ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2013
Design considerations for dose-expansion cohorts in phase I trials.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Evaluating the role of phase I expansion cohorts in oncologic drug development.Investigational new drugs · 2017Pooled it
- A review of seamless phase I/II trial designs towards oncology dose optimization with examples of clinical pharmacology considerations in early drug development.European journal of clinical pharmacology · 2026Review
- A short review of dose-finding adaptive trial designs for clinical pharmacologists and non-statisticians in oncology.European journal of clinical pharmacology · 2026Review
- Assessing the risks and benefits of investigational new drugs in adult phase-I oncology trials in China, 2013-2021.Investigational new drugs · 2025Review
- Using Dose-Escalation and -Expansion Cohort Study as Pivotal Trial for Targeted Anticancer Drug Approval.JCO precision oncology · 2025Review
- Adaptive Bayesian information borrowing methods for finding and optimizing subgroup-specific doses.Clinical trials (London, England) · 2024Review
- An Overview of Phase 2 Clinical Trial Designs.International journal of radiation oncology, biology, physics · 2022Review
- Precision Bayesian phase I-II dose-finding based on utilities tailored to prognostic subgroups.Statistics in medicine · 2021Article
- Unified exact design with early stopping rules for single arm clinical trials with multiple endpoints.Statistical methods in medical research · 2021Article
- A modular framework for early-phase seamless oncology trials.Clinical trials (London, England) · 2021Article
- Model of a Queuing Approach for Patient Accrual in Phase 1 Oncology Studies.JAMA network open · 2020Article
- Efficient dose-finding for drug combination studies involving a shift in study populations.Contemporary clinical trials communications · 2020Article
- Seamless Designs: Current Practice and Considerations for Early-Phase Drug Development in Oncology.Journal of the National Cancer Institute · 2019Review
- How to design a dose-finding study using the continual reassessment method.BMC medical research methodology · 2019Article
- Design considerations for early-phase clinical trials of immune-oncology agents.Journal for immunotherapy of cancer · 2018Article
- Article
- Article
- Use of Expansion Cohorts in Phase I Trials and Probability of Success in Phase II for 381 Anticancer Drugs.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Statistical controversies in clinical research: building the bridge to phase II-efficacy estimation in dose-expansion cohorts.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Article
- Sequential monitoring of Phase I dose expansion cohorts.Statistics in medicine · 2017Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Phase I trials are increasingly including dose-expansion cohorts after the maximum-tolerated dose (MTD) has been reached to better characterize the toxicity profile or identify early signs of efficacy within a specific disease population. This article provides guidelines on how to monitor safety and re-evaluate the MTD using data obtained from expansion cohorts of phase I protocols. We illustrate how to implement a sequential monitoring rule for safety using a completed phase I trial that included an expansion cohort. We compare the accuracy of the revised MTD with the MTD obtained before expansion and with the true MTD based on simulated trials. The percent of trials that led to a change in the MTD, how far the revised MTD was from the true MTD, and the toxicity rates associated with each level are reported. When toxicity outcomes from the expansion cohort are taken into account, there is a 50% chance that a new, higher MTD will be recommended. Significant improvement in the accuracy of the MTD is obtained 30% of the time (ie, revised MTD is exactly the true MTD), and moderate improvement is obtained 80% of the time when the revised MTD is within a level from true MTD. Failure to include toxicity outcomes from additional patients treated during the expansion phase may result in a less accurate estimate of the MTD. This article provides investigators of phase I protocols with methodological tools to monitor safety and/or efficacy for patients accrued during the expansion phase and to update or confirm the established MTD.
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