Heterogeneity and study size in random-effects meta-analysis

It is well known that heterogeneity between studies in a meta-analysis can be either caused by diversity, for example, variations in populations and interventions, or caused by bias, that is, variations in design quality and conduct of the studies. Heterogeneity that is due to bias is difficult to deal with. On the other hand, heterogeneity that is due to diversity is taken into account by a standard random-effects model. However, such a model generally assumes that heterogeneity does not vary according to study-level variables such as the size of the studies in the meta-analysis and the type of study design used. This paper develops models that allow for this type of variation in heterogeneity and discusses the properties of the resulting methods. The models are fitted using the maximum-likelihood method and by modifying the Paule--Mandel method. Furthermore, a real-world argument is given to support the assumption that the inter-study variance is inversely proportional to study size. Under this assumption, the corresponding random-effects method is shown to be connected with standard fixed-effect meta-analysis in a way that may well appeal to many clinicians. The models and methods that are proposed are applied to data from two large systematic reviews.