SynthesisBritish journal of cancer2020
Pre-clinical animal models are poor predictors of human toxicities in phase 1 oncology clinical trials.
Synthesis in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Assessing the Carcinogenic Potential of Jet Fuels: A Fit-for-Purpose Systematic Literature Review.Journal of occupational and environmental medicine · 2026Pooled it
- Exploring the potential of computer simulation models in drug testing and biomedical research: a systematic review.Frontiers in pharmacology · 2025Pooled it
- Species, cell proliferation state and oxygen partial pressure are major factors in the in vitro toxicity of repurposed potential ADPKD drugs in human and murine renal proximal tubule cells.Archives of toxicology · 2026Article
- Development of a 3D-bioprinted tumour-on-chip with tunable hydrogel properties for monitoring colorectal cancer cell migration and invasion.Materials today. Bio · 2026Article
- Engineering human multi-organ tissue chip niches for drug absorption, distribution, metabolism, excretion and toxicity prediction.Nature biomedical engineering · 2026Review
- Systems biology framework for the rational design of operational conditions for in vitro/in vivo translation of tissue models.Science advances · 2026Article
- Digital Twin models to address long-term treatment toxicities in children and young adults with cancer.NPJ digital medicine · 2026Review
- Review
- Organ-on-a-Chip Technology and Global Multi-Omics: Current Applications and Future Directions.MedComm · 2026Review
- Introduction to animal modelling: factors and tools for choosing the optimal model for sarcoma research-a comprehensive literature review.Translational cancer research · 2026Review
- Advancing transcriptomics-based mechanistic assessment of nephrotoxicity in vitro using the human RPTEC/TERT1 TXG-MAPr gene co-expression network.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Need for NAMs: A systematic evidence synthesis revealing over half a century of drug development failure.NAM journal · 2026Article
- Persistent clinical attrition does not establish animal models as a root cause of drug-development failures.NAM journal · 2026Article
- Carbon Quantum Dots Assisted Virus Tracking: From Skin to Brain.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Six decades of evidence: biological factors predominate among reported reasons for clinical drug failure:NAM journal · 2026Article
- From vivarium to NAM-centred laboratory: A practical framework for managing infrastructure, expertise and organisational transition.NAM journal · 2026Article
- Organoid: a promising solution to current challenges in cancer immunotherapy.npj biomedical innovations · 2025Review
- Navigating complexity in modern toxicology: the role of omics in short-term in vivo studies.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Alternatives to animal testing are the future - it's time that journals, funders and scientists embrace them.Nature · 2025Article
- 33 Unresolved Questions in Nanoscience and Nanotechnology.ACS nano · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
backgroundOur objective was to determine the correlation between preclinical toxicity found in animal models (mouse, rat, dog and monkey) and clinical toxicity reported in patients participating in Phase 1 oncology clinical trials.
methodsWe obtained from two major early-Phase clinical trial centres, preclinical toxicities from investigational brochures and clinical toxicities from published Phase 1 trials for 108 drugs, including small molecules, biologics and conjugates. Toxicities were categorised according to Common Terminology Criteria for Adverse Events version 4.0. Human toxicities were also categorised based on their reported clinical grade (severity). Positive predictive values (PPV) and negative predictive values (NPV) were calculated to determine the probability that clinical studies would/would not show a particular toxicity category given that it was seen in preclinical toxicology analysis. Statistical analyses also included kappa statistics, and Matthews (MCC) and Spearman correlation coefficients.
resultsOverall, animal toxicity did not show strong correlation with human toxicity, with a median PPV of 0.65 and NPV of 0.50. Similar results were obtained based on kappa statistics and MCC.
conclusionsThere is an urgent need to assess more novel approaches to the type and conduct of preclinical toxicity studies in an effort to provide better predictive value for human investigation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.