Extended clinical evaluation

Phase III Extended Clinical Evaluation. Determines the effects of the medication on a large group of patients who have the disease or disorder. If the medication proves effective, then the pharmaceutical manufacturer submits a New Drug Application (NDA) to the Food and Drug Administration for approval to market the medication. 

It is not possible or desirable to identify a recipe for the safety studies that should be conducted with gene therapy products to support either the first dose in humans or extended clinical evaluation. Each product should be treated on a case-by-case basis, taking into consideration a number of important factors, including the clinical indication, the duration of expression of the gene, and whether DNA transfer will be in vivo or ex vivo. 

Metrifonate [52-68-6] (24) is itself not an AChE inhibitor, but is none2ymaticaIly converted into an active irreversible inhibitor of the en2yme. The compound is relatively specific for AChE over butyrylcholinesterase (135) and the irreversible nature of its inhibition gives rise to an extended duration of action. Some clinical experience has been gained through its use to treat schistosomiasis (136,137) and it is undergoing clinical evaluation for AD. 

The fluorescence-guided identification of human brain tumours and tumour margins during surgery was evaluated to facilitate the accuracy and safety of tumour resection and minimize the probabifity of tumour recurrence. For this purpose, ICG [136], fluorescein [137], 5-aminofluorescein albumin conjugate [131], and ALA [138] have been studied in selected patients or extended clinical trials. 

Bandi, Z. (1979). Eastman Kodak Ektachem glucose/BUN analyzer The results of an extended clinical trial and of the evaluation by the College of American Pathologists. Clin. Chem. 25, 1125, Abstr. 315. 

Bandi, Z.L., Fuller, J.B., Bee, D.E. and James, G.P. (1981). Extended clinical trial and evaluation of glucose determination with the Eastman Kodak Ektachem GLU/BUN analyzer. Clin. Chem. 27, 27-34. 

In the light of these considerations, it was recommended that efforts to develop therapeutic radiopharmaceuticals be extended in the framework of other CRPs in the future. Such CRPs ideally will focus on extending the work towards the clinical evaluation of Lu-DOTATATE. All safety aspects such as radiation dosimetry and toxicology need to be developed in participating laboratories, and procedures for labelling and distribution that would enable suitable and reproducible handling of therapeutic levels of radioactivity need to be estabhshed. 

Clinical evaluation The compound will extend survival in early-onset, severe Type I SMA patients whose life expectancy is normally 1-2 years of age. 

Current guidelines for toxicity evaluation of ophthalmic formulations involve both single and multiple applications, dependent on the proposed clinical use [39]. The multiple applications may extend over a 9-month period and incorporate evaluations of ocular irritation and toxicity, systemic toxicity, and determinations of systemic exposure (toxicokinetics). In many cases the systemic exposure from an ocular route is less than by parenteral administration, information that will assist in determining whether additional studies may be needed to establish systemic safety of the ophthalmic preparation. U.S. and international guidance documents are available [71,72], and regulations and tests have been summarized for ophthalmic preparations [39,73,74],... 

Finally, therapeutic sequencing of different hormonal agents is fast becoming a common clinical practice, and fulvestrant is a good treatment choice to extend the opportunity for using endocrine therapies before reliance upon cytotoxic chemotherapy is necessary. Further research is required in order to evaluate the optimal sequence, both in clinical practice as well as in the laboratory, to choose the correct treatment of breast cancer in each person after the appearance of tamoxifen-induced drug resistance (Robertson 2004 Osipo et al. 2004 Johnston 2004 Robertson et al. 2005). 

None of the clinical trials carried out to evaluate the effects of raloxifene, extending from 8 weeks to 4 years, detected stimulating effects of the drug on endometrium. Consequently, an antiestrogenic, or neutral, profile of raloxifene on endometrium has been vindicated. 

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