Pooling in Integrated Safety Databases

Abstract

New Drug Applications require the formation of an integrated safety summary as part of the license submission. The objective of this summary is to identify important serious adverse events and to characterize more common, nonserious adverse events. This review typically involves pooling the data across different studies and comparing the event rates on the drug and a common comparator (placebo or active). The most common approach is to collapse data from all studies and summarize them as if they came from a single study. From a scientific viewpoint this is not optimal as between study variability is not accounted for. The dangers of simple pooling are demonstrated with a real example. It is argued that where appropriate, more use should be made of statistical techniques that account for between-study variability; this will be particularly relevant when the treatment allocation ratio is unbalanced across studies.