Drug Safety And Therapeutic Index - Principles Of Pharmacological Screening And Of The Clinical Transferability Of Animal-Experiments Results

Compounds can be admitted as drugs only, if their effectivity and relative intoxicity are demonstrated by pharmacological and clinical trials. The characterisation of these two properties must therefore be the leading idea and final goal of the first steps in preclinical screening. This point was stressed by N. Brock, who propagated the use of the therapeutic index (defined by him as the ratio of the DE5 (toxic) to the DE95(curative) at propriate animal models) as a quantitative measure of these properties. The definition and interpretation of this measure (as well as an equivalent measure, the so-called "coefficient of danger") are discussed in this paper. A preclinical screening procedure based on this therapeutic index is introduced, which allows decisions with preassigned error probabilities at minimum experimental effort. As reliability measure for clinical inferences this use of the a posteriori probability according to Bayes' theorem is proposed.