Where are we heading? Challenges in evidence-based severity assessment

Keubler, Lydia M.; Hoppe, Nils; Potschka, Heidrun; Talbot, Steven R.; Vollmar, Brigitte; Zechner, Dietmar; Häger, Christine; Bleich, André

doi:10.1177/0023677219877216

Cited by 29 publications

(51 citation statements)

References 95 publications

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“…This takes into account the multidimensional nature of severity, reflecting not only pain and distress but also affective emotional states. Therefore, the chosen parameters for severity assessment should be multimodal 30 . This concept is supported by growing evidence in the literature.…”

Section: Discussionmentioning

confidence: 99%

“…To exclude selection bias, we calculated the models’ severity level with a full set of available variables: body weight change, burrowing behavior, MGS score and telemetry-derived parameters including hr, hrv and temperature. These parameters were selected based on increasing evidence of their suitability in various model systems as well as several round-table discussions within our German Research Foundation (DFG)-funded research consortium 2591, which focuses on severity assessment in animal-based research (www.severity-assessment.de) 7,8,31 .…”

Section: Discussionmentioning

confidence: 99%

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One score to rule them all: severity assessment in laboratory mice

Talbot

Struve

Wassermann

et al. 2020

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18Animal welfare and the refinement of experimental procedures are fundamental aspects of 19 biomedical research. They provide the basis for robust experimental designs and reproducibility of 20 results. In many countries, the determination of welfare is a mandatory legal requirement and 21 implies the assessment of the degree of the severity that an animal experiences during an 22 experiment. However, for an effective severity assessment, an objective and exact 23 approach/system/strategy is needed. In light of these demands, we have developed the Relative 24 Severity Assessment (RELSA) score. 25 This comprehensive composite score was established on the basis of physiological and behavioral 26 data from a surgical mouse study. Body weight, the Mouse Grimace Scale score, burrowing behavior, 27 and the telemetry-derived parameters heart rate, heart rate variability, temperature, and general 28 activity were used to investigate the quality of indicating severity during postoperative recovery. The 29 RELSA scores not only revealed individual severity levels but also allowed a comparison of severity in 30 distinct mouse models addressing colitis, sepsis, and restraint stress using a k-means clustering 31 approach with the maximum achieved RELSA scores. 32We discriminated and classified data from sepsis nonsurvivors into the highest relative severity level. 33Data from mice after intraperitoneal transmitter implantation and sepsis survivor al were located in 34 the next lower cluster, while data from mice subjected to colitis and restraint stress were placed in 35 the lowest severity cluster. Analysis of individual variables and their combinations revealed model-36and time-dependent contributions to severity levels. 37In conclusion, we propose the RELSA score as a validated tool for objective real-time applicability in 38 severity assessment and as a first step towards a unified and accessible risk assessment tool in 39 biomedical research. As an effective severity assessment system, it will fundamentally improve 40 animal welfare, as well as data quality and reproducibility. 41Laboratory Animals 3 or the European Directive on the protection of animals used for scientific 48 purposes 4 . Animal welfare describes a status of high quality of life, which relies on the consideration 49 and promotion of things to achieve good animal welfare 5,6 . Its assessment requires the monitoring of 50 animal affective states with both positive and negative valance 7 . The term severity assessment more 51 specifically addresses the categorization of negative affective states of animals under experimental 52 conditions; however, both the promotion of welfare and assessment of severity aim at the 53 recognition of any sign of suffering and thereby are essential for possible interventions to relieve the 54 burden during experiments and promote the refinement of procedures. Nevertheless, to achieve 55 compliance with scientific and regulatory requirements, an exact, evidence-based severity 56 assessment and the classification of severity ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

One score to rule them all: severity assessment in laboratory mice

Talbot

Struve

Wassermann

et al. 2020

Preprint

Self Cite

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“…scientific-political relevance [2,9,[25][26][27]. Transparent communication about animal-based research should ideally be based on reliable and solid assessment of the burden associated with experimental models and interventions.…”

Section: Plos Onementioning

confidence: 99%

“…Thus, evidence-based severity assessment in neuroscience research requires tailored and sensitive approaches developed to provide comprehensive information about behavioral, biochemical, and/or physiological parameters, which reflect distress or an altered emotional state of the animals. On the other hand, classification of severity needs to meet requirements of practicability and feasibility for the daily management of animal facilities [9].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, approaches for the selection of appropriate and informative evidence-based severity assessment parameters and for the development of composite measure schemes are urgently needed [9]. Focusing on animal models with induced or spontaneous seizures, we provide an example of an approach starting with a large set of candidate parameters assessed in different models and a selection process based on multivariate statistical analyses.…”

Section: Introductionmentioning

confidence: 99%

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Design of composite measure schemes for comparative severity assessment in animal-based neuroscience research: A case study focussed on rat epilepsy models

et al. 2020

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Comparative severity assessment of animal models and experimental interventions is of utmost relevance for harm-benefit analysis during ethical evaluation, an animal welfarebased model prioritization as well as the validation of refinement measures. Unfortunately, there is a lack of evidence-based approaches to grade an animal's burden in a sensitive, robust, precise, and objective manner. Particular challenges need to be considered in the

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