ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2018
Phase I-II clinical trial design: a state-of-the-art paradigm for dose finding.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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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.
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Who cites it
49 citing papers in PubMed.
- Comparison of efficacy discrepancy between early-phase clinical trials and phase III trials of PD-1/PD-L1 inhibitors.Journal for immunotherapy of cancer · 2024Trial
- Trial
- Bayesian adaptive model selection design for optimal biological dose finding in phase I/II clinical trials.Biostatistics (Oxford, England) · 2023Trial
- A phase 1-2 trial of sitravatinib and nivolumab in clear cell renal cell carcinoma following progression on antiangiogenic therapy.Science translational medicine · 2022Trial
- Generalized phase I-II designs to increase long term therapeutic success rate.Pharmaceutical statisticsTrial
- Information borrowing in phase II randomized dose-ranging clinical trials in oncology.BMC medical research methodology · 2026Article
- BAR12: Bayesian Autoregressive Phase 1-2 Design for Cell Therapy Trials With Manufacturing Changes.Statistics in medicine · 2026Article
- A Bayesian pharmacokinetics integrated phase I-II design to optimize dose-schedule regimes.Biostatistics (Oxford, England) · 2025Article
- Randomized optimal selection design for dose optimization.Biometrics · 2025Article
- A robust Bayesian dose optimization design with backfill and randomization for phase I/II clinical trials.Statistical methods in medical research · 2025Article
- Analysis of Phase I Clinical Trial Design of Anti-Cancer Agents.Therapeutic innovation & regulatory science · 2025Article
- Totality of the Evidence: Optimizing Dosage Selection Strategies in Oncology.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- BARD: A seamless two-stage dose optimization design integrating backfill and adaptive randomization.Clinical trials (London, England) · 2025Article
- Using circulating tumor DNA as a novel biomarker of efficacy for dose-finding designs in oncology.Statistical methods in medical research · 2025Article
- Review
- A Novel Adaptive Design Approach for Early-Phase Clinical Trials to Optimize Vaccine Dosage.China CDC weekly · 2025Article
- Clinical trials in otology and neurotology: state of the science.Frontiers in neurology · 2025Review
- REDOMA: Bayesian random-effects dose-optimization meta-analysis using spike-and-slab priors.Statistics in medicine · 2024Article
- Moving the needle for oncology dose optimization: A call for action.CPT: pharmacometrics & systems pharmacology · 2024Article
- Risk-benefit trade-offs and precision utilities in phase I-II clinical trials.Clinical trials (London, England) · 2024Article
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5 authors.
Funding
Abstract
Background: Conventional phase I algorithms for finding a phase-2 recommended dose (P2RD) based on toxicity alone is problematic because the maximum tolerated dose (MTD) is not necessarily the optimal dose with the most desirable risk-benefit trade-off. Moreover, the increasingly common practice of treating an expansion cohort at a chosen MTD has undesirable consequences that may not be obvious. Patients and methods: We review the phase I-II paradigm and the EffTox design, which utilizes both efficacy and toxicity to choose optimal doses for successive patient cohorts and find the optimal P2RD. We conduct a computer simulation study to compare the performance of the EffTox design with the traditional 3 + 3 design and the continuous reassessment method. Results: By accounting for the risk-benefit trade-off, the EffTox phase I-II design overcomes the limitations of conventional toxicity-based phase I designs. Numerical simulations show that the EffTox design has higher probabilities of identifying the optimal dose and treats more patients at the optimal dose. Conclusions: Phase I-II designs, such as the EffTox design, provide a coherent and efficient approach to finding the optimal P2RD by explicitly accounting for risk-benefit trade-offs underlying medical decisions.
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