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      Quantifying heterogeneity in individual participant data meta-analysis with binary outcomes

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          Abstract

          Background

          In meta-analyses (MA), effect estimates that are pooled together will often be heterogeneous. Determining how substantial heterogeneity is is an important aspect of MA.

          Method

          We consider how best to quantify heterogeneity in the context of individual participant data meta-analysis (IPD-MA) of binary data. Both two- and one-stage approaches are evaluated via simulation study. We consider conventional I 2 and R 2 statistics estimated via a two-stage approach and R 2 estimated via a one-stage approach. We propose a simulation-based intraclass correlation coefficient (ICC) adapted from Goldstein et al. to estimate the I 2, from the one-stage approach.

          Results

          Results show that when there is no effect modification, the estimated I 2 from the two-stage model is underestimated, while in the one-stage model, it is overestimated. In the presence of effect modification, the estimated I 2 from the one-stage model has better performance than that from the two-stage model when the prevalence of the outcome is high. The I 2 from the two-stage model is less sensitive to the strength of effect modification when the number of studies is large and prevalence is low.

          Conclusions

          The simulation-based I 2 based on a one-stage approach has better performance than the conventional I 2 based on a two-stage approach when there is strong effect modification with high prevalence.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13643-017-0630-4) contains supplementary material, which is available to authorized users.

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          Most cited references19

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          Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

          Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I 2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R 2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I 2, which we call . We also provide a multivariate H 2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I 2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd.
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            A general parametric approach to the meta-analysis of randomized clinical trials.

            Meta-analysis provides a systematic and quantitative approach to the summary of results from randomized studies. Whilst many authors have published actual meta-analyses concerning specific therapeutic questions, less has been published about comprehensive methodology. This article presents a general parametric approach, which utilizes efficient score statistics and Fisher's information, and relates this to different methods suggested by previous authors. Normally distributed, binary, ordinal and survival data are considered. Both the fixed effects and random effects model for treatments are described.
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              Meta-analysis of continuous outcomes combining individual patient data and aggregate data.

              Meta-analysis of individual patient data (IPD) is the gold-standard for synthesizing evidence across clinical studies. However, for some studies IPD may not be available and only aggregate data (AD), such as a treatment effect estimate and its standard error, may be obtained. In this situation, methods for combining IPD and AD are important to utilize all the available evidence. In this paper, we develop and assess a range of statistical methods for combining IPD and AD in meta-analysis of continuous outcomes from randomized controlled trials. The methods take either a one-step or a two-step approach. The latter is simple, with IPD reduced to AD so that standard AD meta-analysis techniques can be employed. The one-step approach is more complex but offers a flexible framework to include both patient-level and trial-level parameters. It uses a dummy variable to distinguish IPD trials from AD trials and to constrain which parameters the AD trials estimate. We show that this is important when assessing how patient-level covariates modify treatment effect, as aggregate-level relationships across trials are subject to ecological bias and confounding. We thus develop models to separate within-trial and across-trials treatment-covariate interactions; this ensures that only IPD trials estimate the former, whilst both IPD and AD trials estimate the latter in addition to the pooled treatment effect and any between-study heterogeneity. Extension to multiple correlated outcomes is also considered. Ten IPD trials in hypertension, with blood pressure the continuous outcome of interest, are used to assess the models and identify the benefits of utilizing AD alongside IPD. Copyright (c) 2007 John Wiley & Sons, Ltd.
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                Author and article information

                Contributors
                bo.chen4@mail.mcgill.ca
                andrea.benedetti@mcgill.ca
                Journal
                Syst Rev
                Syst Rev
                Systematic Reviews
                BioMed Central (London )
                2046-4053
                6 December 2017
                6 December 2017
                2017
                : 6
                : 243
                Affiliations
                [1 ]ISNI 0000 0004 1936 8649, GRID grid.14709.3b, Department of Epidemiology, Biostatistics and Occupational Health, , McGill University, ; Purvis Hall, 1020 Pine Avenue West, Montreal, Canada
                [2 ]ISNI 0000 0004 1936 8649, GRID grid.14709.3b, Respiratory Epidemiology and Clinical Research Unit, , McGill University, ; 2155 Guy St. 4th Floor, Office 412, Montreal, 24105 Canada
                Article
                630
                10.1186/s13643-017-0630-4
                5718085
                29208048
                25ddff45-a1f1-42d1-b9eb-047b5077cc6a
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 9 November 2016
                : 17 November 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000036, Institute of Population and Public Health;
                Funded by: FundRef http://dx.doi.org/10.13039/501100000156, Fonds de Recherche du Québec - Santé;
                Categories
                Methodology
                Custom metadata
                © The Author(s) 2017

                Public health
                individual participant data meta-analysis (ipd-ma),heterogeneity,two-stage and one-stage approaches,i2

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