Date of Award

2007

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Gideon Koren

Second Advisor

Dr. Mike Rieder

Abstract

Background: Pemoline was introduced in 1975 in the U.S. for ADHD in children. Pemoline was withdrawn from the market 30 years later, due to fatal hepatotoxicity associated with its use. Objective: To create a system that will estimate the potential association between a serious adverse event and a medication early in its marketing cycle.

Method: All cases of acute liver failure (ALF) associated with pemoline reported to the FDA and all published articles on topic were reviewed. The incidence rate of idiopathic ALF was synthesized from the published literature. The data were analysed by using the Fisher Exact test and Relative Risks (RR).

Results: As early as 1978, there was a significant signal indicating that pemoline is associated with ALF. Conclusion: This method enables researchers, drug companies and regulators to identify uncommon adverse drug reactions, caused mostly by new medications, earlier in the course of marketing and thus prevent serious human risk.

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