Phase II and phase III failures: 2013–2015
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?
Failure of phase II and III clinical trials is largely attributed to a lack of efficacy.
“Failure of phase II and III clinical trials is largely attributed to a lack of efficacy,47”
From Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy (2025) · cites this paper as [47]
Fewer than 1 in 10 drugs succeed from phase I through to marketing authorization, with the success rate being disease-specific.
“It is largely for these reasons that fewer than 1 in 10 drugs succeed in running the gauntlet from phase I through to marketing authorization, with the success rate being disease-specific 7 .”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [7]
Cites
Phase II and Phase III attrition rates 2011–2012
Arrowsmith, J., & Miller, P. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4090 · Cited by 697 · see citing works
Graul, A., Cruces, E., Dulsat, C., et al. (2016) · Drugs of today · doi:10.1358/dot.2016.52.2.2472346 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Why 90% of clinical drug development fails and how to improve it?
Sun, D., Gao, W., Hu, H., & Zhou, S. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.02.002 · Cited by 1,763 · see citing works
Zheng, J., Haberland, V., Baird, D., Walker, V., Haycock, P., Hurle, M., Gutteridge, A., Erola, P., Liu, Y., Luo, S., et al. (2019) · doi:10.1101/627398 · Cited by 812 · see citing works
Mendelian randomization in cardiometabolic disease: challenges in evaluating causality
Holmes, M. V., Ala-Korpela, M., & Smith, G. D. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.78 · Cited by 679 · see citing works
A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models
Ren, F., Aliper, A., Chen, J., Zhao, H., Rao, S., Kuppe, C., Ozerov, I. V., Zhang, M., Witte, K., Kruse, C., et al. (2025) · Nature Biotechnology · doi:10.1038/s41587-024-02143-0 · Cited by 348 · see citing works
“6a and Supplementary Information 9).”
InfluentialPerformance assessment and economic analysis of a human Liver-Chip for predictive toxicology
Ewart, L., Apostolou, A., Briggs, S. A., Carman, C. V., Chaff, J. T., Heng, A. R., Jadalannagari, S., Janardhanan, J., Jang, K.-J., Joshipura, S. R., et al. (2022) · Communications Medicine · doi:10.1038/s43856-022-00209-1 · Cited by 337 · see citing works
“We modeled safety-related failures, efficacy-related failures, and other failures (e.g., commercial and strategy related) with parameters derived from the literature (primarily from Harrison 2016,7,9,24,25).”
MethodLessons Learned from Alzheimer Disease: Clinical Trials with Negative Outcomes
Cummings, J. (2018) · Clinical and Translational Science · doi:10.1111/cts.12491 · Cited by 298 · see citing works
Cummings, J., Ritter, A., & Zhong, K. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179901 · Cited by 176 · see citing works
Holmes, M. V., Richardson, T. G., Ference, B. A., Davies, N. M., & Davey Smith, G. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-020-00493-1 · Cited by 184 · see citing works
Imaging of anticancer drug action in single cells
Miller, M. A., & Weissleder, R. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.41 · Cited by 92 · see citing works
A microfluidic platform for functional testing of cancer drugs on intact tumor slices
Rodriguez, A. D., Horowitz, L. F., Castro, K., Kenerson, H., Bhattacharjee, N., Gandhe, G., Raman, A., Monnat, R. J., Yeung, R., Rostomily, R. C., et al. (2020) · Lab on a Chip · doi:10.1039/c9lc00811j · Cited by 77 · see citing works
Peng, T., Ma, X., Hua, W., Wang, C., Chu, Y., Sun, M., Fermi, V., Hamelmann, S., Lindner, K., Shao, C., et al. (2025) · Cell Stem Cell · doi:10.1016/j.stem.2025.01.002 · Cited by 86 · see citing works
Choi, G.-W., Lee, Y.-B., & Cho, H.-Y. (2019) · Pharmaceutics · doi:10.3390/pharmaceutics11040168 · Cited by 76 · see citing works
“The main cause of failure in clinical trials is poor efficacy [3].”
BackgroundLi, Y., Sang, S., Ren, W., Pei, Y., Bian, Y., Chen, Y., & Sun, H. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113874 · Cited by 77 · see citing works
Refining animal research: The Animal Study Registry
Bert, B., Heinl, C., Chmielewska, J., Schwarz, F., Grune, B., Hensel, A., Greiner, M., & Schönfelder, G. (2019) · PLOS Biology · doi:10.1371/journal.pbio.3000463 · Cited by 67 · see citing works
Bailey, J., & Balls, M. (2019) · BMC Medical Ethics · doi:10.1186/s12910-019-0352-3 · Cited by 51 · see citing works
Patient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer
Rizzo, G., Bertotti, A., Leto, S. M., & Vetrano, S. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01970-2 · Cited by 51 · see citing works
Humanized mouse as a tool to predict immunotoxicity of human biologics
Yong, K. S. M., Her, Z., Tan, S. Y., Tan, W. W. S., Liu, M., Lai, F., Heng, S. M., Fan, Y., Chang, K. T. E., Wang, C.-I., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.553362 · Cited by 13 · see citing works
Challenges and Potential of Using Digital Biomarkers in Healthcare and Clinical Trials
Lieberwirth, J. K., Mittermaier, M., & Stern, A. D. (2026) · Communications Medicine · doi:10.1038/s43856-026-01450-8 · Cited by 13 · see citing works
Multi-organ model assessment of neurotoxicity following exposure of liver spheroids to drugs
Wu, W., Anas, F., Koc, B., Tian, L., Hasselkus, R., Rezania, D., Sharareh, S., Farberov, L., Zlotnik, D., Alon, A., et al. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118021 · Cited by 5 · see citing works
Abi-Gerges, N., McMahon, C., Vargas, H., Sager, P., Chui, R., Stevens, D., Davila, J., Schaub, J. R., Wu, J. C., del Rio, C., et al. (2019) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2019.106582 · Cited by 3 · see citing works
- Authors
- Harrison, R. K.
- Affiliations
- Clarivate (United States) (US)
- Corresponding author
- Harrison, Richard K.
- ORCID
- Harrison, Richard K.
- Venue
- Nature Reviews Drug Discovery
- Published
- 2016-11-04
- Volume
- 15
- Issue
- 12
- Pages
- 817-818
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W2547330766
- Cited by
- 636
- References
- 2
- Citations by year
- 2026: 79 · 2025: 79 · 2024: 104 · 2023: 76 · 2022: 53 · 2021: 62 · 2020: 66 · 2019: 57 · 2018: 33 · 2017: 26 · 2016: 1
- Type
- other
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- drug development, lack of efficacy
- MeSH terms
- Humans, Treatment Failure, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic
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
