title: Flaws in animal studies exploring statins and impact on meta-analysis.
abstract: BACKGROUND
  Animal experiments should be appropriately designed, correctly analysed and transparently reported to increase their scientific validity and maximise the knowledge gained from each experiment. This systematic review of animal experiments investigating statins evaluates their quality of reporting and methodological aspects as well as their implications for the conduction of meta-analyses.
  
  
  METHODS
  We searched medline and embase for studies reporting research on statins in mice, rats and rabbits. We collected detailed information about the characteristics of studies, animals and experimental methods.
  
  
  RESULTS
  We retrieved 161 studies. A little over half did not report randomisation (55%) and most did not describe blinding (88%). All studies reported details on the experimental procedure, although many omitted information about animal gender, age or weight. Four percent did not report the number of animals used. None reported the sample size. Fixed- and random-effects models gave different results (ratio of effect size increased by five folds). Heterogeneity was consistently substantial within animal models, for which accounting for covariates had minimal impact. Publication bias is highly suspected across studies.
  
  
  CONCLUSIONS
  Although statins showed efficacy in animal models, preclinical studies highlighted fundamental problems in the way in which such research is conducted and reported. Results were often difficult to interpret and reproduce. Different meta-analytic approaches were highly inconsistent: a reliable approach to estimate the true parameter was imperceptible. Policies that address these issues are required from investigators, editors and institutions that care about the quality standards and ethics of animal research.
authors.affiliation: Clinical Epidemiology Unit, IRCCS Orthopedic Institute Galeazzi, Milan, Italy; Department of Biomedical Science for Health, University of Milan, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moja
authors.forename: Valentina
authors.initials: V
authors.lastname: Pecoraro
authors.forename: Laura
authors.initials: L
authors.lastname: Ciccolallo
authors.forename: Luigi
authors.initials: L
authors.lastname: Dall'Olmo
authors.forename: Gianni
authors.initials: G
authors.lastname: Virgili
authors.forename: Silvio
authors.initials: S
authors.lastname: Garattini
mesh_terms: D032761:Animal Experimentation / Q000592:standards*; D000818:Animals; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015201:Meta-Analysis as Topic; D051379:Mice; D017594:Publication Bias; D011817:Rabbits; D051381:Rats; D012107:Research Design / Q000592:standards; D013223:Statistics as Topic
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Animal models; bias; meta-analysis; translational medical research