approval are limited in their ability to detect rare safety problems. Prior to receiving U.S. Food and Drug Administration (FDA) approval, a drug will have been tested in hundreds to thousands of patients. Generally, drugs cannot confidently be linked to safety problems until they have been tested in tens of thousands to hundreds of thousands of people. With current methods, it is unlikely that rare safety problems will be identified prior to approval.

There is, however, an emerging safety science that seeks to change this paradigm by attempting to understand a drug’s safety or toxicity earlier in its development. This emerging science is focused in two areas. One is the use of various basic sciences, including genomics, metabolomics, pharmacogenomics, and others, to understand the mechanisms underlying toxicity and to predict when a particular compound will have safety issues. The other is the use of new analytical tools for mining large data sets to identify signals that indicate safety problems (e.g., those associated with a class of drugs, those associated with particular molecular entities, or those associated with particular genetic profiles) and even to derive insights regarding a drug’s mechanism of toxicity.

The application of emerging science to drug safety is one of the goals of the FDA’s Critical Path Initiative. A 2004 FDA white paper, Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products, describes this evolution as follows:

Not enough applied scientific work has been done to create new tools to get fundamentally better answers about how the safety and effectiveness of new products can be demonstrated, in faster time frames, with more certainty, and at lower costs. In many cases, developers have no choice but to use the tools and concepts of the last century to assess this century’s candidates. As a result, the vast majority of investigational products that enter clinical trials fail…. A new product development toolkit—containing powerful new scientific and technical methods such as animal or computer-based predictive models, biomarkers for safety and effectiveness, and new clinical evaluation techniques—is urgently needed to improve predictability and efficiency along the critical path from laboratory concept to commercial product. (FDA, 2004:5)

Since the publication of that report, significant progress has been made in the development of just such techniques. But the diffusion of these innovations in drug development and drug review has been limited. To address this concern, the Institute of Medicine’s Forum on Drug Discovery, Development, and Translation sponsored a public workshop—Emerging Safety Science—with the goal of surveying new technologies that can be used to better understand and predict the safety and toxicity of new drugs. The workshop was held April 23–24, 2007, at the FDA’s White Oak Conference Center.



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