Pharmacokinetic-Pharmacodynamic modeling of Continuous
and Categorical data in NONMEM
(A NONMEM Workshop for intermediate and advanced users)

St. Petersburg, Russia, June 21-23, 2009
(Prior to the PAGE meeting)

Overview

The Uppsala Pharmacometrics group is happy to announce a NONMEM Workshop on Pharmacokinetic-Pharmacodynamic (PK/PD) modeling of Continuous and Categorical data tailored for Intermediate and Advanced NONMEM users. The Uppsala group has been involved in developing NONMEM models and methodology for over fifteen years and has extensive experience in development of PKPD models, model building procedures and methods for modeling continuous and categorical data using non-linear mixed-effects modeling in NONMEM. In parallel, informative diagnostics for model building and model evaluation have been developed, evaluated and integrated into the user-friendly software Perl-speaks-NONMEM (PsN) and Xpose 4 (described below).

In this course the Uppsala group will present modeling strategies, techniques and implementations (using NONMEM) for the handling of PK and PD information in population models. PD models for continuous data as well as binary, ordered categorical, count, and (repeated) time to event data will be discussed. The course will also include new models and methods for graphical evaluation of continuous and categorical PK/PD models.

The course will consist of both lectures and hands-on computer exercises using NONMEM VI, PsN and Xpose 4. Self-instructive material is provided for further studies and exploration of examples within the field. The participants will be provided with a NONMEM library of example code for a wide range of PKPD models applied in different disease areas.

Course Outline

• Day 1 – Modeling strategies for PKPD data and models for continuous data
  • Modeling strategies for PKPD data
• Baseline and Biological rhythm models
• Placebo effects and Disease progression models
• Drug effect and physiological component models
• Model building diagnostics for  PKPD models
• Stochastic models for PKPD data
• Introduction to PsN and Xpose
• Hands-on computer exercises with NONMEM VI, PsN and Xpose

• Day 2 – PKPD modeling for categorical data and time-to-event data
• Models, diagnostics and model building for binary data
• Models, diagnostics and model building for ordered categorical data
• Models, diagnostics and model building for non-ordered categorical data
• Models, diagnostics and model building for (repeated) time-to-event data
• Models, diagnostics and model building for count data
• Hands-on computer exercises for all types of events with NONMEM VI, PsN and Xpose

• Day 3 – PD models for categorical data (0.5 day)
• Markov models for categorical data
• Models for a mixture of continuous and categorical data
• Drop-out models
• Hands-on computer exercises with NONMEM VI, PsN and Xpose

Prerequisite
Experience with performing NONMEM analyses. Basic knowledge of PK/PD models.

Practical Information

The course starts the 21st of June 2009 (registration at 8.30 am, lectures start at 9.00 am). The course ends at 12.00 pm the 23rd of June 2009. There will be a welcome reception on the first day.

Course Fee
Regular fee: €1,800 (early bird - before March 1, 2009), €2,300 (late bird - after March 1, 2009)
Student/Post-doc fee: €1,250

Registration fee includes: hardcopy folder, extensive electronic material including lectures, exercises, programs (PsN and Xpose), additional self-study material including hands-ons and solutions. Morning and afternoon refreshments, lunch and a welcome reception are included.

Note: Attendance is strictly limited to 50 with a limited “reduced fee” places available for Students/Post-docs. Registration will be offered on the basis of first come, first served.

To register
Please register online at
www.dinkurs.se/applyance/?event_id=1940

PLEASE NOTE: prices on this registration site are in Swedish Kronor, based on the exchange rate for Tuesday, January 13, 2009.

If you have problems, e-mail Andrew Hooker at andrew.c.hooker@gmail.com

Registation is not complete until payment is recieved.

Cancellation: Refunds will be provided on or before February 15, 2009. Registrants are welcome to swap their place with another person at any time.

Computer hardware/software
The course will include hands-on training, with the participants working on their own computers.  All programs will run from a USB memory-stick and participants will not be required to install any programs on their computer. NOTE: All participants must bring their own Windows laptops. PsN and Xpose 4 are freeware and may be installed on participants’ computers for use after the course.

Xpose 4 is a model building aid for population analysis using NONMEM. Xpose produces various plots and analyses to facilitate data set checkout, goodness-of-fit analysis, model exploration and visualization, model diagnostics, candidate covariate identification and model comparison.  Xpose 4 is written in the programming language R with a modular and object oriented design and allows for integration into nearly any model building platform.  New functionality in Xpose 4 allows the user to create simulation based reference diagnostics, create visual and numerical predictive check plots, compute the conditional weighted residuals and modify standard Xpose graphics to create publication quality figures.  Xpose 4 also makes use of the new features in NONMEM VI including the visualization of non-parametric parameter distributions and individual objective function contributions.  Xpose is freely available at xpose.sf.net.

Perl-speaks-NONMEM (PsN) is a collection of Perl modules and programs aiding in the development of non-linear mixed effect models using NONMEM. The functionality ranges from simpler tasks such as parameter estimate extraction from output files, data file sub setting and resampling, to advanced computer-intensive statistical methods. PsN includes both stand-alone tools as well as development libraries for method developers.  PsN is freely available at psn.sf.net.

Instructors
Prof. Mats Karlsson
Mats Karlsson is professor of Pharmacometrics at Uppsala University, Sweden where he leads a research group of about twenty-five modelers. He received his PhD in pharmacokinetics from this university in 1989 and has been a research fellow at University of Glasgow and University of California, San Francisco, and a visiting professor at Georgetown University, Washington DC. He has received the Giorgio Segre Prize from EUFEPS and is editor for the Journal of Pharmacokinetics and Pharmacodynamics. His research interests focus on methodological aspects of non-linear mixed effects model building and applied PKPD modeling. He has published over one hundred fifty original research articles in the area of PK and PKPD.

Dr Lena Friberg
Lena Friberg is an associate professor of Pharmacometrics at Uppsala University, Sweden. Lena obtained her PhD from Uppsala University in 2003 and received a fellowship from Knut & Alice Wallenberg foundation for a 1.5 year postdoc at University of Queensland, Australia, and a 3 year research position at Uppsala University. Lena is now a researcher in pharmacometrics and a part-time lecturer. Her research is focused on development of (mechanistic) PKPD-models for effects and adverse events of drugs used in different disease areas, for example oncology, infection, schizophrenia and rheumatoid arthritis.  

Dr Andrew Hooker
Andrew Hooker is an associate professor of pharmacometrics at Uppsala University, Sweden. Andrew received his PhD in Bioengineering from the University of Washington, Seattle, USA in 2003, and then moved to Sweden as a Pfizer post-doctoral fellow at Uppsala University.  His research focuses on methodological problems associated with building and evaluating pharmacometric models as well as optimal experimental design. Andrew is a primary developer of both Xpose 4 and the optimal design program PopED. 

Dr Ulrika Simonsson
Ulrika Simonsson is an associate professor of Phamacokinetics at Uppsala University, Sweden. Ulrika received her PhD from Uppsala University in 2000 and spent one year as a postdoc fellow at Pharsight, MountainView, CA. She has a 2 years experience of working at AstraZeneca where she received an innovation award for implementation of model-based drug development as well as a reward as a talented young scientist. Her research involves development of PKPD models for several therapeutic areas such as anticoagulation, tuberculosis, HIV, malaria and pain.