Publication Date:
2010
Short description:
In Search of Safe and Effective Medicines / Tomasi, Paolo. - In: EUROPEAN PHARMACEUTICAL CONTRACTOR. - ISSN 1364-369X. - Winter 2010:(2010).
abstract:
The principle of using children as the subjects of scientific studies has attracted a considerable degree of controversy. In the past, children used to be ‘protected’ from research, having been recognised as subjects who are vulnerable and unable to provide informed consent. Many of the medicinal products currently used to treat the paediatric population have not been studied or authorised for such use. Market forces alone have proven insufficient to stimulate development of medicinal products for the paediatric population.
EU Regulation 1901/2006 – the ‘Paediatric Regulation’ – provides a systematic approach to the development of medicinal products intended for use in the paediatric population (1). This legal framework followed the first US initiative (the Best Pharmaceuticals for Children Act), which has been in place since 1997.
Pharmaceutical companies are now required to perform clinical studies in children before being able to apply for marketing authorisation of a new medicinal product in the EU (or for a new indication, dosage form or route of administration of an authorised, patented product), unless they have agreed a waiver or a deferral with the Paediatric Committee (PDCO) of the European Medicines Agency (EMA).
CONDUCTING CLINICAL TRIALS IN CHILDREN
The term ‘children’ includes the paediatric population from birth to 18 years. This group’s characteristics are extremely diverse; weights can start at less than 1kg but extend up to a typical young adult’s weight, while cognitive development, physical and sexual maturation and biochemical characteristics are all elements that change with each individual. When organising a good clinical trial in children, certain factors require close inspection.
Need, Feasibility and Design of Trials
Once the paediatric need(s) and the study question have been clarified, the possibility of replacing some studies, or reducing the number of patients involved, through extrapolation, modelling and simulation should be discussed. Unnecessary clinical trials in children should be avoided, and the use of extrapolation for efficacy is encouraged by current guidelines (2). If extrapolation is not possible, new clinical data are needed.
In some instances, a feasibility study should be undertaken in order to determine whether it is possible to complete a significant clinical trial. The analysis of feasibility should always be justified with available evidence. A properly conducted feasibility study may constitute the basis to request regulatory agencies to grant a waiver from conducting clinical trials in one or more subsets of the paediatric population. A paediatric trial should not be an adaptation of the adult protocol, but must be conceived and developed in its own right. This may involve particular attention to the exploration of alternative designs.
Bayesian approaches, for example, have been used successfully in sequential dose-finding studies. This may allow a reduction in the number of patients that are required to arrive at a reliable conclusion when performing efficacy studies in children, when the inclusion of weighted prior evidence from studies in adults is admissible (partial extrapolation).
Paediatric studies may need very different primary endpoints from those of adult studies: different effect size; a better spontaneous outcome in the control group; or the inability of the child to perform a particular test. If the primary endpoint suitable for adult trials cannot be used in children, in many cases it should still be included as a secondary endpoint in order to allow comparison among different trials in children (and in adults). The time of assessment for a primary or secondary endpoint can be different in children and adolescents (shor
EU Regulation 1901/2006 – the ‘Paediatric Regulation’ – provides a systematic approach to the development of medicinal products intended for use in the paediatric population (1). This legal framework followed the first US initiative (the Best Pharmaceuticals for Children Act), which has been in place since 1997.
Pharmaceutical companies are now required to perform clinical studies in children before being able to apply for marketing authorisation of a new medicinal product in the EU (or for a new indication, dosage form or route of administration of an authorised, patented product), unless they have agreed a waiver or a deferral with the Paediatric Committee (PDCO) of the European Medicines Agency (EMA).
CONDUCTING CLINICAL TRIALS IN CHILDREN
The term ‘children’ includes the paediatric population from birth to 18 years. This group’s characteristics are extremely diverse; weights can start at less than 1kg but extend up to a typical young adult’s weight, while cognitive development, physical and sexual maturation and biochemical characteristics are all elements that change with each individual. When organising a good clinical trial in children, certain factors require close inspection.
Need, Feasibility and Design of Trials
Once the paediatric need(s) and the study question have been clarified, the possibility of replacing some studies, or reducing the number of patients involved, through extrapolation, modelling and simulation should be discussed. Unnecessary clinical trials in children should be avoided, and the use of extrapolation for efficacy is encouraged by current guidelines (2). If extrapolation is not possible, new clinical data are needed.
In some instances, a feasibility study should be undertaken in order to determine whether it is possible to complete a significant clinical trial. The analysis of feasibility should always be justified with available evidence. A properly conducted feasibility study may constitute the basis to request regulatory agencies to grant a waiver from conducting clinical trials in one or more subsets of the paediatric population. A paediatric trial should not be an adaptation of the adult protocol, but must be conceived and developed in its own right. This may involve particular attention to the exploration of alternative designs.
Bayesian approaches, for example, have been used successfully in sequential dose-finding studies. This may allow a reduction in the number of patients that are required to arrive at a reliable conclusion when performing efficacy studies in children, when the inclusion of weighted prior evidence from studies in adults is admissible (partial extrapolation).
Paediatric studies may need very different primary endpoints from those of adult studies: different effect size; a better spontaneous outcome in the control group; or the inability of the child to perform a particular test. If the primary endpoint suitable for adult trials cannot be used in children, in many cases it should still be included as a secondary endpoint in order to allow comparison among different trials in children (and in adults). The time of assessment for a primary or secondary endpoint can be different in children and adolescents (shor
Iris type:
1.1 Articolo in rivista
List of contributors:
Tomasi, Paolo
Published in: