Time-to-Event Analysis in PK/PD Modeling: Computation and Model Selection

• Activity Number: 607
• Type: Topic Contributed
• Date/Time: Thursday, August 4, 2011 : 8:30 AM to 10:20 AM
• Sponsor: Section on Risk Analysis
• Author(s): Munni Begum*+
• Companies: Ball State University
• Keywords: Risk assessment ; Pharmacokinetics ; Pharmacodynamics ; Dose-response ; Cox Proportional Hazards Model

Abstract

The risk assessment process of environmental agents includes several tasks: hazard identification, exposure assessment, dose-response or concentration-response modeling, and risk characterization. It is the dose-response modeling where we primarily employ statistical analysis. In this paper we consider an integrated approach to obtain predicted concentrations from the pharmacokinetic (PK) modeling and use these as target tissue exposure in the pharmacodynamic (PD) modeling. Both discrete and continuous responses are considered with an emphasis to modeling time-to-event data. The computational aspects and the model selection problem are discussed for semi-parametric Cox Proportional Hazards Model as a PD model. A simulation study followed by the risk assessment of the heavy metal arsenic is conducted using the integrated PK/PD model to address the uncertainty factors of arsenic risk assessment.