Clinical studies/trials setting

Development and validation of PD assays to confirm drug effect on molecular target in pre-clinical studies and clinical trials conducted under an exploratory INDA, or in a traditional Phase I/II setting... 

The use of estimates of treatment effect based on indirect comparisons when there is a common comparator has recently been shown on many occasions to agree with the results of head-to-head clinical trials (Song et al. 2003). Clearly a more challenging situation exists where there is not a common parameter, for example, in a recent study of the relative cost effectiveness of newer drugs for treatment of epilepsy (Wilby et al. 2003). In this study, Bayesian Markov chain Monte Carlo models for multiparameter synthesis were used (Ades 2003). Here, complex models were used to analyze a set of clinical studies involving a series of clinical alternatives, including the two alternatives of interest. 

A related issue in pharmacoeconomics trials is the generalizability of the health care delivery system of the patients in the study. A pharmacoeco-nomic study conducted through health a maintenance organization using its members as subjects may observe less referrals to specialist physicians than would the same clinical study in a different practice setting. This effect may be even more pronounced in multinational clinical trials, in which health care systems, physician education, and patients expectations for treatment differ by country. 

The Clinical Trial Department is responsible for setting up a clinical trials register, and, in collaboration with interested parties, establishing guidelines for clinical studies in Belgium. 

Potentially harmful drug interactions may not be identified during controlled clinical trials, due to the exclusion of patients taking concomitant medications, which are not allowed to be taken during a study. For example, terfenadine, a novel nonsedating antihistamine which was found to cause a serious and potentially fatal cardiac arrhythmia, torsades de pointes, when administered with keto-conazole or erythromycin, and this could not realistically have been expected to be identified in the clinical trial setting. The mechanism of this adverse drug interaction was found to be due to cumulation of unmetabolized terfenadine, due to inhibition of cytochrome P-450 (CYP) by ketoconazole or erythromycin the parent terfenadine molecule is usually cleared very rapidly when there is no concomitant CYP inhibitor. 

Use and extrapolation of efficacy data The effects of treatments on efficacy endpoints can be used for several different purposes. They may be used to set a new hypothesis in further clinical studies. This is particularly the case for unexpected findings, such as a negative result despite a well conducted trial, or a positive result which is difficult to interpret, such as failing to show a difference between several doses of a... 

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