Most medicines have never been adequately tested for safety and efficacy in pediatric populations and preterm, infants and children are particularly vulnerable to adverse drug reactions. Pediatric Drug Development: Concepts and Applications, Second Edition, addresses the unique challenges in conducting effective drug research and development in pediatric populations. This new edition covers the legal and ethical issues of consent and assent, the additional legal and safety protections for children, and the appropriate methods of surveillance and assessment for children of varying ages and maturity, particularly for patient reported outcomes. It includes new developments in biomarkers and surrogate endpoints, developmental pharmacology and other novel aspects of global pediatric drug development. It also encompasses the new regulatory initiatives across EU, US and ROW designed to encourage improved access to safe and effective medicines for children globally. From an international team of expert contributors Pediatric Drug Development: Concepts and Applications is the practical guide to all aspects of the research and development of safe and effective medicines for children.

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
Agnès Saint-Raymond

15 Five years of pediatric legislation in the European Union
Agnès 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