chapter  21
10 Pages

Translating Promising Experimental Approaches to Clinical Trials

In most cases (oncology being an exception), traditional phase I clinical trials are performed in healthy volunteers in an attempt to remove variables due to underlying disease and deteriorations in physiology and because of the intensity of the monitoring required. A new chemical entity (NCE) cannot (should not) be introduced into man without an assessment of the risk-benefit ratio, which requires knowledge of its safety profile in animals. As the first clinical studies are traditionally safety studies, the initial administrations are performed using doses that are low relative to the no observable adverse event level (NOAEL) found in animal testing. This requires practical knowledge of toxic effects and an understanding of the dose-response relationship. It should be obvious that in order to accurately translate the animal results into expected behavior in man, the quality of the material used in each case should be known and be similar. It should also be obvious that if the proposed testing is of an existing compound that involves a (new) route of administration or dosage level, or use in a patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the compound, then additional relevant preclinical safety testing may be necessary.