19 T.W. Alexander Drive
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info@samsi.info

2010-11 Program on Semiparametric Bayesian Inference: Applications in Pharmacokinetics and Pharmacodynamics
July 12-23, 2010

Research Foci
Description of Activities
Application
Schedule
Further Information

Research Foci

Pharmacokinetics (PK) is the study of the time course of drug concentration resulting from a particular dosing regimen. PK is often studied in conjunction with pharmacodynamics (PD). PD explores what the drug does to the body, i.e., the relationship of drug concentrations and a resulting pharmcological effect. Pharmacogenetics (PGx) studies the genetic variation that determines differing response to drugs. Understanding the PK, PD and PGx of a drug is important for evaluating efficacy and determining how best to use such agents clinically.

Hierarchical models have allowed great progress in statistical inference in many application areas. Hierarchical models for PK and PD data that allow borrowing of strength across a patient population are known as population PK/PD models. These models have allowed investigators to learn about important sources of variation in drug absorption, disposition, metabolism, and excretion, allowing the researchers to begin to tailor drug therapy to individuals. Newer Bayesian non-parametric population models and semi-parametric models offer the promise of individualizing therapy and discovering subgroups among patients even further, by freeing modelers from restrictive assumptions about underlying distributions of key parameters across the population. The purpose of this program is to bring together a mix of experts in PK and PD modeling, non-parametric Bayesian inference, and computation.

The aims of the program and workshop are (i) to identify the critical new developments of inference methods for PK and PD data; (ii) to determine open challenges; and (iii) to establish inference for PK and PD as an important motivating application area of non-parametric Bayes. We believe that (iii) is particularly important for new and promising researchers.

The Program Leaders Committee is currently comprised of Gary Rosner and Peter Mueller (M.D. Anderson Cancer Center). A program committee of five area experts will oversee the scheduling of the first week workshop program.

Description of Activities

The program will begin with a week of tutorials and workshop activities. There will be extended, tutorial-style talks during morning sessions, and contributed and invited research talks during the afternoons. Afternoon talks will be selected to complement topics covered in the morning sessions.

At the end of the first week workshop research working groups will be formed. The working groups will tackle particular research problems in the area. Working group activities can include workshop-style presentations by group members to stimulate discussion on specific issues. Potential themes for these working groups and workshop sessions include

semi-parametric population PK/PD models
dose individualization
probability models for PK/PGx networks
joint inference for PK and PD data

Application

REGISTRATION IS CLOSED. CAPACITY HAS BEEN REACHED

Please make reservations at the Radisson RTP as soon as possible. The SAMSI room block and rate ($109) is effective until July 2, 2010. After this date, there is no guarantee a room will be available. If you have a change in plans, individual room reservations must be cancelled 72 hours prior to arrival. Check-in is at 3:00 PM; check-out is 12:00 noon.

Schedule

Monday, July 12, 2010
Radisson RTP

Tutorials

8:00-8:45 a.m.	Registration and Continental Breakfast
8:45-9:00	Welcome & Overview
9:00-10:45	Tutorial 1 Wes Johnson, Univ. of California-Irvine and David Dunson, Duke University Bayesian Nonparametrics: An Overview
10:45-11:15	Break
11:15-12:30	Tutorial 1, continued
12:30-1:30	Lunch
1:30-3:00	Tutorial 2 David D'Argenio, University of Southern California and Paolo Vicini, Pfizer Pharmacokinetics (PK) and Pharmacodynamics (PD)
3:00-3:30	Break
3:30-5:00	Tutorial 2, continued

Tuesday, July 13, 2010
Radisson RTP

Opening Workshop

8:00-9:00 a.m.	Registration and Continental Breakfast
9:00-Noon	Prior Elicitation and Construction
9:00-9:45	Wes Johnson, Univ. of California-Irvine On the Value of Incorporating Scientific Input in Modeling and Data Analysis, and How to Do it Without (too much) Pain
9:45-10:30	Peter Thall, MDACC Prior Elicitation in Bayesian Clinical Trial Design
10:30-11:00	Break
11:00-11:45	Siva Sivaganesan, University of Cincinnati Sample Size: How Many Subjects
11:45-12:00	Discussion
Noon-1:00	Lunch
1:00-2:30	Lang Li, Indiana University and Paolo Vicini, Pfizer Identifiability and Prior Regularization: A PK-PD Modeling View
2:30-3:00	Break
3:00-3:45	Robert Leary, Pharsight Computational Challenges of Nonlinear Mixed Effects Analysis for PK/PD Modeling
3:45-4:30	Sujit Ghosh, N.C. State University Application of Nonlinear Mixed Models Involving ODEs
4:30-5:00	Discussion

Wednesday, July 14, 2010
Radisson RTP

8:00-9:00 a.m.	Registration and Continental Breakfast
9:00-Noon	Joint PK and PD
9:00-9:45	Wojciech Krzyzanski, State University of New York PD/PD Modeling of Therapeutic Effects of Erythropoietin
9:45-10:30	Michele Guidani, University of New Mexico NP Bayes Functional Regression for a PK/PD Semi-Mechanistic Model
10:30-11:00	Break
11:00-11:45	Thanasis Kottas, Univ. of California-Santa Cruz A Bayesian Nonparametric Modeling Approach for Developmental Toxicology Data
11:45-12:00	Discussion
Noon-1:00	Lunch
1:00-2:30	David Conti, University of Southern California; Duncan Thomas, University of Southern California Bayesian Hierarchical and PD/PK Modeling for Complex Pathways in Molecular Epidemiology
2:30-3:00	Mike Reed, Duke University Why Metabolism is a Challenge for Statistical Analysis: the Case of Substrate Inhibition
3:00-3:30	Break
3:30-4:15	Peter Mueller, MD Anderson Nonparametric Bayesian Models for Population PK/PD
4:15-5:00	Donatello Telesca, Univ. of California-Los Angeles Modeling Pk/PGx Data
5:00-5:30	Discussion

Thursday, July 15, 2010
Radisson RTP

8:00-8:45 a.m.	Registration and Continental Breakfast
9:00-12:30	DDP, Mixture Models and Related Models
9:00-9:45	Subharup Guha, University of Missouri Posterior Simulation in Countable Mixture Models for Large Data Sets
9:45-10:30	Steve MacEachern, Ohio State University Nonparametric Bayesian Models for Related Subpopulations
10:30-11:00	Break
11:00-11:45	Maria de Iorio, Imperial College Nonparametric Approaches for Heterogeneous Longitudinal Data
11:45-12:30	Tatiana Tatarinova, University of Glamorgan Analysis of Biological Time Series Data in Data-Rich Situations
12:30-1:30	Lunch
1:30-2:10	Roger Jelliffe, University of Southern California Tools for Individualizing Drug Dosage Regimens for Patients
2:10-2:50	William Gillespie, Metrum Institute Examples of Decison-Focused Modeling and Simulation in Clinical Drug Development and Some Methodology R&D Opportunities They Suggest
2:50-3:30	Gary Rosner, Johns Hopkins University Optimal Design with Bayesian Nonparametric Priors
3:30-4:00	Break
4:00-5:00	David D'Argenio, University of Southern California; William Gillespie, Metrum Institute; Roger Jelliffe, University of Southern California; Bob Leary, Pharsight Implementation and Available Software
5:00-5:30	Poster Advertisement Session: 2 minute ads by each poster presenter
6:00-8:00	Poster Session and Reception SAMSI will provide poster presentation boards and tape. The board dimensions are 4 ft. wide by 3 ft. high. They are tri-fold with each side being 1 ft. wide and the center 2 ft. wide. Please make sure your poster fits the board. The boards can accommodate up to 16 pages of paper measuring 8.5 inches by 11 inches.
8:00-	Informal Debate: Parametric PD Models vs. Nonparametric PD Models

Friday, July 16, 2010
Radisson RTP

8:00-9:00 a.m.	Registration and Continental Breakfast
9:00-12:15	Nonparametric Bayes and Clustering for Random Effects Distributions:
9:00-9:45	David Dahl, Texas A&M University Strategies for Incorporating Prior Information in Random Partition Models with Examples
9:45-10:30	Mahlet Tadesse, Georgetown University Stochastic Partitioning and Model-based Clustering with Variable Selection
10:30-11:00	Break
11:00-11:45	Julien Cornebise, University of British Columbia Inference for Mixed Effects Stochastic Differential PKPD Models with Particle MCMC
11:45-12:15	Gary Rosner, Johns Hopkins University and Peter Mueller, University of Texas Summary and Discussion
12:15-1:30	Lunch
1:30-2:30	Formation of Working Groups
2:30-3:00	Break
3:00-4:00	Initial Discussions

Monday, July 19 - Thursday, July 22
SAMSI, RTP, Rooms 104, 150, 201, 203, 259

Monday, July 19
William Gillespie, Metrum Institute
Part II of Examples of Decison-Focused Modeling and Simulation in Clinical Drug Development and Some Methodology R&D Opportunities They Suggest

Tuesday, July 20
Susie Bayarri, University of Valencia
Dealing with Uncertainty in Mechanistic Models 101

Working Groups - TBA
Possible Themes:

Identifiability and Prior Regularization
Joint PK and PD Modeling
PK/PD Simulation for Design and Dose Individualization
Pharmacogenomics and Networks
Nonparametric Bayes and Clustering for PK and PD Population Analysis

12:00-1:30

Lunch

Friday, July 23
SAMSI

9:30-12:00	Presentations by working groups and discussion about future projects
12:00-1:30	Lunch
1:30	Adjourn

Further Information

For additional information about the program, send an email to bayesummer@samsi.info.

Please send a letter describing your interest, along with a vita (if a new researcher), to the indicated e-mail address.

2010-11 Program on Semiparametric Bayesian Inference: Applications in Pharmacokinetics and Pharmacodynamics July 12-23, 2010