Pediatric Drug Development

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, USDianne Murphy, Director, Office of Pediatric Therapeutics, Office of the Commissioner, US Food and Drug Administration, Silver Spring, MD, USJulia Dunne, Vigilance and Risk Management in Medicines (VRMM), Medicines and Healthcare Products Regulatory Agency, London, UKLisa L. Mathis, Executive Director for Global Regulatory Affairs and Safety (GRAAS), Amgen Incorporated, Thousand Oaks, California, US

• List of ContributorsPrefacePart I: PAST, PRESENT, AND FUTURE OF PEDIATRIC DRUG DEVELOPMENT  1 Pediatric Drug Development and Therapeutics: Continued Progress for Better Drugs for ChildrenAndrew E. Mulberg, Lisa Mathis, Julia Dunne and Dianne Murphy2 History of Children and the Development of Regulations at the FDARobert M. Ward and Steven Hirschfeld3 Population Dynamics, Demographics, and Disease Burden of Infants and Children Across the WorldAshley Malins and Christopher-Paul Milne4 Pharmaceutical Economics and Market Access for Pediatric  MedicationsChristopher-Paul Milne and Ashley Malins5 The Global Pediatric Market and Drivers of Pediatric Drug DevelopmentE. Michael D. Scott6 Industry Benchmarks in Pediatric Clinical TrialsCarolyn A. Campen and Cindy Levy-PetelinkarPart II: ETHICAL UNDERPINNINGS  7 Ethical and practical considerations in conducting neonatal researchMichelle Roth-Cline and Robert M. Nelson8 Ethical considerations in conducting pediatric research Michelle Roth-Cline and Robert M. Nelson9 The Consent and Assent Process in Pediatric Clinical TrialsM. Renee SimarPart III: REGULATORY GUIDELINES FOR PEDIATRIC DRUG DEVELOPMENT  10 A Sponsor’s Perspective of US RegulationsSamuel Maldonado11 FDA experience of extrapolation of efficacy to the pediatric population from adult and other dataJulia Dunne, William J. Rodriguez and Dianne Murphy12 Accelerated Approval and other regulatory approaches to the development of drugs for serious or life-threatening diseases in pediatricsTherese Cvetkovich13 Rare Diseases and Orphan DrugsAnne R. Pariser and Lynne P. Yao14 European PerspectiveAgnès Saint-Raymond15 Five years of pediatric legislation in the European UnionAgnès Saint-Raymond and Ralf Herold16 Japanese PerspectiveHidefumi Nakamura and Shunsuke Ono17 Pediatric Device Development in the United StatesPriya Venkataraman-Rao and Joy Samuels-ReidPart IV: PRECLINICAL SAFETY ASSESSMENT  18 Introduction and OverviewTimothy P. Coogan and Melissa S. Tassinari19 Juvenile Animal Toxicity Assessments: Decision Strategies and Study DesignLuc M. De Schaepdrijver,  Graham P. Bailey, Timothy P. Coogan and Jennifer L. Ingram-Ross20 Absorption, Distribution, Metabolism and Excretion (ADME) and Pharmacokinetic Assessments in Juvenile AnimalsLoeckie L. de Zwart, Johan G. Monbaliu and Pieter P. Annaert21 A Global Regulatory PerspectiveKaren Davis-Bruno, Jacqueline Carleer, Beatriz Silva Lima and Melissa S. Tassinari22 Disease specific models to enhance Pediatric drug developmentNiraj R. Mehta and Sruthi KingPart V: PHARMACOLOGICAL PRINCIPLES IN PEDIATRIC DRUG DEVELOPMENT  23 Pediatric Clinical Pharmacology in Regulatory and Drug Development Sciences:  Lessons learned and the Path ForwardGilbert J. Burckart and Jeremiah Momper24 Development and Clinical Trial DesignKathleen A. Neville, Ralph E. Kauffman, and Susan M. Abdel-Rahman25 Developmental Hepatic Pharmacology in PediatricsMartin Otto Behm26 Applications of Population Pharmacokinetics for Pediatric Drug DevelopmentJeremiah Momper, Gilbert J. Burckart and Pravin Jadhav27 Applications of Pharmacogenomics to Pediatric Drug Development Gilbert J. Burckart, Dionna Green and Padmaja Mummaneni28 Pharmacometrics Applications to Pediatric TrialsDevin Pastoor, Mallika Lala, Jogarao V.S. GobburuPart VI: CLINICAL TRIAL OPERATIONS  29 Brain and Central Nervous System Development: Physiological Considerations for Assessment of Long-Term SafetyKachikwu Illoh30 Cognitive Development Considerations for Long-Term Safety Exposures in ChildrenMary Pipan, Paul Wang,  and Rebecca Thompson-Penna31 Cardiovascular and QTc IssuesBert Suys and  Luc Dekie32 Pediatric bone and adult bone – physiological differencesFrancisco A. Sylvester and Erica L. Wynn33 Renal Function IssuesKatia Boven34 Growth and Physical DevelopmentAlisha J. Rovner and  Babette S. Zemel35 Development of Drugs for Pediatric CancersKristen M. Snyder, Martha Donoghue, Whitney S. Helms, and Gregory ReamanPart 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 Laughon37 Recruitment and Retention of Minority populations in Clinical TrialsBenjamin Ortiz and Sergio Guerrero38 Conducting Clinical Trials in Developing and Emerging Countries:  Review and Case StudyKevin D. Hill and Jennifer S. Li39 The Importance of Geographic Differences in Pediatric Clinical TrialsAlexandar Cvetkovich MuntañolaPart VIII: CLINICAL EFFICACY AND SAFETY ENDPOINTS  40 Clinical Laboratory Testing in Clinical Trials for Pediatric SubjectsAndrew E. Mulberg and Ethan D. Hausman  41 Surrogate Endpoints: Application in Pediatric Clinical TrialsGeert Molenberghs42 Clinical Outcome Assessments for Clinical Trials in ChildrenElektra J. Papadopoulos,  Donald L. Patrick,  Melissa S. Tassinari,  Andrew E. Mulberg,  Carla Epps,  Anne R. Pariser and  Laurie B. Burke43 Challenges in Evaluating the Safety of Pediatric Therapeutic Agents in Trials and Post-Marketing StudiesAnn W. McMahon, Chris Feudtner and Dianne Murphy44 Endpoints in Rare DiseasesAnne R. Pariser and Lynne P. YaoPart IX: FORMULATION, CHEMISTRY, AND MANUFACTURING CONTROLS  45 Formulation, Chemistry, and Manufacturing ControlsGerard P. McNally and Aniruddha M. Railkar46 Drug Delivery Challenges for the Pediatric Patient: Novel Forms for  ConsiderationAnn Zajicek  47 The Jelly Bean Test: A Novel Technique To Help Children Swallow MedicationsRobbyn E. Sockolow and Aliza B. SolomonIndex