An Analysis of the Use of Animal Models in Predicting Human Toxicology and Drug Safety

Jarrod Bailey, Michelle Thew and Michael Balls

Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse and rabbit), to augment our previously-published analysis of canine data. In common with our dog analysis, the resulting LRs show: a) that the absence of toxicity in the animal provides little or virtually no evidential weight that adverse drug reactions (ADRs) will also be absent in humans; and b) that, while the presence of toxicity in these species can add considerable evidential weight for human risk, the LRs are extremely inconsistent, varying by over two orders of magnitude for different classes of compounds and their effects. Therefore, 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.

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Strategies for the Reduction of Live Animal Use in Microsurgical Training and Education

Harald Schöffl, Stefan M. Froschauer, Karin M. Dunst, Dietmar Hager, Oskar Kwasny and Georg M. Huemer

Education and training in microsurgical techniques have historically relied on the use of live animal models. Due to an increase in the numbers of microsurgical operations in recent times, the number of trainees in this highly-specialised surgical field has continued to grow. However, strict legislation, greater public awareness, and an increasing sensitivity toward the ethical aspects of scientific research and medical education, emphatically demand a significant reduction in the numbers of animals used in surgical and academic education. Hence, a growing number of articles are reporting on the use of alternatives to live animals in microsurgical education and training. In this review, we report on the current trends in the development and use of microsurgical training models, and on their potential to reduce the number of live animals used for this purpose. We also share our experiences in this field, resulting from our performance of numerous microsurgical courses each year, over more than ten years. The porcine heart, in microvascular surgery training, and the fresh chicken leg, in microneurosurgical and microvascular surgery training, are excellent models for the teaching of basic techniques to the microsurgical novice. Depending on the selected level of expertise of the trainee, these alternative models are capable of reducing the numbers of live animals used by 80–100%. For an even more enhanced, “closer-to-real-life” scenario, these non-animated vessels can be perfused by a pulsatile pump. Thus, it is currently possible to provide excellent and in-depth training in microsurgical techniques, even when the number of live animals used is reduced to a minimum. With these new and innovative techniques, trainees are able to learn and prepare themselves for the clinical situation, with the sacrifice of considerably fewer laboratory animals than would have occurred previously.
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“I’m Not Going to Make a Song and Dance about It…”

Jon Richmond

Having been involved with the biomedical sciences and alternatives for 30 of the 50 years since Russell and Burch published The Principles of Humane Experimental Technique, I feel well placed to speak of the contributions made by FRAME over the last 40 years. FRAME has promoted the development and use of alternatives by presenting the “better science” arguments to scientists, promoting informed discussion, changing opinions and changing behaviours. FRAME has also contributed constructively to the political debate, and was instrumental in promoting legislation which incorporated the principles of the Three Rs. Times are changing, and the Three Rs are increasing being politicised: and FRAME is particularly well placed to ensure that good science and good welfare, rather than ideology, remain the basis for interest in and progress with the Three Rs.
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