Development and validation

Careful planning and implementation of humane endpoints requires a certain measure of expertise. Prior to the start of the experiment, its course must be anticipated and a decision about when to implement a humane endpoint must be reached.

The exact time of the endpoint is dependent on the objective of the experiment, but it should be chosen before the onset of distress or as soon as possible thereafter. Preferably, the endpoint is chosen on the basis of objective criteria. The remarks relating to moral and scientific considerations for humane endpoints, listed in the paragraph Why humane endpoints should be kept in mind.

Before having identified the relevant endpoint, the following aspects have to be dealt with:

• an analysis of test on critical steps in terms of pain and distress;
• identification and evaluation of potential endpoints;
• validation of selected endpoints;
• acceptance of the selected endpoints by users (e.g. principle investigators or, in case of regulatory tests; the relevant authorities).

Dependent of the experiment the endpoints (ideally) satisfy the following criteria:

• easy to monitor;
• reproducible;
• not labor-intensive;
• valid prediction of disease progression;
• relevant (equivalent) and robust (little variation);
• maximal reduction of pain and discomfort.

In practical terms, the following three steps must be taken to arrive at suitable humane endpoints:

1. objective definition and registration of signs of pain and distress in the experiment;
2. selection based on the significance of these signs;
3. assurance of the scientific validity (satisfies to a large degree the above criteria).