# Exploration of refined humane endpoints for melioidosis in BALB/c mice

## TL;DR

Researchers found a new humane endpoint for melioidosis in mice that reduces suffering without affecting study results.

## Contribution

A refined humane endpoint combining weight loss and clinical signs is proposed for melioidosis research in mice.

## Key findings

- A 25% weight loss threshold and/or clinical score ≥5 over 48 hours reduced median 'sign-days' by 21 days.
- The new endpoint maintained 100% sensitivity and 93% specificity across studies.
- The endpoint did not alter the scientific outcomes of the studies.

## Abstract

The development of humane endpoints is critical for refining scientific studies involving animals. Body weight and clinical signs of disease data collected in four recent studies assessing medical countermeasures for utility against the disease melioidosis in mice were further analyzed. Here we used this information to ascertain whether a suitable alternative humane endpoint could be identified. A total of 66 possible alternative humane endpoints were explored, which varied the threshold values of the ‘percentage body weight loss post-challenge’ and ‘the clinical signs over time’ following cessation of treatment. The findings indicated a suitable alternative endpoint of a percentage weight loss threshold of 25%, and/or using an average total clinical signs score ≥5 over a 48-h period. This endpoint resulted in a sizeable reduction in median ‘sign-days’ (total clinical score multiplied by the number of days remaining in study) per mouse of 21 days (ranging from 8 to 56 between studies), while maintaining 100% sensitivity and 93% specificity (ranging from 79% to 97% between studies). In addition, the risk of altering the scientific outcome of each study remained low when utilizing this new endpoint. In conclusion, current humane endpoints in this setting can be refined without negatively impacting the key study findings.

The authors analyzed four melioidosis studies in mice to identify refined humane endpoints (25% weight loss and/or clinical score ≥5) that improve animal welfare while maintaining study integrity.