Paediatric Medicines: Global development and clinical investigations

Paediatric Medicines: Global development and clinical investigations

Regulatory

Paediatric Medicines: Global development and clinical investigations is the essential report for any company needing to assess the impact of new legislation on paediatric drug development and the resulting opportunities for the pharmaceutical industry.

Paediatrics expert Prof Imti Choonara and associates, brings you completely up-to-date on new developments in legislation, regulation and the practical aspects of performing clinical trials of drugs for children. Emphasis is placed on the commercial opportunities that are likely to arise for the pharmaceutical and generics industries.

The report describes how pharmaceutical companies can undertake paediatric clinical trials at an early stage in each relevant product's development, and satisfy the pressing need for paediatric medicines with minimum investment.

This publication answers your key questions, including:

How will EU legislation and international harmonisation guidelines promote the development of medicinal products for children?
What incentives should be provided for companies to develop paediatric drugs in the future?
How can paediatric drug development be incorporated into an R&D portfolio?
How can companies prepare to conduct successful paediatric clinical trials?
How can companies learn from the US experience?

Paediatric Medicines also contains information on current US and European clinical investigators' networks, and contact details for both the centres and investigators.

Published: December 2000
Pages: c100
Ref: BS1084E
Price: £495/$1,045/¥119,000

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CONTENTS
LIST OF TABLES
ABOUT THE AUTHORS
EXECUTIVE SUMMARY
ABBREVIATIONS

CHAPTER 1 INTRODUCTION
1.1 The need for drug evaluation in children
1.1.1 Toxicity
1.1.2 Legislation
1.1.3 Therapeutic orphan
1.1.4 Unlicensed and off-label prescribing
1.1.5 Key messages
1.2 Drug toxicity in children
1.2.1 Thalidomide
1.2.2 Sodium valproate
1.2.3 Salicylates (aspirin)
1.2.4 Propofol
1.2.5 Formulation
1.2.6 Percutaneous toxicity
1.2.7 Mechanisms of drug toxicity in children
1.2.8 Key messages

CHAPTER 2 REGULATORY AND LEGISLATIVE REQUIREMENTS AND GUIDANCE AFFECTING PAEDIATRIC CLINICAL TRIALS
2.1 Regulatory and legislative changes
2.1.1 US
2.1.1.1 Food and Drug Administration Modernisation Act
2.1.1.2 Paediatric Rule
2.1.2 Europe
2.1.2.1 European guidance
2.1.3 Australia
2.1.3.1 Exemption of evaluation fees
2.1.4 International Conference on Harmonisation Guidance
2.1.5 Key messages
2.2 The impact of the new guidelines
2.2.1 US
2.2.2 Europe
2.2.2.1 Are clinical trials in children economically viable?
2.2.2.2 Financial incentives
2.2.2.3 Difficulties in carrying out clinical trials in children
2.2.2.4 Investigators networks
2.3 Key messages

CHAPTER 3 ETHICAL CONSIDERATIONS
3.1 Background
3.1.1 The Nuremberg Code
3.1.2 The Declaration of Helsinki
3.1.3 Guideline for Good Clinical Practice
3.2 The culture for research involving children
3.2.1 Guidelines in the US
3.2.2 Guidelines in the UK
3.3 Specific issues
3.3.1 Risks and benefits
3.3.2 Consent and assent
3.4 Conclusion
3.5 Key messages

CHAPTER 4 PRACTICAL SOLUTIONS TO THE LACK OF FORMULATIONS OF MEDICINES FOR CHILDREN
4.1 Lack of appropriate paediatric formulations
4.2 Options for paediatric pharmacists
4.3 Reasons for the lack of paediatric formulations
4.4 Withdrawal of liquid formulations
4.5 New developments and innovative formulations
4.6 Key messages

CHAPTER 5 PAEDIATRIC CLINICAL PHARMACOLOGY
5.1 Drug absorption
5.2 Distribution
5.3 Metabolism
5.3.1 CYP3A activity
5.3.2 CYP1A2 activity
5.3.3 Non-cytochrome P450 drug metabolising enzymes
5.4 Glucuronidation and sulphation
5.5 Renal function
5.6 Conclusion and key messages
5.7 Training of investigators
5.7.1 Analytical methods
5.7.2 Age-related delivery systems
5.7.3 Validity of animal models
5.7.4 Neonatal clinical pharmacology
5.8 European Network for Drug Investigation in Children
5.9 Key messages

CHAPTER 6 CONDUCTING CLINICAL TRIALS OF DRUGS FOR CHILDREN
6.1 The design of clinical trials in children
6.1.1 The need for the medicine
6.1.2 Early questions
6.1.3 Clinical value of the medicine
6.1.4 Use of placebo
6.1.5 Age categories
6.1.6 Timing of initiation of paediatric studies
6.1.7 Pharmacokinetics
6.1.8 Non-invasive methods
6.1.9 Pharmacodynamics
6.1.10 Key messages
6.2 Carrying out the clinical trial
6.2.1 Sourcing paediatric patients
6.2.2 Location and environment
6.2.3 Recruiting paediatric patients
6.2.4 Hospital networks
6.2.5 Which investigators?
6.2.6 Informed consent
6.2.7 Funding the study
6.2.8 Key messages
6.3 Pharmacovigilance
6.3.1 Surveillance in hospitalised inpatients
6.3.2 Surveillance in outpatients
6.3.3 The neonate
6.3.4 Targeted surveillance
6.3.5 Age-specific assessment
6.3.6 Spontaneous monitoring
6.3.7 Clinical trials
6.3.8 Key messages

CHAPTER 7 FUTURE CONSIDERATIONS AND CONCLUSIONS
7.1 Market exclusivity
7.2 Limitations of FDAMA
7.3 Withdrawal of medicines
7.4 Incentives in Europe
7.5 The needs of children
7.6 Clinical trials in children
7.7 Key messages

REFERENCES

APPENDIX 1 CURRENT INVESTIGATOR NETWORKS
A.1 The American Paediatric Pharmacology Research Unit Network
A.2 European Network for Drug Investigation in Children