Increased right thalamus volume was only seen in first-episode medication-naive patients, and increased grey matter in the bilateral anterior cingulate cortex only in medication wash-out patients. In meta-regression analyses the percentage of female patients in each study was negatively correlated with reduced grey matter in the right hippocampus.ConclusionsBy excluding interference from medication effects, the present study identified grey matter reduction in the prefrontal–limbic network in MDD. The subgroup meta-analysis results suggest that an increased right thalamus volume might be a trait directly related to MDD, while an increased anterior cingulate cortex volume might be an effect of medication. The meta-regression results perhaps reveal the structural underpinning of the sex differences in epidemiological and clinical aspects of MDD.

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