title: Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics.
abstract: BACKGROUND
  Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I2 statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic.
  
  
  METHODS
  We review 18 IPD meta-analyses of RCTs into treatments for cancer, in order to quantify the amount of heterogeneity present and also to discuss practical methods for explaining heterogeneity.
  
  
  RESULTS
  Differing results were obtained when the standard Q and I2 statistics were used to test for the presence of heterogeneity. The two meta-analyses with the largest amount of heterogeneity were investigated further, and on inspection the straightforward application of a random effects model was not deemed appropriate. Compared to the standard Q statistic, the generalised Q statistic provided a more accurate platform for estimating the amount of heterogeneity in the 18 meta-analyses.
  
  
  CONCLUSIONS
  Explaining heterogeneity via the pre-specification of trial subgroups, graphical diagnostic tools and sensitivity analyses produced a more desirable outcome than an automatic application of the random effects model. Generalised Q statistic methods for quantifying and adjusting for heterogeneity should be incorporated as standard into statistical software. Software is provided to help achieve this aim.
authors.affiliation: MRC Clinical Trials Unit, 222 Euston Road, London NW1 2DA, UK. jack.bowden@mrc-bsu.cam.ac.uk
authors.forename: Jack
authors.initials: J
authors.lastname: Bowden
authors.forename: Jayne F
authors.initials: JF
authors.lastname: Tierney
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Copas
authors.forename: Sarah
authors.initials: S
authors.lastname: Burdett
mesh_terms: D000704:Analysis of Variance; D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D006801:Humans; D015201:Meta-Analysis as Topic; D009369:Neoplasms / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D013223:Statistics as Topic