Clinical trials developmental phase

Preliminary Testing Data Any data generated during the developmental and clinical trial phases of the drug may be useful to determine the expected manufacturing process variability. The process variability is an important factor to define the sampling plan to be used in the stability study. 

A pharmaceutical product must fulfil its purpose under all recommended conditions and it must do so reproducibly. Experience shows that efficacy in controlled experiments does not guarantee that the product does the same and to the same degree under practical conditions. Pharmaceuticals for humans must be tested in human beings for their pharmacodynamic and pharmacokinetic characteristics to prove their effectiveness and safety. These clinical trials are normally carried out in three stages, each phase involving an increased number of patients. Clinical trials in humans are usually the most critical, most expensive, and most time-consuming developmental step and can account for more than one half of the development costs. 

Especially in combination with alternative approaches such as toxicogenom-ics or a phase 0 clinical trial based on microdosing, fish embryo assays have a strong potential for reducing drug developmental costs in the near future.15-109 This is also demonstrated by a growing number of enterprises in which lead development and initial preclinical safety evaluation is performed with embryos... 

Clinical concern Transient hypothyroxinemia of prematurity (THOP) occiu s in 50% of extremely low gestational age neonates (ELGANs 24-28 weeks) and is a major factor of neurodevelopment abnormalities (cognitive delay, cerebral palsy, hearing loss, mental retardation, blindness or epilepsy) [9 ]. THOP characterised by very low total and free T4 levels and normal TSH may be safely treated with continuous infusion of 4 gg/kg/day levothyroxine for 42 days to produce a biochemical euthyroid state (phase I/II trials) [1(P]. There is a pressing need for a phase III trial of thyroid hormone that is of sufficient duration and size to determine whether a clinically important reduction in risk of developmental impairments in ELGANs can be achieved [11 ]. 

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