Endpoint Matrix: a conceptual tool to promote consideration of the multiple dimensions of humane endpoints

Abstract

Summary This paper proposes a framework to support appropriate application of endpoints in animal experimentsUsing examples of practical tools designed to aid ethical reflection and decision-making (e.g., Lindl et al., 2012;Mepham, 1996;England and Millar, 2008), it is proposed here that there is a need to formally structure the detailed ethical analysis and practical decision-making required in fully embracing this important refinement strategy. Initially, best practice guidance on the application of humane endpoints is discussed. Hendriksen et al. (2011) articulate the complexity of this concept and we extend this work to suggest that there exist several different types of experimental endpoints which are important for the articulation of "humane."We propose that the concept of "unpredicted" should be considered alongside "scientific" and "justifiable" when determining endpoints, with each requiring individual consideration alongside an understanding of their interactions. through the development of an endpoint matrix we provide a format for the consideration of each of these three types of endpoint, suggesting that: a) Each type of endpoint is accurately defined; b) The practical application of each endpoint to the experiment is determined; and c) Information is collected which will allow endpoints to be accurately detected. It is suggested that the further development and use of the endpoint matrix will result in the appropriate selection of the most humane endpoint and should reduce overall animal suffering through more effective use of this refinement strategy.

Statutory Imposed Terms of Stress, Distress, Well-Being and Animal Welfare: Suggested Guidelines for Humane Endpoints in Animal Studies

“…Ashall& Millar [19] have proposed several different types of experimental endpoints which are important for the articulation of "humane".Most laboratories and federal regulators have accepted that the concept of "unpredicted" should be considered alongside "scientific" and "justifiable" when determining critical decision-making endpoints, with each requiring individual consideration alongside an understanding of their interactions. Through the development of an endpoint matrix Ashall& Millar [19] have provided a format for the consideration of each of these three types of endpoints, suggesting that: a) Each type of endpoint is accurately defined;…”

“…Through the development of an endpoint matrix Ashall& Millar [19] have provided a format for the consideration of each of these three types of endpoints, suggesting that: a) Each type of endpoint is accurately defined;…”

“…Unless adverse events can be managed under the clinical guidance of the staff veterinarian that alleviates or mitigates the suffering OR if the scientific endpoint can be achieved well before the identified justifiable endpoint, adverse events might therefore lead to humane intervention before the scientific endpoint is achieved. To address this scenario, Ashall& Millar [19] have proposed a detailed decision matrix that can be used to assist the research team in formulating a response in such situations.…”

Critical evaluation of challenges and future use of animals in experimentation for biomedical research

“…This refinement can thus not only improve the welfare of the animals but might also improve the experimental outcomes. 23 Ashall and Miller 26 have mentioned a perfect way to consider humane endpoints for the study using the endpoint matrix which divides possible humane endpoints into three main categories: scientific endpoints; justifiable endpoints; and unpredicted endpoints. Scientific endpoints are based on the actual outcome achieved after the experiment and hence termination of the study at a given point.…”

The power of automated behavioural homecage technologies in characterizing disease progression in laboratory mice: A review

“…the point where the potential scientific benefits of a study are outweighed by the pain or distress induced, EU, 2010). When severity limits/justifiable humane endpoints are met interventions such as analgesic administration or humane killing can be carried out (EU, 2010;Ashall and Millar, 2014). Scientific humane endpoints refer to criteria that allow early termination of experiments before animals experience significant harm while still meeting the experimental objectives (NC3Rs, 2013;Ashall and Millar, 2014).…”