The 2024 revision of the World Medical Association’s Declaration of Helsinki requires that medical research involving human participants be scientifically sound, capable of generating reliable and valid knowledge, and designed to avoid research waste. Because the Declaration also requires that human research be based on preclinical evidence, the quality of the preclinical evidence used to justify clinical studies is fundamental to its ethical framework. However, substantial evidence indicates that preclinical animal research frequently suffers from poor methodological quality, publication and reporting bias, limited reproducibility and poor translation to human health. These shortcomings can result in a preclinical evidence base that is unreliable, insufficiently predictive, or of limited relevance to humans, thereby undermining assessments of scientific validity and risk–benefit that underpin decisions to initiate human studies. Within the broader framework of biomedical research waste, avoidable deficiencies in research prioritisation, design, conduct, reporting and translation also result in the unnecessary use of animals, financial resources and scientific effort. We therefore argue that the Declaration should more explicitly require that decisions to initiate human research be supported by a reliable, valid and relevant preclinical evidence base. Strengthening this requirement would improve the protection of research participants, while creating incentives to reduce avoidable animal research waste. We further argue that the World Medical Association’s Statement on Animal Use in Biomedical Research should be revised in parallel, to explicitly recognise animal research waste as an ethical and scientific concern, and to promote scientifically robust and ethically justified preclinical research.
Computed tomography angiography (CTA) is critical for evaluating abdominal diseases in veterinary patients. However, mastering bolus tracking remains a challenge for novice trainees, due to its steep learning curve and narrow temporal window. We evaluated the effectiveness of a 3D-printed canine hepatic artery phantom as a simulator-based training tool to improve technical proficiency in CT bolus tracking. The phantom was integrated into a closed-loop circuit with a peristaltic pump to replicate physiologic contrast kinetics. Eighteen participants, who were stratified by level of experience (A, experienced; B, intermediate; C, beginner), completed three repeated trials of a standardised bolus tracking protocol. Training efficacy was assessed by using objective timing metrics, and subjective pre- and post-training evaluations and subjective Likert scale-based questionnaires. Total operation time significantly decreased in Groups B and C, while Group A showed a non-significant reduction. Significant improvements in region of interest (ROI) placement time were observed across all groups. Furthermore, participants reported significant increases in conceptual understanding, procedural confidence and anatomical recognition. Use of the 3D-printed canine hepatic artery phantom is a feasible ethical alternative to the use of animals for such training purposes, effectively standardising technical proficiency in veterinary radiology. The study findings support the integration of high-fidelity phantom use into veterinary radiology curricula, to bridge the gap between theory and clinical practice.
Korea has published an annual national census of laboratory animal use since 2008, but whether growth in the level of oversight reflects progress on the Three Rs ( replacement , reduction , refinement ), and how Korea compares internationally in these respects, is unclear. In order to investigate this further, six years of Animal and Plant Quarantine Agency (APQA) census data (2019–2024 inclusive), supplemented by press releases where primary reports were incomplete, were analysed descriptively (with data gaps clearly marked). The analysis showed that total animal use rose by 23.8%. Animal use in the most severe pain/distress category (Grade E) increased every year, from 40.1% to 51.5% of total animal use (2019 versus 2024). This opposes declining trends in the EU, Great Britain and Canada, in terms of implementing refinement strategies that shift the animal use into a less severe category. Quality control (QC) testing was already dominant in 2019 (65.8% of regulatory testing) and reached 70.3% in 2024; for 2023–2024, this type of testing was 98.0–98.3% rodent-based, despite the availability of validated in vitro alternatives. An apparent decline in efficacy testing reflects normalisation after the COVID-19 surge, rather than a sustained reduction. Korea’s proportion of animal use in the highest-severity category (51.5%; 2,364,100 animals in 2024) is markedly greater than Great Britain’s (3.4%; 48,224 in 2024), Canada’s (2.6%; 98,441 in 2024) or the EU’s (8.5%; 784,048 in 2022), despite a broadly comparable reporting scope (which far exceeds the USA’s or Japan’s incomplete reporting). The analysis revealed that growth in the comprehensive recording of animal use in Korea has not been matched by progress on refinement , reduction or replacement . Current priorities are identified as: enacting pending legislation on the use of alternative methods; and incentivising the adoption of species-specific approaches, particularly for rodent-based QC assays.
The Institute for In Vitro Sciences (IIVS) has sponsored a series of workshops with the aim of developing recommendations for scientific and technical approaches to conducting in vitro assays to assess potential toxicity within and across tobacco and nicotine products. As well as providing a background overview of oral tobacco and nicotine products, this report focuses on the methods used to generate extracts from these products for in vitro testing, the recommended best testing practices, and suggested areas for future research. This publication was developed by a working group of workshop members, in conjunction with the ninth IIVS in vitro workshop entitled 'In Vitro Models for Testing Oral Tobacco and Nicotine Products and Continued Discussion of In Vitro Models of Toxicity and Disease', which was held in January 2024.
The development of antidepressants has traditionally relied on vertebrate models. Drosophila melanogaster offers a promising alternative approach, yet evidence of antidepressant-like effects is fragmented. The aim of this systematic review was to analyse the literature on the effects of antidepressants on D. melanogaster behaviours. A comprehensive search of a number of bibliographic databases (i.e. PubMed, Web of Science, Scopus and EMBASE) was followed by a further screening of the retrieved articles (i.e. inclusion of studies on any D. melanogaster strain, sex, age, dose or outcome, tested in any behavioural assay; exclusion of reviews, studies on co-treatments and/or on non-prototypical antidepressants, and studies lacking control groups). This resulted in the final selection of 12 articles, comprising 146 studies. Most studies involved adult flies (k = 131), males (k = 56), fluoxetine treatment (k = 109) and courtship outcomes (k = 85). Some studies involved larvae (k = 15), females (k = 39), treatment with other antidepressants (citalopram, k = 12; desipramine, k = 6; amitriptyline, k = 2; imipramine, k = 2) and other outcomes (locomotion, k = 11; sucrose preference, k = 5; light preference, k = 2; aggression, k = 2; climbing, k = 1). Studies on larvae had, on average, larger sample sizes than studies on adult flies, resulting in more conclusive effect sizes. The effect sizes indicated that most studies presented inconclusive effects. However, sucrose preference, courtship and light preference were outcomes with conclusive findings, depending on the conditions (sex, treatment, stress), and thus these may represent more reliable indicators of antidepressant effects. However, the lack of consistency among studies precluded drawing any definitive conclusions on reliable indicators. In addition, incomplete reporting precluded an accurate risk-of-bias assessment. These findings highlight the need for standardisation and transparent reporting, in order to establish flies as a reproducible, ethically acceptable alternative to vertebrates in antidepressant research.
