A Bayesian Adaptive Design in Cancer Phase I Trials Using Dose Combinations in the Presence of a Baseline Covariate
Joint Authors
Diniz, Márcio Augusto
Kim, Sungjin
Tighiouart, Mourad
Source
Journal of Probability and Statistics
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-11-01
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
A Bayesian adaptive design for dose finding of a combination of two drugs in cancer phase I clinical trials that takes into account patients heterogeneity thought to be related to treatment susceptibility is described.
The estimation of the maximum tolerated dose (MTD) curve is a function of a baseline covariate using two cytotoxic agents.
A logistic model is used to describe the relationship between the doses, baseline covariate, and the probability of dose limiting toxicity (DLT).
Trial design proceeds by treating cohorts of two patients simultaneously using escalation with overdose control (EWOC), where at each stage of the trial, the next dose combination corresponds to the α quantile of the current posterior distribution of the MTD of one of two agents at the current dose of the other agent and the next patient’s baseline covariate value.
The MTD curves are estimated as function of Bayes estimates of the model parameters at the end of trial.
Average DLT, pointwise average bias, and percent of dose recommendation at dose combination neighborhoods around the true MTD are compared between the design that uses the covariate and the one that ignores the baseline characteristic.
We also examine the performance of the approach under model misspecifications for the true dose-toxicity relationship.
The methodology is further illustrated in the case of a prespecified discrete set of dose combinations.
American Psychological Association (APA)
Diniz, Márcio Augusto& Kim, Sungjin& Tighiouart, Mourad. 2018. A Bayesian Adaptive Design in Cancer Phase I Trials Using Dose Combinations in the Presence of a Baseline Covariate. Journal of Probability and Statistics،Vol. 2018, no. 2018, pp.1-11.
https://search.emarefa.net/detail/BIM-1197705
Modern Language Association (MLA)
Diniz, Márcio Augusto…[et al.]. A Bayesian Adaptive Design in Cancer Phase I Trials Using Dose Combinations in the Presence of a Baseline Covariate. Journal of Probability and Statistics No. 2018 (2018), pp.1-11.
https://search.emarefa.net/detail/BIM-1197705
American Medical Association (AMA)
Diniz, Márcio Augusto& Kim, Sungjin& Tighiouart, Mourad. A Bayesian Adaptive Design in Cancer Phase I Trials Using Dose Combinations in the Presence of a Baseline Covariate. Journal of Probability and Statistics. 2018. Vol. 2018, no. 2018, pp.1-11.
https://search.emarefa.net/detail/BIM-1197705
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1197705