From animal welfare, ethical and often scientific aspects, avoidance of mortality is the ideal for which to strive. However, in practice, animals can die in the laboratory (as opposed to being humanely killed to implement humane endpoints or at the end of a procedure). For example, many commonly used mouse strains have a background incidence of morbidity and mortality, and the sheer numbers in which many strains are housed make it unfortunately inevitable that a number will be ‘found dead’. The essential question to ask is to what extent mortality can be prevented, for example by:
- working to improve predictors of death within procedures so that humane endpoints can be refined,
- identifying predictors of background morbidity or mortality (unconnected with procedures), so that these can be better foreseen within day to day monitoring protocols, or
- challenging regulatory requirements for death or morbidity as an endpoint
Under the EU Directive (PDF 720KB), if animals are ‘found dead’ it is assumed that severity was severe unless there is evidence otherwise. Exceptions can be made in some cases, for example if death is rapid and observed, without signs of suffering, or if prior knowledge of the model or intervention would indicate that suffering was unlikely – but these are likely to be few. The emphasis should be on improving the ability to detect indicators of mortality, and on challenging any assumptions that mortality is ‘inevitable’ or that endpoints cannot be refined. Perceptions about the ability to predict death often change; for example, telemetered body temperature using microchips has greatly improved the ability to predict death in a number of fields. It is good practice for researchers and named persons to keep up with the literature and to identify any new approaches that may be suitable for trialling at the facility.
Death as an endpoint – Directive 2010/63 EU states that ‘Death as the end-point of a procedure shall be avoided as far as possible and replaced by early and humane end-points’. Any perceived or actual regulatory requirements for death as an endpoint should be rigorously examined and critically challenged. For example, the OECD (PDF 160KB) recognises that ‘with increasing knowledge and experience, investigators in animal research will be able to identify more specific, early humane endpoints in the form of clinical signs for impending death or severe pain and distress. This would permit international harmonisation of these humane endpoints.’ Researchers and establishments should challenge regulatory bodies to accept evidence that death can be predicted and accept data obtained from tests in which humane endpoints have been defined and implemented.