Simulation for Designing Clinical Trials: A Pharmacokinetic-Pharmacodynamic Modeling Perspective by Hui Kimko, Stephen B. Duffull

Summary

Providing more than just a comprehensive history, critical vocabulary, insightful compilation of motivations, and clear explanation of the state-of-the-art of modern clinical trial simulation, this book supplies a rigorous framework for employing simulation as an experiment, according to a predefined simulation plan, that reflects good simulation practices. The book discusses how to clinical trial designs according to their probability for success, techniques to define distributions of virtual subjects' characteristics, methods to determine the sensitivity of the trial design, and the population relationship between dosing schedules and patient response.

TABLE OF CONTENTS :

Introduction to Simulation for Design of Clinical Trials, H.C. Kimko and S.B. Duffull 

MODELS FOR SIMULATION 
Input-Output Models, N.H. G. Holford 
Defining Covariate Distribution Models for Clinical Trial Simulation, D.R. Mould 
Protocol Deviations and Execution Models, H. Kastrissios and P.l Girard 
Determination of Model Appropriateness, P.J. Williams and E. I. Ette 

COMPUTATION IN SIMULATION 
Computational Considerations in Clinical Trial Simulations, J.C. Pezzullo and H.C. Kimko 

ANALYSES OF THE SIMULATIONS 
Analysis of Simulated Clinical Trials, E.I. Ette, C.J. Godfrey, S. Ogenstad, and P.J. Williams 
Sensitivity Analysis of Pharmacokinetic and Pharmacodynamic Models in Clinical Trial Simulation and Design, I.A. Nestorov 
Choice of Best Design, J.P.R. Monteleone and S.B. Duffull 

PERSPECTIVES ON CLINICAL TRIAL SIMULATION 
Clinical Trial Simulation (CTS): A Regulatory Clinical Pharmacology Perspective, P.I.D. Lee and L.J. Lesko 
Academic Perspective: Modeling and Simulation as a Teaching Tool, N.H.G. Holford and M.O. Karlsson 
Modeling and Simulation of Clinical Trials: An Industry Perspective, T. Goggin, R. Gieschke, G. Pillai, B. Fotteler, P. Jordan, and J.-L. Steimer 
History-Informed Perspectives on the Modeling and Simulation of Therapeutic Drug Actions, J. Urquhart 

APPLICATIONS 
Evaluation of Random Sparse Sampling Designs for a Population Pharmacokinetic Study: Assessment of Power and Bias Using Simulation, M.M. Hutmacher and K.G. Kowalski 
Use of Modeling and Simulation to Optimize Dose-Finding Strategies, J.W. Mandema and W. Wang 
Model-Based Integration for Clinical Trial Simulation and Design: A Phase II Case Study for Naratriptan, I.A. Nestorov, G. Graham, S.B. Duffull, and L. Aarons 
Prediction of Hemodynamic Responses in Hypertensive and Elderly Subjects from Healthy Volunteer Data: The Example of Intravenous Nicardipine, P. Francheteau, H. Merdjan, M. Guerret, S. Kirkesseli, P. Sassano, and J.-L. Steimer 
Assessment of QTc Interval Prolongation in a Phase I Study Using Monte Carlo Simulation, P.L. Bonate 
Optimizing a Bayesian Dose-Adjustment Scheme for a Pediatric Trial: A Simulation Study, M.R. Gastonguay, E. Gibiansky, L. Gibiansky, and J.S. Barrett 

Index