Comparison of Treatment Effects between Animal Experiments and Clinical Trials: Systematic Review
Open accessAbstract
OBJECTIVE: To examine concordance between treatment effects in animal experiments and clinical trials. Study design Systematic review. DATA SOURCES: Medline, Embase, SIGLE, NTIS, Science Citation Index, CAB, BIOSIS. STUDY SELECTION: Animal studies for interventions with unambiguous evidence of a treatment effect (benefit or harm) in clinical trials: head injury, antifibrinolytics in haemorrhage, thrombolysis in acute ischaemic stroke, tirilazad in acute ischaemic stroke, antenatal corticosteroids to prevent neonatal respiratory distress syndrome, and bisphosphonates to treat osteoporosis. Review methods Data were extracted on study design, allocation concealment, number of randomised animals, type of model, intervention, and outcome. RESULTS: Corticosteroids did not show any benefit in clinical trials of treatment for head injury but did show a benefit in animal models (pooled odds ratio for adverse functional outcome 0.58, 95% confidence interval 0.41 to 0.83). Antifibrinolytics reduced bleeding in clinical trials but the data were inconclusive in animal models. Thrombolysis improved outcome in patients with ischaemic stroke. In animal models, tissue plasminogen activator reduced infarct volume by 24% (95% confidence interval 20% to 28%) and improved neurobehavioural scores by 23% (17% to 29%). Tirilazad was associated with a worse outcome in patients with ischaemic stroke. In animal models, tirilazad reduced infarct volume by 29% (21% to 37%) and improved neurobehavioural scores by 48% (29% to 67%). Antenatal corticosteroids reduced respiratory distress and mortality in neonates whereas in animal models respiratory distress was reduced but the effect on mortality was inconclusive (odds ratio 4.2, 95% confidence interval 0.85 to 20.9). Bisphosphonates increased bone mineral density in patients with osteoporosis. In animal models the bisphosphonate alendronate increased bone mineral density compared with placebo by 11.0% (95% confidence interval 9.2% to 12.9%) in the combined results for the hip region. The corresponding treatment effect in the lumbar spine was 8.5% (5.8% to 11.2%) and in the combined results for the forearms (baboons only) was 1.7% (-1.4% to 4.7%). CONCLUSIONS: Discordance between animal and human studies may be due to bias or to the failure of animal models to mimic clinical disease adequately.
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A review of 221 animal experiments found agreement in human studies just 50% of the time-essentially randomly.
“A review of 221 animal experiments found agreement in human studies just 50% of the time—essentially randomly (11).”
From Limitations of Animal Studies for Predicting Toxicity in Clinical Trials (2019) · cites this paper as [11]
The Discussion reports agreement for three of six interventions, which supports the 50% figure at the intervention level—not as a rate across 221 individual experiments. The Methodological strengths and weaknesses section says the authors cannot provide a precise estimate of agreement or generalize from six interventions. Our copy does not substantiate the 221 figure or the conclusion that agreement was essentially random. (LLM, conf=0.88)
Experimental — accuracy not yet measuredConventional culture models and animal experiments often fail to predict efficacy and safety of novel drugs, resulting in loss of money, time, and effort.
“Although extensive testing with conventional culture models and animal experiments are commonly carried out before performing clinical trials, these models often fail to predict efficacy and safety of novel drugs, which results in loss of enormous amounts of money, time, and effort.80”
From Microfluidic Organ-on-a-Chip Models of Human Intestine (2018) · cites this paper as [80]
The Introduction says animal models are usually tested before clinical trials, and the Discussion reports that animal and clinical outcomes differed for three of six interventions. But the Methodological strengths and weaknesses section cautions against generalizing from those six interventions. The paper does not assess conventional culture models or establish failures to predict drug safety or resulting losses of money, time, and effort. Page numbers were not available for these passages. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAnimal models are required for studying both physiological and behavioral mechanisms of Alzheimer's disease, but interspecies differences may result in unexpected results in clinical trials.
“Animal models are required for studying both physiological and behavioral mechanisms of AD, but interspecies differences may result in unexpected results in clinical trials [123,124].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [124]
The Introduction says biological differences between species can limit how animal findings apply to humans, and the Discussion reports differing animal and clinical results for some interventions. But the paper does not study Alzheimer's disease or say animal models are required to investigate its physiological and behavioral mechanisms; the Methodological strengths and weaknesses section explicitly says it cannot assess the value of animal research for studying biological mechanisms. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPerel et al. compared the effects of 6 interventions between animals and humans with systematic literature reviews, with half of them concordant.
“Perel et al. compared the effects of 6 interventions between animals and humans with systematic literature reviews, with half of them concordant [59].”
From Animal to human translation: a systematic scoping review of reported concordance rates (2019) · cites this paper as [59]
Animal experiments have contributed significantly to understanding the mechanisms of disease.
“In general, animal experiments have contributed significantly to our understanding of the mechanisms of disease, but their value in predicting the effectiveness of treatment strategies has limitations [80,81,82].”
From Space Radiation: The number one risk to astronaut health beyond low earth orbit (2014) · cites this paper as [81]
The value of animal experiments in predicting the effectiveness of treatment strategies has limitations.
“In general, animal experiments have contributed significantly to our understanding of the mechanisms of disease, but their value in predicting the effectiveness of treatment strategies has limitations [80,81,82].”
From Space Radiation: The number one risk to astronaut health beyond low earth orbit (2014) · cites this paper as [81]
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- Authors
- Perel, P., Roberts, I., Sena, E., Wheble, P., Briscoe, C., Sandercock, P., Macleod, M., Mignini, L. E., Jayaram, P., & Khan, K. S.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- University of Edinburgh (GB)
- Centro Rosarino de Estudios Perinatales (AR)
- Birmingham Women's Hospital (GB)
- Corresponding author
- Perel, Pablo
- ORCID
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2006-12-15
- Volume
- 334
- Issue
- 7586
- Pages
- 197
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC1781970
- OpenAlex
- W2156801000
- Cited by
- 827
- References
- 37
- Citations by year
- 2026: 38 · 2025: 32 · 2024: 39 · 2023: 40 · 2022: 45 · 2021: 66 · 2020: 47 · 2019: 47 · 2018: 46 · 2017: 44 · 2016: 45 · 2015: 53 · 2014: 49 · 2013: 36 · 2012: 39
- FWCI
- 6.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- BMJ (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- WBI Studies Repository (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- DigitalGeorgetown (Georgetown University Library) (submittedVersion)
- Funders
- Pfizer
- Medical Research Council
- Health Technology Assessment Programme
- Topics
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- clinical trials, translational research, traumatic brain injury, antifibrinolytic agents, hemorrhage, thrombolysis, ischemic stroke, tirilazad, antenatal corticosteroids, neonatal respiratory distress syndrome, bisphosphonates, osteoporosis, alendronate, bone mineral density
- MeSH terms
- Animals, Clinical Trials as Topic, Humans, Research Design, Bias, Treatment Outcome, Models, Animal, Animal Experimentation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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