will dramatically impact the future of drug safety and that advancing this science will require increased support.

In March 2004, the FDA released a document titled Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products (FDA, 2004). The release of this document marked the launch of the agency’s Critical Path Initiative, designed to revolutionize the drug development pathway. The FDA explained that, despite technological advances, the drug development community is still using the last century’s methods to develop and test new drugs, biological therapies, and medical devices. In fact, a drug entering the Phase I clinical stage of development in 1985 was more likely to reach the market than one entering in 2000 (Lloyd, 2002–2003). During 1995–2000, an average of 1 out of 8 new compounds entering Phase I development reached the market, compared with an average of 1 out of 13 during 2000–2002. Thus between 1995 and 2002, the chance of reaching the market declined from 14 to 8 percent (Gilbert, 2003). One of the primary goals of the Critical Path Initiative is to increase the efficiency of the development process by building safety into products throughout their development life cycle.


Dr. Woodcock emphasized the need for safety research and described the FDA’s limited ability to take the lead in the conduct of such research. The type of postapproval research needed to improve drug safety extends well beyond the surveillance activities discussed in Chapter 5. Safety research is lacking in part because there is no particular body or entity charged with conducting it. While some research gaps can be filled through existing consortia, collaborations (e.g., with the National Institutes of Health [NIH] and the Centers for Education and Research on Therapeutics [CERTs]), and other mechanisms, the magnitude of the knowledge gap and the FDA’s currently very limited capacity to fill that gap need to be recognized. The cost of a single large comparative safety study, for example, could exceed the entire appropriated budget of the Center for Drug Evaluation and Research (CDER). Considering that funding for CDER totals approximately $500 million for fiscal year 2007—of which about $240 million is from user fees, $225 million is base appropriations, and $16 million is dedicated for orphan drug research grants—less than a few million dollars remains to fund research (after infrastructure costs, salaries, document and adverse event processing costs, etc. are also subtracted).

Dr. Woodcock briefly outlined a broad spectrum of urgent safety science research needs, most of which focus on mechanisms, not just causal associations:

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