Clinical development plans

NCI (1996) Clinical Development Plan Genistein. National Cancer Institute (NCI) Chemoprevention Branch and Agent Development Committee. J Cell Biochem. 26S 114-26. 

The nature, timing, and extent of the initial nonclinical toxicology effort must be consistent with the clinical development plan that it must support. The ICH guidelines further specify the extent and duration of nonclinical studies that are required to initiate or continue clinical studies. Therefore, it is important that the clinical development plan, at least the initial stages, be clearly delineated so that clinical studies are not delayed owing to the lack of appropriate nonclinical studies. 

A sponsor of a medical product entering the development phase must have a clinical development plan, which is created by experienced executives and consultants having expertise and experience in the disease state for which the product is intended. Once the plan is created, with appropriate input from regulators, the plan drives a clinical development budget, with consideration of the desired timeframe for projected producf approval. After the plan is created, the management team determines the "make vs. buy" strategy, which determines the elements of fhe plan that will be outsourced. 

The clinical development plan to be supported would be idealized, with minimal delays between phases and without substantive changes to the test article (e.g., no changes to manufacturing process or formulation) or the route of administration. 

The proposed clinical development plan is summarized in Table 7.2 and illustrated in Figure 7.1. Based on the therapeutic target(s) and mechanism(s)... 

The design and conduct of the clinical studies presented in the examples below was in conformance with these principles. Subjects were included only after informed consent was given. All studies were part of a sound clinical development plan of the sponsor. 

ICH/M3 provides information about which studies -and of what duration - are needed before the different clinical phases of development can be started. In addition to this, timing of preclinical studies in dependence of clinical development plans, there are recommendations under which conditions different population can be included into clinical trials, populations such as men, women of childbearing potential or pregnant women and finally pediatric populations. 

Prepare or Review Overall Clinical Development Plan... 

The statement that the proof of effectiveness would be derived from "well-controlled investigations" has been the cornerstone of the FDA s position for the requirement of two positive adequate and well-controlled clinical trialS/ both of which must demonstrate effectiveness at the P < 0.05 level (16). However/ in practice/ most clinical development plans include more than just two studies to document efficacy and evaluate safety. In a pilot study reported by Peck (1) of a cohort of 12 of the 51 NDAs that were approved by the FDA in 1994-1995/ the total number of clinical trials in each submission ranged from 23 to 150. In those trials that were designed to establish efficacy and evaluate safety/ the number of study participants ranged from 1/000 to 13/000. Peck has pointed out that these NDAs probably reflect clinical plans that were designed in the mid-1980s. 

Label-Driven Question-Based Clinical Development Plan 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). 

In addition/ the following clinical/regulatory questions are representative of those that need to be considered in designing a clinical development plan to meet U.S. regulatory requirements ... 

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