title: Subgroup effects despite homogeneous heterogeneity test results.
abstract: BACKGROUND
  Statistical tests of heterogeneity are very popular in meta-analyses, as heterogeneity might indicate subgroup effects. Lack of demonstrable statistical heterogeneity, however, might obscure clinical heterogeneity, meaning clinically relevant subgroup effects.
  
  
  METHODS
  A qualitative, visual method to explore the potential for subgroup effects was provided by a modification of the forest plot, i.e., adding a vertical axis indicating the proportion of a subgroup variable in the individual trials. Such a plot was used to assess the potential for clinically relevant subgroup effects and was illustrated by a clinical example on the effects of antibiotics in children with acute otitis media.
  
  
  RESULTS
  Statistical tests did not indicate heterogeneity in the meta-analysis on the effects of amoxicillin on acute otitis media (Q = 3.29, p = 0.51; I2 = 0%; T2 = 0). Nevertheless, in a modified forest plot, in which the individual trials were ordered by the proportion of children with bilateral otitis, a clear relation between bilaterality and treatment effects was observed (which was also found in an individual patient data meta-analysis of the included trials: p-value for interaction 0.021).
  
  
  CONCLUSIONS
  A modification of the forest plot, by including an additional (vertical) axis indicating the proportion of a certain subgroup variable, is a qualitative, visual, and easy-to-interpret method to explore potential subgroup effects in studies included in meta-analyses.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. r.h.h.groenwold@umcutrecht.nl
authors.forename: Rolf H H
authors.initials: RH
authors.lastname: Groenwold
authors.forename: Maroeska M
authors.initials: MM
authors.lastname: Rovers
authors.forename: Jacobus
authors.initials: J
authors.lastname: Lubsen
authors.forename: Geert Jmg
authors.initials: GJ
authors.lastname: van der Heijden
mesh_terms: D000208:Acute Disease; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001699:Biometry / Q000379:methods*; D002648:Child; D003627:Data Interpretation, Statistical; D006801:Humans; D015201:Meta-Analysis as Topic; D010033:Otitis Media / Q000188:drug therapy; D012044:Regression Analysis; D018709:Statistics, Nonparametric
chemical_list: D000900:Anti-Bacterial Agents; D000658:Amoxicillin