Nonclinical studies in animals and in in vitro systems are essential steps in the development of a new chemical entity, both to demonstrate actions indicative of efficacy and to examine toxicity as a guide to safety. The scientific basis of prediction and extrapolation are examined, with special references to factors that lead to uncertainty in suggesting potential hazards in man.
CalabreseEJ, Principles of animal extrapolation. Chichester, U.K.: Wiley; 1983.
2.
RoloffMV. Human risk assessment. London: Taylor & Francis; 1987.
3.
TardiffRGRodricksJV. Toxic substances and human risk. New York: Plenum; 1987.
4.
WalkerSRParrishJA. Innovation and new drug development. In WalkerBCWalkerSR, eds. Trends and changes in drug research and development. Dordrecht: Luwer; 1988: 1–28.
5.
LumleyCEWalkerSR. Predictive value of toxicity tests in rodents and non-rodents. Arch Toxicol.1987;S9: 297–305.
6.
SpeirsCJGriffinJR. A survey of the first year of operation of the new procedure affecting the conduct of clinical trials in the United Kingdom. Br J Clin Pharmacol.1983;15: 649–655.
7.
ScheinPSDavisRDCarterSNewmanJScheinDRRallDP. The evaluation of anti-cancer drugs in dogs and monkeys for the prediction of qualitative toxicities in man. Clin Pharmacol Ther.1970;11: 3–40.
