Confidence intervals for the overall effect size in random-effects meta-analysis.

AbstractObjectivesThe results of existing studies on bisphenol A (BPA) and puberty timing did not reach a consensus. Thereby we performed this meta-analytic study to explore the association between BPA exposure in urine and puberty timing.MethodsMeta-analysis of the pooled odds ratios (OR), prevalence ratios (PR) or hazards ratios (HR) with 95% confidence intervals (CI) were calculated and estimated using fixed-effects or random-effects models based on between-study heterogeneity.ResultsA total of 10 studies involving 5621 subjects were finally included. The meta-analysis showed that BPA exposure was weakly associated with thelarche (PR: 0.96, 95% CI: 0.93–0.99), while no association was found between BPA exposure and menarche (HR: 0.99, 95% CI: 0.89–1.12; OR: 1.02, 95% CI: 0.73–1.43), and pubarche (OR: 1.00, 95% CI: 0.79–1.26; PR: 1.00, 95% CI: 0.95–1.05).ConclusionsThere was no strong correlation between BPA exposure and puberty timing. Further studies with large sample sizes are needed to verify the relationship between BPA and puberty timing.

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EXPRESS: A meta-analysis of aspirin and subarachnoid haemorrhage in patients with intracranial aneurysms yields different results to the general population

International Journal of Stroke ◽

10.1177/17474930211004888 ◽

2021 ◽

pp. 174749302110048

Author(s):

Frederick Ewbank ◽

Jacqueline Birks ◽

Diederik Bulters

Keyword(s):

General Population ◽

Subarachnoid Haemorrhage ◽

Confidence Intervals ◽

Random Effects ◽

Intracranial Aneurysms ◽

Meta Analysis ◽

Risk Of Bias ◽

Random Effects Models ◽

Hazard Ratios ◽

Unruptured Intracranial Aneurysms

Abstract Background Some studies have shown a protective association between aspirin use and subarachnoid haemorrhage (SAH). Other studies have found no relationship or the reverse. These studies differ in their study populations and definitions of SAH. Aims Our aim was to establish 1) if there is an association between aspirin and SAH, 2) how this differs between the general population and those with intracranial aneurysms. Summary of review Studies reporting aspirin use and the occurrence of SAH were included and grouped based on population (general population vs aneurysm population). Odds ratios, hazard ratios and confidence intervals were combined in random-effects models. 11 studies were included. Overall, there was an association between aspirin and SAH (OR 0.68 [0.48, 0.96]). However, populations were diverse and heterogeneity between studies high (p<0.00001), questioning the validity of combining these studies and justifying analysis by population. In the general population there was no difference in aspirin use between individuals with and without SAH (OR 1.15 [0.96, 1.38]). In patients with intracranial aneurysms, aspirin use was greater in patients without SAH (OR 0.37 [0.24, 0.58]), although these studies were at higher risk of bias. Conclusions There is an association between aspirin use and SAH in patients with intracranial aneurysms. This apparent protective relationship is not seen in the general population. Prospective randomised studies are required to further investigate the effect of aspirin on unruptured intracranial aneurysms.

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Abstract 3789: Nessun Dorma : Have the Risks of Rosiglitazone been Exaggerated?

Circulation ◽

10.1161/circ.116.suppl_16.ii_861-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

George A Diamond ◽

Sanjay Kaul

Keyword(s):

Confidence Intervals ◽

Effect Size ◽

Fixed Effects ◽

Meta Analysis ◽

Cardiovascular Death ◽

Sensitivity Analyses ◽

Odds Ratios ◽

True Effect Size ◽

Index Study ◽

The Stability

Background A highly publicized meta-analysis of 42 clinical trials comprising 27,844 diabetics ignited a firestorm of controversy by charging that treatment with rosiglitazone was associated with a “…worrisome…” 43% greater risk of myocardial infarction ( p =0.03) and a 64% greater risk of cardiovascular death ( p =0.06). Objective The investigators excluded 4 trials from the infarction analysis and 19 trials from the mortality analysis in which no events were observed. We sought to determine if these exclusions biased the results. Methods We compared the index study to a Bayesian meta-analysis of the entire 42 trials (using odds ratio as the measure of effect size) and to fixed-effects and random-effects analyses with and without a continuity correction that adjusts for values of zero. Results The odds ratios and confidence intervals for the analyses are summarized in the Table . Odds ratios for infarction ranged from 1.43 to 1.22 and for death from 1.64 to 1.13. Corrected models resulted in substantially smaller odds ratios and narrower confidence intervals than did uncorrected models. Although corrected risks remain elevated, none are statistically significant (*p<0.05). Conclusions Given the fragility of the effect sizes and confidence intervals, the charge that roziglitazone increases the risk of adverse events is not supported by these additional analyses. The exaggerated values observed in the index study are likely the result of excluding the zero-event trials from analysis. Continuity adjustments mitigate this error and provide more consistent and reliable assessments of true effect size. Transparent sensitivity analyses should therefore be performed over a realistic range of the operative assumptions to verify the stability of such assessments especially when outcome events are rare. Given the relatively wide confidence intervals, additional data will be required to adjudicate these inconclusive results.

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Methods to calculate uncertainty in the estimated overall effect size from a random‐effects meta‐analysis

Research Synthesis Methods ◽

10.1002/jrsm.1319 ◽

2018 ◽

Vol 10 (1) ◽

pp. 23-43 ◽

Cited By ~ 22

Author(s):

Areti Angeliki Veroniki ◽

Dan Jackson ◽

Ralf Bender ◽

Oliver Kuss ◽

Dean Langan ◽

...

Keyword(s):

Random Effects ◽

Effect Size ◽

Meta Analysis

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Effectiveness of a Pharmacogenetic Tool at Improving Treatment Efficacy in Major Depressive Disorder: A Meta-Analysis of Three Clinical Studies

Pharmaceutics ◽

10.3390/pharmaceutics11090453 ◽

2019 ◽

Vol 11 (9) ◽

pp. 453 ◽

Cited By ~ 2

Author(s):

Vilches ◽

Tuson ◽

Vieta ◽

Álvarez ◽

Espadaler

Keyword(s):

Random Effects ◽

Effect Size ◽

Clinical Studies ◽

Clinical Utility ◽

Meta Analysis ◽

Severe Depression ◽

P Value ◽

Drug Selection ◽

Mild Depression ◽

Depressive Patients

Several pharmacogenetic tests to support drug selection in psychiatric patients have recently become available. The current meta-analysis aimed to assess the clinical utility of a commercial pharmacogenetic-based tool for psychiatry (Neuropharmagen®) in the treatment management of depressive patients. Random-effects meta-analysis of clinical studies that had examined the effect of this tool on the improvement of depressive patients was performed. Effects were summarized as standardized differences between treatment groups. A total of 450 eligible subjects from three clinical studies were examined. The random effects model estimated a statistically significant effect size for the pharmacogenetic-guided prescription (d = 0.34, 95% CI = 0.11–0.56, p-value = 0.004), which corresponded to approximately a 1.8-fold increase in the odds of clinical response for pharmacogenetic-guided vs. unguided drug selection. After exclusion of patients with mild depression, the pooled estimated effect size increased to 0.42 (95% CI = 0.19–0.65, p-value = 0.004, n = 287), corresponding to an OR = 2.14 (95% CI = 1.40–3.27). These results support the clinical utility of this pharmacogenetic-based tool in the improvement of health outcomes in patients with depression, especially those with moderate–severe depression. Additional pragmatic RCTs are warranted to consolidate these findings in other patient populations.

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Nutraceutical supplements in management of pain and disability in osteoarthritis: a systematic review and meta-analysis of randomized clinical trials

Scientific Reports ◽

10.1038/s41598-020-78075-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Dawood Aghamohammadi ◽

Neda Dolatkhah ◽

Fahimeh Bakhtiari ◽

Fariba Eslamian ◽

Maryam Hashemian

Keyword(s):

Pain Intensity ◽

Physical Function ◽

Random Effects ◽

Effect Size ◽

Meta Analysis ◽

Effect Sizes ◽

Cochrane Library ◽

Random Effects Model ◽

Womac Index ◽

Pain Subscale

AbstractThis study designed to evaluate the effect of nutraceutical supplementation on pain intensity and physical function in patients with knee/hip OA. The MEDLINE, Web of Science, Cochrane Library, Scopus, EMBASE, Google Scholar, Science direct, and ProQuest in addition to SID, Magiran, and Iranmedex were searched up to March 2020. Records (n = 465) were screened via the PICOS criteria: participants were patients with hip or knee OA; intervention was different nutritional supplements; comparator was any comparator; the outcome was pain intensity (Visual analogue scale [VAS]) and physical function (Western Ontario and McMaster Universities Arthritis [WOMAC] index); study type was randomized controlled trials. The random effects model was used to pool the calculated effect sizes. The standardized mean difference (SMD) of the outcome changes was considered as the effect size. The random effects model was used to combine the effect sizes. Heterogeneity between studies was assessed by Cochran's (Q) and I2 statistics. A total of 42 RCTs were involved in the meta-analysis. Nutritional supplementation were found to improve total WOMAC index (SMD = − 0.23, 95% CI − 0.37 to − 0.08), WOMAC pain (SMD = − 0.36, 95% CI − 0.62 to − 0.10) and WOMAC stiffness (SMD = − 0.47, 95% CI − 0.71 to − 0.23) subscales and VAS (SMD = − 0.79, 95% CI − 1.05 to − 0.05). Results of subgroup analysis according to the supplementation duration showed that the pooled effect size in studies with < 10 months, 10–20 months and > 20 months supplementation duration were 0.05, 0.27, and 0.36, respectively for WOMAC total score, 0.14, 0.55 and 0.05, respectively for WOAMC pain subscale, 0.59, 0.47 and 0.41, respectively for WOMAC stiffness subscale, 0.05, 0.57 and 0.53, respectively for WOMAC physical function subscale and 0.65, 0.99 and 0.12, respectively for VAS pain. The result suggested that nutraceutical supplementation of patients with knee/hip OA may lead to an improvement in pain intensity and physical function.

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Comparative Effectiveness of Lenalidomide Plus Dexamethasone for the Treatment of Refractory/Relapsed Multiple Myeloma: A Systematic Review and Mixed Treatment Comparison

Blood ◽

10.1182/blood.v120.21.4076.4076 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4076-4076

Author(s):

Sallie Stradwick ◽

Nick Freemantle ◽

John Snowden ◽

Felipe Rodrigues ◽

Nic Brereton

Keyword(s):

Multiple Myeloma ◽

Combination Therapy ◽

Confidence Intervals ◽

Random Effects ◽

Comparative Effectiveness ◽

Fixed Effects ◽

Meta Analysis ◽

Treatment Comparison ◽

Mixed Treatment ◽

Secondary Outcomes

Abstract Abstract 4076 OBJECTIVES: To evaluate the comparative effectiveness of lenalidomide (25 mg) plus dexamethasone (40 mg) (LEN/dex) for the treatment of relapsed/refractory multiple myeloma (RRMM) compared to thalidomide and bendamustine. Primary outcome of interest was time to progression (TTP). Secondary outcomes of interest were overall response rates (ORR) and overall survival (OS). METHODS: A comprehensive systematic literature review was conducted to identify any randomised controlled trials (RCTs) investigating the clinical efficacy of specified therapies for the treatment of RRMM. Specified therapies included lenalidomide, thalidomide and bendamustine. Of these therapies, only LEN/dex combination therapy is approved in RRMM but bendamustine and thalidomide (monotherapy or in combination with dexamethasone) have also shown activity in the treatment of myeloma. Electronic databases were searched from March 2002 to 2012 (language unrestricted. Randomized clinical trials were independently evaluated against predetermined criteria for inclusion and determined to be eligible for the meta-analysis prior to any outcome assessment. Fixed effects and random effects mixed-treatment comparisons (MTC) were carried out, adopting the methods described by Lu and Ades1. MTCs estimate the comparative effectiveness of multiple treatments using an evidence base of trials that individually do not compare all treatment options. Results for TTP were reported as hazard ratios (HR) and 95% confidence intervals and an associated probability of best treatment. Results for binary variables (ORR, OS) were reported as odds ratios (OR) and 95% confidence intervals. RESULTS: Sixteen original RCTs met the initial inclusion criteria; twelve (N = 3,590), nine (N = 3,350) and six (N = 2,295) of which were able to be connected to form a network of evidence which provided the heterogeneous trial base for MTC analysis of ORR, OS, and TTP comparison, respectively. Two trials directly investigated the efficacy of LEN/dex (N = 353) and three trials assessed the efficacy of thalidomide monotherapy (N = 785). No RCTs were identified that investigated the efficacy of bendamustine or thalidomide/dexamethasone combination therapy in RRMM. There were too few studies (investigating treatment arms of interest) relative to the number of trials in the network to formally estimate or test for heterogeneity. Therefore a fixed effects network meta-analysis was used instead of a random effects network meta-analysis. Comparability of trial populations was assessed and discussed in detail since these could not be adjusted for in the statistical model. Age, sex, baseline disease characteristics, time since diagnosis and medical history were similar between study populations. TTP analysis was statistically significant and favoured LEN/dex over thalidomide monotherapy: HR = 2.34 [1.31, 4.17]. The associated probability of LEN/dex being the best treatment within the evidence network is 97.9%. Secondary outcomes analysis were also statistically significant in favour of LEN/dex over thalidomide monotherapy (ORR: OR = 10.48 [4.75, 22.81]; OS: OR = 1.43 [1.12, 1.84]). CONCLUSIONS: Results demonstrated statistically significant superiority of lenalidomide plus dexamethasone therapy versus thalidomide monotherapy for the treatment of RRMM. No analyses were possible versus bendamustine or thalidomide/dexamethasone combination therapy due to the lack of RCTs investigating the efficacy of these therapeutic regimens in RRMM. Disclosures: Stradwick: Celgene International: Consultancy. Freemantle:BresMed: Consultancy. Off Label Use: Thalidomide monotherapy activity in the treatment of myeloma. Brereton:Celgene International: Consultancy.

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Confidence intervals for random effects meta-analysis and robustness to publication bias

Statistics in Medicine ◽

10.1002/sim.4029 ◽

2010 ◽

Vol 29 (29) ◽

pp. 2969-2983 ◽

Cited By ~ 76

Author(s):

Masayuki Henmi ◽

John B. Copas

Keyword(s):

Confidence Intervals ◽

Publication Bias ◽

Random Effects ◽

Meta Analysis

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Meta-analysis of the impacts of water management on aquatic communities

Canadian Journal of Fisheries and Aquatic Sciences ◽

10.1139/f07-175 ◽

2008 ◽

Vol 65 (3) ◽

pp. 437-447 ◽

Cited By ~ 74

Author(s):

Tim J Haxton ◽

C Scott Findlay

Keyword(s):

Water Management ◽

Confidence Intervals ◽

Effect Size ◽

Meta Analysis ◽

Ecological Impacts ◽

Aquatic Communities ◽

Flow Modification ◽

Meta Analyses ◽

Fail Safe ◽

Habitat Generalists

Systematic meta-analyses were conducted on the ecological impacts of water management, including effects of (i) dewatering on macroinvertebrates, (ii) a hypolimnetic release on downstream aquatic fish and macro invertebrate communities, and (iii) flow modification on fluvial and habitat generalists. Our meta-analysis indicates, in general, that (i) macroinvertebrate abundance is lower in zones or areas that have been dewatered as a result of water fluctuations or low flows (overall effect size, –1.64; 95% confidence intervals (CIs), –2.51, –0.77), (ii) hypolimnetic draws are associated with reduced abundance of aquatic (fish and macroinvertebrates) communities (overall effect size, –0.84; 95% CIs, –1.38, –0.33) and macroinvertebrates (overall effect size, –0.73; 95% CIs, –1.24, –0.22) downstream of a dam, and (iii) altered flows are associated with reduced abundance of fluvial specialists (–0.42; 95% CIs, –0.81, –0.02) but not habitat generalists (overall effect size, –0.14; 95% CIs, –0.61, 0.32). Publication bias is evident in several of the meta-analyses; however, multiple experiments from a single study may be contributing to this bias. Fail-safe Ns suggest that many (>100) studies showing positive or no effects of water management on the selected endpoints would be required to qualitatively change the results of the meta-analysis, which in turn suggests that the conclusions are reasonably robust.

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Predictive physiological anticipatory activity preceding seemingly unpredictable stimuli: An update of Mossbridge et al’s meta-analysis

F1000Research ◽

10.12688/f1000research.14330.2 ◽

2018 ◽

Vol 7 ◽

pp. 407 ◽

Cited By ~ 4

Author(s):

Michael Duggan ◽

Patrizio Tressoldi

Keyword(s):

Confidence Intervals ◽

Publication Bias ◽

Effect Size ◽

Statistical Estimation ◽

Meta Analysis ◽

Weighted Mean ◽

Weighted Effect Size ◽

Credible Intervals ◽

Weighted Effect ◽

Anticipatory Activity

Background: This is an update of the Mossbridge et al’s meta-analysis related to the physiological anticipation preceding seemingly unpredictable stimuli which overall effect size was 0.21; 95% Confidence Intervals: 0.13 - 0.29 Methods: Nineteen new peer and non-peer reviewed studies completed from January 2008 to June 2018 were retrieved describing a total of 27 experiments and 36 associated effect sizes. Results: The overall weighted effect size, estimated with a frequentist multilevel random model, was: 0.28; 95% Confidence Intervals: 0.18-0.38; the overall weighted effect size, estimated with a multilevel Bayesian model, was: 0.28; 95% Credible Intervals: 0.18-0.38. The weighted mean estimate of the effect size of peer reviewed studies was higher than that of non-peer reviewed studies, but with overlapped confidence intervals: Peer reviewed: 0.36; 95% Confidence Intervals: 0.26-0.47; Non-Peer reviewed: 0.22; 95% Confidence Intervals: 0.05-0.39. Similarly, the weighted mean estimate of the effect size of Preregistered studies was higher than that of Non-Preregistered studies: Preregistered: 0.31; 95% Confidence Intervals: 0.18-0.45; No-Preregistered: 0.24; 95% Confidence Intervals: 0.08-0.41. The statistical estimation of the publication bias by using the Copas selection model suggest that the main findings are not contaminated by publication bias. Conclusions: In summary, with this update, the main findings reported in Mossbridge et al’s meta-analysis, are confirmed.

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