ArticleNature genetics2024
Genetic factors associated with reasons for clinical trial stoppage.
Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Multi-ancestry whole genome sequencing analysis of lean body mass.Genome biology · 2025Pooled it
- A systematic review on the generative AI applications in human medical genetics.Frontiers in genetics · 2025Pooled it
- Genome-scale perturbation signatures from primary human CD4bioRxiv : the preprint server for biology · 2026Article
- Target-biology and interactome-derived signatures predict target-level associations with safety-related drug attrition.Scientific reports · 2026Article
- Artificial intelligence in drug discovery - what it is, where we stand and the path forward.Nature reviews. Drug discovery · 2026Review
- Article
- Translating genome-wide association studies at multiple scales: Drug target prioritization, cellular architectures, and organ imaging.Cell genomics · 2026Review
- Single-cell multi-omic integration analysis prioritizes druggable genes and reveals cell-type-specific causal effects in glioblastomagenesis.Journal of translational medicine · 2026Article
- Double strand breaks drive toxicity in a Huntington's disease mouse model with or without somatic expansion.Nature communications · 2026Article
- The Human Pleiotropic Map of GWAS Associations and Therapeutic Implications.bioRxiv : the preprint server for biology · 2026Article
- Genomics of drug target prioritization for complex diseases.Nature reviews. Genetics · 2026Review
- The Virtual Biotech: A Multi-Agent AI Framework for Therapeutic Discovery and Development.bioRxiv : the preprint server for biology · 2026Article
- CRISPR-based functional genomic screening in neurodegeneration: mechanistic insights into AD, PD, and ALS.Frontiers in aging neuroscience · 2026Review
- Single-cell analysis of the synovium and infrapatellar fat pad identifies key pathogenic genes and drug targets in osteoarthritis.International journal of clinical and experimental pathology · 2026Article
- The China Brain Multi-omics Atlas Project (CBMAP).Molecular psychiatry · 2026Review
- Temporal trends in evidence supporting novel drug target discovery.Nature communications · 2025Article
- Large language models in clinical trials: applications, technical advances, and future directions.BMC medicine · 2025Review
- Axon Regeneration and Functional Recovery after Spinal Cord Injury is Enhanced by Allele-Specific ApoE Neuronal Action through LRP8.bioRxiv : the preprint server for biology · 2025Article
- Drug and Clinical Candidate Drug Data in ChEMBL.Journal of medicinal chemistry · 2025Review
- Circulating Protein Mediators Linking Genetically Predicted Smoking to Abdominal Aortic Aneurysm: A Genomic-Proteomic Analysis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Many drug discovery projects are started but few progress fully through clinical trials to approval. Previous work has shown that human genetics support for the therapeutic hypothesis increases the chance of trial progression. Here, we applied natural language processing to classify the free-text reasons for 28,561 clinical trials that stopped before their endpoints were met. We then evaluated these classes in light of the underlying evidence for the therapeutic hypothesis and target properties. We found that trials are more likely to stop because of a lack of efficacy in the absence of strong genetic evidence from human populations or genetically modified animal models. Furthermore, certain trials are more likely to stop for safety reasons if the drug target gene is highly constrained in human populations and if the gene is broadly expressed across tissues. These results support the growing use of human genetics to evaluate targets for drug discovery programs.
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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.