Humane endpoints

Use of humane endpoints in animal experiments describes the setting of clear, predictable and irreversible criteria that allow early termination of the experiments before the animals experience significant harm whilst still meeting the experimental objectives. Some examples of possible criteria include body temperature, body weight, precise clinical signs and blood markers. Suffering may be alleviated by, for example, modifying the experimental design, or treatment or euthanasia of the animals. Thus, for experiments that previously might have used the number of animals dying versus the number surviving as their scientific output, the scientific output becomes the number of animals surviving versus the numbers humanely killed after exhibiting certain clinical signs that reliably suggest that death was inevitable.

Use of humane endpoints is just one manifestation of refinement and, in particular, they are best utilised with prospective planning for their use, not ad hoc to address welfare concerns as they might arise. While humane endpoints should be considered for all experiments involving animals, they are essential in those situations where potential suffering or death may be involved (e.g. acute toxicology, or animal models of infection, cancer or inflammatory disease).

In planning experiments using animals it is important to understand that it is not always necessary for an animal model to share all properties of a disease or condition in humans. It may be sufficient that the animal model is similar in some relevant aspects. Thus it may not be necessary to reproduce a condition or effect in every detail (and potential severity) as may be seen in humans. The purpose of the animal model could be to provide sufficient information to determine or produce a valid effect. So, for example, using animals to study arthritis may not actually require chronic painful joint disease to be manifested, just an increase or decrease in urinary cartilage breakdown products to be measured. The humane and the scientific endpoint thus become, in this example, the changes seen in cartilage breakdown products. These effects could be regarded as indirect, or surrogate, humane endpoints, as they occur prior to any observable suffering or clinical manifestation of the condition.

In using humane endpoints it is important that they are scientifically valid, predictive and accurate. In this context, an example of an accurate endpoint in an arthritis study would be one, or several, that reliably demonstrates at an earlier stage the more severe pathology that would appear later if the condition progressed. In some circumstances pilot studies using small numbers of animals may be necessary to determine the onset and progress of adverse effects and identify early scientific and humane endpoints. For an endpoint to be predictive it must be clear that the adverse effect seen in the animal is a direct effect of the experimental challenge and not, for example, because of some general malaise or secondary affect due to technique. Validation and monitoring of other parameters are required to ensure robust predictivity of the endpoint and minimal interference with scientific objectives.

In designing an experiment and considering humane endpoints the scientist should:

• Consider, at the planning stage, the experimental result they wish to achieve and what might be the earliest observable indicators of that effect prior to observable signs of animal suffering
• Develop specific endpoints for each experiment, after consulting general references on humane endpoints (see the Resources Panel) and any specific references within them relevant to the study being planned
• Consult existing literature related specifically to the particular research protocols, other scientists experienced in the area, and veterinary surgeons (e.g. NVS) and animal welfare officers (e.g. NACWO), to ascertain likely adverse effects and clinical signs
• Work with veterinary surgeons and animal welfare officers to place these adverse effects and clinical signs in their context of severity on the animal (see FELASA 1994)
• Balance the scientific outputs of the project with the minimum of adverse effects on the animal and its clinical signs, and so define the planned humane scientific endpoints
• Apply, monitor and record use of, humane endpoints during the experiment, review and change as required, and include all this information when publishing the results of the study
• Ensure appropriate training and competencies for all those engaged in monitoring animals for signs of adverse effects and implementing humane endpoints