FRAME is calling for more collaboration between alternatives organisations and the pharmaceutical industry following publication of a new investigation of preclinical drugs trials using laboratory animals.

Scientific papers covering more than 2,300 substances tested on rats, mice and rabbits were analysed to measure the likelihood ratio that chemicals showing no adverse reactions would behave the same way in humans.

The paper, published in FRAME's scientific journal ATLA, says: "The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of continued animal use. Our results for these additional preclinical species have important implications for their use in predicting human toxicity, and suggest that alternative methods are urgently required."

The work was carried out by the same team who investigated the use of dogs in human drugs tests last year, and they concluded that animal results are extremely inconsistent.

Director of the FRAME Alternatives Laboratory Dr Andrew Bennett says the paper highlights the need for more relevant, more valid, non-animal tests, but believes they can only be found if all those involved work together to look for them.

"Toxicity data from animal studies can be seriously misleading but it is no good just saying that animal tests don't work - we have to find methods that can identify potential risks and benefits.

"There are major issues for companies in the pharmaceutical sector. Large numbers of compounds that appear to have functional activity in animals show little potency in humans, while others that show no adverse reactions in animals later prove harmful in human trials.

"Research and development effort is often wasted because of the poor reliability of animal-based methods. If we are to find useful, safe drugs in the future it is vital that all interested parties work together to find valid, non-animal methods that will identify them", Dr Bennett said.

Preclinical tests require the use of two species, usually one rodent (rat or mouse) and one non-rodent (often dogs) before drugs enter clinical trials in humans. The second species is intended to identify those substances harmful to humans that were missed by the rodent tests.

The latest study is a development of a paper published last year, which showed that use of dogs to test drugs intended for humans gave results that were little better than chance. The latest statistical analysis of results from rats, mice and rabbits supported those findings. This is in part to be expected as drugs now being developed are increasingly aimed at specific human cell responses.

FRAME was established in 1969 to promote the concept of alternatives to laboratory animal use in medical research and toxicity testing. The charity is dedicated to developing and validating alternative methods, and working actively with all interested parties to achieve greater human safety.

The paper, An Analysis of the Use of Animal Models in Predicting Human Toxicology and Drug Safety, was written by Jarrod Bailey and Michelle Thew of the British Union for the Abolition of Vivisection (BUAV) and Michael Balls, FRAME's life president. (Full text attached)

The original project was a joint venture between FRAME, The Kennel Club and the BUAV. It was a study analysing data from more than two thousand published papers where dogs were used to predict toxicity responses in humans.

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