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      U is for Unease: Reasons for Mistrusting Overlap Measures for Reporting Clinical Trials

      Statistics in Biopharmaceutical Research
      Informa UK Limited

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          Issues in the selection of a summary statistic for meta-analysis of clinical trials with binary outcomes.

          Meta-analysis of binary data involves the computation of a weighted average of summary statistics calculated for each trial. The selection of the appropriate summary statistic is a subject of debate due to conflicts in the relative importance of mathematical properties and the ability to intuitively interpret results. This paper explores the process of identifying a summary statistic most likely to be consistent across trials when there is variation in control group event rates. Four summary statistics are considered: odds ratios (OR); risk differences (RD) and risk ratios of beneficial (RR(B)); and harmful outcomes (RR(H)). Each summary statistic corresponds to a different pattern of predicted absolute benefit of treatment with variation in baseline risk, the greatest difference in patterns of prediction being between RR(B) and RR(H). Selection of a summary statistic solely based on identification of the best-fitting model by comparing tests of heterogeneity is problematic, principally due to low numbers of trials. It is proposed that choice of a summary statistic should be guided by both empirical evidence and clinically informed debate as to which model is likely to be closest to the expected pattern of treatment benefit across baseline risks. Empirical investigations comparing the four summary statistics on a sample of 551 systematic reviews provide evidence that the RR and OR models are on average more consistent than RD, there being no difference on average between RR and OR. From a second sample of 114 meta-analyses evidence indicates that for interventions aimed at preventing an undesirable event, greatest absolute benefits are observed in trials with the highest baseline event rates, corresponding to the model of constant RR(H). The appropriate selection for a particular meta-analysis may depend on understanding reasons for variation in control group event rates; in some situations uncertainty about the choice of summary statistic will remain. Copyright 2002 John Wiley & Sons, Ltd.
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            Analysis of categorical data by linear models.

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              A general methodology for the analysis of experiments with repeated measurement of categorical data.

              This paper is concerned with the analysis of multivariate categorical data which are obtained from repeated measurement experiments. An expository discussion of pertinent hypotheses for such situations is given, and appropriate test statistics are developed through the application of weighted least squares methods. Special consideration is given to computational problems associated with the manipulation of large tables including the treatment of empty cells. Three applications of the methodology are provided.
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                Author and article information

                Journal
                Statistics in Biopharmaceutical Research
                Statistics in Biopharmaceutical Research
                Informa UK Limited
                1946-6315
                May 2011
                May 2011
                : 3
                : 2
                : 302-309
                Article
                10.1198/sbr.2010.10024
                6eaf1653-f9d4-4987-ae83-49b7ca35bced
                © 2011
                History

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