ReviewCurrent gene therapy2009
Uncertainty in the translation of preclinical experiments to clinical trials. Why do most phase III clinical trials fail?
Review in Current gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Impact of Omega-3 Polyunsaturated Fatty Acids on Alcohol Use and Negative Consequences: A Systematic Review.Nutrition reviews · 2025Pooled it
- Human endothelial colony-forming cells in regenerative therapy: A systematic review of controlled preclinical animal studies.Stem cells translational medicine · 2020Pooled it
- Synthetic control methods for n-of-1 and parallel-group trials in Alzheimer's disease: A proof-of-concept study using the I-CONECT.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Autologous olfactory mucosal cell transplants in clinical spinal cord injury: a randomized double-blinded trial in a canine translational model.Brain : a journal of neurology · 2012Trial
- Trials for Rare Cancers Are More Successful than those for Common Cancers.ESMO rare cancers · 2026Article
- Evaluation of CNS xenograft brain tumour response to MRI-guided focused ultrasound in combination with radiation therapy.British journal of cancer · 2026Article
- Mesenchymal Stem Cells and Extracellular Vesicles: Bridging the Translational Gap in Regenerative Medicine.International journal of molecular sciences · 2026Article
- Photobiomodulation for skeletal muscle regeneration: mechanisms, dosimetry, and translational challenges.Frontiers in bioengineering and biotechnology · 2026Review
- MicroRNAs in lung cancer: their role in tumor progression, biomarkers, diagnostic, prognostic, and therapeutic relevance.Discover oncology · 2025Review
- Review
- The Original Mouse Models of Glioblastoma: Analysis of Pathophysiological Characteristics of Transplanted Tumor Tissue.Sovremennye tekhnologii v meditsine · 2025Article
- Unravelling Secondary Brain Injury: Insights from a Human-Sized Porcine Model of Acute Subdural Haematoma.Cells · 2024Article
- Coagulation Protease-Driven Cancer Immune Evasion: Potential Targets for Cancer Immunotherapy.Cancers · 2024Review
- Elastin-like Recombinamer Hydrogels as Platforms for Breast Cancer Modeling.Biomacromolecules · 2023Article
- Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment.Journal of clinical medicine · 2023Review
- Predicting Valproate-Induced Liver Injury Using Metabolomic Analysis of Ex Ovo Chick Embryo Allantoic Fluid.Metabolites · 2023Article
- Current State of Modeling Human Psychiatric Disorders Using Zebrafish.International journal of molecular sciences · 2023Review
- Evaluating preclinical evidence for clinical translation in childhood brain tumours: Guidelines from the CONNECT, PNOC, and ITCC brain networks.Frontiers in oncology · 2023Article
- Metabolomics as a Crucial Tool to Develop New Therapeutic Strategies for Neurodegenerative Diseases.Metabolites · 2022Review
- Between two stools: preclinical research, reproducibility, and statistical design of experiments.BMC research notes · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
A large majority of Phase III, large scale, clinical trials will fail, including gene therapy trials. This paper attempts to address some of the causes that may have inadvertently led to such a high failure rate. After briefly reviewing the detailed and high quality work that goes both into the preparation and conduct of such large Phase III clinical trials, and the preclinical science that is used to support and originate such trials, this paper proposes a novel approach to translational medicine which would increase the predictability of success of Phase III clinical trials. We propose that a likely cause of such failures is the lack of "robustness" in the preclinical science underpinning the Phase I/II and III clinical trials. Robustness is defined as stability/reproducibility in the face of challenges. Many times preclinical experiments are tested in a very narrow set of experimental conditions. Thus, when such approaches are finally tested in the context of human disease, the challenge provided by the varied age of patients, the complex genetic makeup of human populations, and the complexities of the diseases to be treated provide challenges which were never tested or modeled. We believe that the introduction of revised approaches to preclinical science, including the use of the latest developments in statistical, scientific, mathematical, and biological models, ought to lead to more robust preclinical experimentation with its subsequent translation, to more robust Phase III clinical trials.
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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.