Journal ArticleDOI
Two-dimensional dose finding in discrete dose space.
Kai Wang,Anastasia Ivanova +1 more
TLDR
This article proposes a Bayesian design that uses a parsimonious working model for the dose-toxicity relationship and shows that the new design is more effective in identifying the maximum-tolerated combinations than one-dimensional designs applied at each dose level of one of the agents.Abstract:
The objective of a Phase I trial with two agents is to find a set of maximum-tolerated dose combinations that yield a prespecified toxicity rate. In this article, we consider the case where several doses of one agent are fixed and the goal is to find the maximum-tolerated dose of the other agent to be used in combination with each of the doses of agent one. We propose a Bayesian design that uses a parsimonious working model for the dose-toxicity relationship. We show that the new design is more effective in identifying the maximum-tolerated combinations than one-dimensional designs applied at each dose level of one of the agents.read more
Citations
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Journal ArticleDOI
Continual reassessment method for partial ordering.
TL;DR: A new two-dimensional dose-finding method for multiple-agent trials that simplifies to the continual reassessment method (CRM), introduced by O'Quigley, Pepe, and Fisher (1990, Biometrics 46, 33-48), when the ordering is fully known, enables the assumption of a monotonic dose-toxicity curve to be relaxed.
Journal ArticleDOI
Bayesian dose finding in oncology for drug combinations by copula regression
Guosheng Yin,Ying Yuan +1 more
TL;DR: A Bayesian adaptive design for dose finding that is based on a copula‐type model to account for the synergistic effect of two or more drugs in combination to search for the maximum tolerated dose combination.
Journal ArticleDOI
A Latent Contingency Table Approach to Dose Finding for Combinations of Two Agents
Guosheng Yin,Ying Yuan +1 more
TL;DR: A Bayesian adaptive design for dose finding based on latent 2 × 2 tables is proposed, which continuously update the posterior estimates for the unknown parameters associated with marginal probabilities and the correlation parameter based on the data from successive patients.
Journal ArticleDOI
A Parallel Phase I/II Clinical Trial Design for Combination Therapies
TL;DR: Simulation studies show that the proposed design saves sample size, has better power, and efficiently assigns more patients to doses with higher efficacy levels, compared to a conventional phase I and phase II trial.
Journal ArticleDOI
Dose-finding design for multi-drug combinations:
TL;DR: A new dose-finding design which relaxes the monotonicity assumption and can serve as a link between single and multiple-agent dosefinding trials and can be considered a multivariate generalization of the CRM.
References
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Journal ArticleDOI
Continual reassessment method: a practical design for phase 1 clinical trials in cancer.
TL;DR: A new approach to the design and analysis of Phase 1 clinical trials in cancer and a particularly simple model is looked at that enables the use of models whose only requirements are that locally they reasonably well approximate the true probability of toxic response.
Journal ArticleDOI
Design and analysis of phase I clinical trials.
TL;DR: In Monte Carlo simulations, two two-stage designs are found to provide reduced bias in maximum likelihood estimation of the MTD in less than ideal dose-response settings and several designs to be nearly as conservative as the standard design in terms of the proportion of patients entered at higher dose levels.
Journal ArticleDOI
Some practical improvements in the continual reassessment method for phase I studies
TL;DR: Modifications to the Continual Reassessment Method (CRM) are presented, in which one assigns more than one subject at a time to each dose level, and each dose increase is limited to one level, which makes the CRM acceptable to clinical investigators.
Journal ArticleDOI
A comparison of two phase I trial designs.
Edward L. Korn,Douglas Midthune,T. Timothy Chen,Larry Rubinstein,Michaele C. Christian,Richard M. Simon +5 more
TL;DR: The results indicate that with the continual reassessment method, more patients will be treated at very high doses and the trials will take longer to complete.
Journal ArticleDOI
Dose-finding with two agents in Phase I oncology trials
TL;DR: An adaptive two‐stage Bayesian design for finding one or more acceptable dose combinations of two cytotoxic agents used together in a Phase I clinical trial is proposed and a simulation study is presented.
Related Papers (5)
Dose-finding with two agents in Phase I oncology trials
Continual reassessment method: a practical design for phase 1 clinical trials in cancer.
Bayesian dose finding in oncology for drug combinations by copula regression
Guosheng Yin,Ying Yuan +1 more