Pediatric Drug Development 2e – Concepts and Applications

Andrew E. Mulberg, Division Deputy Director, Gastroenterology and Inborn Error Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, US Dianne Murphy, Director, Office of Pediatric Therapeutics, Office of the Commissioner, US Food and Drug Administration, Silver Spring, MD, US Julia Dunne, Vigilance and Risk Management in Medicines (VRMM), Medicines and Healthcare Products Regulatory Agency, London, UK Lisa L. Mathis, Executive Director for Global Regulatory Affairs and Safety (GRAAS), Amgen Incorporated, Thousand Oaks, California, US

List of Contributors Preface Part I: PAST, PRESENT, AND FUTURE OF PEDIATRIC DRUG DEVELOPMENT 1 Pediatric Drug Development and Therapeutics: Continued Progress for Better Drugs for Children Andrew E. Mulberg, Lisa Mathis, Julia Dunne and Dianne Murphy 2 History of Children and the Development of Regulations at the FDA Robert M. Ward and Steven Hirschfeld 3 Population Dynamics, Demographics, and Disease Burden of Infants and Children Across the World Ashley Malins and Christopher-Paul Milne 4 Pharmaceutical Economics and Market Access for Pediatric Medications Christopher-Paul Milne and Ashley Malins 5 The Global Pediatric Market and Drivers of Pediatric Drug Development E. Michael D. Scott 6 Industry Benchmarks in Pediatric Clinical Trials Carolyn A. Campen and Cindy Levy-Petelinkar Part II: ETHICAL UNDERPINNINGS 7 Ethical and practical considerations in conducting neonatal research Michelle Roth-Cline and Robert M. Nelson 8 Ethical considerations in conducting pediatric research Michelle Roth-Cline and Robert M. Nelson 9 The Consent and Assent Process in Pediatric Clinical Trials M. Renee Simar Part III: REGULATORY GUIDELINES FOR PEDIATRIC DRUG DEVELOPMENT 10 A Sponsor s Perspective of US Regulations Samuel Maldonado 11 FDA experience of extrapolation of efficacy to the pediatric population from adult and other data Julia Dunne, William J. Rodriguez and Dianne Murphy 12 Accelerated Approval and other regulatory approaches to the development of drugs for serious or life-threatening diseases in pediatrics Therese Cvetkovich 13 Rare Diseases and Orphan Drugs Anne R. Pariser and Lynne P. Yao 14 European Perspective Agnes Saint-Raymond 15 Five years of pediatric legislation in the European Union Agnes Saint-Raymond and Ralf Herold 16 Japanese Perspective Hidefumi Nakamura and Shunsuke Ono 17 Pediatric Device Development in the United States Priya Venkataraman-Rao and Joy Samuels-Reid Part IV: PRECLINICAL SAFETY ASSESSMENT 18 Introduction and Overview Timothy P. Coogan and Melissa S. Tassinari 19 Juvenile Animal Toxicity Assessments: Decision Strategies and Study Design Luc M. De Schaepdrijver, Graham P. Bailey, Timothy P. Coogan and Jennifer L. Ingram-Ross 20 Absorption, Distribution, Metabolism and Excretion (ADME) and Pharmacokinetic Assessments in Juvenile Animals Loeckie L. de Zwart, Johan G. Monbaliu and Pieter P. Annaert 21 A Global Regulatory Perspective Karen Davis-Bruno, Jacqueline Carleer, Beatriz Silva Lima and Melissa S. Tassinari 22 Disease specific models to enhance Pediatric drug development Niraj R. Mehta and Sruthi King Part V: PHARMACOLOGICAL PRINCIPLES IN PEDIATRIC DRUG DEVELOPMENT 23 Pediatric Clinical Pharmacology in Regulatory and Drug Development Sciences: Lessons learned and the Path Forward Gilbert J. Burckart and Jeremiah Momper 24 Development and Clinical Trial Design Kathleen A. Neville, Ralph E. Kauffman, and Susan M. Abdel-Rahman 25 Developmental Hepatic Pharmacology in Pediatrics Martin Otto Behm 26 Applications of Population Pharmacokinetics for Pediatric Drug Development Jeremiah Momper, Gilbert J. Burckart and Pravin Jadhav 27 Applications of Pharmacogenomics to Pediatric Drug Development Gilbert J. Burckart, Dionna Green and Padmaja Mummaneni 28 Pharmacometrics Applications to Pediatric Trials Devin Pastoor, Mallika Lala, Jogarao V.S. Gobburu Part VI: CLINICAL TRIAL OPERATIONS 29 Brain and Central Nervous System Development: Physiological Considerations for Assessment of Long-Term Safety Kachikwu Illoh 30 Cognitive Development Considerations for Long-Term Safety Exposures in Children Mary Pipan, Paul Wang, and Rebecca Thompson-Penna 31 Cardiovascular and QTc Issues Bert Suys and Luc Dekie 32 Pediatric bone and adult bone physiological differences Francisco A. Sylvester and Erica L. Wynn 33 Renal Function Issues Katia Boven 34 Growth and Physical Development Alisha J. Rovner and Babette S. Zemel 35 Development of Drugs for Pediatric Cancers Kristen M. Snyder, Martha Donoghue, Whitney S. Helms, and Gregory Reaman Part VII: CLINICAL TRIAL OPERATIONS AND GOOD CLINICAL TRIALS 36 Recruitment and Retention in Pediatric Clinical Trials: Focus on Networks in the US and EU Rosalind L. Smyth, Geetinder Kaur, Daniel Benjamin Jr, and Matthew Laughon 37 Recruitment and Retention of Minority populations in Clinical Trials Benjamin Ortiz and Sergio Guerrero 38 Conducting Clinical Trials in Developing and Emerging Countries: Review and Case Study Kevin D. Hill and Jennifer S. Li 39 The Importance of Geographic Differences in Pediatric Clinical Trials Alexandar Cvetkovich Muntanola Part VIII: CLINICAL EFFICACY AND SAFETY ENDPOINTS 40 Clinical Laboratory Testing in Clinical Trials for Pediatric Subjects Andrew E. Mulberg and Ethan D. Hausman 41 Surrogate Endpoints: Application in Pediatric Clinical Trials Geert Molenberghs 42 Clinical Outcome Assessments for Clinical Trials in Children Elektra J. Papadopoulos, Donald L. Patrick, Melissa S. Tassinari, Andrew E. Mulberg, Carla Epps, Anne R. Pariser and Laurie B. Burke 43 Challenges in Evaluating the Safety of Pediatric Therapeutic Agents in Trials and Post-Marketing Studies Ann W. McMahon, Chris Feudtner and Dianne Murphy 44 Endpoints in Rare Diseases Anne R. Pariser and Lynne P. Yao Part IX: FORMULATION, CHEMISTRY, AND MANUFACTURING CONTROLS 45 Formulation, Chemistry, and Manufacturing Controls Gerard P. McNally and Aniruddha M. Railkar 46 Drug Delivery Challenges for the Pediatric Patient: Novel Forms for Consideration Ann Zajicek 47 The Jelly Bean Test: A Novel Technique To Help Children Swallow Medications Robbyn E. Sockolow and Aliza B. Solomon Index