title: Meta-analysis: a unifying meta-likelihood approach framing unobserved heterogeneity, study covariates, publication bias, and study quality.
abstract: OBJECTIVE
  This contribution provides a unifying concept for meta-analysis integrating the handling of unobserved heterogeneity, study covariates, publication bias and study quality. It is important to consider these issues simultaneously to avoid the occurrence of artifacts, and a method for doing so is suggested here.
  
  
  METHODS
  The approach is based upon the meta-likelihood in combination with a general linear nonparametric mixed model, which lays the ground for all inferential conclusions suggested here.
  
  
  RESULTS
  The concept is illustrated at hand of a meta-analysis investigating the relationship of hormone replacement therapy and breast cancer. The phenomenon of interest has been investigated in many studies for a considerable time and different results were reported. In 1992 a meta-analysis by Sillero-Arenas et al. concluded a small, but significant overall effect of 1.06 on the relative risk scale. Using the meta-likelihood approach it is demonstrated here that this meta-analysis is due to considerable unobserved heterogeneity. Furthermore, it is shown that new methods are available to model this heterogeneity successfully. It is argued further to include available study covariates to explain this heterogeneity in the meta-analysis at hand.
  
  
  CONCLUSIONS
  The topic of HRT and breast cancer has again very recently become an issue of public debate, when results of a large trial investigating the health effects of hormone replacement therapy were published indicating an increased risk for breast cancer (risk ratio of 1.26). Using an adequate regression model in the previously published meta-analysis an adjusted estimate of effect of 1.14 can be given which is considerably higher than the one published in the meta-analysis of Sillero-Arenas et al. In summary, it is hoped that the method suggested here contributes further to a good meta-analytic practice in public health and clinical disciplines.
authors.affiliation: Division for International Health, Institute for Social Medicine, Epidemiology, and Health Economics, Charité Medical School Berlin, Free University Berlin/Humboldt University at Berlin, Fabeckstr. 60-62, 14195 Berlin, Germany. dankmar.boehning@charite.de
authors.forename: D
authors.initials: D
authors.lastname: Böhning
mesh_terms: D016001:Confidence Intervals; D005858:Germany; D016013:Likelihood Functions; D015201:Meta-Analysis as Topic; D017594:Publication Bias; D012106:Research / Q000592:standards*; D018401:Sample Size