scholarly journals Methods to address confounding and other biases in meta-analyses: Review and recommendations

2021 ◽  
Author(s):  
Maya B Mathur ◽  
Tyler VanderWeele
Keyword(s):  
Meta Analysis ◽  
Internal Validity ◽  
Sensitivity Analyses ◽  
Eligibility Criteria ◽  
Unmeasured Confounding ◽  
Affect Studies ◽  
Evidence Strength ◽  
Recent Developments ◽  
Meta Analyses ◽  
Do So

Meta-analyses contribute critically to cumulative science, but they can produce misleading conclusions if their constituent primary studies are biased, for example by unmeasured confounding in nonrandomized studies. We provide practical guidance on how meta-analysts can address confounding and other biases that affect studies' internal validity, focusing primarily on sensitivity analyses that help quantify how biased the meta-analysis estimates might be. We review a number of sensitivity analysis methods to do so, especially recent developments that are straightforward to implement and interpret and that use somewhat less stringent statistical assumptions than earlier methods. We give recommendations for how these methods could be applied in practice and illustrate using a previously published meta-analysis. Sensitivity analyses can provide informative quantitative summaries of evidence strength, and we suggest reporting them routinely in meta-analyses of potentially biased studies. This recommendation in no way diminishes the importance of defining study eligibility criteria that reduce bias and of characterizing studies’ risks of bias qualitatively.

scholarly journals Methods to Address Confounding and Other Biases in Meta-Analyses: Review and Recommendations

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Maya B. Mathur ◽  
Tyler J. VanderWeele
Keyword(s):  
Meta Analysis ◽  
Internal Validity ◽  
Sensitivity Analyses ◽  
Annual Review ◽  
Publication Date ◽  
Eligibility Criteria ◽  
Affect Studies ◽  
Evidence Strength ◽  
Recent Developments ◽  
Meta Analyses

Meta-analyses contribute critically to cumulative science, but they can produce misleading conclusions if their constituent primary studies are biased, for example by unmeasured confounding in nonrandomized studies. We provide practical guidance on how meta-analysts can address confounding and other biases that affect studies’ internal validity, focusing primarily on sensitivity analyses that help quantify how biased the meta-analysis estimates might be. We review a number of sensitivity analysis methods to do so, especially recent developments that are straightforward to implement and interpret and that use somewhat less stringent statistical assumptions than do earlier methods. We give recommendations for how these newer methods could be applied in practice and illustrate using a previously published meta-analysis. Sensitivity analyses can provide informative quantitative summaries of evidence strength, and we suggest reporting them routinely in meta-analyses of potentially biased studies. This recommendation in no way diminishes the importance of defining study eligibility criteria that reduce bias and of characterizing studies’ risks of bias qualitatively. Expected final online publication date for the Annual Review of Public Health, Volume 43 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Laser Influence on Dental Sensitivity Compared to Other Light Sources Used During In-office Dental Bleaching: Systematic Review and Meta-analysis

2020 ◽  
Vol 45 (6) ◽  
pp. 589-597
Author(s):  
BGS Casado ◽  
EP Pellizzer ◽  
JR Souto Maior ◽  
CAA Lemos ◽  
BCE Vasconcelos ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Color Change ◽  
Meta Analysis ◽  
Present Review ◽  
Cochrane Library ◽  
Light Sources ◽  
Eligibility Criteria ◽  
Tooth Color ◽  
Significant Difference ◽  
Meta Analyses

Clinical Relevance The use of laser light during bleaching will not reduce the incidence or severity of sensitivity and will not increase the degree of color change compared with nonlaser light sources. SUMMARY Objective: To evaluate whether the use of laser during in-office bleaching promotes a reduction in dental sensitivity after bleaching compared with other light sources. Methods: The present review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and is registered with PROSPERO (CDR42018096591). Searches were conducted in the PubMed/Medline, Web of Science, and Cochrane Library databases for relevant articles published up to August 2018. Only randomized clinical trials among adults that compared the use of laser during in-office whitening and other light sources were considered eligible. Results: After analysis of the texts retrieved during the database search, six articles met the eligibility criteria and were selected for the present review. For the outcome dental sensitivity, no significant difference was found favoring any type of light either for intensity (mean difference [MD]: −1.60; confidence interval [CI]: −3.42 to 0.22; p=0.09) or incidence (MD: 1.00; CI: 0.755 to 1.33; p=1.00). Regarding change in tooth color, no significant differences were found between the use of the laser and other light sources (MD: −2.22; CI: −6.36 to 1.93; p=0.29). Conclusions: Within the limitations of the present study, laser exerts no influence on tooth sensitivity compared with other light sources when used during in-office bleaching. The included studies demonstrated that laser use during in-office bleaching may have no influence on tooth color change.

scholarly journals Risk of dementia in gout and hyperuricaemia: a meta-analysis of cohort studies

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e041680
Author(s):  
Shu-Yue Pan ◽  
Rui-Juan Cheng ◽  
Zi-Jing Xia ◽  
Qiu-Ping Zhang ◽  
Yi Liu
Keyword(s):  
Cohort Studies ◽  
Quality Assessment ◽  
Publication Bias ◽  
Data Extraction ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
Crystal Formation ◽  
Medical Subject Headings ◽  
Eligibility Criteria

ObjectivesGout, characterised by hyperuricaemia with monosodium urate crystal formation and inflammation, is the most common inflammatory arthritis in adults. Recent studies have found that elevated uric acid levels are related to the occurrence of dementia. We conducted a study to investigate the association between dementia and gout or hyperuricaemia.DesignSystematic review and meta-analysis of cohort studies.Data sourcesStudies were screened from inception to 28 June 2019 by searching Medline, Embase and the Cochrane Library databases.Eligibility criteriaCohort studies comparing the risk of dementia in patients with gout and hyperuricaemia versus non-gout and non-hyperuricaemia controls were enrolled.Data extraction and analysisTwo reviewers separately selected studies and extracted data using the Medical Subject Headings without restriction on languages or countries. The adjusted HRs were pooled using the DerSimonian and Laird random effects model. Sensitivity analyses were conducted to evaluate the stability of the results. Publication bias was evaluated using Egger’s and Begg’s tests. Quality assessment was performed according to the Newcastle-Ottawa Scale.ResultsFour cohort studies that met the inclusion criteria were included in our meta-analysis. We found that gout and hyperuricaemia did not increase the risk of dementia, with a pooled HR of 0.94 (95% CI 0.69 to 1.28), but might decrease the risk of Alzheimer’s disease (AD), with a pooled HR of 0.78 (95% CI 0.64 to 0.95). There was little evidence of publication bias. Quality assessment of the included studies was high (range: 6–8 points).ConclusionsOur study shows that gout and hyperuricaemia do not increase the risk of dementia. However, gout and hyperuricaemia might have a protective effect against AD. Due to the limited number of research articles, more investigations are needed to demonstrate the potential relationship between dementia and gout or hyperuricaemia.

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 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.

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 Robust metrics and sensitivity analyses for meta-analyses of heterogeneous effects

2020 ◽  
Author(s):  
Maya B Mathur ◽  
Tyler VanderWeele
Keyword(s):  
R Package ◽  
Point Estimation ◽  
Effect Sizes ◽  
Sensitivity Analyses ◽  
Robust Methods ◽  
Heterogeneous Effects ◽  
Evidence Strength ◽  
Meta Analyses ◽  
Effect Heterogeneity ◽  
Statistical Metrics

We recently suggested new statistical metrics for routine reporting in random-effects meta-analyses to convey evidence strength for scientifically meaningful effects under effect heterogeneity. First, given a chosen threshold of meaningful effect size, we suggested reporting the estimated proportion of true effect sizes above this threshold. Second, we suggested reporting the proportion of effect sizes below a second, possibly symmetric, threshold in the opposite direction from the estimated mean. Our previous methods applied when the true effects are approximately normal, when the number of studies is relatively large, and when the proportion is between approximately 0.15 and 0.85. Here, we additionally describe robust methods for point estimation and inference that perform well under considerably more general conditions, as we validate in an extensive simulation study. The methods are implemented in the R package MetaUtility (function prop_stronger). We describe application of the robust methods to conducting sensitivity analyses for unmeasured confounding in meta-analyses.

scholarly journals Evaluation of Preeclampsia Results after Use of Metformin in Gestation: Systematic Review and Meta-analysis

2018 ◽  
Vol 40 (11) ◽  
pp. 713-721 ◽  
Author(s):  
Iramar Nascimento ◽  
Guilherme Dienstmann ◽  
Matheus de Souza ◽  
Raquel Fleig ◽  
Carla Hoffmann ◽  
...  
Keyword(s):  
Systematic Review ◽  
Treatment Time ◽  
Meta Analysis ◽  
Cochrane Collaboration ◽  
Eligibility Criteria ◽  
Time Segment ◽  
Meta Analyses ◽  
The Cochrane Collaboration ◽  
Lower Correlation

Objective Does the use of metformin have an influence on the outcomes of preeclampsia (PE)? Sources of Data The descriptors pregnancy, metformin, treatment, and preeclampsia associated with the Boolean operators AND and OR were found in the MEDLINE, LILACS, Embase and Cochrane databases. A flowchart with exclusion criteria and inclusion strategy using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, and eligibility criteria was used. Data were extracted regarding the type of study, the applied dosage, treatment time, segment, bias risks, and the Patient, Intervention, Comparison and Outcome (PICO) strategy to identify the quality of the study. Selection of Studies Total number of journals in the initial search (n = 824); exclusions from repeated articles on different search engines (n = 253); exclusions after reading the titles, when the title had no correlations with the proposed theme (n = 164); exclusions due to incompatibility with the criteria established in the methodological analysis (n = 185), exclusion of articles with lower correlation with the objective of the present study (n = 187); and final bibliographic selection (n = 35). Data Collection At first, a systematic review of the literature was performed. Subsequently, from the main selection, randomized and non-randomized trials with metformin that presented their results in absolute and relative numbers of PE outcomes were selected. The variables were treated statistically in the meta-analysis with the Review Manager software (RevMan), version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration. Denmark in the Hovedistaden region. Synthesis of Data The study showed that metmorfin presented greater preventive effects for pregnancy-induced hypertension and was less effective for PE. Conclusion Metformin may gain place in preventive treatments for PE, once the dosages, the gestational age, and treatment time are particularly evaluated. A methodological strategy with an improved perspective of innovative and/or carefully progressive dosages during pregnancy to avoid side effects and the possibility of maternal-fetal risks is suggested.

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 Comparing the Effects of Docosahexaenoic and Eicosapentaenoic Acids on Inflammation Markers Using Pairwise and Network Meta-Analyses of Randomized Controlled Trials

2020 ◽  
Author(s):  
Cécile Vors ◽  
Janie Allaire ◽  
Sonia Blanco Mejia ◽  
Tauseef A Khan ◽  
John L Sievenpiper ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Eligibility Criteria ◽  
Necrosis Factor Alpha ◽  
Assessment Development ◽  
Evaluation Approach ◽  
Tnf Α ◽  
Mean Differences ◽  
Meta Analyses

ABSTRACT Recent data from randomized clinical trials (RCTs) suggest that DHA may have stronger anti-inflammatory effects than EPA. This body of evidence has not yet been quantitatively reviewed. The aim of this study was to compare the effect of DHA and EPA on several markers of systemic inflammation by pairwise and network meta-analyses of RCTs. MEDLINE, EMBASE, and The Cochrane Library were searched through to September 2019. We included RCTs of ≥7 d on adults regardless of health status that directly compared the effects of DHA with EPA and RCTs of indirect comparisons, in which the effects of DHA or EPA were compared individually to a control fatty acid. Differences in circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and adiponectin were the primary outcome measures. Data were pooled by pairwise and network meta-analysis and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic) in the pairwise meta-analysis. Inconsistency and transitivity were evaluated in the network meta-analysis. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Eligibility criteria were met by 5 RCTs (N = 411) for the pairwise meta-analysis and 20 RCTs (N = 1231) for the network meta-analysis. In the pairwise meta-analysis, DHA and EPA had similar effects on plasma CRP [MDDHA versus EPA = 0.14 mg/L (95% CI: –0.57, 0.85); I2 = 61%], IL-6 [MDDHA versus EPA = 0.10 pg/mL (–0.15, 0.34); I2 = 40%], and TNF-α [MDDHA versus EPA = –0.10 pg/mL (–0.37, 0.18); I2 = 40%]. In the network meta-analysis, the effects of DHA and EPA on plasma CRP [MDDHA versus EPA = –0.33 mg/L (–0.75, 0.10)], IL-6 [MDDHA versus EPA = 0.09 pg/mL (–0.12, 0.30)], and TNF-α [MDDHA versus EPA = –0.02 pg/mL (–0.25, 0.20)] were also similar. DHA and EPA had similar effects on plasma adiponectin in the network meta-analysis. Results from pairwise and network meta-analyses suggest that supplementation with either DHA or EPA does not differentially modify systemic markers of subclinical inflammation.

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