Detecting heterogeneity of intervention effects using analysis and meta-analysis of differences in variance between arms of a trial

AbstractRandomised controlled trials (RCTs) with continuous outcomes usually only examine mean differences in response between trial arms. If the intervention has heterogeneous effects (e.g. the effect of the intervention differs by individual characteristics), then outcome variances will also differ between arms. However, power of an individual trial to assess heterogeneity is lower than the power to detect the same size of main effect. The aim of this work was to describe and implement methods for examining heterogeneity of effects of interventions, in trials with individual patient data (IPD) and also in meta-analyses using summary data. Several methods for assessing differences in variance were applied using IPD from a single trial, and summary data from two meta-analyses.In the single trial there was agreement between methods, and the difference in variance was largely due to differences in depression at baseline. In two meta-analyses, most individual trials did not show strong evidence of a difference in variance between arms, with wide confidence intervals. However, both meta-analyses showed evidence of greater variance in the control arm, and in one example this was perhaps because mean outcome in the control arm was higher.Low power of individual trials to examine differences in variance can be overcome using meta-analysis. Evidence of differences in variance should be followed-up to identify potential effect modifiers and explore other possible causes such as varying compliance.

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Effect of ranolazine on glycaemia in adults with and without diabetes: a meta-analysis of randomised controlled trials

Open Heart ◽

10.1136/openhrt-2017-000706 ◽

2018 ◽

Vol 5 (2) ◽

pp. e000706

Author(s):

Ik Hur Teoh ◽

Moulinath Banerjee

Keyword(s):

Glycaemic Control ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Chronic Stable Angina ◽

Controlled Trials ◽

Haemoglobin A1c ◽

Significant Difference ◽

Mean Differences ◽

Randomised Controlled ◽

Meta Analyses

BackgroundRanolazine is an antianginal drug reported to have hypoglycaemic effects.ObjectivesTo assess the effect of ranolazine versus placebo on glycaemic control for adults with and without diabetes.MethodsA systematic search of seven databases was conducted to identify all randomised controlled trials that compared the effect of ranolazine versus placebo on haemoglobin A1c (HbA1c) and/or fasting plasma glucose (FPG) and/or incidence of hypoglycaemia. We used mean differences in HbA1c and FPG to express intervention effect estimates and analysed the data with random-effects model for meta-analyses using Revman 5.3.ResultsWe identified seven trials including 6543 subjects to assess the effect of ranolazine on HbA1c and/or FPG. A separate trial that included 944 subjects was included to assess the effect of ranolazine on hypoglycaemia. The change in HbA1c for all patients was −0.36% (95% CI −0.57% to −0.15%; p=0.0004, I2=78%). In patients with diabetes, the change in HbA1c was −0.41% (95% CI −0.58% to −0.25%; p<0.00001, I2=65%). There was no significant difference in FPG between ranolazine and placebo groups (−2.58 mmol/L, 95% CI −7.02 to 1.85; p=0.25; I2=49%) or incidence of hypoglycaemia between ranolazine and placebo groups (OR 1.70, 95% CI 0.89 to 3.26; p=0.61, I2=0%).ConclusionsOur meta-analytic findings support the fact that ranolazine improves HbA1c without increasing the risk of hypoglycaemia. It therefore has a potential of having an additional benefit of improving glycaemic control in patients with chronic stable angina and diabetes.

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Dental caries and preterm birth: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2017-018556 ◽

2018 ◽

Vol 8 (3) ◽

pp. e018556 ◽

Cited By ~ 9

Author(s):

Madhu Wagle ◽

Francesco D’Antonio ◽

Eirik Reierth ◽

Purusotam Basnet ◽

Tordis A Trovik ◽

...

Keyword(s):

Systematic Review ◽

Preterm Birth ◽

Dental Caries ◽

Meta Analysis ◽

Random Effect ◽

Primary Objective ◽

Case Control Studies ◽

The Difference ◽

Mean Differences ◽

Meta Analyses

ObjectivesThe primary objective of this systematic review was to evaluate the association between dental caries and preterm birth (PTB). The secondary objective was ascertaining the difference between women with dental caries who experienced PTB and those who did not with regard to decayed, missing and filled teeth (DMFT), and decayed, missing and filled surfaces (DMFS) indices.MethodsMEDLINE, Embase, CINAHL and Cochrane databases were searched initially in November 2015 and repeated in December 2016. We included observational cohort and case–control studies. Only studies reporting the risk of PTB in women affected compared with those not affected by dental caries in pregnancy were included. Random-effect meta-analyses were used to compute the summary OR of PTB among women with caries versus women without caries, and the mean difference in either DMFT or DMFS indices between women experiencing PTB and those without PTB.ResultsNine observational studies (4826 pregnancies) were included. Women affected by dental caries during pregnancy did not show a significantly higher risk of PTB (OR: 1.16, 95% CI 0.90 to 1.49, P=0.25, I2=35%). Also, the women with PTB did not show significantly higher DMFT or DMFS indices (summary mean differences: 1.56, P=0.10; I2=92% and −0.15, P=0.9, I2=89%, respectively).ConclusionDental caries does not appear to be a substantial risk factor for PTB.Trial registration numberNCT01675180; Pre-results.

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Comparative efficacy and safety of interventions for treating head lice: a protocol for systematic review and network meta-analysis

BMJ Paediatrics Open ◽

10.1136/bmjpo-2021-001129 ◽

2021 ◽

Vol 5 (1) ◽

pp. e001129

Author(s):

Bill Stevenson ◽

Wubshet Tesfaye ◽

Julia Christenson ◽

Cynthia Mathew ◽

Solomon Abrha ◽

...

Keyword(s):

Systematic Review ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Grey Literature ◽

Risk Of Bias ◽

Controlled Trials ◽

Head Lice ◽

Efficacy And Safety ◽

Randomised Controlled ◽

Meta Analyses

BackgroundHead lice infestation is a major public health problem around the globe. Its treatment is challenging due to product failures resulting from rapidly emerging resistance to existing treatments, incorrect treatment applications and misdiagnosis. Various head lice treatments with different mechanism of action have been developed and explored over the years, with limited report on systematic assessments of their efficacy and safety. This work aims to present a robust evidence summarising the interventions used in head lice.MethodThis is a systematic review and network meta-analysis which will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement for network meta-analyses. Selected databases, including PubMed, Embase, MEDLINE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials will be systematically searched for randomised controlled trials exploring head lice treatments. Searches will be limited to trials published in English from database inception till 2021. Grey literature will be identified through Open Grey, AHRQ, Grey Literature Report, Grey Matters, ClinicalTrials.gov, WHO International Clinical Trials Registry and International Standard Randomised Controlled Trials Number registry. Additional studies will be sought from reference lists of included studies. Study screening, selection, data extraction and assessment of methodological quality will be undertaken by two independent reviewers, with disagreements resolved via a third reviewer. The primary outcome measure is the relative risk of cure at 7 and 14 days postinitial treatment. Secondary outcome measures may include adverse drug events, ovicidal activity, treatment compliance and acceptability, and reinfestation. Information from direct and indirect evidence will be used to generate the effect sizes (relative risk) to compare the efficacy and safety of individual head lice treatments against a common comparator (placebo and/or permethrin). Risk of bias assessment will be undertaken by two independent reviewers using the Cochrane Risk of Bias tool and the certainty of evidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations guideline for network meta-analysis. All quantitative analyses will be conducted using STATA V.16.DiscussionThe evidence generated from this systematic review and meta-analysis is intended for use in evidence-driven treatment of head lice infestations and will be instrumental in informing health professionals, public health practitioners and policy-makers.PROSPERO registration numberCRD42017073375.

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Protective Treatments against Endothelial Glycocalyx Degradation in Surgery: A Systematic Review and Meta-Analysis

Applied Sciences ◽

10.3390/app11156994 ◽

2021 ◽

Vol 11 (15) ◽

pp. 6994

Author(s):

Hasnain Q. R. B. Khan ◽

Gwendolen C. Reilly

Keyword(s):

Systematic Review ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Mean Difference ◽

The Body ◽

Endothelial Glycocalyx ◽

Controlled Trials ◽

Post Operation ◽

Mean Differences ◽

Randomised Controlled

The aim was to explore the body of literature focusing on protective treatments against endothelial glycocalyx degradation in surgery. A comprehensive systematic review of relevant articles was conducted across databases. Inclusion criteria: (1) treatments for the protection of the endothelial glycocalyx in surgery; (2) syndecan-1 used as a biomarker for endothelial glycocalyx degradation. Outcomes analysed: (1) mean difference of syndecan-1 (2) correlation between glycocalyx degradation and inflammation; (3) correlation between glycocalyx degradation and extravasation. A meta-analysis was used to present mean differences and 95% confidence intervals. Seven articles with eight randomised controlled trials were included. The greatest change from baseline values in syndecan-1 concentrations was generally from the first timepoint measured post-operatively. Interventions looked to either dampen the inflammatory response or fluid therapy. Methylprednisolone had the highest mean difference in plasma syndecan-1 concentrations. Ulinastatin showed correlations between alleviation of degradation and preserving vascular permeability. In this systematic review of 385 patients, those treated were more likely than those treated with placebo to exhibit less shedding of the endothelial glycocalyx. Methylprednisolone has been shown to specifically target the transient increase of glycocalyx degradation immediately post-operation and has displayed anti-inflammatory effects. We have proposed suggestions for improved uniformity and enhanced confidence for future randomised controlled trials.

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Pre-post effect sizes should be avoided in meta-analyses

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796016000809 ◽

2016 ◽

Vol 26 (4) ◽

pp. 364-368 ◽

Cited By ~ 72

Author(s):

P. Cuijpers ◽

E. Weitz ◽

I. A. Cristea ◽

J. Twisk

Keyword(s):

Comparison Group ◽

Meta Analysis ◽

Effect Sizes ◽

Behaviour Therapy ◽

Natural Processes ◽

Cognitive Behaviour ◽

Post Test ◽

The Difference ◽

Meta Analyses ◽

Highly Cited

AimsThe standardised mean difference (SMD) is one of the most used effect sizes to indicate the effects of treatments. It indicates the difference between a treatment and comparison group after treatment has ended, in terms of standard deviations. Some meta-analyses, including several highly cited and influential ones, use the pre-post SMD, indicating the difference between baseline and post-test within one (treatment group).MethodsIn this paper, we argue that these pre-post SMDs should be avoided in meta-analyses and we describe the arguments why pre-post SMDs can result in biased outcomes.ResultsOne important reason why pre-post SMDs should be avoided is that the scores on baseline and post-test are not independent of each other. The value for the correlation should be used in the calculation of the SMD, while this value is typically not known. We used data from an ‘individual patient data’ meta-analysis of trials comparing cognitive behaviour therapy and anti-depressive medication, to show that this problem can lead to considerable errors in the estimation of the SMDs. Another even more important reason why pre-post SMDs should be avoided in meta-analyses is that they are influenced by natural processes and characteristics of the patients and settings, and these cannot be discerned from the effects of the intervention. Between-group SMDs are much better because they control for such variables and these variables only affect the between group SMD when they are related to the effects of the intervention.ConclusionsWe conclude that pre-post SMDs should be avoided in meta-analyses as using them probably results in biased outcomes.

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

BMJ Open ◽

10.1136/bmjopen-2017-017868 ◽

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.

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Acupuncture for Tourette Syndrome: A Systematic Review

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/1834646 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Jinna Yu ◽

Yongming Ye ◽

Jun Liu ◽

Yang Wang ◽

Weina Peng ◽

...

Keyword(s):

Tourette Syndrome ◽

Western Medicine ◽

Data Extraction ◽

Cochrane Collaboration ◽

Fixed Effect Model ◽

Study Selection ◽

Mean Differences ◽

Randomised Controlled ◽

Meta Analyses ◽

The Cochrane Collaboration

Tourette syndrome (TS) is a neuropsychiatric disorder that affects both children and adults. We searched for randomised controlled trials (RCTs) using acupuncture to treat TS written in English or Chinese without restrictions on publication status. Study selection, data extraction, and assessment of study quality were conducted independently by two reviewers. Meta-analyses were performed using Review Manager (RevMan) 5.3 software from the Cochrane Collaboration. Data were combined with the fixed-effect model based on a heterogeneity test. Results were presented as risk ratios for dichotomous data and mean differences (MDs) for continuous data. This review included 7 RCTs with a total of 564 participants. The combined results showed that acupuncture may have better short-term effect than Western medicine for TS and that acupuncture may be an effective adjuvant therapy in improving the effect of Western medicine on TS, but the evidence is limited because of existing biases. Rigorous high-quality RCTs are needed to verify these findings.

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P.041 Adult craniopharyngioma: case series, systematic review and meta-analysis

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2017.126 ◽

2017 ◽

Vol 44 (S2) ◽

pp. S24-S24

Author(s):

C Dandurand ◽

AA Sepehry ◽

MH Asadi Lari ◽

R Akagami ◽

PA Gooderham

Keyword(s):

Meta Analysis ◽

Case Series ◽

Gross Total Resection ◽

Subtotal Resection ◽

Total Resection ◽

Childhood Population ◽

Institutional Experience ◽

The Difference ◽

Meta Analyses ◽

Case Basis

Background: The optimal therapeutic approach for adult craniopharyngioma remains controversial. Some advocate for gross total resection (GTR), while others support subtotal resection followed by adjuvant radiotherapy (STR + XRT). Methods: MEDLINE (1946 to July 1st 2016) and EMBASE (1980 to June 30th 2016) were systematically reviewed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. At our institution, from 1975 to 2013, 33 patients were treated with initial surgical resection for adult onset craniopharyngioma. 22 patients were included in the present case series. Results: Eligible studies (n=21) were identified from the literature in addition to a case series of our institutional experience. Three groups were available for analysis: GTR, STR + XRT, and STR. The rates of recurrence were 17 %, 27 % and 45%, respectively. This differs from childhood population. The difference in risk of recurrence after GTR vs. STR + XRT did not reach significance (OR: 0.63, 95% confidence interval: 0.33-1.24, P=0.18). This maybe because of low pooled sample size (n=99) who underwent STR+XRT. Conclusions: This is the first and largest meta-analysis examining rate of recurrence in adult craniopharyngioma. Thus, when safe and feasible, a goal of gross total resection should be favored. Each patient should be considered on a case-by-case basis.

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

10.21203/rs.3.rs-25274/v1 ◽

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.

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The Effectiveness of Psychological Therapies for Anxiety Disorders in Adolescents: A Meta-Analysis

Clinical Child and Family Psychology Review ◽

10.1007/s10567-021-00364-2 ◽

2021 ◽

Author(s):

Holly J. Baker ◽

Peter J. Lawrence ◽

Jessica Karalus ◽

Cathy Creswell ◽

Polly Waite

Keyword(s):

Anxiety Disorder ◽

Anxiety Disorders ◽

Symptom Severity ◽

Meta Analysis ◽

Post Treatment ◽

Adolescent Anxiety ◽

Psychological Therapies ◽

Randomised Controlled ◽

Meta Analyses ◽

Active Controls

AbstractAnxiety disorders are common in adolescence but outcomes for adolescents are unclear and we do not know what factors moderate treatment outcome for this age group. We conducted meta-analyses to establish the effectiveness of psychological therapies for adolescent anxiety disorders in (i) reducing anxiety disorder symptoms, and (ii) remission from the primary anxiety disorder, compared with controls, and examine potential moderators of treatment effects. The protocol was registered with PROSPERO (CRD42018091744). Electronic databases (Web of Science, MEDLINE, Psycinfo, EMBASE) were searched from January 1990 to December 2019. 2511 articles were reviewed, those meeting strict criteria were included. Random effects meta-analyses were conducted. Analyses of symptom severity outcomes comprised sixteen studies (CBT k = 15, non-CBT k = 1; n = 766 adolescents), and analyses of diagnostic remission outcomes comprised nine (CBT k = 9; n = 563 adolescents). Post-treatment, those receiving treatment were significantly more likely to experience reduced symptom severity (SMD = 0.454, 95% CI 0.22–0.69) and remission from the primary anxiety disorder than controls (RR = 7.94, 95% CI 3.19–12.7) (36% treatment vs. 9% controls in remission). None of the moderators analysed were statistically significant. Psychological therapies targeting anxiety disorders in adolescents are more effective than controls. However, with only just over a third in remission post-treatment, there is a clear need to develop more effective treatments for adolescents, evaluated through high-quality randomised controlled trials incorporating active controls and follow-up data.

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