ArticleStatistics in biopharmaceutical research
Dose expansion cohorts in Phase I trials.
Article in Statistics in biopharmaceutical research. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed.
- Review
- CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.EClinicalMedicine · 2025Article
- Phase I/II Design for Selecting Subgroup-Specific Optimal Biological Doses for Prespecified Subgroups.Statistics in medicine · 2024Article
- Bayesian sequential monitoring strategies for trials of digestive cancer therapeutics.BMC medical research methodology · 2024Article
- Treating patients with geographic atrophy: are we there yet?International journal of retina and vitreous · 2023Review
- Enhancing reporting quality and impact of early phase dose-finding clinical trials: CONSORT Dose-finding Extension (CONSORT-DEFINE) guidance.BMJ (Clinical research ed.) · 2023Article
- Controlled amplification in oncology dose-finding trials.Contemporary clinical trials · 2023Article
- A Road Map for Designing Phase I Clinical Trials of Radiotherapy-Novel Agent Combinations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Review
- SEMIPARAMETRIC DOSE FINDING METHODS FOR PARTIALLY ORDERED DRUG COMBINATIONS.Statistica Sinica · 2022Article
- Optimizing the Therapeutic Window of Targeted Drugs in Oncology: Potency-Guided First-in-Human Studies.Clinical and translational science · 2021Article
- Perspectives for the Use of CAR-T Cells for the Treatment of Multiple Myeloma.Frontiers in immunology · 2021Review
- Continual reassessment method with regularization in phase I clinical trials.Journal of biopharmaceutical statistics · 2020Article
- Innovation in Regulatory Science Is Meeting Evolution of Clinical Evidence Generation.Clinical pharmacology and therapeutics · 2019Article
- How to design a dose-finding study using the continual reassessment method.BMC medical research methodology · 2019Article
- Motivating sample sizes in adaptive Phase I trials via Bayesian posterior credible intervals.Biometrics · 2018Article
- Design considerations for early-phase clinical trials of immune-oncology agents.Journal for immunotherapy of cancer · 2018Article
- Sequential monitoring of Phase I dose expansion cohorts.Statistics in medicine · 2017Article
- Dimension of model parameter space and operating characteristics in adaptive dose-finding studies.Statistics in medicine · 2016Article
- Integrating the escalation and dose expansion studies into a unified Phase I clinical trial.Contemporary clinical trials · 2016Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
A rapidly increasing number of Phase I dose-finding studies, and in particular those based on the standard 3+3 design, are being prolonged with the inclusion of dose expansion cohorts (DEC) in order to better characterize the toxicity profiles of experimental agents and to study disease-specific cohorts. These trials consist of two phases: the usual dose escalation phase that aims to establish the maximum tolerated dose (MTD), and the dose expansion phase that accrues additional patients, often with different eligibility criteria, and where additional information is collected. Current protocols do not always specify whether and how the MTD will be updated in light of the new data accumulated from the DEC. In this paper, we propose methods that allow monitoring of safety in the DEC by re-evaluating the MTD in light of additional information. Our working assumption is that, regardless of the design being used for dose escalation, during the DEC we are experimenting in the neighborhood of a target dose with an acceptable rate of toxicity. We refine our initial estimate of the MTD by continuing experimentation in the immediate vicinity of the initial estimate of the MTD. The auxiliary information provided in such an evaluation can include toxicity, pharmacokinetic, efficacy or other endpoints. We consider approaches specifically focused on the aims of DEC that examine efficacy alone or simultaneously with safety and compare the proposed tests via simulations.
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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.