Costs clinical development plan

Safety lead optimization efforts are used to maximize resources and early decision-making for the purposes of reducing costs and animal use and removing the least favorable compounds early during the discovery phase, when there is most flexibility in optimizing the candidate molecule. The ultimate goal is to identify a lead development candidate that has the most superior safety characteristics and, for those safety issues identified, a well-characterized risk assessment to reduce clinical attrition due to toxicity and inform the clinical development plan. 

Safety pharmacology studies are ultimately tailored to the specific characteristics of an NCE and the clinical indication(s) for which the NCE is proposed. Therefore, ideally, an understanding of the NCE s clinical development plan (and its regulatory hurdles) should precede and guide safety pharmacology study selection for an NCE. Typically, this takes place as an evolution of the TPP, and the sooner it evolves, preferably using expert input, then the more likely that the relevant safety pharmacology studies will be selected with efficiency and economies of time and cost. 

The Integrated Preclinical Development Plans The total time, materials and costs associated with preclinical support for phase 1 through registration are summarized in Table 7.7 and the integrated preclinical support to clinical development is illustrated in Figure 7.5. 

Various methods have been and are used for the calculation of internal costs, two of which have been published widely the Hoechst Marion Roussel model, derived and published by Thom Hill (Hill and Hubbard 1996) and the MSD BARDS model (Papazian and Wise 1995). A reliable and reproducible method must include the calculation of the cost of a full time equivalent (FTE) employee for each function or task involved in executing and managing the project. Hill s model (Table 42.4) provides a useful illustration of how this may translate into sterling or dollars. This exercise is in itself useful (i.e. even if there are no definite plans to outsource), since clinical development functions are working increasingly in an environment of cost containment. Obviously, such calculations also provide a necessary basis for the comparison of internal costs vs. proposed CRO costs for... 

Proper and comprehensive planning of a clinical trial is essential to the successful development of any drug. Clinical trial design is a subject whose scope is too broad to be undertaken in this text, and only a brief overview of the subject is presented below. The interested reader is referred to the Further Reading section at the end of this chapter. The general principles presented below are relevant to phase II, and particularly phase III, clinical trials. As the bulk of the estimated 300-500 million required to develop a drug is spent on clinical trials, a poorly planned and/or executed clinical trial can be very costly to the drug developer. 

A well planned simulation project increases the likelihood of providing meaningful and timely simulation results that will enhance the design and improve the efficiency, robustness, power, and informativeness of preclinical and clinical studies. An increase in the efficiency and power of clinical trials should reduce the number of studies and time needed to complete the drug development process with the resultant reduction in cost of pharmacotherapy to the consumer. 

Following discussion and acceptance of the SA results, including both model-based and trial-based input factor adjustments, the efficacy trial simulations may proceed as planned. For each possible trial design, the appropriate input factors and output responses are simulated and results are compared to determine the most appropriate design. As discussed previously, this final decision likely will not only be based on a specific p-value or trial power, but will also include valuations based on trial duration, monetary cost, or information gained or lost toward continuing development goals (e.g., an overall measure of clinical utility). 

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