Safety Signal Detection in the Drug Development Process

Safety Signal Detection in the Drug Development Process

Ramin B. Arani, Antoni F.Z. Wisniewski
Copyright: © 2016 |Pages: 26
DOI: 10.4018/978-1-4666-8726-4.ch005
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Abstract

Drug development is a complex set of inter-linked processes in which the cumulative understanding of a drug's safety and efficacy profile is shaped during different learning phases. Often, drugs are approved based on limited safety information, for example in highly at risk or rare disease populations. Therefore, post approval, regulatory organizations have mandated proactive surveillance strategies that include the collection of reported adverse events experienced by exposed populations, some of whom may have been on treatment for extended periods of time. Analyzing these accumulating adverse event reports to understand their clinical significance, given the limitations imposed by the methods of data collection, is a complicated task. The aim of this chapter is to provide the readers with a general understanding of safety signal detection and assessment, followed by a description of statistical methods (both classical and Bayesian) typically utilized for quantifying the strength of association between a drug and an adverse event.
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Background

For the sake of clarity the following definitions are assumed throughout this chapter:

An adverse drug reaction (ADR) is `a noxious and unintended response to a medicinal product for which there is a reasonable possibility that the product caused the response.’ (International Conference on Harmonisation, 1994)

An adverse event (AE) is defined as `any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causative relationship with this treatment.’(International Conference on Harmonisation, 1996)

Disproportionality analysis (DPA) is `the application of computer assisted computational and statistical methods to large safety databases for the purpose of systematically identifying drug-event pairs reported at disproportionately higher frequencies relative to what a statistical independence model would predict.’(J. Almenoff et al., 2005)

A drug-event pair is the combination of a medicinal product and an adverse event which has appeared in at least one case report entered into a spontaneous report [safety] database.(CIOMS Working Group VIII, 2010)

The safety profile of a drug or other therapeutic intervention can defined as the aggregate knowledge of the severity and frequency of adverse drug reactions and other risks related to the use of the intervention.

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