Statistical assessment of the association between vaccination and rare adverse events post-licensure

Once a new vaccine has been licensed and is in widespread use, it is import ant to be able to detect and investigate adverse events which may be associ ated with the vaccine. This is particularly important for rare events which may have been missed in pre-licensure studies. Recent studies investigatin g adverse events following vaccination have used either a population or a s ample. of the population (cohort studies), cases matched to controls (case- control studies), or just information on the cases themselves (self-control led case-series studies). In this paper, the three methods are reviewed and compared and examples are given of recent applications. The effects of pot ential sources of bias are demonstrated using a data set on MMR vaccine and convulsions. (C) 2001 Elsevier Science Ltd. All rights reserved.