title: Plea for routinely presenting prediction intervals in meta-analysis.
abstract: Evaluating the variation in the strength of the effect across studies is a key feature of meta-analyses. This variability is reflected by measures like τ(2) or I(2), but their clinical interpretation is not straightforward. A prediction interval is less complicated: it presents the expected range of true effects in similar studies. We aimed to show the advantages of having the prediction interval routinely reported in meta-analyses.
  
  
  
  We show how the prediction interval can help understand the uncertainty about whether an intervention works or not. To evaluate the implications of using this interval to interpret the results, we selected the first meta-analysis per intervention review of the Cochrane Database of Systematic Reviews Issues 2009-2013 with a dichotomous (n=2009) or continuous (n=1254) outcome, and generated 95% prediction intervals for them.
  
  
  
  In 72.4% of 479 statistically significant (random-effects p<0.05) meta-analyses in the Cochrane Database 2009-2013 with heterogeneity (I(2)>0), the 95% prediction interval suggested that the intervention effect could be null or even be in the opposite direction. In 20.3% of those 479 meta-analyses, the prediction interval showed that the effect could be completely opposite to the point estimate of the meta-analysis. We demonstrate also how the prediction interval can be used to calculate the probability that a new trial will show a negative effect and to improve the calculations of the power of a new trial.
  
  
  
  The prediction interval reflects the variation in treatment effects over different settings, including what effect is to be expected in future patients, such as the patients that a clinician is interested to treat. Prediction intervals should be routinely reported to allow more informative inferences in meta-analyses.
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences (RIHS), Nijmegen, The Netherlands.
authors.forename: Joanna
authors.initials: J
authors.lastname: IntHout
authors.affiliation: Department of Medicine, Stanford Prevention Research Center, Stanford University School of Humanities and Sciences, Stanford, California, USA Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, California, USA Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA.
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences (RIHS), Nijmegen, The Netherlands.
authors.forename: Maroeska M
authors.initials: MM
authors.lastname: Rovers
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences (RIHS), Nijmegen, The Netherlands.
authors.forename: Jelle J
authors.initials: JJ
authors.lastname: Goeman
mesh_terms: D006801:Humans; D015201:Meta-Analysis as Topic; D011336:Probability; D011643:Publishing; D058028:Research Report
keywords: Clinical trial; Cochrane Database of Systematic Reviews; Heterogeneity; Meta-analysis; Prediction interval; Random effects