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Drug Safety

, Volume 26, Issue 3, pp 159–186 | Cite as

Quantitative Methods in Pharmacovigilance

Focus on Signal Detection
  • Manfred Hauben
  • Xiaofeng Zhou
Review Article

Abstract

Pharmacovigilance serves to detect previously unrecognised adverse events associated with the use of medicines. The simplest method for detecting signals of such events is crude inspection 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. This article seeks to make automated signal detection methods transparent to drug safety professionals of various backgrounds. This is accomplished by first providing a brief overview of the evolution of signal detection followed by a series of sections devoted to the methods with the greatest utilisation 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 are discussed. Pharmacovigilance specialists should not be intimidated by the mathematics. Understanding the theoretical basis of these methods should enhance the effective assessment and possible implementation of these techniques by drug safety professionals.

Keywords

Signal Score Information Component Spontaneous Reporting System Proportional Reporting Ratio Medicine Control Agency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Dedicated to the memory of my father Richard S. Hauben, MD.

We are grateful for the thoughtful insights and encouragement of Dr Ana Szarfman of the FDA and Andrew Bate of the WHO Collaborating Centre for International Drug Monitoring.

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Copyright information

© Adis International Limited 2003

Authors and Affiliations

  1. 1.Safety Evaluation and Epidemiology, Pfizer Inc.New YorkUSA
  2. 2.New York University School of MedicineNew YorkUSA
  3. 3.New York Medical CollegeValhallaUSA
  4. 4.Clinical Safety and Risk Management, Worldwide Regulatory Affairs, Pfizer Inc.Ann ArborUSA

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