Essentials of Translational Pediatric Drug Development

From Past Needs to Future Opportunities

1st Edition - July 22, 2024
Editors: Elke Gasthuys, Karel Allegaert, Lien Dossche, Mark Turner
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 8 8 4 5 9 - 4
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 0 4 2 9 - 2

Essentials of Translational Pediatric Drug Development: From Past Needs to Future Opportunities provides integrated and up-to-date insights relevant for both translational resear… Read more

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Essentials of Translational Pediatric Drug Development: From Past Needs to Future Opportunities provides integrated and up-to-date insights relevant for both translational researchers and clinicians active in the field of pediatric drug development. The book covers all key aspects from different stakeholder perspectives, providing a literature overview and careful reflection on state-of-the-art approaches. It will be an ideal guide for researchers in the field who are designing and performing high quality, innovative pediatric-adapted drug development by helping them define needs/challenges and possible solutions that advance and harmonize pediatric drug development.

Despite the broad consensus that children merit the same quality of drug treatment as any other age group, children remain frequently neglected during drug research and development. Even with the adoption of multiple legislations addressing this problem, the lack of efficacy and safety data of marketed as well as newly developed drugs still remain in the pediatric population.

Cover image
Title page
Table of Contents
Copyright
Contributors
Section I. From past to current needs in pediatric drug research
Chapter 1. Preface: Overview of pediatric drug development and pharmacovigilance
Introduction
Elements of drug development
Approaches to drug development
Clinical pediatric drug development
Foundational research
Goals of drug development
Doing studies
The importance of collaboration
Not in scope
Chapter 2. Historical perspective
Labeling of medicines
Therapeutic orphans
Pediatric medicines initiatives
Pediatric medicine networks
Pediatric clinical pharmacology
Chapter 3. Parents' and children's needs in the drug development process
Introduction: Unmet needs for pediatric patients
Pediatric drug development
The specific parents/children's needs for accessing early diagnosis/screening programs, innovative treatments, clinical trials, and compassionate use programs
The specific parents/children's needs for empowerment and training to be active actors in research and for their health
Authors' final reflections
Chapter 4. The needs from the regulatory authorities' perspective—current status and worldwide initiatives
Introduction
Definitions
The regulatory requirements for the drug submission process
Acts, laws, and guidance
Data
Data scope
Burden of proof
How regulators work?
Has the regulatory approach changed over the years and what will the future bring?
Concluding thoughts
Chapter 5. Optimal pediatric drug development— the partnership between patients/parents, academia, regulatory authorities and industry: The pharmaceutical industry's perspective
Pharmaceutical industry's participation in pediatric drug development
Pharmaceutical industry involvement in all phases of pediatric drug development
Preclinical research
Development of pediatric formulations
Clinical research
Postmarketing monitoring
Partnership between the pharmaceutical industry and other stakeholders within pediatric drug research
Patients/parents
Academia/clinicians in clinical practice and research
Regulatory authorities
Co-operation among pharmaceutical companies
Organization of pharmaceutical industry pediatric drug research
The future of pharmaceutical industry pediatric drug research
Chapter 6. The needs, challenges, and opportunities from the academic researchers' perspective
Academia participate in translational pediatric drug research
Roles of academia within pediatric drug research
Interplay between academia and other stakeholders within pediatric drug research
Organization of academic pediatric drug research
Conclusions: The future for academia participating in pediatric drug research
Chapter 7. The health care provider's needs in the pediatric drug development process
Introduction and background of prescribing medicines for children
Current daily clinical practice: Challenges and (practical) approaches
Practical approaches to current prescribing challenges
Future perspectives: Needs and priorities
Section II. Designing pediatric drug research: From bench to bedside and back
Chapter 8. Application of in vitro models for pediatric translational research
Introduction
Methods
In vitro models for protein activity measurements
ADME protein abundance measurements on pediatric tissues
Discussion
Chapter 9. Application of preclinical juvenile animal models
Introduction
Regulatory perspective
Animal species and age categories to be considered
Study design
Reproducibility and translatability of animal research
Conclusions
Chapter 10. Application of pediatric-adapted modeling and simulation approaches
Quantitative pharmacology in pediatric drug development
Allometric approaches
Physiologically based pharmacokinetic modeling
Population pharmacokinetics
Moving pediatric adapted modeling and simulation approaches toward maturity
Conclusion
Chapter 11. The promise of omics approaches for pediatric drug development
Introducing OMICS
Chapter 12. Generation and interpretation of big data in pediatric drug development
Introduction
RWD and RWE definitions
Sources of real-world data—overview
Quality and privacy challenges for pediatric RWD
Legislations and organized efforts that have encouraged the development of RWD
Regulatory guidance documents and laws
Existing RWD guidelines
ICH guidelines
HIPAA/GDPR and patient confidentiality and access concerns/sensitive variables
Institutional review boards/research ethics committees (IRB/REC)
Applications and examples
Workforce and resource needs
Conclusions
Chapter 13. Investigational medicinal products considerations in pediatric clinical drug trials
Introduction
Investigational products
Challenges in investigational product supply chain
What is a drug?
Drug formulation development
Age-appropriate formulations
Quality management in pharmaceutical manufacturing
Good manufacturing practice
Manufacturing process development and validation
Blinding in clinical trials
Investigational product label
Supply chain management
Transport, storage, and distribution of investigational products
Role of the qualified person
Site logistics
Risk proportionate approaches to the management of investigational products
Prospective—From drug substance to investigational product supply
Conclusions
Chapter 14. Co-designing pediatric clinical trials with multistakeholders: A step-by-step approach
Introduction
The role of CYP in the design and/or conduct of pediatric clinical trials
Practicalities of involving CYP
Involving children and young people in a life science sponsored study: A case study
Public/private partnership—pilot project
Strategic and operational aspects of PPI within Pfizer
“How-to” involve CYP in a clinical trial protocol design of an eczema study
Our approach and lessons learned
Defining partnership and collaboration goals
Identifying patient partners and initiating a partnership
Contracts and confidentiality agreements
Maintaining confidentiality
Disclosure of conflicts of interest
Costings
Logistics
Reflections and conclusion
Section III. Improving the performance of pediatric drug research: Big changes start with small steps
Chapter 15. Principles of performing pediatric clinical drug trials
Main principles of conducting clinical trials in children
Involving child and/or parent within a trial design
Adapting trial study team for pediatric needs
Limiting sampling and optimizing outcomes
Communication optimization between site and sponsor (and research network)
Designing the pediatric clinical trial
Multicenter trials
Site initiation
Trial start and conduct
Trial practicalities and limitations
Monitoring trial quality and patient safety
Clinical trial closure, reporting, and publications
Take home messages and future perspectives
Appendix
Chapter 16. Regulatory considerations in the design and conduct of pediatric clinical trials
Introduction to the regulatory perspective on pediatric clinical trials
What makes pediatric product development unique?
Approaches for optimizing pediatric product development
Selecting a pediatric dose
Considerations for the design and conduct of pediatric clinical therapeutics trials
Putting it all together: Planning a pediatric product development program
Communicating with regulatory authorities
International collaboration and harmonization
Future directions
Disclaimer
Chapter 17. Ethical consideration in the design and conduct of pediatric clinical trials
Introduction
Short history of the pediatric clinical research ethics
Ethical principles of pediatric clinical trials
Ethical elements of pediatric clinical trials
Children and their legal representatives
Design of pediatric clinical trial—ethical perspective
Concepts of risks, burden, and benefit
Designing informed consents, assents and patient information
Recruitment to clinical trials
Basic elements of the informed consent process
Respecting child's rights and understanding disagreements
Ethical review
Lay summary of clinical trial results
Chapter 18. Performing clinical drug trials in acute and critically ill neonates and children
Developmental and pathophysiological changes in critically ill children
The contemporary approach to drug development in NICU/PICU
Practical aspects of the design and conduct of research studies
Ethics
Policy issues
Opportunities
Future perspectives and take home messages
Chapter 19. Performing clinical drug trials in children with a rare disease
What conditions are necessary to achieve clinical trial readiness?
Challenges in designing and delivering PRD clinical trials and current solutions to address these
Conclusions
Chapter 20. Policy of pediatric oncology drug development
Introduction
A paradigm shift in drug development for childhood cancers
Need to consider childhood cancers separately from adult cancers
The regulatory context and precompetitive multi-stakeholder collaboration
Equal access to innovation and precision medicine: new models of partnership and funding
Current challenges/unmet needs
Future perspectives and take home messages
Chapter 21. Practice of pediatric oncology drug development
Need for mechanism-of-action approach in pediatric oncology drug development
Preclinical research
Revised framework for early-phase clinical trials
Currently unmet challenges/needs
Future perspectives and take home messages
Chapter 22. Pediatric drug formulations
The need for formulated drug products
The need for pediatric formulated drug products
Historic landscape of pediatric formulations
Main challenges in developing pediatric formulations
Relative bioavailability and the introduction of a pediatric product
Palatability of medicines and acceptability
Oral liquid dosage forms
Oral solid dosage forms
Nasal formulations
Inhaled formulations
Rectal formulations
Cutaneous/transdermal formulations
Eye and ear formulations
Parenteral formulations
Additional considerations for enteral feeding tubes
Innovations in pediatric formulation development
Conclusions
Chapter 23. Worldwide network initiatives in improving pediatric drug research
Introduction
The rationale and roles of clinical research networks
Types of clinical research networks
Services and use-cases of clinical trial networks
Challenges
Future needs and recomendations
Conclusions
Supplementary material
Chapter 24. The patients'/parents' voice within pediatric drug research
Introduction: conceptual approach regarding the active involvement of CYP involvement in drug development
Tracing the historical development of the involvement of CYP in pediatric drug development
Involvement of patients and parents in regulatory activities
Tools and resources for involving patients and parents in the drug development process
The role of patients and caregivers in pediatric clinical trials networks
Diversity and representativeness: they are not “hard to reach,” we need to extend our arms
Conclusion: standardizing practice to ensure the meaningful and ethical involvement of patients through an accountable process
Acknowledgments
Chapter 25. Pediatric drug development issues during public health emergencies
Introduction and overview
Considerations during a PHEIC
Effect of PHEICs on chronic health conditions
Effect of PHEICs on research
Children during PHEICs
Influence of PHEICs on individual liberty and effects on communities
Ethical foundations of research during PHEICs
Potential ethical framework for conducting pediatric drug trials during PHEICs
Clinical trials during PHEICs with a focus on pediatric drug development
Lessons learned from the COVID-19 pandemic and the effect on pediatric drug development
Actions before and during a PHEIC
Potential practical framework for conducting pediatric trials during PHEICs
Conclusion
Section IV. Future perspectives in pediatric drug research: The road to better drugs for children
Chapter 26. The future of pediatric drug research: Science, context, and collaboration
The science of drug development
The context of drug development
Collaboration in drug development
Conclusion
Index

Elke Gasthuys

Elke Gasthuys is a Postdoctoral researcher at Ghent University, focusing on advanced modelling and simulations tools (PopPK/PD, PBPK, Systems biology) within drug research. Her main focus lies within the fields of inflammatory bowel disease; cystic fibrosis and enuresis, with special emphasis on the pediatric population. Her PhD thesis focused on developing a juvenile conventional piglet model at the Faculty of Veterinary Sciences, Ghent University, Belgium. Her research project was embedded within a broader research project (SAFEPEDRUG), aiming to improve pediatric drug research by integrating juvenile animal models and modelling and simulation tools to adapt pediatric clinical trial designs.

Affiliations and expertise

Postdoctoral researcher, Ghent University, Belgium

Karel Allegaert

Karel Allegaert is a pediatrician-neonatologist and clinical pharmacologist, appointed as Professor at KU Leuven, Belgium and as senior clinical consultant at Erasmus MC Rotterdam, the Netherlands. His main clinical research focuses on perinatal and developmental pharmacology. This includes active involvement in clinical studies, as well as educational and consultancies to different stakeholders, like authorities and industry. He is an author, reviewer and editor for a broad range of journals and textbooks in the fields of clinical pharmacology and pediatrics. These activities have resulted in relevant awards like the Galenus clinical researcher award (Belgium, 2009) for neonatal clinical pharmacology research and an appointment as ordinary member of the Royal Academy of Medicine, Belgium (2015).

Affiliations and expertise

Pediatrician-neonatologist and Clinical Pharmacologist, Professor, KU Leuven, Belgium; Senior clinical consultant, Erasmus MC Rotterdam, The Netherlands

Lien Dossche

Lien Dossche is a full-time academic staff member at Ghent University, focusing on clinical activities as a Pediatrician and clinical research. After obtaining a medical degree at Ghent University in 2012, she started her specialization in Pediatrics at the Ghent University Hospital. Following her training as a Pediatrician, she completed a fellowship in Pediatric Nephrology at the Great Ormond Street Hospital in London. Since March 2015, she has combined her clinical activities with translational clinical research as a PhD candidate, focusing on the use of desmopressin in children with enuresis. She is a member of the IPNA (International Pediatric Nephrology Association), the ESPN (European Society of Paediatric Nephrology) and the ESPN Working Group on CAKUT/UTI/Bladder Dysfunction.

Affiliations and expertise

Full-time Academic Staff Member, Ghent University, Belgium

Mark Turner

Mark Turner is a Professor of Neonatology and Research Delivery at the University of Liverpool, UK. He has worked clinically for 30 years and has experience in many aspects of pediatric drug development including excipients, formulations, drug safety, and development and implementation of Pediatric Investigation Plans. He has led Phase 0 (microdosing) through Phase 3 studies. Currently, he co-leads European and international initiatives that promote a strategic approach to pediatric drug development through the development of research standards and infrastructure for clinical trials networks. He works in public private partnership with industry, regulators, academia, and advocates for babies, children, young people and their families. He was elected as an Honorary Fellow of the Faculty of Pharmaceutical Medicine.

Affiliations and expertise

Professor of Neonatology and Research Delivery, University of Liverpool, UK

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Essentials of Translational Pediatric Drug Development

From Past Needs to Future Opportunities

Purchase options

Save 50% on book bundles

Institutional subscription on ScienceDirect

Elke Gasthuys

Karel Allegaert

Lien Dossche

Mark Turner