iments conducted using human cells) and their uses in lead identification and optimization (the process used by companies to identify and select the candidate[s] most likely to succeed throughout the development process), safety evaluation, and off-target activities, as well as in clinical prediction and exploration of putative biomarkers.

  • Chapter 4 reviews various uses of and methods for toxicogenomics (the conduct of gene expression analyses to help predict the toxic effects of compounds and provide insights into the mechanisms of toxicity).

  • Chapter 5 describes how metabolomics (the detection and quantification of small molecules, or metabolites) is being used to gather information on drug toxicities and their underlying mechanisms.

  • Chapter 6 considers drugs that are toxic in only a subset of patients. Using the case of the anti-HIV drug Abacavir, it describes how pharmacogenetics (the study of genetic variations that affect an individual’s response to a drug) can be used to identify these patients so as to prevent or at least anticipate toxicity.

  • Chapter 7 presents a case study involving the experiences of the Predictive Safety Testing Consortium, formed by the C-Path Institute to bring industry, academia, and the FDA together to investigate qualifying nephrotoxicity biomarkers (quantifiable biological responses that can provide information on disease states or drug responses) for use in safety testing.

  • Chapter 8 describes new approaches to pharmacovigilance (the process of collecting, monitoring, and evaluating adverse event data from patients and health care providers to identify drug safety issues). These approaches include an online signal management program, new methods for analyzing data from the FDA’s Adverse Event Reporting System, and proposals for a large-scale active surveillance network.

  • Chapter 9 considers how to integrate the various approaches to safety science and create feedback loops that will allow information to be shared throughout the system. Means of achieving such integration include building interdisciplinary knowledge; creating databases that allow easier identification of associations between compounds and adverse events; understanding the relevance of animal models; and developing “bridging” biomarkers that can bridge, or translate, early preclinical findings to clinical findings.

  • Finally, Chapter 10 addresses areas in which further work is needed and outlines possible next steps.



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