Poor Translatability of Biomedical Research Using Animals — A Narrative Review
Open accessAbstract
The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity — that is, safety issues revealed in human trials that were not apparent in animal tests — or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing. Here, we review several disease areas, and consider how the use of animal models has failed to offer effective new treatments. We also make some suggestions as to how the more human-relevant new approach methodologies might be applied to address this.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The need for human research is emphasized by the poor translation of drug trials from animal to human models.
“This need for human research is also emphasized by the poor translation of drug trials from animal to human models [72].”
From The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review (2025) · cites this paper as [72]
Cites
Ngandu, T., Lehtisalo, J., Solomon, A., Levälahti, E., Ahtiluoto, S., Antikainen, R., Bäckman, L., Hänninen, T., Jula, A., Laatikainen, T., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(15)60461-5 · Cited by 3,689 · see citing works
Raise standards for preclinical cancer research
Begley, C. G., & Ellis, L. M. (2012) · Nature · doi:10.1038/483531a · Cited by 2,979 · see citing works
Dorsey, E. R., Elbaz, A., Nichols, E., Abbasi, N., Abd-Allah, F., Abdelalim, A., Adsuar, J. C., Ansha, M. G., Brayne, C., Choi, J.-Y. J., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30295-3 · Cited by 2,816 · see citing works
Alzheimer’s disease drug-development pipeline: Few candidates, frequent failures
Cummings, J. L., Morstorf, T., & Zhong, K. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt269 · Cited by 1,744 · see citing works
Human organs-on-chips for disease modelling, drug development and personalized medicine
Ingber, D. E. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00466-9 · Cited by 1,589 · see citing works
Alzheimer's disease: experimental models and reality
Drummond, E., & Wisniewski, T. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1662-x · Cited by 810 · see citing works
Webster, S. J., Bachstetter, A. D., Nelson, P. T., Schmitt, F. A., & Van Eldik, L. J. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00088 · Cited by 755 · cited 2× · see citing works
“It has been shown that, although FAD and LOAD are characterised by the same behavioural and pathological features,40 animal models of FAD do neither recapitulate the genetics41 nor the onset and progression of LOAD.42,43 —”
BackgroundLimitations of Animal Studies for Predicting Toxicity in Clinical Trials
Van Norman, G. A. (2019) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2019.10.008 · Cited by 709 · see citing works
Clinical trials of new drugs for Alzheimer disease
Huang, L.-K., Chao, S.-P., & Hu, C.-J. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-019-0609-7 · Cited by 702 · cited 1× · see citing works
“Atabecestat,(28) Pioglitazone,(29) the FYN inhibitor AZD0530,(30) and ITI-007 (lumateperone, originally developed for the treatment of schizophrenia).(31,32) So far, 155 interventional clinical trials aimed at testing drugs for AD have been terminated (as of 5 July 2022, according to publicly available data in clinica…”
BackgroundAlzheimer’s disease drug development pipeline: 2021
Cummings, J., Lee, G., Zhong, K., Fonseca, J., & Taghva, K. (2021) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12179 · Cited by 539 · cited 1× · see citing works
“Compared to previous analyses, the 2021 pipeline review showed an increase of mechanistic approaches for the treatment of AD, with drugs targeting a variety of different targets, particularly in Phase II trials.(21) Since the 2020 pipeline review, nine trials in Phase I, 18 trials in Phase II and seven trials in Phase…”
ResultKnopman, D. S., Jones, D. T., & Greicius, M. D. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12213 · Cited by 524 · see citing works
Si, L., Bai, H., Rodas, M., Cao, W., Oh, C. Y., Jiang, A., Moller, R., Hoagland, D., Oishi, K., Horiuchi, S., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00718-9 · Cited by 440 · cited 1× · see citing works
“The acceleration in focused research activity that came about as a consequence of the recent pandemic illustrated howNAMs can rapidly be applied for understanding disease progression and for repurposing previously approved drugs to provide muchneeded treatment options.(243,244) Recently, the US Food and Drug Administr…”
BackgroundPistollato, F., Iglesias, R. C., Ruiz, R., Aparicio, S., Crespo, J., Lopez, L. D., Manna, P. P., Giampieri, F., & Battino, M. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.03.012 · Cited by 247 · see citing works
Self-citationMechanisms of aging in senescence-accelerated mice
Carter, T. A., Greenhall, J. A., Yoshida, S., Fuchs, S., Helton, R., Swaroop, A., Lockhart, D. J., & Barlow, C. (2005) · Genome Biology · doi:10.1186/gb-2005-6-6-r48 · Cited by 64 · see citing works
An Assessment of the Role of Chimpanzees in AIDS Vaccine Research
Bailey, J. (2008) · Alternatives to Laboratory Animals · doi:10.1177/026119290803600403 · Cited by 49 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Roadblocks confronting widespread dissemination and deployment of Organs on Chips
Alver, C. G., Drabbe, E., Ishahak, M., & Agarwal, A. (2024) · Nature Communications · doi:10.1038/s41467-024-48864-3 · Cited by 74 · see citing works
Old, V. J., Davies, M. J., Papamargaritis, D., Choudhary, P., & Watson, E. L. (2025) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.13677 · Cited by 55 · see citing works
- Authors
- Marshall, L. J., Bailey, J., Cassotta, M., Herrmann, K., & Pistollato, F.
- Affiliations
- Humane World for Animals (US)
- Animal Free Research UK (GB)
- Oltre la Sperimentazione Animale (OSA)
- Johns Hopkins University (US)
- European Commission (BE)
- Corresponding author
- Herrmann, Kathrin
- Venue
- Alternatives to Laboratory Animals
- Publisher
- SAGE Publications
- Published
- 2023-03
- Volume
- 51
- Issue
- 2
- Pages
- 102-135
- ISSN
- 0261-1929 (ISSN-L)
- 2632-3559
- OpenAlex
- W4323532768
- Cited by
- 219
- References
- 15
- Citations by year
- 2026: 105 · 2025: 62 · 2024: 44 · 2023: 8
- FWCI
- 10.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alternatives to Laboratory Animals (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Health Sciences › Medicine › Physiology › Biomedical Ethics and Regulation
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- translational failure, animal models, drug toxicity, drug efficacy, preclinical drug testing, organ-on-a-chip, animal experimentation, clinical trial safety
- MeSH terms
- Animals, Humans, Models, Animal, Biomedical Research
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 ›
Are you an author, or do you see a problem with this page? Request a review
