Refinement Alternatives

Humane Endpoints

What is a humane endpoint?

The term "humane endpoint" refers to the point at which an experimental animal's pain and/or distress is terminated, minimized or decreased by taking actions such as killing the animal humanely, terminating a painful procedure or giving treatment to relieve pain and/or distress. Therefore, using humane endpoints in animal experiments or testing provides an alternative to the use of more severe signs of animal pain and distress, including death, and contributes to refinement.

Implementation of a humane endpoint in a scientific study should ensure that the scientific goal of the study is reached while minimizing the impact for the animal. While humane endpoints should be considered for all experiments involving animals, they are essential in those situations with a strong potential for pain and distress (e.g., acute toxicology, or animal models of infection, cancer or inflammatory disease).

Humane endpoints are best established prior to the commencement of a study; they should not be negotiated during a study either to meet "new" scientific aims or to address welfare concerns as they arise.

Selecting a humane endpoint

A moribund animal is one that is close to death and may be unresponsive to stimuli, exhibit dyspnea (breathlessness), hypothermia, prostration, etc. However, before the animal gets to the point of being moribund, detailed observations of the animal can help to set an earlier experimental endpoint, and thereby decrease the pain and/or distress to the animal. In designing an experiment and considering humane endpoints, investigators should:

  • consider the experimental result they wish to achieve and what might be the earliest observable indicators of that effect prior to observable signs of animal pain and/or distress, keeping in mind that a moribund state will also invariably affect scientific results;
  • consider that it may not be necessary to reproduce a condition or effect in every detail (and potential severity) as may be seen in humans (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 excretion of cartilage breakdown products to be measured);
  • develop specific endpoints for each experiment after consulting references on humane endpoints and a clinical veterinarian, to ascertain likely adverse effects and clinical signs;
  • make appropriate observations of the animals (behaviour, physiology, etc.) to determine which are the most significant indicators of pain and/or distress in the specific circumstances of the research;
  • determine which observations are the most significant predictors of further deterioration in the animal's condition, and identify the earliest point at which those signs appear more frequent observations may be necessary at first to determine a definitive schedule;
  • apply, monitor and record the use of humane endpoints during the experiment these should be reviewed and changed in consultation with the veterinarian and ACC;
  • use pilot studies using small numbers of animals when necessary to determine the onset and progress of adverse effects and identify early scientific and humane endpoints;
  • include all information about humane endpoints used when publishing the results of the study; and
  • ensure appropriate training and competencies for all those engaged in monitoring animals for signs of adverse effects.

Humane endpoint score sheets

The use of observational checklists or score sheets for scoring the animal's condition in a study provides an objective basis on which decisions about endpoints can be made. The advantages of score sheets are that specific observations are not overlooked or taken for granted. In addition, such score sheets help improve observational skills, particularly with the smaller laboratory animals where some of the conventional clinical observations made on larger animals are not readily determined (e.g., temperature, heart rate and respiratory rate). However, score sheets do not cover all abnormalities or observations, and thus are only a useful way to record certain findings. They cannot replace a thorough examination of the animal.

(This section has been adapted from the NC3Rs website and CCAC guidelines)

For more information on humane endpoints, the following resources may be useful:

CCAC resources
Online resources

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