Making Paradigm

A clinical development plan cannot be considered complete until the required resources (people/ fundS/ equipment/ siteS/ clinical supplies/ etc.) are identified for each major objective. 

For those who desigii/ track/ and make decisions regarding the progress of clinical development programs/ the inclusion within the development plan of critical decision pointS/ with prespecified go/no-go criteria/ provides a focus for the clinical development team. The key clinical drug development decisions are identified in Table 33.2/ with the critical go/no-go decisions being shown in boldface. These critical decisions will be expanded on later in this chapter. It is important to note that the driver for these decisions is our question-based label-driven clinical development plan. Indeed/ the creation of a label-driven question-based clinical development plan not only increases the efficiency and speed of the clinical development process/ but also supports the question-based review by the FDA of an NDA/ as described by Lesko and Williams (35). 

As discussed in detail in Chapter 27/ a critically important point is that/ on average/ only 1 out of 12 

Whal is the intended clinical disease model (prevention, treatment, cure, or diagnosis)  

Are animal safety and activity data adequate to justify human clinical trials  

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Just what do we mean when we say that something is complex To make it slightly easier, we should really be ask two separate questions. First, What is a complex system , followed by What is complex behavior While neither of these two questions is particularly easy to answer rigorously, the task is, conceptually at least, made easier if we use cellular automata as paradigms for both they not only constitute the prototypical complex dynamical system, but their behavior literally spans the spectrum from nuii-rule-like triviality to Conway s Lifo-rule-like computa tional universality the latter of which arguably represents as complex a behavior as is likely to be found anywhere. With this image in mind, let us address the above two questions. 

Except in the occasional introductions that students seldom read, science texts make little attempt to describe the sorts of problems that the professional may be asked to solve or to discuss the variety of techniques that experience has made available for their solution. Instead, these books exhibit, from the very start, concrete problem-solutions that the profession has come to accept as paradigms [as exemplars], and they then ask the student either with a pencil and paper or in the laboratory, to solve for himself problems very closely modelled in method and substance upon those through which the text has led him (italics Kuhn, 1963, p. 351). 

Shaik, S., Filatov, M., Schroder, D., Schwarz, H., 1998, Electronic Structure Makes a Difference Cytochrome P-450 Mediated Hydroxylations of Hydrocarbons as a Two-State Reactivity Paradigm , Chem. Eur. J., 4, 193. 

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