Clinical Trial Simulations: Applications and Trends (AAPS Advances in the Pharmaceutical Sciences Series Book 1)

This edition presents a review of the principles and progress surrounding clinical trial simulations (CTS), along with case studies illustrating CTS in various therapeutic and application areas. In addition, the book expands on the utility of CTS for informing decisions during drug development and regulatory review. Each chapter has been written by esteemed authors who have demonstrated expertise in state-of-the-art application of CTS. The target audience for the volume includes researchers and scientists who wish to consider use of simulations in the design, analysis, regulatory review or guidance of clinical trials, and academic researchers and others working in drug development (e.g., clinicians, senior managers, project planning and regulatory affairs professionals). The focus is on the effective utilization of CTS in decision mechanisms. Readers will gain broad knowledge on how CTS can improve the efficiency, informativeness, speed and economy of model-based drug development and regulation. **Holly H.C. Kimko**, PhD is a senior pharmacometrics leader (Research Fellow) at the Department of Advanced Modeling & Simulation in Johnson & Johnson Pharmaceutical Research & Development, LLC, New Jersey, and Adjunct Professor in the faculty of the Pharmacy School of Rutgers University, New Jersey. She was previously Assistant Professor in the Center for Drug Development Science in Georgetown University Medical School, Washington DC. Trained in biochemistry and pharmacy, Dr. Kimko earned her Ph.D. degree in Pharmaceutical Science from the State University of New York, Buffalo. She has published key papers on indirect response modeling and applications of CTS, and co-edited __Simulation for Designing Clinical Trials__. **Carl C. Peck**, MD is Adjunct Professor, Center for Drug Development Science in the Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, California. He was previously Director of the FDA Center for Drug Evaluation and Research, Assistant U.S. Surgeon General, and President of the American Society for Clinical Pharmacology and Therapeutics. Dr. Peck has also held professorial appointments in the faculties of UCSF, USUHS, and Georgetown University. He is an author of more than 150 original research papers, chapters and books concerning advanced concepts and techniques of quantitative pharmacology, trial designs, and pharmaco-statistical modeling and simulation. This edition presents a review of the principles and progress surrounding clinical trial simulations (CTS), along with case studies illustrating CTS in various therapeutic and application areas.¡ In addition, the book expands on the utility of CTS for informing decisions during drug development and regulatory review. Each chapter has been written by esteemed authors who have demonstrated expertise in state-of-the-art application of CTS.¡ The target audience for the volume includes researchers and scientists who wish to consider use of simulations in the design, analysis, ¡regulatory review¡or guidance of clinical trials, and academic researchers and others working in drug development (e.g., clinicians, senior managers, project planning and regulatory affairs professionals). The focus is on the effective utilization¡ of CTS in decision mechanisms. Readers will gain broad knowledge on how CTS can improve the efficiency, informativeness, speed and economy of model-based drug development and regulation. Holly H.C. Kimko, PhD¡is a senior pharmacometrics leader (Research Fellow) at the Department of Advanced Modeling & Simulation in Johnson & Johnson Pharmaceutical Research & Development, LLC, New Jersey, and Adjunct Professor in the faculty of the Pharmacy School of Rutgers University, New Jersey.¡ She was previously Assistant Professor in the Center for Drug Development Science in Georgetown University Medical School, Washington DC. Trained in biochemistry and pharmacy, Dr. Kimko earned her Ph. D. degree in Pharmaceutical Science from the State University of New York, Buffalo.¡ She has published key papers on indirect response modeling and applications of CTS, and co-edited Simulation for Designing Clinical Trials. Carl C. Peck, MD¡is Adjunct Professor, Center for Drug Development Science in the Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, California.¡ He was previously Director of the FDA Center for Drug Evaluation and Research, Assistant U.S. Surgeon General, and President of the American Society for Clinical Pharmacology and Therapeutics.¡ Dr. Peck has also held professorial appointments in the faculties of UCSF, USUHS, and Georgetown University.¡ He is an author of more than 150 original research papers, chapters and books concerning advanced concepts and techniques of quantitative pharmacology, trial designs, and pharmaco-statistical modeling and simulation This edition presents a review of the principles and progress surrounding clinical trial simulations (CTS), along with case studies illustrating CTS in various therapeutic and application areas. In addition, the book expands on the utility of CTS for informing decisions during drug development and regulatory review. Each chapter has been written by esteemed authors who have demonstrated expertise in state-of-the-art application of CTS. The target audience for the volume includes researchers and scientists who wish to consider use of simulations in the design, analysis, regulatory review or guidance of clinical trials, and academic researchers and others working in drug development (e.g., clinicians, senior managers, project planning and regulatory affairs professionals). The focus is on the effective utilization of CTS in decision mechanisms. Readers will gain broad knowledge on how CTS can improve the efficiency, informativeness, speed and economy of model-based drug development and regulation. Holly H.C. Kimko, PhD is a senior pharmacometrics leader (Research Fellow) at the Department of Advanced Modeling & Simulation in Johnson & Johnson Pharmaceutical Research & Development, LLC, New Jersey, and Adjunct Professor in the faculty of the Pharmacy School of Rutgers University, New Jersey. She was previously Assistant Professor in the Center for Drug Development Science in Georgetown University Medical School, Washington DC. Trained in biochemistry and pharmacy, Dr. Kimko earned her Ph. D. degree in Pharmaceutical Science from the State University of New York, Buffalo. She has published key papers on indirect response modeling and applications of CTS, and co-edited Simulation for Designing Clinical Trials. Carl C. Peck, MD is Adjunct Professor, Center for Drug Development Science in the Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, California. He was previously Director of the FDA Center for Drug Evaluation and Research, Assistant U.S. Surgeon General, and President of the American Society for Clinical Pharmacology and Therapeutics. Dr. Peck has also held professorial appointments in the faculties of UCSF, USUHS, and Georgetown University. He is an author of more than 150 original research papers, chapters and books concerning advanced concepts and techniques of quantitative pharmacology, trial designs, and pharmaco-statistical modeling and simulation Front Matter....Pages i-xvi Front Matter....Pages 13-13 Clinical Trial Simulation and Quantitative Pharmacology....Pages 1-11 Front Matter....Pages 13-13 Contribution of Modeling and Simulation Studies in the Regulatory Review: A European Regulatory Perspective....Pages 15-36 Contribution of Modeling and Simulation in the Regulatory Review and Decision-Making: U.S. FDA Perspective....Pages 37-57 Front Matter....Pages 59-59 Decision-Making in Drug Development: Application of a Model Based Framework for Assessing Trial Performance....Pages 61-83 Decision-Making in Drug Development: Application of a Clinical Utility Index SM ....Pages 85-107 Adaptive Trial Designs....Pages 109-130 Keys of Collaboration to Enhance Efficiency and Impact of Modeling and Simulation....Pages 131-148 Leveraging Pharmacometrics in Early Phase Anti-inflamatory Drug Development....Pages 149-172 Front Matter....Pages 173-173 The Application of Drug-Disease Models in the Development of Anti-Hyperglycemic Agents....Pages 175-198 Modeling and Simulation in the Development of Cardiovascular Agents....Pages 199-226 Viral Dynamic Modeling and Simulations in HIV and Hepatitis C....Pages 227-250 A Model-Based PK/PD Antimicrobial Chemotherapy Drug Development Platform to Simultaneously Combat Infectious Diseases and Drug Resistance....Pages 251-279 PKPD and Disease Modeling: Concepts and Applications to Oncology....Pages 281-306 Application of Pharmacokinetic–Pharmacodynamic Modeling and Simulation for Erythropoietic Stimulating Agents....Pages 307-323 Model Based Development of an Agent for the Treatment of Generalized Anxiety Disorder....Pages 325-340 Balancing Efficacy and Safety in the Clinical Development of an Atypical Antipsychotic, Paliperidone Extended-Release....Pages 341-357 Front Matter....Pages 359-359 Application of Modeling and Simulation in the Development of Protein Drugs....Pages 361-396 Modeling and Simulation in Pediatric Research and Development....Pages 397-429 Front Matter....Pages 431-431 Disease Progression Analysis: Towards Mechanism-Based Models....Pages 433-455 Using a Systems Biology Approach to Explore Hypotheses Underlying Clinical Diversity of the Renin Angiotensin System and the Response to Antihypertensive Therapies....Pages 457-482 Front Matter....Pages 431-431 Recent Developments in Physiologically Based Pharmacokinetic Modeling....Pages 483-499 Covariate Distribution Models in Simulation....Pages 501-522 Back Matter....Pages 527-538 This edition includes both updates and new uses and issues concerning CTS, along with case studies of how clinical trial simulations are being applied in various therapeutic and application areas. Importantly, the book expands on the utility of CTS for informing decisions during drug development and regulatory review. Each chapter author was selected on the basis of demonstrated expertise in state-of-the-art application of CTS. The target audience for this volume includes researchers and scientists who wish to consider use of simulations in the design, analysis, or regulatory review and guidance of clinical trials. This book does not embrace all aspects of trial design, nor is it intended as a complete recipe for using computers to design trials. Rather, it is an information source that enables the reader to gain understanding of essential background and knowledge for practical applications of simulation for clinical trial design and analysis. It is assumed that the reader has a working understanding of pharmacokinetics and pharmacodynamics, modeling, pharmacometric analyses, and/or the drug development and regulatory processes. There have been tremendous advancements in application of modeling and simulation (M&S) in drug development during the last decade. The pharmaceutical companies started to pay more attention to implement simulation exercises in drug development in order to achieve cost effectiveness. The Food and Drug Administration (FDA) published a white paper titled, Critical Path Initiatives, in March 2004. This puts forward model based drug development that calls for use of quantitative M&S to facilitate informed decisions. The European Medicines Agency (EMEA) also encourages use of simulations in guiding drug development. With this much interest, Clinical Trial Simulations will serve as a reference to understand how clinical trial simulations are being used in drug development. Clinical Trial Simulations compiles the topics of recent interest and the case studies of how clinical trial simulations were used in various therapeutic areas. It is divided into parts that describe subjects that have gained interest recently; application of M&S in regulatory decisions; application of M&S in various therapeutic areas; and special use of M&S. Holly H.c. Kimko, Carl C. Peck, Editors. Includes Bibliographical References And Index.