ABSTRACT
On average, it now takes approximately at least 10 years of pharmaceutical
research and development time and approximately $1.7 billion to bring a new
molecule to bridge the gap of growing demands of unmet medical needs (1-
8). It is also interesting to note that there is a failure rate of approximately
50% in Phase III late stage development in the industry (1,5,7). A schema on
the drug development value chain is presented in Figure 1. Drug development
proceeds in stages, as a molecule moves from preclinical to clinical development,
eventually through registration and, in the process, valuable knowledge on the
preclinical and clinical properties is gained that is consistent with the learning
and confirming paradigm. It takes even more to keep the drug as a viable
option for therapy post-approval as new information becomes available on the
safety and efficacy of the drug in a wider patient population (8). As an
example of post-marketing events, Table 1 lists the drugs withdrawn from the
market due to safety-related reasons. The promise of new technologies that
have spanned the entire breadth and width of drug development from combina-
torial chemistry approaches to high throughput screens and the advances in
genomic sciences appear not to have made a significant impact on the drug devel-
opment statistics yet (6). This is reflected in the declining number of new mole-
cular (or chemical) entities received by the United States Food and Drug
Administration (FDA) as compared to the early 1990s (1). The scope of
knowledge-based drug development is illustrated in Figure 2, one recurring
aspect of which, namely dose optimization, is the theme of this book.
