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      Sequential methods for random-effects meta-analysis

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          Abstract

          Although meta-analyses are typically viewed as retrospective activities, they are increasingly being applied prospectively to provide up-to-date evidence on specific research questions. When meta-analyses are updated account should be taken of the possibility of false-positive findings due to repeated significance tests. We discuss the use of sequential methods for meta-analyses that incorporate random effects to allow for heterogeneity across studies. We propose a method that uses an approximate semi-Bayes procedure to update evidence on the among-study variance, starting with an informative prior distribution that might be based on findings from previous meta-analyses. We compare our methods with other approaches, including the traditional method of cumulative meta-analysis, in a simulation study and observe that it has Type I and Type II error rates close to the nominal level. We illustrate the method using an example in the treatment of bleeding peptic ulcers. Copyright © 2010 John Wiley & Sons, Ltd.

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          Most cited references35

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          Statistical Power Analysis for the Behavioral Scienses

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            A multiple testing procedure for clinical trials.

            A multiple testing procedure is proposed for comparing two treatments when response to treatment is both dichotomous (i.e., success or failure) and immediate. The proposed test statistic for each test is the usual (Pearson) chi-square statistic based on all data collected to that point. The maximum number (N) of tests and the number (m1 + m2) of observations collected between successive tests is fixed in advance. The overall size of the procedure is shown to be controlled with virtually the same accuracy as the single sample chi-square test based on N(m1 + m2) observations. The power is also found to be virtually the same. However, by affording the opportunity to terminate early when one treatment performs markedly better than the other, the multiple testing procedure may eliminate the ethical dilemmas that often accompany clinical trials.
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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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                Author and article information

                Journal
                Stat Med
                sim
                Statistics in Medicine
                John Wiley & Sons, Ltd.
                0277-6715
                1097-0258
                30 April 2011
                28 December 2010
                : 30
                : 9
                : 903-921
                Affiliations
                [a ]simpleMRC Biostatistics Unit, Institute of Public Health Robinson Way, Cambridge CB2 0SR, U.K.
                [b ]simpleMedical and Pharmaceutical Statistics Research Unit, Department of Mathematics and Statistics, Lancaster University Lancaster LA1 4YF, U.K.
                [c ]simpleWolfson Institute of Preventive Medicine, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London London EC1M 6BQ, U.K.
                Author notes
                *Correspondence to: Julian P. T. Higgins, MRC Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge CB2 0SR, U.K
                Article
                10.1002/sim.4088
                3107948
                21472757
                742f31d9-1e3b-4986-9198-4b8458b61e9a
                Copyright © 2011 John Wiley & Sons, Ltd.

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 28 August 2008
                : 23 August 2010
                Categories
                Research Article

                Biostatistics
                cumulative meta-analysis,prior distributions,meta-analysis,prospective meta-analysis,sequential methods

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