Table of Contents

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

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 Muntañola

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

About the Author

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