ArticleInternational journal of environmental research and public health2021
Using an Interaction Parameter in Model-Based Phase I Trials for Combination Treatments? A Simulation Study.
Article in International journal of environmental research and public health, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- A Novel Method for Inserting Dose Levels Mid-Trial in Early-Phase Oncology Combination Studies.Statistics in medicine · 2026Article
- Using circulating tumor DNA as a novel biomarker of efficacy for dose-finding designs in oncology.Statistical methods in medical research · 2025Article
- Seamless monotherapy-combination phase I dose-escalation model-based design.Clinical trials (London, England) · 2025Article
- On Inclusion of Covariates in Model Based Dose Finding Clinical Trial Designs.Statistics in medicine · 2025Article
- Joint TITE-CRM: A Design for Dose Finding Studies for Therapies with Late-Onset Safety and Activity Outcomes.Statistics in biopharmaceutical research · 2025Article
- SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.EClinicalMedicine · 2025Article
- A comparison of model-free phase I dose escalation designs for dual-agent combination therapies.Statistical methods in medical research · 2024Article
- Local continual reassessment methods for dose finding and optimization in drug-combination trials.Statistical methods in medical research · 2023Article
- Dose finding studies for therapies with late-onset toxicities: A comparison study of designs.Statistics in medicine · 2022Article
- Practical implementation of the partial ordering continual reassessment method in a Phase I combination-schedule dose-finding trial.Statistics in medicine · 2022Article
- Modeling synergism in early phase cancer trials with drug combination with continuous dose levels: is there an added value?Brazilian journal of biometrics · 2022Article
- A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial.Pharmaceutical statistics · 2022Article
- Practical recommendations for implementing a Bayesian adaptive phase I design during a pandemic.BMC medical research methodology · 2022Article
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Authors and funding
4 authors.
Funding
Abstract
There is growing interest in Phase I dose-finding studies studying several doses of more than one agent simultaneously. A number of combination dose-finding designs were recently proposed to guide escalation/de-escalation decisions during the trials. The majority of these proposals are model-based: a parametric combination-toxicity relationship is fitted as data accumulates. Various parameter shapes were considered but the unifying theme for many of these is that typically between 4 and 6 parameters are to be estimated. While more parameters allow for more flexible modelling of the combination-toxicity relationship, this is a challenging estimation problem given the typically small sample size in Phase I trials of between 20 and 60 patients. These concerns gave raise to an ongoing debate whether including more parameters into combination-toxicity model leads to more accurate combination selection. In this work, we extensively study two variants of a 4-parameter logistic model with reduced number of parameters to investigate the effect of modelling assumptions. A framework to calibrate the prior distributions for a given parametric model is proposed to allow for fair comparisons. Via a comprehensive simulation study, we have found that the inclusion of the interaction parameter between two compounds does not provide any benefit in terms of the accuracy of selection, on average, but is found to result in fewer patients allocated to the target combination during the trial.
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