Jackknife empirical likelihood confidence intervals for assessing heterogeneity in meta-analysis of rare binary event data

2021 ◽  
pp. 106440
Author(s):  
Guanshen Wang ◽  
Yichen Cheng ◽  
Min Chen ◽  
Xinlei Wang
2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Hui Meng ◽  
Yunping Zhou ◽  
Yunxia Jiang

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.


2021 ◽  
pp. 174749302110048
Author(s):  
Frederick Ewbank ◽  
Jacqueline Birks ◽  
Diederik Bulters

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.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
George A Diamond ◽  
Sanjay Kaul

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.


2013 ◽  
Vol 178 (6) ◽  
pp. 993-1004 ◽  
Author(s):  
B. Takkouche ◽  
P. Khudyakov ◽  
J. Costa-Bouzas ◽  
D. Spiegelman

2017 ◽  
Vol 14 (2) ◽  
pp. 192-200 ◽  
Author(s):  
Motoi Odani ◽  
Satoru Fukimbara ◽  
Tosiya Sato

Background/Aim: Meta-analyses are frequently performed on adverse event data and are primarily used for improving statistical power to detect safety signals. However, in the evaluation of drug safety for New Drug Applications, simple pooling of adverse event data from multiple clinical trials is still commonly used. We sought to propose a new Bayesian hierarchical meta-analytic approach based on consideration of a hierarchical structure of reported individual adverse event data from multiple randomized clinical trials. Methods: To develop our meta-analysis model, we extended an existing three-stage Bayesian hierarchical model by including an additional stage of the clinical trial level in the hierarchical model; this generated a four-stage Bayesian hierarchical model. We applied the proposed Bayesian meta-analysis models to published adverse event data from three premarketing randomized clinical trials of tadalafil and to a simulation study motivated by the case example to evaluate the characteristics of three alternative models. Results: Comparison of the results from the Bayesian meta-analysis model with those from Fisher’s exact test after simple pooling showed that 6 out of 10 adverse events were the same within a top 10 ranking of individual adverse events with regard to association with treatment. However, more individual adverse events were detected in the Bayesian meta-analysis model than in Fisher’s exact test under the body system “Musculoskeletal and connective tissue disorders.” Moreover, comparison of the overall trend of estimates between the Bayesian model and the standard approach (odds ratios after simple pooling methods) revealed that the posterior median odds ratios for the Bayesian model for most adverse events shrank toward values for no association. Based on the simulation results, the Bayesian meta-analysis model could balance the false detection rate and power to a better extent than Fisher’s exact test. For example, when the threshold value of the posterior probability for signal detection was set to 0.8, the false detection rate was 41% and power was 88% in the Bayesian meta-analysis model, whereas the false detection rate was 56% and power was 86% in Fisher’s exact test. Limitations: Adverse events under the same body system were not necessarily positively related when we used “system organ class” and “preferred term” in the Medical Dictionary for Regulatory Activities as a hierarchical structure of adverse events. For the Bayesian meta-analysis models to be effective, the validity of the hierarchical structure of adverse events and the grouping of adverse events are critical. Conclusion: Our proposed meta-analysis models considered trial effects to avoid confounding by trial and borrowed strength from both within and across body systems to obtain reasonable and stable estimates of an effect measure by considering a hierarchical structure of adverse events.


2010 ◽  
Vol 27 (6) ◽  
pp. 1429-1435 ◽  
Author(s):  
Yongsong Qin ◽  
J.N.K. Rao ◽  
Changbao Wu

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