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Essentials of translational pediatric drug development : from past needs to future opportunities /

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.

Bibliographic Details
Corporate Author: ScienceDirect (Online service)
Other Authors: Gasthuys, Elke (Editor), Allegaert, Karel (Editor), Dossche, Lien (Editor), Turner, Mark (Neonatologist) (Editor)
Format: eBook
Language:English
Published: London, United Kingdom ; San Diego, CA, United States ; Cambridge, MA, United States : Elsevier, Academic Press, an Imprint of Elsevier, [2024]
Subjects:
Pediatric pharmacology.
Drug development.
Drugs > Design.
Drug Design
Pharmacologie pédiatrique.
Médicaments > Développement.
Médicaments > Conception.
Electronic books.
Online Access:Connect to the full text of this electronic book
Table of Contents:
  • Front Cover
  • ESSENTIALS OF TRANSLATIONAL PEDIATRIC DRUG DEVELOPMENT
  • ESSENTIALS OF TRANSLATIONAL PEDIATRIC DRUG DEVELOPMENT: FROM PAST NEEDS TO FUTURE OPPORTUNITIES
  • Copyright
  • Contents
  • Contributors
  • I
  • From past to current needs in pediatric drug research
  • 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
  • Pharmacovigilance
  • Pharmacovigilance tailored to children
  • Doing studies
  • The importance of collaboration
  • Not in scope
  • References
  • 2
  • Historical perspective
  • Labeling of medicines
  • Therapeutic orphans
  • Pediatric medicines initiatives
  • Worldwide initiatives to stimulate pediatric clinical trials
  • The US legislation
  • The European Pediatric Regulation
  • "Better Medicines for Children" resolution of the World Health Assembly
  • Pediatric medicines initiatives in other countries across the globe
  • ICH E11: Harmonizing the development of pediatric medicines
  • Pediatric medicine networks
  • Pediatric clinical pharmacology
  • References
  • 3
  • Parents' and children's needs in the drug development process
  • Introduction: Unmet needs for pediatric patients
  • Pediatric drug development
  • What are the benefits of pediatric and clinical trial regulations?
  • Pediatric regulation in the United States (US) and in the European Union (EU)
  • Novel EU clinical trial regulation
  • Research
  • Agenda setting and translational research
  • Pediatric patient-centered clinical trials
  • Clinical trials at home
  • Clinical trial awareness and communication
  • Consent for clinical research
  • Data sharing
  • Registries and data platforms.
  • The specific parents/children's needs for accessing early diagnosis/screening programs, innovative treatments, clinical tri ...
  • Early diagnosis
  • Innovative treatments
  • Access to cross-border clinical trials
  • Compassionate use (early access) programs
  • The specific parents/children's needs for empowerment and training to be active actors in research and for their health
  • Empowerment and training
  • The role of patient organizations
  • Involvement of children/young patients
  • Pediatric networks
  • Authors' final reflections
  • References
  • Further reading
  • 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
  • Acts/laws
  • Data
  • Data requirements
  • Data scope
  • Preclinical or nonclinical
  • Clinical
  • Instructions for the use of a therapeutic
  • Burden of proof
  • How regulators work?
  • Regulators' profile
  • Communication
  • Between regulatory agencies
  • With other stakeholders
  • Follow-up file submission
  • Decision-making
  • Post-marketing
  • Has the regulatory approach changed over the years and what will the future bring?
  • Concluding thoughts
  • References
  • Further reading
  • Additional interesting references
  • 5
  • Optimal pediatric drug development- the partnership between patients/parents, academia, regulatory authorities ...
  • Pharmaceutical industry's participation in pediatric drug development
  • Pharmaceutical industry involvement in all phases of pediatric drug development
  • Drug discovery
  • 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
  • References
  • 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
  • Drug discovery and development
  • Preclinical research
  • Clinical research
  • Postmarketing pharmacovigilance
  • Repurposing
  • Interplay between academia and other stakeholders within pediatric drug research
  • Pharmaceutical industry
  • Governmental authorities
  • Healthcare professionals
  • Involvement of patients and parents in the clinical research process
  • Organization of academic pediatric drug research
  • Role of the academic institutions: Education, training, and facilities
  • Education/training
  • Facilities
  • Academic expertise core facilities
  • Academic clinical trial units
  • Academic technology transfer offices
  • Funding
  • Open science
  • Impact
  • Initiatives examples
  • Conclusions: The future for academia participating in pediatric drug research
  • References
  • 7
  • The health care provider's needs in the pediatric drug development process
  • Introduction and background of prescribing medicines for children
  • Introduction
  • Historical aspects and background
  • Current daily clinical practice: Challenges and (practical) approaches
  • The current clinical situation: Global extent of off-label and unlicensed medicines use in children
  • Off-label use
  • Unlicensed medicine use
  • Insufficient access to on-label medicines
  • Practical approaches to current prescribing challenges
  • Off-label medicines
  • When to prescribe off-label medicines?.
  • Challenges when prescribing off-label medicines
  • How to prescribe off-label medicines?
  • Use of pediatric medicine formularies
  • Benefit-risk assessment off-label medicine use in children
  • Informed consent
  • Unlicensed medicines
  • Challenges when prescribing unlicensed medicines
  • Possible approaches when prescribing unlicensed medicines
  • Pediatric medicine development as a possible solution
  • health care providers in collaboration with other stakeholders
  • Future perspectives: Needs and priorities
  • References
  • II
  • Designing pediatric drug research: From bench to bedside and back
  • 8
  • Application of in vitro models for pediatric translational research
  • Introduction
  • Methods
  • In vitro models for protein activity measurements
  • Types of in vitro models in translational pediatric research
  • Experimental conditions for activity assays with in vitro pediatric models
  • Data sets generated with in vitro pediatric or juvenile ADME models
  • In vitro studies with tissues derived from pediatric donors
  • In vitro studies with tissues derived from neonatal or juvenile animals
  • Translation of in vitro ADME activity data by IVIVE approaches
  • ADME protein abundance measurements on pediatric tissues
  • Positioning of protein content analysis in translational pediatric research
  • Technological state-of-the-art of quantitative proteomics
  • Application of quantitative proteomics to reveal ontogeny of DMEs and transport proteins
  • Application of proteomics data in relation to in vitro ADME tools
  • Discussion
  • References
  • 9
  • Application of preclinical juvenile animal models
  • Introduction
  • Regulatory perspective
  • Pediatric Investigation Plan and Pediatric Study Plan
  • Designing the nonclinical strategy
  • Need for a juvenile animal toxicity study
  • Timing of juvenile animal toxicity studies.
  • Animal species and age categories to be considered
  • Mice
  • Rat
  • Rabbit
  • Dog
  • Sheep
  • Pig
  • Nonhuman primates
  • Age of the animals
  • Study design
  • Study end-points
  • Route of administration
  • Dose selection
  • Formulation and excipients
  • ADME
  • Reproducibility and translatability of animal research
  • The reproducibility crisis: the standardization fallacy
  • The translatability crisis: animal models
  • Conclusions
  • References
  • 10
  • Application of pediatric-adapted modeling and simulation approaches
  • Quantitative pharmacology in pediatric drug development
  • Basic PK/PD concepts of small and large molecules
  • Exposure-response relationships
  • Overview of the available toolbox
  • Allometric approaches
  • Selecting an allometric exponent
  • When is allometric scaling appropriate?
  • Allometric scaling from preclinical animal species
  • Allometric scaling of monoclonal antibodies
  • Physiologically based pharmacokinetic modeling
  • Core principles of PBPK modeling
  • Building a pediatric-PBPK model
  • Step 1: Gather drug-dependent data to define a drug model
  • Step 2: Learn and confirm in an adult population
  • Step 3: Verify and apply the PBPK model in children
  • Pediatric PBPK model applications
  • Dose selection and study design
  • Drug-drug interactions
  • Special pediatric populations and disease effects
  • Protein drugs
  • Pharmacodynamics and toxicology
  • Population pharmacokinetics
  • PopPK modeling and simulation
  • Integration with allometric scaling and ontogeny
  • Linking PK with PD
  • Moving pediatric adapted modeling and simulation approaches toward maturity
  • Rational selection and application of available modeling and simulation tools
  • The pediatric diseased populations
  • Pediatric and developmental pharmacodynamics
  • Conclusion
  • References.
  • 11
  • The promise of omics approaches for pediatric drug development.