ArticleStatistics in medicine2016
Dimension of model parameter space and operating characteristics in adaptive dose-finding studies.
Article in Statistics in medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Trial
- BAR12: Bayesian Autoregressive Phase 1-2 Design for Cell Therapy Trials With Manufacturing Changes.Statistics in medicine · 2026Article
- BARD: A seamless two-stage dose optimization design integrating backfill and adaptive randomization.Clinical trials (London, England) · 2025Article
- On Inclusion of Covariates in Model Based Dose Finding Clinical Trial Designs.Statistics in medicine · 2025Article
- Phase I/II Design for Selecting Subgroup-Specific Optimal Biological Doses for Prespecified Subgroups.Statistics in medicine · 2024Article
- Local continual reassessment methods for dose finding and optimization in drug-combination trials.Statistical methods in medical research · 2023Article
- Stopping rules for phase I clinical trials with dose expansion cohorts.Statistical methods in medical research · 2022Article
- Phase I clinical trials in adoptive T-cell therapies.Journal of the Royal Statistical Society. Series C, Applied statistics · 2021Article
- Adaptive dose-finding based on safety and feasibility in early-phase clinical trials of adoptive cell immunotherapy.Clinical trials (London, England) · 2020Article
- Improving safety of the continual reassessment method via a modified allocation rule.Statistics in medicine · 2020Article
- Coherence principles in interval-based dose finding.Pharmaceutical statistics · 2020Article
- How to design a dose-finding study using the continual reassessment method.BMC medical research methodology · 2019Article
- A web tool for designing and conducting phase I trials using the continual reassessment method.BMC cancer · 2018Article
- A Bayesian dose-finding design incorporating toxicity data from multiple treatment cycles.Statistics in medicine · 2017Article
- Integrating the escalation and dose expansion studies into a unified Phase I clinical trial.Contemporary clinical trials · 2016Article
- On the relative conservativeness of Bayesian logistic regression method in oncology dose-finding studies.Pharmaceutical statisticsArticle
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Authors and funding
6 authors.
Funding
Abstract
Adaptive, model-based, dose-finding methods, such as the continual reassessment method, have been shown to have good operating characteristics. One school of thought argues in favor of the use of parsimonious models, not modeling all aspects of the problem, and using a strict minimum number of parameters. In particular, for the standard situation of a single homogeneous group, it is common to appeal to a one-parameter model. Other authors argue for a more classical approach that models all aspects of the problem. Here, we show that increasing the dimension of the parameter space, in the context of adaptive dose-finding studies, is usually counter productive and, rather than leading to improvements in operating characteristics, the added dimensionality is likely to result in difficulties. Among these are inconsistency of parameter estimates, lack of coherence in escalation or de-escalation, erratic behavior, getting stuck at the wrong level, and, in almost all cases, poorer performance in terms of correct identification of the targeted dose. Our conclusions are based on both theoretical results and simulations. Copyright © 2016 John Wiley & Sons, Ltd.
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