What are humane endpoints?
A humane endpoint can be defined as:
‘the earliest indicator in an animal experiment of (potential) pain and/or distress that, within the context of moral justification and scientific endpoints to be met, can be used to avoid or limit pain and/or distress by taking actions such as humane killing or terminating or alleviating the pain and distress’ (Hendriksen and Morton, 1999).
Some elements of this definition can be further explained as follows:
- ‘….potential pain….’ (Hendriksen): indicates that also non-clinical endpoints might be used e.g. pre-clinical parameters such as hormone level changes, biochemical parameters or gene up/down regulations as an indicator for pain/distress later on in the disease process or even physiological parameters such as induction of antibody titres.
- ‘…within the context of the scientific endpoints….” (Wallace, Hendriksen): applying humane endpoints should always be balanced against the scientific endpoint(s).
- ‘….taking actions such as…’ (CCAC, Hendriksen): alleviation of pain/distress or terminating the painful/stressful procedure are also considered to be a humane endpoint.
The following conclusions can be drawn from this definition. A humane endpoint :
- Not necessarily means the humane killing of the animal, but could also result in interventions to alleviate the stressful/painful experimental procedure (e.g. performing surgery) or providing analgesics.
- Is not necessarily based on clinical signs but could also start from pre-clinical signs or from physiological or molecular biomarkers predictive of pain/distress later on in the disease process.
- Should be balanced against the scientific endpoints to be met. Thus, pain and distress might be intrinsic to a certain experimental model (e.g. arthritis). However, in this case the humane endpoint should never be beyond the scientific endpoint.
- Should never be beyond the level of moral justification.
A humane endpoint can be considered as a possible refinement alternative for those experiments that involve pain and discomfort to the animals. In the Netherlands annually about 2,7 percent of all animals used in research experience more than ‘moderate/severe’ (Zo Doende 2014, an annual report of the Netherlands Food and Consumer Product Safety Authority, only in Dutch).
Biomedical research areas with relatively high percentages of pain and distress are cancer research, toxicity studies, vaccine potency studies, infectious disease studies and autoimmune disease studies.
Applying humane endpoints should seriously be considered when animal experiments involve severe pain and suffering.
Above the mentioned definition, several other definitions are being used to describe a humane endpoint, like for example the following glostest of the OECD, the CCAC and Wallace:
- The earliest indicator in an animal of pain, distress, suffering, or impending death on the basis of which an animal is killed (definition OECD);
- “The point at which an experimental animal's pain and/or distress is terminated, minimized or reduced, by taking actions such as killing the animal humanely, terminating a painful procedure, or giving treatment to relieve pain and/or distress” (definition CCAC).
- 'The limits placed on the amount of pain and distress any laboratory animal will be allowed to experience within the context of the scientific endpoints to be met’ (Wallace 2000)