In the UK, laboratory-housed dogs are primarily used as a non-rodent species in the safety testing of new medicines and other chemical entities. The use of animals in research is governed by the Animals (Scientific Procedures) Act (1986, amended 2012) and legislation is underpinned by the principles of humane experimental technique: Replacement, Reduction and Refinement. A link between animal welfare and the quality of data produced has been shown in other species (e.g. rodents, nonhuman primates), however, no established, integrated methodology for identifying or monitoring welfare and quality of data output previously existed in the laboratory-housed dog. In order to investigate the effects of planned Refinements to various aspects of husbandry and regulated procedures, this project sought to integrate behavioural, physiological and other measures (e.g. cognitive bias, mechanical pressure threshold) and to provide a means for staff to monitor welfare whilst also establishing the relationship between welfare and quality of data output. Affective state was identified using an established method of cognitive bias testing, before measuring welfare at ‘baseline’ using measures of behaviour and physiology. Dogs then underwent ‘positive’ and ‘negative’ behavioural challenges to identify the measures most sensitive to changing welfare and most suitable for use in a framework. The resulting Welfare Assessment Framework, developed in three groups of dogs from contrasting backgrounds within the facility, found a consistent pattern of behaviour, cardiovascular function, affect and mechanical pressure threshold (MPT). Dogs with a negative affective state had higher blood pressure at baseline than those with positive affective states, and the magnitude of the effect of negative welfare suggests that welfare may act as a confound in the interpretation of cardiovascular data. The responses to restraint included increases in blood pressure and heart rate measures which approached ceiling levels, potentially reducing the sensitivity of measurement. If maintained over time this response could potentially have a negative health impact on other organ systems and affecting the data obtained from those. Dogs with a negative welfare state also had a lower mechanical pressure threshold, meaning they potentially experienced greater stimulation from unpleasant physical stimuli. Taken together with the behaviours associated with a negative welfare state (predominantly vigilant or stereotypic behaviours) the data suggest that dogs with a negative welfare state have a greater behavioural and physiological response to stimuli in their environment; as such, data obtained from their use is different from that obtained from dogs with a positive welfare state. This was confirmed by examining the effect size (Cohen’s d ) resulting from the analysis of affective state on cardiovascular data. An increase in variance, particularly in the small dog numbers typical of safety assessment studies, means a reduction in the power of the study to detect the effect under observation; a decrease in variation has the potential to reduce the number of dogs use, in line with the principle of Reduction and good scientific practice. The development of the framework also identified areas of the laboratory environment suitable for Refinement (e.g. restriction to single-housing and restraint) and other easily-implemented Refinements (e.g. feeding toy and human interaction) which could be used to improve welfare. As a result of this, a Welfare Monitoring Tool (WMT) in the form of a tick sheet was developed for technical and scientific staff to identify those dogs at risk of reduced welfare and producing poor quality data, as well as to monitor the effects of Refinements to protocols. Oral gavage is a common regulated procedure, known to be potentially aversive and was identified as an area in need of Refinement. A program of desensitisation and positive reinforcement training was implemented in a study also comparing the effects of a sham dose condition versus a control, no-training, condition. A number of the measures used, including home pen behaviour, behaviour during dosing, MPT and the WMT showed significant benefits to the dogs in the Refined condition. Conversely, dogs in the sham dose condition showed more signs of distress and took longer to dose than dogs in the control condition. The welfare of control dogs was intermediate to sham dose and Refined protocol dogs. This project identified a positive relationship between positive welfare and higher quality of data output. It developed and validated a practical and feasible means of measuring welfare in the laboratory environment in the Welfare Assessment Framework, identified areas in need of Refinement and developed practical ways to implement such Refinements to husbandry and regulated procedures. As such it should have wide implications for the pharmaceutical industry and other users of dogs in scientific research.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:629016 |
| Date | January 2014 |
| Creators | Hall, Laura E. |
| Contributors | Buchanan-Smith, Hannah M.; Robinson, Sally; Caldwell, Christine |
| Publisher | University of Stirling |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1893/21156 |
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