PapersFlow Research Brief
Animal testing and alternatives
Research Guide
What is Animal testing and alternatives?
Animal testing and alternatives is a field in health sciences that addresses the conduct, reporting, and ethical standards of animal research studies while developing in vitro methods, cytotoxicity assays, and other approaches to reduce or replace animal use in preclinical testing.
This field encompasses 54,019 works focused on improving animal research through ARRIVE guidelines, ethical considerations, and systematic reviews to enhance reproducibility. Key efforts target challenges in translating animal findings to humans, publication bias, and sample size determination in preclinical studies. In vitro testing and cytotoxicity assays serve as primary alternatives to traditional animal models.
Topic Hierarchy
Research Sub-Topics
ARRIVE Guidelines for Animal Research Reporting
This sub-topic evaluates compliance, updates like ARRIVE 2.0, and impact on reproducibility in preclinical studies. Researchers develop tools for guideline implementation and assessment.
In Vitro Cytotoxicity Assays as Animal Alternatives
Focuses on high-throughput assays like MTT, LDH release, and 3D spheroid models replacing animal LD50 tests. Validation against in vivo data and regulatory acceptance are key.
Ethical Considerations in Animal Experimentation
Examines 3Rs principles, IACUC protocols, and moral frameworks like utilitarianism in research design. Includes pain assessment and welfare monitoring.
Risk of Bias in Animal Studies
Develops tools like SYRCLE for assessing randomization, blinding, and confounding in preclinical research. Meta-analyses quantify bias impacts on effect sizes.
Translation from Animal Models to Human Clinical Trials
Analyzes failures in predictivity, species differences in pharmacokinetics, and strategies like human-on-chip for better translation. Case studies highlight successes and pitfalls.
Why It Matters
ARRIVE guidelines maximize published information from animal studies and minimize unnecessary experiments, as outlined in "Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research" by Kilkenny et al. (2010), which has 7016 citations. Dose conversion practices between animals and humans, detailed in "A simple practice guide for dose conversion between animals and human" by Nair and Jacob (2016) with 5443 citations, support accurate preclinical dosing for drug development. Tools like SYRCLE’s risk of bias assessment in "SYRCLE’s risk of bias tool for animal studies" by Hooijmans et al. (2014), cited 3672 times, enable systematic reviews that identify flaws in animal research translation to human applications, reducing wasted resources in pharmaceutical industries.
Reading Guide
Where to Start
"Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research" by Kilkenny et al. (2010) introduces core reporting standards essential for understanding animal study quality before exploring alternatives or ethics.
Key Papers Explained
"Guide for the Care and Use of Laboratory Animals" by National Research Council (2011) establishes foundational care standards, which "Ethical guidelines for investigations of experimental pain in conscious animals" by Zimmermann (1983) builds on for pain-specific ethics. "Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research" by Kilkenny et al. (2010) and its update "The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research" by Percie du Sert et al. (2020) refine reporting practices informed by these standards. "SYRCLE’s risk of bias tool for animal studies" by Hooijmans et al. (2014) then enables evaluation of studies adhering to prior guidelines.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
ARRIVE 2.0 by Percie du Sert et al. (2020) represents the latest evolution in reporting standards, emphasizing transparent methods for in vivo experiments amid ongoing translation challenges. Focus shifts to integrating risk of bias tools like SYRCLE with in vitro alternatives, though no recent preprints detail new developments.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Guide for the Care and Use of Laboratory Animals | 2011 | National Academies Pre... | 16.2K | ✕ |
| 2 | Superoxide dismutase: Improved assays and an assay applicable ... | 1971 | Analytical Biochemistry | 12.5K | ✕ |
| 3 | Ethical guidelines for investigations of experimental pain in ... | 1983 | Pain | 7.7K | ✕ |
| 4 | Improving Bioscience Research Reporting: The ARRIVE Guidelines... | 2010 | PLoS Biology | 7.0K | ✓ |
| 5 | Improving bioscience research reporting: The ARRIVE guidelines... | 2010 | Journal of Pharmacolog... | 6.3K | ✓ |
| 6 | A simple practice guide for dose conversion between animals an... | 2016 | Journal of Basic and C... | 5.4K | ✕ |
| 7 | The ARRIVE guidelines 2.0: Updated guidelines for reporting an... | 2020 | PLoS Biology | 5.0K | ✓ |
| 8 | The 1996 Guide for the Care and Use of Laboratory Animals | 1997 | ILAR Journal | 4.4K | ✓ |
| 9 | SYRCLE’s risk of bias tool for animal studies | 2014 | BMC Medical Research M... | 3.7K | ✓ |
| 10 | Animal tissue techniques | 1962 | W.H. Freeman eBooks | 3.7K | ✕ |
Frequently Asked Questions
What are the ARRIVE guidelines?
The ARRIVE guidelines provide a checklist to improve reporting of in vivo animal experiments by ensuring complete disclosure of study details. Developed in 2010 and updated to version 2.0 in 2020, they address deficiencies in bioscience research reporting. "The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research" by Percie du Sert et al. (2020) outlines these updates for better reproducibility.
How do researchers convert doses from animals to humans?
Interspecies allometric scaling converts doses by accounting for differences in body surface area and metabolism between species. "A simple practice guide for dose conversion between animals and human" by Nair and Jacob (2016) provides practical formulas for this extrapolation in preclinical studies. Accurate conversion reduces errors when initiating human trials from animal data.
What ethical guidelines apply to animal pain research?
"Ethical guidelines for investigations of experimental pain in conscious animals" by Zimmermann (1983) establishes standards for minimizing suffering in pain studies. These guidelines require justification of animal use and appropriate analgesia. They remain a reference for ethical conduct in preclinical research.
What tools assess bias in animal studies?
SYRCLE’s risk of bias tool evaluates domains like selection bias and performance bias in animal intervention studies. Described in "SYRCLE’s risk of bias tool for animal studies" by Hooijmans et al. (2014), it adapts Cochrane principles for preclinical research. Systematic reviews use it to improve evidence quality.
What standards guide laboratory animal care?
"Guide for the Care and Use of Laboratory Animals" by National Research Council (2011) sets federal standards for housing, veterinary care, and use in U.S. research. It emphasizes welfare and oversight by institutional committees. The guide influences global practices in preclinical studies.
Open Research Questions
- ? How can publication bias in animal studies be fully mitigated to improve translation to human trials?
- ? What refinements to ARRIVE 2.0 guidelines would further enhance reproducibility across diverse preclinical models?
- ? Which in vitro alternatives most accurately predict human outcomes compared to specific animal models?
- ? How should sample sizes be optimally determined for heterogeneous animal populations in preclinical studies?
- ? What factors most limit the success of dose extrapolation from rodents to humans in drug development?
Recent Trends
The ARRIVE guidelines advanced to version 2.0 in "The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research" by Percie du Sert et al. , with 5017 citations, updating the 2010 originals by Kilkenny et al. that garnered 7016 and 6302 citations respectively.
2020This reflects sustained emphasis on reproducibility in the 54,019 works, though growth data over 5 years remains unavailable and no preprints or news from the last 12 months indicate shifts.
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