Needs of nonclinical studies in big animals from the view of investigators of clinical trials

Abstract

Available safety and efficacy data are limited in clinical trials and even no human data exist in first human studies. The main interest of investigators is securing safety of subjects in early clinical trials and the investigators pay most attention to safety data obtained by studies such as toxicology study and safety pharmacology studies. Such studies are performed mainly in small animals and investigators are used to interpreting data from small animals. Indeed, the safety of subjects has been secured by those data, so many investigators don’t feel urgent necessity of data from big animals except safety pharmacology data and cardiac safety data in dogs. The thought can be extended to pharmacokinetic data since human pharmacokinetics can’t be predicted from animal data even from primates. However, investigators of medical institutes belonging to JACIC (Japan Association of Contract Institutes for Clinical Pharmacology), who perform early clinical trials, reported their interest in nonclinical studies proving efficacy of investigational new drug besides its safety. Pharmacological actions are explored from the level of receptors in cells to biomarkers and biological responses of whole body and investigators may rely on responses in whole body. These responses may be found not only in big animals but in small animals. The point is whether an appropriate model is selected or not. Species of animals may differ according to target diseases. As an investigator in early clinical trials, I’d like to have data from appropriate models which can be extrapolated to human response with explanation of validity of the models. In the workshop, I will show update of the JACIC survey concerning attitudes to nonclinical data in investigators.