Biomaterial Database

A model-based approach in the estimation of the maximum tolerated dose in phase I cancer clinical trials. 2006

Weili He, and Jun Liu, and Bruce Binkowitz, and Hui Quan

Clinical Biostatistics, Merck Research Labs, Merck & Co., Inc., Rahway, NJ 07065, USA. weili_he@merck.com

The primary aim of a phase I cancer clinical trial is to determine the maximum tolerated dose (MTD) of a new agent. The MTD is determined as the highest dose level of a potential therapeutic agent at which the patients have experienced an acceptable level of dose limiting toxicity. Although many other types of designs have been proposed in recent years, the traditional algorithm-based designs, especially the 3+3 designs, are still widely used due to their practical simplicity. Simulation studies have shown that the traditional algorithm-based designs cannot provide reasonable estimates of the MTD due to their intrinsic design limitations. In this paper, we propose a model-based approach in the estimation of the MTD following a traditional 3+3 design. Simulation results indicate that our model-based approach produces much less biased estimates of the MTD compared to the estimates obtained from the traditional 3+3 designs. Furthermore, our model-based approach can be easily extended to any traditional A+B design.

UI	MeSH Term	Description	Entries
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D003198	Computer Simulation	Computer-based representation of physical systems and phenomena such as chemical processes.	Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D003627	Data Interpretation, Statistical	Application of statistical procedures to analyze specific observed or assumed facts from a particular study.	Data Analysis, Statistical,Data Interpretations, Statistical,Interpretation, Statistical Data,Statistical Data Analysis,Statistical Data Interpretation,Analyses, Statistical Data,Analysis, Statistical Data,Data Analyses, Statistical,Interpretations, Statistical Data,Statistical Data Analyses,Statistical Data Interpretations
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000465	Algorithms	A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.	Algorithm
D000970	Antineoplastic Agents	Substances that inhibit or prevent the proliferation of NEOPLASMS.	Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D015233	Models, Statistical	Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.	Probabilistic Models,Statistical Models,Two-Parameter Models,Model, Statistical,Models, Binomial,Models, Polynomial,Statistical Model,Binomial Model,Binomial Models,Model, Binomial,Model, Polynomial,Model, Probabilistic,Model, Two-Parameter,Models, Probabilistic,Models, Two-Parameter,Polynomial Model,Polynomial Models,Probabilistic Model,Two Parameter Models,Two-Parameter Model
D017321	Clinical Trials, Phase I as Topic	Works about studies performed to evaluate the safety of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in healthy subjects and to determine the safe dosage range (if appropriate). These tests also are used to determine pharmacologic and pharmacokinetic properties (toxicity, metabolism, absorption, elimination, and preferred route of administration). They involve a small number of persons and usually last about 1 year. This concept includes phase I studies conducted both in the U.S. and in other countries.	Clinical Trials, Phase I,Drug Evaluation, FDA Phase I,Evaluation Studies, FDA Phase I,Human Microdosing Trial,Phase 1 Clinical Trial,Phase I Clinical Trial,Phase I Clinical Trials,Clinical Trials, Phase 1,Drug Evaluation, FDA Phase 1,Drug Evaluation, FDA Phase I as Topic,Evaluation Studies, FDA Phase 1,Human Microdosing Trials,Microdosing Trials, Human,Phase 1 Clinical Trials,Microdosing Trial, Human,Trial, Human Microdosing,Trials, Human Microdosing
D020714	Maximum Tolerated Dose	The highest dose of a biologically active agent given during a chronic study that will not reduce longevity from effects other than carcinogenicity. (from Lewis Dictionary of Toxicology, 1st ed)	Maximal Tolerated Dose,Maximally Tolerated Dose,Dose, Maximal Tolerated,Dose, Maximally Tolerated,Dose, Maximum Tolerated,Doses, Maximal Tolerated,Doses, Maximally Tolerated,Doses, Maximum Tolerated,Maximal Tolerated Doses,Maximally Tolerated Doses,Maximum Tolerated Doses,Tolerated Dose, Maximal,Tolerated Dose, Maximally,Tolerated Dose, Maximum,Tolerated Doses, Maximal,Tolerated Doses, Maximally,Tolerated Doses, Maximum