{"title":"Permutation Tests Are a Useful Alternative Approach for Statistical Hypothesis Testing in Small Sample Sizes.","authors":"Theresa Unseld, Lisa Ruckerbauer, Benjamin Mayer","doi":"10.1177/02611929251326882","DOIUrl":"https://doi.org/10.1177/02611929251326882","url":null,"abstract":"<p><p>Results interpretation and statistical analysis of animal study data is challenging, since the sample sizes involved are usually very small. The application of frequently used approaches to statistical hypothesis testing, e.g. <i>t</i>-tests or ANOVA methods, rely on specific distributional assumptions being satisfied. It can be hard to reliably assess these assumptions in animal studies with group sizes of usually less than ten animals. Non-parametric analysis methods might be considered as an alternative, but it is well-known that these approaches have lower statistical power in some situations. Following the Three Rs principles, it would be desirable to apply a class of statistical tests that is able to deal with a small number of observations, without the need for specific distributional assumptions. Thus, in this paper, we assess the application of permutation tests which seem to be able to meet both the above requirements. The performance of these permutation tests was compared with standard statistical tests by means of four real-world data examples from animal studies. The results demonstrated that permutation tests have good computational properties, leading to the conclusion that they could be a useful alternative approach when analysing small sample size animal study data for which distributional assumptions may not hold.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"2611929251326882"},"PeriodicalIF":2.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spotlight on Three Rs Progress.","authors":"","doi":"10.1177/02611929251323970","DOIUrl":"10.1177/02611929251323970","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"67-69"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maneesha Deckha, Margot Michel, David Azilagbetor, Charlotte Blattner, Rosa Maria Cajiga Morales, Gail Davies, Bernice Elger, Sara Faizee, Marie Fox, Vanessa Gerritsen, Adrian Heuss, Laura Kämpfen, Edwin Louis-Maerten, Nicole Lüthi, Aoife Milford, Nico Dario Müller, Kirsten Persson, Merel Ritskes-Hoitinga, Barbara Rothen-Rutishauser, Andreas Rüttimann, Katerina Stoykova, Saskia Stucki, Miriam A Zemanova
{"title":"Accelerating Animal Replacement: How Universities Can Lead - Results of a One-Day Expert Workshop in Zurich, Switzerland.","authors":"Maneesha Deckha, Margot Michel, David Azilagbetor, Charlotte Blattner, Rosa Maria Cajiga Morales, Gail Davies, Bernice Elger, Sara Faizee, Marie Fox, Vanessa Gerritsen, Adrian Heuss, Laura Kämpfen, Edwin Louis-Maerten, Nicole Lüthi, Aoife Milford, Nico Dario Müller, Kirsten Persson, Merel Ritskes-Hoitinga, Barbara Rothen-Rutishauser, Andreas Rüttimann, Katerina Stoykova, Saskia Stucki, Miriam A Zemanova","doi":"10.1177/02611929251317434","DOIUrl":"https://doi.org/10.1177/02611929251317434","url":null,"abstract":"<p><p>This report is a result of an interdisciplinary workshop held at the Collegium Helveticum in Zurich, Switzerland in February 2024, in which ideas for accelerating NAMs (New Approach Methodologies) in Swiss universities were shared and discussed. Due to regional differences in university organisation and funding structures, not all recommendations will be transferable to all regions worldwide. All participants were qualified to contribute to the discussion, due to their knowledge and experience of the Three Rs, in particular with regard to their implementation. The workshop participants believed that universities, which play a pioneering role in so many other areas, should also exploit their innovative potential in the field of animal-free research. The workshop uncovered four areas that would need to be addressed in order to achieve a significant change in university science culture and do more justice to the Three Rs, namely: language - innovative framing (pro-replacement framing in official university statements); knowledge transfer - communicating innovative findings in teaching (redirecting curriculum); change of values within science faculties; and structured implementation and well-coordinated planning of the transformation (establishment of a 'transition unit'). Specific strategies for implementing these four areas are outlined. In addition, we discuss why the replacement of animal testing should be an essential goal for universities, why this goal has not yet been achieved, and why concerted efforts toward change are required.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"53 2","pages":"106-118"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial.","authors":"Judith C Madden","doi":"10.1177/02611929251325009","DOIUrl":"10.1177/02611929251325009","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"65-66"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Implementing the EURL ECVAM Recommendation on Non-Animal-Derived Antibodies in One EU Member State - Denmark.","authors":"Bente Lakjer, Rosemary Goddard Svendsen","doi":"10.1177/02611929251324520","DOIUrl":"10.1177/02611929251324520","url":null,"abstract":"<p><p>In 2020, the EU Commission's Joint Research Centre published the <i>EURL ECVAM Recommendation on Non-Animal-Derived Antibodies</i>. In advance of the publication of this EURL ECVAM Recommendation, Landsforeningen Forsøgsdyrenes Værn arranged for an expert presentation on non-animal-derived antibodies to the Animal Experimentation Council, which is the body responsible for the review and approval of projects involving animals in Denmark. The main concerns of Council Members following the presentation were the widespread unfamiliarity with phage display methodology in Denmark, and how it would be possible to adapt licensing decisions. Before deciding how to approach the implementation of the Recommendation, the animal experimentation authority Dyreforsøgstilsynet, of which the Animal Experimentation Council and its secretariat are part, probed the wider scientific community and requested an opinion from the National Committee on Laboratory Animals and Alternatives. Wider scientific opinion in Denmark spanned those who were, to a certain extent, positive toward the non-animal methodology and those who were sceptical. Consequently, the approach chosen by the Danish authority is to encourage and monitor the uptake of non-animal methods, while allowing time for adjustment. Change has been slow, but the seeds of change are sown.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"98-105"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph Henriquez, Matthew Merrell, Carey Mathesius, Raja Settivari, Lynea Murphy, Susan Kisielewski, Jessica LaRocca, Kathleen Mikles, Sean Gehen
{"title":"An Approach to Setting Vertebrate Animal-use Benchmarks for Agrochemical and GM Crop Testing to Facilitate Future Animal Reduction Efforts.","authors":"Joseph Henriquez, Matthew Merrell, Carey Mathesius, Raja Settivari, Lynea Murphy, Susan Kisielewski, Jessica LaRocca, Kathleen Mikles, Sean Gehen","doi":"10.1177/02611929251323270","DOIUrl":"10.1177/02611929251323270","url":null,"abstract":"<p><p>Agrochemical active ingredients are among the most toxicologically evaluated chemical substances, and genetically modified (GM) crops must be evaluated for safety and nutritional adequacy. Traditionally, these evaluations are conducted <i>in vivo.</i> There are concerted efforts in the agrochemical sector to reduce animal testing, but there is also an emphasis on updating test guidelines and fulfilling new data package requirements, which can both result in increased animal testing. The purpose of this project was to generate benchmarks for the numbers of vertebrate animals used in: a) evaluating agrochemical pesticidal active ingredients for human health hazards; and b) assessing GM crops for safety and nutritional adequacy, based on guideline studies for data package requirements. To achieve this, guideline studies employing vertebrates, as required by regulatory bodies for developing global data packages for new active ingredients and for GM crops, were listed. These listed guideline studies were reviewed, in terms of the study details and the required animal-use, which was determined based on best testing practices. For historical animal-use benchmarking, Corteva's six most recent agrochemical pesticidal active ingredients and four most recent GM crop events were evaluated. Across the six most recently developed active ingredients, an average of approximately 10,000 mammals were used for the testing of each (range: 5500-19,000); across the four most recently developed GM crops, the average number of vertebrates similarly used for each was approximately 1200 (range: 1000-1500). Though regulatory testing requirements are likely to change with time, as new technologies become available, this project has established a theoretical minimum requirement to help drive aspirational animal reduction goals, identified regulatory challenges associated with the reduction of animal-use, and helped to refine Corteva's vertebrate animal-use tracking approaches.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"84-97"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reviewing Current Guidance for the 'R' of Replacement and Rethinking it with the 'Replacement Checklist'.","authors":"Juliet P Dukes, Amy Beale, Celean Camp","doi":"10.1177/02611929251319265","DOIUrl":"10.1177/02611929251319265","url":null,"abstract":"<p><p>Research involving the use of animals follows the Three Rs principles of <i>replacement</i>, <i>reduction</i> and <i>refinement</i>. Based on the principle of <i>replacement</i>, UK and EU legislation requires that technologies or alternative approaches directly replacing or avoiding the use of animals in experiments must be used wherever scientifically possible. However, <i>replacement</i> is often not thoroughly considered, and failures in the existing system of checks and balances are widespread. Existing guidance and advice on searching for and identifying alternative approaches and replacement techniques is confusing and misleading, and this contributes to the lack of knowledge and confidence in addressing <i>replacement</i> and the structural and procedural barriers around it. In this paper, we propose simple improvements to existing processes and a basic practical checklist, to help researchers identify and assess scientifically satisfactory replacement approaches. This tool will also support members of funding review panels, Animal Welfare and Ethical Review Bodies (AWERBs), Animal Welfare Bodies (AWBs), Animal Ethics Committees, and those editing and reviewing scientific journals in their scrutiny of applications, applicants and publications - particularly with regard to the use of alternative approaches and how these potential approaches were explored.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"72-83"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to Report of the First ONTOX Hackathon: Hack to Save Lives and Avoid Animal Suffering. The Use of Artificial Intelligence in Toxicology - A Potential Driver for Reducing/Replacing Laboratory Animals in the Future.","authors":"","doi":"10.1177/02611929251322945","DOIUrl":"https://doi.org/10.1177/02611929251322945","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":" ","pages":"2611929251322945"},"PeriodicalIF":2.4,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}