9.6.5.5  Be aware that the effect of a characteristic may not always be identified

Many characteristics that might have important effects on how well an intervention works cannot be investigated using subgroup analysis or meta-regression. These are characteristics of participants that might vary substantially within studies, but which can only be summarized at the level of the study. An example is age. Consider a collection of clinical trials involving adults ranging from 18 to 60 years old. There may be a strong relationship between age and intervention effect that is apparent within each study. However, if the mean ages for the trials are similar, then no relationship will be apparent by looking at trial mean ages and trial-level effect estimates. The problem is one of aggregating individuals’ results and is variously known as aggregation bias, ecological bias or the ecological fallacy (Morgenstern 1982, Greenland 1987, Berlin 2002). It is even possible for the differences between studies to display the opposite pattern to that observed within each study.