Mohamed Amine Bayar1, Anastasia Ivanova2, Gwénaël Le Teuff3. 1. Service de Biostatistique et d'Épidémiologie, Gustave Roussy, Villejuif, France; INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. 2. Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 3. Service de Biostatistique et d'Épidémiologie, Gustave Roussy, Villejuif, France; INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. Electronic address: gwenael.leteuff@gustaveroussy.fr.
Abstract
BACKGROUND AND OBJECTIVE: The continual reassessment method (CRM) is a model-based dose-finding design for single-agent phase I oncology trials. With the advance of targeted therapies in oncology, more and more phase I trials investigate drug combinations rather than a single agent in order to find one or more maximum tolerated dose combinations. Several designs have been proposed for such dose-finding trials but only a few software packages are available to implement them. One of the designs is the two-dimensional Bayesian CRM proposed by Wang and Ivanova. Our goal was to provide an easy-to-use program to implement this design. METHODS: We developed a new SAS macro, CRM2DIM, for implementing this design. This macro can be used to run a phase I dose-finding trial for two-drug combination and to perform simulations. RESULTS: We describe the program with its different features, including the possibility of running an initial design (start-up rule), the possibility of incorporating historical data, and the choice of using either a power or a logistic regression model with or without interaction term. We illustrate our program by presenting simulation results and by a hypothetical trial example. CONCLUSIONS: The CRM2DIM macro provides a SAS implementation of the two-dimensional Bayesian CRM for dual-agent phase I oncology trials. It is an easy-to-use program that includes many useful features and provides statisticians involved in the early phases of development a new tool for designing dual-agent phase I oncology trials.
BACKGROUND AND OBJECTIVE: The continual reassessment method (CRM) is a model-based dose-finding design for single-agent phase I oncology trials. With the advance of targeted therapies in oncology, more and more phase I trials investigate drug combinations rather than a single agent in order to find one or more maximum tolerated dose combinations. Several designs have been proposed for such dose-finding trials but only a few software packages are available to implement them. One of the designs is the two-dimensional Bayesian CRM proposed by Wang and Ivanova. Our goal was to provide an easy-to-use program to implement this design. METHODS: We developed a new SAS macro, CRM2DIM, for implementing this design. This macro can be used to run a phase I dose-finding trial for two-drug combination and to perform simulations. RESULTS: We describe the program with its different features, including the possibility of running an initial design (start-up rule), the possibility of incorporating historical data, and the choice of using either a power or a logistic regression model with or without interaction term. We illustrate our program by presenting simulation results and by a hypothetical trial example. CONCLUSIONS: The CRM2DIM macro provides a SAS implementation of the two-dimensional Bayesian CRM for dual-agent phase I oncology trials. It is an easy-to-use program that includes many useful features and provides statisticians involved in the early phases of development a new tool for designing dual-agent phase I oncology trials.