Yale University
Department of Statistics

Monday, October 30, 1995
Guangrui Ray Zhu
Food and Drug Administration

Using Nonlinear Mixed Effect Modeling to Define Pharmacological Processes In Population

Seminar to be held in Room 309, 24 LEPH, 60 College Street

Population profile of a drug's mechanism and kinetics in patients, e.g. population pharmacokinetics (PK) and/or pharmacodynamics (PD), can be of important value in accelerating the clinical development process and in increasing the therapeutical success rate of the drug in the overall patient population. The utility of population PK/PD information in improving clinical trial outcome will be addressed along with the new challenges that pharmaco-statisticians face regarding population PK/PD data collection and statistical analyses. In particular, when multiple observations from one or more pharmacological processes at individual level are too weak to accurately describe those process for the individual, nonlinear mixed effect modeling can be used to fit the data from all individuals to still accurately estimate the population parameters. This talk is also going to examine an example of using sparsely collected plasma concentration data from phase III trials to identify the influences of age and the presences of several co-administered anti-epileptic drugs to the pharmacokinetics of a new anti-epileptic drug. Issues to be discussed will include: exploring the nature of the relationship between PK and population covariates, utilization of empirical Bayes estimates to strengthen individual information through data from other individuals in the population, intense computation, and topics for future development.