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      Practical methods for incorporating summary time-to-event data into meta-analysis

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          In systematic reviews and meta-analyses, time-to-event outcomes are most appropriately analysed using hazard ratios (HRs). In the absence of individual patient data (IPD), methods are available to obtain HRs and/or associated statistics by carefully manipulating published or other summary data. Awareness and adoption of these methods is somewhat limited, perhaps because they are published in the statistical literature using statistical notation.


          This paper aims to 'translate' the methods for estimating a HR and associated statistics from published time-to-event-analyses into less statistical and more practical guidance and provide a corresponding, easy-to-use calculations spreadsheet, to facilitate the computational aspects.


          A wider audience should be able to understand published time-to-event data in individual trial reports and use it more appropriately in meta-analysis. When faced with particular circumstances, readers can refer to the relevant sections of the paper. The spreadsheet can be used to assist them in carrying out the calculations.


          The methods cannot circumvent the potential biases associated with relying on published data for systematic reviews and meta-analysis. However, this practical guide should improve the quality of the analysis and subsequent interpretation of systematic reviews and meta-analyses that include time-to-event outcomes.

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          Most cited references 10

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          Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

          Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
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            The existence of publication bias and risk factors for its occurrence.

             K Dickersin (1990)
            Publication bias is the tendency on the parts of investigators, reviewers, and editors to submit or accept manuscripts for publication based on the direction or strength of the study findings. Much of what has been learned about publication bias comes from the social sciences, less from the field of medicine. In medicine, three studies have provided direct evidence for this bias. Prevention of publication bias is important both from the scientific perspective (complete dissemination of knowledge) and from the perspective of those who combine results from a number of similar studies (meta-analysis). If treatment decisions are based on the published literature, then the literature must include all available data that is of acceptable quality. Currently, obtaining information regarding all studies undertaken in a given field is difficult, even impossible. Registration of clinical trials, and perhaps other types of studies, is the direction in which the scientific community should move.
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              Factors influencing publication of research results. Follow-up of applications submitted to two institutional review boards.

              --To investigate factors associated with the publication of research findings, in particular, the association between "significant" results and publication. --Follow-up study. --Studies approved in 1980 or prior to 1980 by the two institutional review boards that serve The Johns Hopkins Health Institutions--one that serves the School of Medicine and Hospital and the other that serves the School of Hygiene and Public Health. --A total of 737 studies were followed up. --Of the studies for which analyses had been reported as having been performed at the time of interview, 81% from the School of Medicine and Hospital and 66% from the School of Hygiene and Public Health had been published. Publication was not associated with sample size, presence of a comparison group, or type of study (eg, observational study vs clinical trial). External funding and multiple data collection sites were positively associated with publication. There was evidence of publication bias in that for both institutional review boards there was an association between results reported to be significant and publication (adjusted odds ratio, 2.54; 95% confidence interval, 1.63 to 3.94). Contrary to popular opinion, publication bias originates primarily with investigators, not journal editors: only six of the 124 studies not published were reported to have been rejected for publication. --There is a statistically significant association between significant results and publication.

                Author and article information

                BioMed Central (London )
                7 June 2007
                : 8
                : 16
                [1 ]Meta-analysis Group, MRC Clinical Trials Unit, London, UK
                [2 ]Centre for Reviews and Dissemination, University of York, UK
                [3 ]School of Public Health, NHMRC Clinical Trials Centre, Sydney, Australia
                [4 ]Cancer Group, MRC Clinical Trials Unit, London, UK
                Copyright © 2007 Tierney et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.




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