• Matthias Briel, Katharina F Müller, Joerg J Meerpohl, Erik von Elm, Britta Lang, Edith Motschall, Viktoria Gloy, Francois Lamontagne, Guido Schwarzer, Dirk Bassler, and OPEN Consortium.
• Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
• Syst Rev. 2013 Jan 1;2:23.

BackgroundSystematic reviews and meta-analyses of pre-clinical studies, in vivo animal experiments in particular, can influence clinical care. Publication bias is one of the major threats of validity in systematic reviews and meta-analyses. Previous empirical studies suggested that systematic reviews and meta-analyses have become more prevalent until 2010 and found evidence for compromised methodological rigor with a trend towards improvement. We aim to comprehensively summarize and update the evidence base on systematic reviews and meta-analyses of animal studies, their methodological quality and assessment of publication bias in particular.Methods/DesignThe objectives of this systematic review are as follows: •To investigate the epidemiology of published systematic reviews of animal studies until present. •To examine methodological features of systematic reviews and meta-analyses of animal studies with special attention to the assessment of publication bias. •To investigate the influence of systematic reviews of animal studies on clinical research by examining citations of the systematic reviews by clinical studies. Eligible studies for this systematic review constitute systematic reviews and meta-analyses that summarize in vivo animal experiments with the purpose of reviewing animal evidence to inform human health. We will exclude genome-wide association studies and animal experiments with the main purpose to learn more about fundamental biology, physical functioning or behavior. In addition to the inclusion of systematic reviews and meta-analyses identified by other empirical studies, we will systematically search Ovid Medline, Embase, ToxNet, and ScienceDirect from 2009 to January 2013 for further eligible studies without language restrictions. Two reviewers working independently will assess titles, abstracts, and full texts for eligibility and extract relevant data from included studies. Data reporting will involve a descriptive summary of meta-analyses and systematic reviews.DiscussionResults are expected to be publicly available later in 2013 and may form the basis for recommendations to improve the quality of systematic reviews and meta-analyses of animal studies and their use with respect to clinical care.

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