Effects of the introduction of in vitro assays on the use of experimental animals in pharmacological research.
The introduction of in vitro assays in pharmacological research has led to a reduction in the number of experimental animals used. But what has been the degree of this reduction, and when did it really start? This report describes the events in a medium-sized pharmaceutical company. Analysis of data collected over the last 12 years shows a five-fold reduction in the number of experimental animals used per compound synthesised. Compounds from compound libraries (large collections of randomly-synthesised molecules) that are being assessed for potential bioactivity in 'high-throughput screening' were not included in this analysis. Over the years, the (average) degree of discomfort for the animals in the experiments did not vary much; with variation generally observed from 1.5 to 2.0 (on a scale from 1-6). There was a peak in the discomfort score of experimental mice in 1997, which could be explained by the initiation of arthritis models that were subsequently refined, resulting in a lower degree of suffering. It might be concluded that the introduction of in vitro assays has indeed brought about a significant reduction in the number of experimental animals required to select a good compound (i.e. one that could progress to the preclinical toxicology phase). However, this development appears to have been neutralised by the low survival rate of new chemical entities in clinical studies, leading to a lower number of compounds per annum that actually reach the market place. Put in this 'productivity perspective', the number of experimental animals required to select a marketable drug has not much changed in the last decade.
Verbost
Pieter M
PM
Department of Pharmacology, Organon, Oss, The Netherlands. pieter.verbost@organon.com
van der Valk
Jan
J
Hendriksen
Coenraad F M
CF
D032761:Animal Experimentation / Q000706:statistics & numerical data*; D000826:Animal Testing Alternatives / Q000639:trends*; D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000639:trends*; D004345:Drug Industry / Q000706:statistics & numerical data / Q000639:trends*; D006168:Guinea Pigs; D051379:Mice; D011817:Rabbits; D051381:Rats