top of page


Pharmacovigilance serves to detect previously undetected adverse drug reactions associated with the use of medicines. The simplest method for detecting signals of such events is qualitative review of lists of spontaneously reported drug-event combinations. Quantitative and automated numerator-based methods such as Bayesian data mining can supplement or supplant these methods. The theoretical basis and limitations of these methods should be understood by drug safety professionals, and automated methods should not be automatically accepted.

Published evaluations of these techniques are mainly limited to large regulatory databases, and performance characteristics may differ in smaller safety databases of drug developers. Head-to-head comparisons of the major techniques have not been published. Regardless of previous statistical training, pharmacovigilance practitioners should understand how these methods work. The mathematical basis of these techniques should not obscure the numerous confounders and biases inherent in the data. Automated signal detection methods are transparent to drug safety professionals of various backgrounds.

To overcome this, an overview of the evolution of signal detection followed by a series of sections devoted to the methods with the greatest utilization and evidentiary support: proportional reporting rations, the Bayesian Confidence Propagation Neural Network and empirical Bayes screening. Sophisticated yet intuitive explanations are provided for each method, supported by figures in which the underlying statistical concepts are explored. Finally the strengths, limitations, pitfalls and outstanding unresolved issues need to be explored.

Understanding the theoretical basis of these methods should enhance the effective assessment and possible implementation of these techniques by drug safety professionals.


bottom of page