ArticleJAMA internal medicine2020
Limitations in Clinical Trials Leading to Anticancer Drug Approvals by the US Food and Drug Administration.
Article in JAMA internal medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
What it found
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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
48 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Use of Second-line Immunotherapy in Control Arms of Randomized Clinical Trials in Kidney Cancer: A Systematic Review.JAMA network open · 2021Pooled it
- Comparing g-computation, propensity score-based weighting, and targeted maximum likelihood estimation for analyzing externally controlled trials with both measured and unmeasured confounders: a simulation study.BMC medical research methodology · 2023Trial
- Drug exposure definitions reported in real-world evidence studies on oncology medicines in patients with colorectal cancer: a scoping review.ESMO real world data and digital oncology · 2026Review
- Clinical Benefit of Multiple Myeloma Drugs at Regulatory Approval in Brazil, Europe, and the USA: A Retrospective Cohort Study (2003-2024).Clinical drug investigation · 2026Article
- Next-Generation Artificial Intelligence Strategies for Mechanistic Cancer Target Discovery and Drug Development: A State-of-the-Art Review.International journal of molecular sciences · 2026Review
- Exploring the therapeutic potential of withaferin A by modulating key oncosignaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Targeting VEGF, PARP, and FRα Pathways in Ovarian Cancer: Clinical Advances with Bevacizumab, Rucaparib, and Mirvetuximab Soravtansine.Journal of clinical medicine · 2026Review
- Systematic review and meta-analysis of chemotherapy-induced adverse drug reactions among children with cancer in Africa.Infectious agents and cancer · 2025Review
- Designing Single-Arm Clinical Trials: Principles, Applications, and Methodological Considerations.Annals of clinical epidemiology · 2025Article
- Perturbation-Theory Machine Learning for Multi-Target Drug Discovery in Modern Anticancer Research.Current issues in molecular biology · 2025Review
- Ligand-Based Approach for Multi-Target Drug Discovery: PTML Modeling of Triple-Target Inhibitors.Current topics in medicinal chemistry · 2025Article
- Single-arm clinical trials: design, ethics, principles.BMJ supportive & palliative care · 2024Review
- The role of the estimand framework in the analysis of patient-reported outcomes in single-arm trials: a case study in oncology.BMC medical research methodology · 2024Article
- Association of differential censoring with survival and suboptimal control arms among oncology clinical trials.Journal of the National Cancer Institute · 2024Article
- Evolution of Diagnoses, Survival, and Costs of Oncological Medical Treatment for Non-Small-Cell Lung Cancer over 20 Years in Osona, Catalonia.Current oncology (Toronto, Ont.) · 2024Article
- Analysis of oncological drugs authorised in Spain in the last decade: association between clinical benefit and reimbursement.The European journal of health economics : HEPAC : health economics in prevention and care · 2024Article
- Unveiling the potential anti-cancer activity of calycosin against multivarious cancers with molecular insights: A promising frontier in cancer research.Cancer medicine · 2024Review
- Polyphenol Mediated Suppression of Hepatocellular Carcinoma (HepG2) Cell Proliferation by Clerodendrum infortunatum L. Root.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Use of suboptimal control arms in randomized clinical trials of investigational cancer drugs in China, 2016-2021: An observational study.PLoS medicine · 2023Observational
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Importance: While there have been multiple assessments of clinical trials leading to anticancer drug approvals by the US Food and Drug Administration (FDA), the cumulative percentage of approvals based on trials with a limitation remains uncertain. Objective: To assess the percentage of clinical trials with limitations in 4 domains-lack of randomization, lack of significant overall survival advantage, inappropriate use of crossover, and use of suboptimal control arms-that led to FDA approvals from June 30, 2014, to July 31, 2019. Design, Setting, and Participants: This observational analysis included all anticancer drug indications approved by the FDA from June 30, 2014, through July 31, 2019. All indications were investigated, and each clinical trial was evaluated for design, enrollment period, primary end points, and presence of a limitation in the domains of interest. The standard-of-care therapy was determined by evaluating the literature and published guidelines 1 year prior to the start of clinical trial enrollment. Crossover was examined and evaluated for optimal use. The percentage of approvals based on clinical trials with any or all limitations of interest was then calculated. Main Outcomes and Measures: Estimated percentage of clinical trials with limitations of interest that led to an anticancer drug marketing authorization by the FDA. Results: A total of 187 trials leading to 176 approvals for 75 distinct novel anticancer drugs by the FDA were evaluated. Sixty-four (34%) were single-arm clinical trials, and 123 (63%) were randomized clinical trials. A total of 125 (67%) had at least 1 limitation in the domains of interest; 60 of the 125 trials (48%) were randomized clinical trials. Of all 123 randomized clinical trials, 37 (30%) lacked overall survival benefit, 31 (25%) had a suboptimal control, and 17 (14%) used crossover inappropriately. Conclusions and Relevance: Two-thirds of cancer drugs are approved based on clinical trials with limitations in at least 1 of 4 essential domains. Efforts to minimize these limitations at the time of clinical trial design are essential to ensure that new anticancer drugs truly improve patient outcomes over current standards.
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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.