scholarly journals The use of one-stage meta-analytic method based on individual participant data for binary adverse events under the rule of three: a simulation study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6295 ◽  
Author(s):  
Liang-Liang Cheng ◽  
Ke Ju ◽  
Rui-Lie Cai ◽  
Chang Xu
Keyword(s):  
Adverse Events ◽  
Coverage Probability ◽  
Meta Analysis ◽  
Random Effect ◽  
Individual Participant Data ◽  
Average Width ◽  
Rule Of Three ◽  
One Stage ◽  
Individual Participant ◽  
The One

Objective In evidence synthesis practice, dealing with binary rare adverse events (AEs) is a challenging problem. The pooled estimates for rare AEs through traditional inverse variance (IV), Mantel-Haenszel (MH), and Yusuf-Peto (Peto) methods are suboptimal, as the biases tend to be large. We proposed the “one-stage” approach based on multilevel variance component logistic regression (MVCL) to handle this problem. Methods We used simulations to generate trials of individual participant data (IPD) with a series of predefined parameters. We compared the performance of the MVCL “one-stage” approach and the five classical methods (fixed/random effect IV, fixed/random effect MH, and Peto) for rare binary AEs under different scenarios, which included different sample size setting rules, effect sizes, between-study heterogeneity, and numbers of studies in each meta-analysis. The percentage bias, mean square error (MSE), coverage probability, and average width of the 95% confidence intervals were used as performance indicators. Results We set 52 scenarios and each scenario was simulated 1,000 times. Under the rule of three (a sample size setting rule to ensure a 95% chance of detecting at least one AE case), the MVCL “one-stage” IPD method had the lowest percentage bias in most of the situations and the bias remained at a very low level (<10%), when compared to IV, MH, and Peto methods. In addition, the MVCL “one-stage” IPD method generally had the lowest MSE and the narrowest average width of 95% confidence intervals. However, it did not show better coverage probability over the other five methods. Conclusions The MVCL “one-stage” IPD meta-analysis is a useful method to handle binary rare events and superior compared to traditional methods under the rule of three. Further meta-analyses may take account of the “one-stage” IPD method for pooling rare event data.

scholarly journals Deriving percentage study weights in multi-parameter meta-analysis models: with application to meta-regression, network meta-analysis and one-stage individual participant data models

2017 ◽  
Vol 27 (10) ◽  
pp. 2885-2905 ◽  
Author(s):  
Richard D Riley ◽  
Joie Ensor ◽  
Dan Jackson ◽  
Danielle L Burke
Keyword(s):  
Meta Analysis ◽  
Information Matrix ◽  
Indirect Evidence ◽  
Parameter Estimates ◽  
Individual Participant Data ◽  
One Stage ◽  
Individual Participant ◽  
Meta Regression ◽  
Multiple Treatments ◽  
Analysis Models

Many meta-analysis models contain multiple parameters, for example due to multiple outcomes, multiple treatments or multiple regression coefficients. In particular, meta-regression models may contain multiple study-level covariates, and one-stage individual participant data meta-analysis models may contain multiple patient-level covariates and interactions. Here, we propose how to derive percentage study weights for such situations, in order to reveal the (otherwise hidden) contribution of each study toward the parameter estimates of interest. We assume that studies are independent, and utilise a decomposition of Fisher’s information matrix to decompose the total variance matrix of parameter estimates into study-specific contributions, from which percentage weights are derived. This approach generalises how percentage weights are calculated in a traditional, single parameter meta-analysis model. Application is made to one- and two-stage individual participant data meta-analyses, meta-regression and network (multivariate) meta-analysis of multiple treatments. These reveal percentage study weights toward clinically important estimates, such as summary treatment effects and treatment-covariate interactions, and are especially useful when some studies are potential outliers or at high risk of bias. We also derive percentage study weights toward methodologically interesting measures, such as the magnitude of ecological bias (difference between within-study and across-study associations) and the amount of inconsistency (difference between direct and indirect evidence in a network meta-analysis).

scholarly journals Tolerability of Duloxetine in the Elderly and in Young Adults: A Protocol and Preliminary Results of a Systematic Review and Individual Participant Data Meta-Analysis of Randomised Placebo-Controlled Trials.

2021 ◽  
Author(s):  
Jean-Charles Roy ◽  
Chloé Rousseau ◽  
Alexis Jutel ◽  
Florian Naudet ◽  
Gabriel Robert
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Elderly Population ◽  
Meta Analysis ◽  
The Elderly ◽  
Search Term ◽  
Individual Participant Data ◽  
Younger Adults ◽  
Individual Participant

Abstract BackgroundDuloxetine is an antidepressant that benefits from a wide range of approval in the elderly population, while its safety for use in the elderly population, compared to younger adults, is not clearly assessed. This protocol outlines a systematic review and individual participant data meta-analysis comparing the tolerability of duloxetine between elderly and younger adults. MethodsOnly randomised controlled clinical trials, comparing duloxetine to placebo, will be included in this meta-analysis. The studies will be selected if participants were adults of less and more than 65 years old, in conditions of use of duloxetine approved by the European Medical Agency (EMA) and the Food and Drug Administration (FDA). The primary outcome will be the rate ratio of serious adverse events under duloxetine compared to placebo, between participants at least 65 years old and younger adults. Second, the number of any adverse events, clinical efficacy and quality of life will be compared between elderly and younger adults under both interventions. The quality of evidence in the tolerability of duloxetine will be assessed using the GRADE system. A two-step random effect meta-analysis will be conducted. Preliminary searches and formal screening of search results against eligibility criteria on have been completed using predefined search term on electronic databases. DiscussionThis study represents the first meta-analysis investigating the safety of duloxetine in the elderly population across all conditions approved by European and American regulatory authorities. The results from this meta-analysis are intended to help prescribers to provide better care for the elderly population.Systematic review registrationThe protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42019130488).

scholarly journals Tolerability of duloxetine in the elderly and in adults: a protocol and preliminary results of a systematic review and individual participant data meta-analysis of randomized placebo-controlled trials

2020 ◽  
Author(s):  
Jean-Charles ROY ◽  
Chloé Rousseau ◽  
Alexis Jutel ◽  
Florian Naudet ◽  
Gabriel Robert
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Elderly Population ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Individual Participant Data ◽  
Younger Adults ◽  
Randomized Controlled ◽  
Individual Participant

Abstract Background. Duloxetine is an antidepressant which benefits from a wide range of approval in elderly population while its safety of use in elderly population, compared to younger adults, is not clearly assessed. A comparison of tolerability of duloxetine between elderly and younger adults would help to rule on this issue. Methods and Design. This protocol outlines a systematic review and meta-analysis of individual participant data (IPD) of all double-blind randomized controlled trials comparing the number of serious adverse events among individuals taking duloxetine in comparison to placebo between participants at least 65 years and younger adults in conditions approved by the European Medical Agency (EMA) and the Food Drug Administration (FDA). Secondarily, will be compared the number of any adverse events, clinical efficacy and quality of life between elderly and younger adults under duloxetine, in comparison to placebo. Relevant studies were selected on ClinicalTrials.gov, Clinicaltrialsregister.eu, data sharing platforms, FDA and EMA websites, and from systematic reviews and meta-analyses of duloxetine on PubMed, following Cochrane’s recommendations. Sponsors and authors from eligible studies were invited to share IPD on data sharing platform or directly with our research team. As data cannot be aggregate into a unique database, a two step-approach meta-analysis will be undertaken. Qualitative results from available data. 77 eligible randomized controlled trials were identified, representing 25303 participants. From online available data, 35 trials were assessed as being at an overall low risk of bias, 31 trials at an unclear risk of bias and 1 at high risk of bias. Evaluation of risk of bias was not feasible for 10 studies. Conclusion. This study would represent the first meta-analysis investigating the safety of duloxetine in elderly population across all conditions approved by European and American regulatory authorities with an overall low risk of bias. Registration. PROSPERO: 2019 CRD42019130488.

scholarly journals Multilevel Meta-Analysis of Individual Participant Data of Single-Case Experimental Designs: One-Stage versus Two-Stage Methods

2020 ◽  
pp. 1-20
Author(s):  
Lies Declercq ◽  
Laleh Jamshidi ◽  
Belén Fernández Castilla ◽  
Mariola Moeyaert ◽  
S. Natasha Beretvas ◽  
...  
Keyword(s):  
Single Case ◽  
Meta Analysis ◽  
Experimental Designs ◽  
Individual Participant Data ◽  
Stage Versus ◽  
Two Stage ◽  
One Stage ◽  
Individual Participant

Abstract 718: The Association of Erectile Dysfunction with Carotid Intima Media Thickness and Endothelial Dysfunction: A Meta-Analysis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Bryan D Vo ◽  
Ehimen Aneni ◽  
Ebenezer Oni ◽  
Wazim Maziak ◽  
Theodore Feldman ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Meta Analysis ◽  
Random Effect ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Individual Participant Data ◽  
Media Thickness ◽  
Individual Participant ◽  
The Relationship ◽  
Random Effect Models

Introduction: A recent meta-analysis showed that erectile dysfunction (ED) was associated with elevated cardiovascular disease (CVD) mortality. However, findings from studies examining the relationship between ED and sub-clinical CVD have been conflicting. This study summarizes the current evidence related to the association of ED and vascular disease as measured by flow mediated dilation (FMD) of the endothelium and carotid intima media thickness (CIMT). Methods: We searched multiple internet databases for published literature on studies assessing the association of ED and FMD, and CIMT between 1964 and 2014. A total of 11 studies met the inclusion criteria for examining the association between ED and FMD, while 7 studies met criteria for assessing the association with CIMT. Fixed-effect and random-effect models were used to assess and compare the standardized mean difference (SMD) of FMD and CIMT between persons with and without ED. Results: From a total of 795 individual participant data (590 with and 205 without ED), persons with ED had a 0.66mm (0.49, 0.83) increase in CIMT by fixed effects model or 0.67mm (0.44, 0.90) by random effects model compared to those without ED. Similarly, from 1055 individual participant data (536 with and 419 without ED), ED was associated with a significant reduction in FMD by both fixed effect (-1.10% (95% CI: -2.10, -0.95)) and random effect models (-1.53% (95% CI: -2.10, -0.95)). There was significant heterogeneity among studies assessing the relationship between ED and FMD (I2 = 93.2%, p<0.001) but not among those comparing CIMT among persons with ED (I2 = 43.5% p=0.09). Conclusion: This study confirms that ED is associated with both worsening endothelial function and increased CIMT. Thus, worsening vascular function may be a pathogenic mechanism for increased CVD morbidity and mortality in persons with ED. A diagnosis of ED should prompt a thorough CV work-up and aggressive preventive management.

scholarly journals Individual Participant Data Meta-Analysis for a Binary Outcome: One-Stage or Two-Stage?

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e60650 ◽  
Author(s):  
Thomas P. A. Debray ◽  
Karel G. M. Moons ◽  
Ghada Mohammed Abdallah Abo-Zaid ◽  
Hendrik Koffijberg ◽  
Richard David Riley
Keyword(s):  
Meta Analysis ◽  
Individual Participant Data ◽  
Binary Outcome ◽  
Two Stage ◽  
One Stage ◽  
Individual Participant

scholarly journals Benefits and harms of Risperidone and Paliperidone for treatment of patients with schizophrenia or bipolar disorder: a meta-analysis involving individual participant data and clinical study reports

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexander Hodkinson ◽  
Carl Heneghan ◽  
Kamal R. Mahtani ◽  
Evangelos Kontopantelis ◽  
Maria Panagioti
Keyword(s):  
Bipolar Disorder ◽  
Clinical Study ◽  
Relative Risk ◽  
Adverse Events ◽  
Meta Analysis ◽  
Data Sources ◽  
Individual Participant Data ◽  
Journal Publications ◽  
Individual Participant ◽  
Clinical Study Reports

Abstract Background Schizophrenia and bipolar disorder are severe mental illnesses which are highly prevalent worldwide. Risperidone and Paliperidone are treatments for either illnesses, but their efficacy compared to other antipsychotics and growing reports of hormonal imbalances continue to raise concerns. As existing evidence on both antipsychotics are solely based on aggregate data, we aimed to assess the benefits and harms of Risperidone and Paliperidone in the treatment of patients with schizophrenia or bipolar disorder, using individual participant data (IPD), clinical study reports (CSRs) and publicly available sources (journal publications and trial registries). Methods We searched MEDLINE, Central, EMBASE and PsycINFO until December 2020 for randomised placebo-controlled trials of Risperidone, Paliperidone or Paliperidone palmitate in patients with schizophrenia or bipolar disorder. We obtained IPD and CSRs from the Yale University Open Data Access project. The primary outcome Positive and Negative Syndrome Scale (PANSS) score was analysed using one-stage IPD meta-analysis. Random-effect meta-analysis of harm outcomes involved methods for coping with rare events. Effect-sizes were compared across all available data sources using the ratio of means or relative risk. We registered our review on PROSPERO, CRD42019140556. Results Of the 35 studies, IPD meta-analysis involving 22 (63%) studies showed a significant clinical reduction in the PANSS in patients receiving Risperidone (mean difference − 5.83, 95% CI − 10.79 to − 0.87, I2 = 8.5%, n = 4 studies, 1131 participants), Paliperidone (− 6.01, 95% CI − 8.7 to − 3.32, I2 = 4.3%, n = 13, 3821) and Paliperidone palmitate (− 7.89, 95% CI − 12.1 to − 3.69, I2 = 2.9%, n = 5, 2209). CSRs reported nearly two times more adverse events (4434 vs. 2296 publication, relative difference (RD) = 1.93, 95% CI 1.86 to 2.00) and almost 8 times more serious adverse events (650 vs. 82; RD = 7.93, 95% CI 6.32 to 9.95) than the journal publications. Meta-analyses of individual harms from CSRs revealed a significant increased risk among several outcomes including extrapyramidal disorder, tardive dyskinesia and increased weight. But the ratio of relative risk between the different data sources was not significant. Three treatment-related gynecomastia events occurred, and these were considered mild to moderate in severity. Conclusion IPD meta-analysis conclude that Risperidone and Paliperidone antipsychotics had a small beneficial effect on reducing PANSS score over 9 weeks, which is more conservative than estimates from reviews based on journal publications. CSRs also contained significantly more data on harms that were unavailable in journal publications or trial registries. Sharing of IPD and CSRs are necessary when performing meta-analysis on the efficacy and safety of antipsychotics.

Estimating interactions in individual participant data meta-analysis. A comparison of methods in practice.

2021 ◽  
Author(s):  
Ruth Walker ◽  
Lesley Stewart ◽  
Mark Simmonds
Keyword(s):  
Random Effects ◽  
Meta Analysis ◽  
Individual Preference ◽  
Detailed Examination ◽  
International Studies ◽  
Individual Participant Data ◽  
Stage Models ◽  
One Stage ◽  
Interaction Terms ◽  
Individual Participant

Abstract Medical interventions may be more effective in some types of individuals than others and identifying characteristics that modify the effectiveness of an intervention is a cornerstone of precision or stratified medicine. The opportunity for detailed examination of treatment-covariate interactions can be an important driver for undertaking an individual participant data (IPD) meta-analysis, rather than a meta-analysis using aggregate data. A number of recent modelling approaches are available. We apply these methods to the Perinatal Antiplatelet Review of International Studies (PARIS) Collaboration IPD dataset and compare estimates between them. We discuss the practical implications of applying these methods, which may be of interest to aid meta-analysists in the use of these, often complex models. Models compared included the two-stage meta-analysis of interaction terms and one-stage models which fit multiple random effects and separate within and between trial information. Models were fitted for nine covariates and five binary outcomes and results compared. Interaction terms produced by the methods were generally consistent. We show that where data are sparse and there is low heterogeneity in the covariate distributions across trials, the meta-analysis of interactions may produce unstable estimates and have issues with convergence. In this IPD dataset, varying assumptions by using multiple random effects in one-stage models or using only within trial information made little difference to the estimates of treatment-covariate interaction. Method choice will depend on datasets characteristics and individual preference.

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