Statistical Modeling of Tumor Regrowth and the Assessment of Drugs Synergy in Animal Experiments

• Activity Number: 57
• Type: Topic Contributed
• Date/Time: Sunday, August 1, 2010 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Eugene Demidenko*+
• Companies: Dartmouth Medical School
• Keywords: tumor regrowth ; Gompretz curve ; cell kill ; mixed model

Abstract

While many studies confirm that the growth of untreated tumors in animals follows the Gompertz curve, modeling the dynamic of tumors after treatment is still a challenging problem of cancer research. Development of predictive parsimonious mathematical tumor-regrowth models with biologically interpreted parameters is a long-standing problem of biostatistics. The goal of the present paper is to share our year-long experience in statistical model building for tumor growth delay data where the rate of regrowh is a function of the drug concentration and/or radiation dose. A rigorous definition of the drug synergy and its statistical testing is presented. Several models with biologically interpreted parameters will be reviewed. Methods of longitudinal data analysis based on linear and nonlinear mixed effects models are emphasized.