- See Also
-
Links
- “C60 In Olive Oil Causes Light-dependent Toxicity and Does Not Extend Lifespan in Mice”, Et Al 2020
- “Publication Rate in Preclinical Research: a Plea for Preregistration”, Et Al 2020
- “Reproducibility of Animal Research in Light of Biological Variation”, Et Al 2020
- “Individual Differences in Behavior Explain Variation in Survival: a Meta-analysis”, Et Al 2019
- “Depression Researchers Rethink Popular Mouse Swim Tests: Animal-rights Group’s Campaign to End Forced-swim Tests Comes amid Debate over Whether Method Is Overused”, 2019b
- “Genetically Heterogeneous Mice Exhibit a Female Survival Advantage That Is Age-specific and Site-specific: Results from a Large Multi-site Study”, Et Al 2019
- “What Exactly Is ‘N’ In Cell Culture and Animal Experiments?”, Et Al 2017
- “A Long Journey to Reproducible Results: Replicating Our Work Took Four Years and 100,000 Worms but Brought Surprising Discoveries”, Et Al 2017
- “Impact of Genetic Background and Experimental Reproducibility on Identifying Chemical Compounds With Robust Longevity Effects”, Et Al 2017
- “Reproducibility and Replicability of Rodent Phenotyping in Preclinical Studies”, Et Al 2016
- “Thermoneutrality, Mice, and Cancer: A Heated Opinion”, 2016
- “Low-dose Paroxetine Exposure Causes Lifetime Declines in Male Mouse Body Weight, Reproduction and Competitive Ability As Measured by the Novel Organismal Performance Assay”, Et Al 2015
- “Baseline Tumor Growth and Immune Control in Laboratory Mice Are Importantly Influenced by Subthermoneutral Housing Temperature”, Et Al 2013
- “Evaluation of Excess Statistical-Significance Bias in Animal Studies of Neurological Diseases”, Et Al 2013
- “Genomic Responses in Mouse Models Poorly Mimic Human Inflammatory Diseases”, Seok & Al 2013
- “Look Back in Anger—what Clinical Studies Tell Us about Preclinical Work”, 2013
- “Improving the Translational Hit of Experimental Treatments in Multiple Sclerosis”, Et Al 2010
- “Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy”, Et Al 2010
- “Systematic Reviews of Animal Experiments Demonstrate Poor Contributions Toward Human Healthcare”, 2008
- “Translating Animal Research into Clinical Benefit”, 2007
- “A Systematic Review of Systematic Reviews and Meta-Analyses of Animal Experiments With Guidelines for Reporting”, Et Al 2006
- “The Future of Teratology Research Is In Vitro”, Et Al 2005
- “Where Is the Evidence That Animal Research Benefits Humans?”, Et Al 2004
- “PME00042”
- “Concordance of the Toxicity of Pharmaceuticals in Humans and in Animals”, Et Al 2000
- “Induction of Drug-Metabolizing Enzymes in Liver Microsomes of Mice and Rats by Softwood Bedding”, 1967
- “The Importance of Being Cross-Bred”, Michie & 1955
- “The Effects of Olfactory Cues on the Maze Learning of White Rats”, 1940
- “Experiments Using Mice Are Often Heavily Publicised - but Very, Very Few of Them Translate into Humans. Anthony King Reports on Why Animal Models Are of Questionable Value.”
- “Two Years Later: Journals Are Not Yet Enforcing the ARRIVE Guidelines on Reporting Standards for Pre-Clinical Animal Studies”, Et Al 2023
- “Can Animal Models of Disease Reliably Inform Human Studies?”, Et Al 2023
- “The Mouse Trap: The Dangers of Using One Lab Animal to Study Every Disease”
- Wikipedia
- Miscellaneous
On the general topic of animal model external validity & translation to humans, a number of op-eds, reviews, and meta-analyses have been done; reading through the literature up to March 2013, I would summarize them as indicating that the animal research literature in general is of considerably lower quality than human research, and that for those and intrinsic biological reasons, the probability of meaningful transfer from animal to human can be astoundingly low, far below 50% and in some categories of results, 0%.
The primary reasons identified for this poor performance are generally: small samples (much smaller than the already underpowered norms in human research), lack of blinding in taking measurements, pseudo-replication due to animals being correlated by genetic relatedness/living in same cage/same room/same lab, extensive non-normality in data, large differences between labs due to local differences in reagents/procedures/personnel illustrating the importance of “tacit knowledge”, publication bias (small cheap samples + little perceived ethical need to publish + no preregistration norms), unnatural & unnaturally easy lab environments (more naturalistic environments both offer more realistic measurements & challenge animals), large genetic differences due to inbreeding/engineering/drift of lab strains mean the same treatment can produce dramatically different results in different strains (or sexes) of the same species, different species can have different responses, and none of them may be like humans in the relevant biological way in the first place.
So it is no wonder that “we can cure cancer in mice but not people” and almost all amazing breakthroughs in animals never make it to human practice; medicine & biology are difficult.
(On normality: Lots of data is not exactly normal, but, particularly in human studies, this is not a big deal because the n are often large enough, eg. n > 20, that the asymptotics have started to work & model misspecification doesn’t produce too large a false positive rate inflation or mis-estimation. Unfortunately, in animal research, it’s perfectly typical to have sample sizes more like n = 5, which in an idealized power analysis of a normally distributed variable might be fine because one is (hopefully) exploiting the freedom of animal models to get a large effect size / precise measurements—except that with n = 5 the data won’t be even close to ~normal or fitting other model assumptions, and a single biased or selected or outlier datapoint can mess it up further.)
See Also
Links
“C60 In Olive Oil Causes Light-dependent Toxicity and Does Not Extend Lifespan in Mice”, Et Al 2020
“C60 in olive oil causes light-dependent toxicity and does not extend lifespan in mice”
“Publication Rate in Preclinical Research: a Plea for Preregistration”, Et Al 2020
“Publication rate in preclinical research: a plea for preregistration”
“Reproducibility of Animal Research in Light of Biological Variation”, Et Al 2020
“Reproducibility of animal research in light of biological variation”
“Individual Differences in Behavior Explain Variation in Survival: a Meta-analysis”, Et Al 2019
“Individual differences in behavior explain variation in survival: a meta-analysis”
“Depression Researchers Rethink Popular Mouse Swim Tests: Animal-rights Group’s Campaign to End Forced-swim Tests Comes amid Debate over Whether Method Is Overused”, 2019b
“Genetically Heterogeneous Mice Exhibit a Female Survival Advantage That Is Age-specific and Site-specific: Results from a Large Multi-site Study”, Et Al 2019
“What Exactly Is ‘N’ In Cell Culture and Animal Experiments?”, Et Al 2017
“What exactly is ‘N’ in cell culture and animal experiments?”
“A Long Journey to Reproducible Results: Replicating Our Work Took Four Years and 100,000 Worms but Brought Surprising Discoveries”, Et Al 2017
“Impact of Genetic Background and Experimental Reproducibility on Identifying Chemical Compounds With Robust Longevity Effects”, Et Al 2017
“Reproducibility and Replicability of Rodent Phenotyping in Preclinical Studies”, Et Al 2016
“Reproducibility and replicability of rodent phenotyping in preclinical studies”
“Thermoneutrality, Mice, and Cancer: A Heated Opinion”, 2016
“Low-dose Paroxetine Exposure Causes Lifetime Declines in Male Mouse Body Weight, Reproduction and Competitive Ability As Measured by the Novel Organismal Performance Assay”, Et Al 2015
“Baseline Tumor Growth and Immune Control in Laboratory Mice Are Importantly Influenced by Subthermoneutral Housing Temperature”, Et Al 2013
“Evaluation of Excess Statistical-Significance Bias in Animal Studies of Neurological Diseases”, Et Al 2013
“Evaluation of Excess Statistical-Significance Bias in Animal Studies of Neurological Diseases”
“Genomic Responses in Mouse Models Poorly Mimic Human Inflammatory Diseases”, Seok & Al 2013
“Genomic responses in mouse models poorly mimic human inflammatory diseases”
“Look Back in Anger—what Clinical Studies Tell Us about Preclinical Work”, 2013
“Look back in anger—what clinical studies tell us about preclinical work”
“Improving the Translational Hit of Experimental Treatments in Multiple Sclerosis”, Et Al 2010
“Improving the translational hit of experimental treatments in multiple sclerosis”
“Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy”, Et Al 2010
“Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy”
“Systematic Reviews of Animal Experiments Demonstrate Poor Contributions Toward Human Healthcare”, 2008
“Systematic Reviews of Animal Experiments Demonstrate Poor Contributions Toward Human Healthcare”
“Translating Animal Research into Clinical Benefit”, 2007
“A Systematic Review of Systematic Reviews and Meta-Analyses of Animal Experiments With Guidelines for Reporting”, Et Al 2006
“The Future of Teratology Research Is In Vitro”, Et Al 2005
“Where Is the Evidence That Animal Research Benefits Humans?”, Et Al 2004
“Where is the evidence that animal research benefits humans?”
“PME00042”
“Concordance of the Toxicity of Pharmaceuticals in Humans and in Animals”, Et Al 2000
“Concordance of the Toxicity of Pharmaceuticals in Humans and in Animals”
“Induction of Drug-Metabolizing Enzymes in Liver Microsomes of Mice and Rats by Softwood Bedding”, 1967
“Induction of Drug-Metabolizing Enzymes in Liver Microsomes of Mice and Rats by Softwood Bedding”
“The Importance of Being Cross-Bred”, Michie & 1955
“The Effects of Olfactory Cues on the Maze Learning of White Rats”, 1940
“The effects of olfactory cues on the maze learning of white rats”
“Experiments Using Mice Are Often Heavily Publicised - but Very, Very Few of Them Translate into Humans. Anthony King Reports on Why Animal Models Are of Questionable Value.”
“Two Years Later: Journals Are Not Yet Enforcing the ARRIVE Guidelines on Reporting Standards for Pre-Clinical Animal Studies”, Et Al 2023
“Can Animal Models of Disease Reliably Inform Human Studies?”, Et Al 2023
“Can Animal Models of Disease Reliably Inform Human Studies?”
“The Mouse Trap: The Dangers of Using One Lab Animal to Study Every Disease”
“The Mouse Trap: The dangers of using one lab animal to study every disease”
Wikipedia
Miscellaneous
-
http://eprints.nottingham.ac.uk/439/1/Willmot_NO_synthase_JFRBM.pdf
-
http://psych.colorado.edu/~carey/pdfFiles/MouseLab_Crabbe.pdf
-
https://academic.oup.com/cardiovascres/article/91/4/649/346880
-
https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.138.944&rep=rep1&type=pdf
-
https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.513.1459&rep=rep1&type=pdf
-
https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.654.7344&rep=rep1&type=pdf
-
https://danbaum.files.wordpress.com/2018/03/jake-leg-new-yorker.pdf
-
https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1553-2712.2003.tb00056.x
-
https://pure.uva.nl/ws/files/3216102/15320_Thesis.pdf#page=103
-
https://www.jstage.jst.go.jp/article/jts1976/20/2/20_2_77/_pdf
-
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1436259/pdf/jrsocmed00293-0087.pdf
-
https://www.sciencedirect.com/science/article/pii/S2405471219302005
-
https://www.tandfonline.com/doi/pdf/10.4161/15384101.2014.950151