Summary
Objectives:
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. [1] 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. [1]. In
summary, it is hoped that the method suggested here contributes further to a good
meta-analytic practice in public health and clinical disciplines.
Keywords Evidence-based medicine - C.A.MAN - meta-analysis - meta-regression - meta-likelihood
- nonparametric maximum meta-likelihood - publication bias - unobserved heterogeneity
