Dose-finding in phase I clinical trials based on toxicity probability intervals.
BACKGROUND
Most phase I clinical trials conducted at the M. D. Anderson Cancer Center use the algorithmic 3 + 3 design, despite the availability of more advanced model-based designs such as the continual reassessment method.


OBJECTIVE
Through simple statistical modeling and computing, we develop a dose-finding design that can be easily understood and implemented by non-statisticians.


METHODS
We propose a beta/binomial Bayesian model and a probabilistic up-and-down rule that allow all possible dose-assignment actions to be tabulated in a spreadsheet. We have developed an Excel macro (available at http://odin.mdacc. tmc.edu/~yuanj) that generates trial monitoring tables, which contain the dose-assignment actions corresponding to various toxicity outcomes.


RESULTS
The new design outperforms the 3 + 3 design and performs comparably to other model-based methods in the literature.


CONCLUSIONS
The proposed method assumes that the observed toxicity is a binary variable and that toxicity increases with dose level.


CONCLUSIONS
The new dose-finding design enables physicians to readily determine dose assignments for new patients by referencing a trial monitoring table.
Ji
Yuan
Y
Department of Bioinformatics and Computational Biology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA. yuanji@mdanderson.org
Li
Yisheng
Y
Nebiyou Bekele
B
B
D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001499:Bayes Theorem; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000706:statistics & numerical data*; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D015233:Models, Statistical; D011336:Probability; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012107:Research Design
D011505:Protein-Tyrosine Kinases