scholarly journals Bayesian Methods for Meta-Analyses of Binary Outcomes: Implementations, Examples, and Impact of Priors

2021 ◽  
Vol 18 (7) ◽  
pp. 3492
Author(s):  
Fahad M. Al Amer ◽  
Christopher G. Thompson ◽  
Lifeng Lin
Keyword(s):  
Bayesian Methods ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Sensitivity Analyses ◽  
Binary Outcomes ◽  
Inverse Gamma ◽  
Log Normal ◽  
Heterogeneity Variance ◽  
Many Sources ◽  
Meta Analyses

Bayesian methods are an important set of tools for performing meta-analyses. They avoid some potentially unrealistic assumptions that are required by conventional frequentist methods. More importantly, meta-analysts can incorporate prior information from many sources, including experts’ opinions and prior meta-analyses. Nevertheless, Bayesian methods are used less frequently than conventional frequentist methods, primarily because of the need for nontrivial statistical coding, while frequentist approaches can be implemented via many user-friendly software packages. This article aims at providing a practical review of implementations for Bayesian meta-analyses with various prior distributions. We present Bayesian methods for meta-analyses with the focus on odds ratio for binary outcomes. We summarize various commonly used prior distribution choices for the between-studies heterogeneity variance, a critical parameter in meta-analyses. They include the inverse-gamma, uniform, and half-normal distributions, as well as evidence-based informative log-normal priors. Five real-world examples are presented to illustrate their performance. We provide all of the statistical code for future use by practitioners. Under certain circumstances, Bayesian methods can produce markedly different results from those by frequentist methods, including a change in decision on statistical significance. When data information is limited, the choice of priors may have a large impact on meta-analytic results, in which case sensitivity analyses are recommended. Moreover, the algorithm for implementing Bayesian analyses may not converge for extremely sparse data; caution is needed in interpreting respective results. As such, convergence should be routinely examined. When select statistical assumptions that are made by conventional frequentist methods are violated, Bayesian methods provide a reliable alternative to perform a meta-analysis.

scholarly journals Double-zero-event studies matter: a re-evaluation of physical distancing, face masks, and eye protection for preventing person-to-person transmission of COVID-19 and its policy impact

2020 ◽  
Author(s):  
Mengli Xiao ◽  
Lifeng Lin ◽  
James S. Hodges ◽  
Chang Xu ◽  
Haitao Chu
Keyword(s):  
Linear Mixed Model ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Event Studies ◽  
Sensitivity Analyses ◽  
Prevention Measures ◽  
Double Zero ◽  
Eye Protection ◽  
Meta Analyses ◽  
Zero Event

Objectives: High-quality meta-analyses on COVID-19 are in urgent demand for evidence-based decision making. However, conventional approaches exclude double-zero-event studies (DZS) from meta-analyses. We assessed whether including such studies impacts the conclusions in a recent systematic urgent review on prevention measures for preventing person-to-person transmission of COVID-19. Study designs and settings: We extracted data for meta-analyses containing DZS from a recent review that assessed the effects of physical distancing, face masks, and eye protection for preventing person-to-person transmission. A bivariate generalized linear mixed model was used to re-do the meta-analyses with DZS included. We compared the synthesized relative risks (RRs) of the three prevention measures, their 95% confidence intervals (CI), and significance tests (at the level of 0.05) including and excluding DZS. Results: The re-analyzed COVID-19 data containing DZS involved a total of 1,784 participants who were not considered in the original review. Including DZS noticeably changed the synthesized RRs and 95% CIs of several interventions. For the meta-analysis of the effect of physical distancing, the RR of COVID-19 decreased from 0.15 (95% CI, 0.03 to 0.73) to 0.07 (95% CI, 0.01 to 0.98). For several meta-analyses, the statistical significance of the synthesized RR was changed. The RR of eye protection with a physical distance of 2 m and the RR of physical distancing when using N95 respirators were no longer statistically significant after including DZS. Conclusions: DZS may contain useful information. Sensitivity analyses that include DZS in meta-analysis are recommended.

Does Ondansetron Modify Sympathectomy Due to Subarachnoid Anesthesia?

2016 ◽  
Vol 124 (4) ◽  
pp. 846-869 ◽  
Author(s):  
Abdullah S. Terkawi ◽  
Dimitris Mavridis ◽  
Pamela Flood ◽  
Jørn Wetterslev ◽  
Rayan S. Terkawi ◽  
...  
Keyword(s):  
Relative Risk ◽  
Evaluation System ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Sensitivity Analyses ◽  
Trial Sequential Analysis ◽  
Assessment Development ◽  
Meta Analyses

Abstract Background Disagreement among many underpowered studies has led to an equivocal understanding of the efficacy of the 5-HT3 antagonist ondansetron in preventing the consequences of sympathectomy after subarachnoid anesthesia. The authors assessed the efficacy of ondansetron with respect to the overall quality and statistical power of the meta-analyses. Methods The authors used a standard and a newer method of meta-analysis, trial sequential analysis (TSA), to estimate adjusted CIs based on how much information has been accrued. They also used random-effects meta-analyses techniques, small trial bias assessment, selection models, sensitivity analyses, and the Grading of Recommendations on Assessment, Development, and Evaluation system. These results from the aforementioned techniques were compared, and importance of consideration of these factors was discussed. Results Fourteen randomized placebo-controlled trials (1,045 subjects) were identified and analyzed. By using conventional meta-analyses, the authors determined that ondansetron was associated with reduction in the incidence of hypotension (relative risk = 0.62 [95% CI, 0.46 to 0.83], P = 0.001; TSA-adjusted CI, 0.34 to 1.12; I2 = 60%, P = 0.002) and bradycardia (relative risk = 0.44 [95% CI, 0.26 to 0.73], P = 0.001; TSA-adjusted CI, 0.05 to 3.85; I2 = 0%, P = 0.84). However, the authors found indications of bias among these trials. TSAs demonstrated that the meta-analysis lacked adequate information size and did not achieve statistical significance when adjusted for sparse data and repetitive testing. The Grading of Recommendations on Assessment, Development, and Evaluation system showed that the results had low to very low quality of evidence. Conclusions The analyses fail to confirm evidence that ondansetron reduces the incidence of hypotension and bradycardia after subarachnoid anesthesia due to the risk of bias and information sizes less than the required. As results from meta-analysis are given significant weight, it is important to carefully evaluate the quality of the evidence that is input.

scholarly journals Beta-binomial models for meta-analysis with binary outcomes: Variations, extensions, and additional insights from econometrics

2021 ◽  
pp. 263208432199622
Author(s):  
Tim Mathes ◽  
Oliver Kuss
Keyword(s):  
Simulation Study ◽  
Count Data ◽  
Negative Binomial ◽  
Meta Analysis ◽  
Negative Binomial Regression ◽  
Binary Outcomes ◽  
Small Scale ◽  
Panel Count Data ◽  
Count Data Models ◽  
Meta Analyses

Background Meta-analysis of systematically reviewed studies on interventions is the cornerstone of evidence based medicine. In the following, we will introduce the common-beta beta-binomial (BB) model for meta-analysis with binary outcomes and elucidate its equivalence to panel count data models. Methods We present a variation of the standard “common-rho” BB (BBST model) for meta-analysis, namely a “common-beta” BB model. This model has an interesting connection to fixed-effect negative binomial regression models (FE-NegBin) for panel count data. Using this equivalence, it is possible to estimate an extension of the FE-NegBin with an additional multiplicative overdispersion term (RE-NegBin), while preserving a closed form likelihood. An advantage due to the connection to econometric models is, that the models can be easily implemented because “standard” statistical software for panel count data can be used. We illustrate the methods with two real-world example datasets. Furthermore, we show the results of a small-scale simulation study that compares the new models to the BBST. The input parameters of the simulation were informed by actually performed meta-analysis. Results In both example data sets, the NegBin, in particular the RE-NegBin showed a smaller effect and had narrower 95%-confidence intervals. In our simulation study, median bias was negligible for all methods, but the upper quartile for median bias suggested that BBST is most affected by positive bias. Regarding coverage probability, BBST and the RE-NegBin model outperformed the FE-NegBin model. Conclusion For meta-analyses with binary outcomes, the considered common-beta BB models may be valuable extensions to the family of BB models.

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.

A comparison of methods for sample size estimation for non-inferiority studies with binary outcomes

2010 ◽  
Vol 20 (6) ◽  
pp. 595-612 ◽  
Author(s):  
Steven A Julious ◽  
Roger J Owen
Keyword(s):  
Sample Size ◽  
Bayesian Methods ◽  
Sensitivity Analyses ◽  
Binary Outcomes ◽  
Sample Size Estimation ◽  
Controlled Trials ◽  
Comparison Of Methods ◽  
Size Estimation ◽  
Control Response ◽  
Established Treatment

Non-inferiority trials are motivated in the context of clinical research where a proven active treatment exists and placebo-controlled trials are no longer acceptable for ethical reasons. Instead, active-controlled trials are conducted where a treatment is compared to an established treatment with the objective of demonstrating that it is non-inferior to this treatment. We review and compare the methodologies for calculating sample sizes and suggest appropriate methods to use. We demonstrate how the simplest method of using the anticipated response is predominantly consistent with simulations. In the context of trials with binary outcomes with expected high proportions of positive responses, we show how the sample size is quite sensitive to assumptions about the control response. We recommend when designing such a study that sensitivity analyses be performed with respect to the underlying assumptions and that the Bayesian methods described in this article be adopted to assess sample size.

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 Incidence of Respiratory Symptoms for Residents Living Near a Petrochemical Industrial Complex: A Meta-Analysis

2020 ◽  
Vol 17 (7) ◽  
pp. 2474
Author(s):  
Wen-Wen Chang ◽  
Hathaichon Boonhat ◽  
Ro-Ting Lin
Keyword(s):  
Respiratory Symptoms ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Random Effect ◽  
Study Groups ◽  
Industrial Complex ◽  
Residential Exposure ◽  
Increased Risk ◽  
Subgroup Analyses ◽  
Meta Analyses

The air pollution emitted by petrochemical industrial complexes (PICs) may affect the respiratory health of surrounding residents. Previous meta-analyses have indicated a higher risk of lung cancer mortality and incidence among residents near a PIC. Therefore, in this study, a meta-analysis was conducted to estimate the degree to which PIC exposure increases the risk of the development of nonmalignant respiratory symptoms among residents. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to systematically identify, select, and critically appraise relevant research. Finally, we identified 16 study groups reporting 5 types of respiratory symptoms: asthma, bronchitis, cough, rhinitis, and wheezing. We estimated pooled odds ratios (ORs) using random-effect models and investigated the robustness of pooled estimates in subgroup analyses by location, observation period, and age group. We determined that residential exposure to a PIC was significantly associated with a higher incidence of cough (OR = 1.35), wheezing (OR = 1.28), bronchitis (OR = 1.26), rhinitis (OR = 1.17), and asthma (OR = 1.15), although the latter two associations did not reach statistical significance. Subgroup analyses suggested that the association remained robust across different groups for cough and bronchitis. We identified high heterogeneity for asthma, rhinitis, and wheezing, which could be due to higher ORs in South America. Our meta-analysis indicates that residential exposure to a PIC is associated with an increased risk of nonmalignant respiratory symptoms.

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.

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.

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