Studies in Support of Special Populations
9. Studies in Children
There is a need for clinical
trials involving children to improve the treatment available to them. Children
represent a vulnerable population - they have developmental, physiological and
psychological differences from adults. Age and development related research is therefore important for their benefit.
Medicines for children need to
be tested scientifically before widespread use. This can only be achieved by
ensuring that medicines which are likely to be of significant clinical value
for children are fully studied. The clinical trials required for this purpose
should be carried out under conditions affording the best possible protection
for the children who take part.
The extent of the studies
needed depends on the current knowledge of the medicine. It also depends on
whether data from studies in adults and children of other age groups can be
extrapolated to the new age group. Some medicines may be used in children from
the early stages of medicines development, however, for a medicine expected to
be used in children, it should be studied in the appropriate age group. When
clinical development is to include studies in children, it is usually
appropriate to begin with older children before extending the trial to younger
children and then infants.
In this case, investigators
need to follow the EMA guidance (CPMP/ICH/2711/99) on clinical investigation of medicinal
products in the paediatric population (infants, children and adolescents up to
the age of 18 years). This guide is the primary guideline for paediatric
medicines development in Europe and stablishes the age classification of
paediatric patients. There is, however, considerable overlap in developmental
(e.g., physical, cognitive, and psychosocial) issues across the age categories.
Ages are defined in completed days, months, or years:
- Preterm newborn infants.
- Term newborn infants (0 to 27 days).
- Infants and toddlers (28 days to 23 months).
- Children (2 to 11 years).
- Adolescents (12 to 16/18 years, depending on region).
When paediatric patients are included in clinical trials, safety data from previous adult human experience would usually represent the most relevant information. This should generally be available before paediatric clinical trials begin. The appropriateness and extent of adult human data should be decided on a case-by-case basis. Extensive adult experience might not be available before paediatric exposures, e.g. for medicines that are for children only.
Before children are included in clinical trials, the following must be completed:
- Repeated-dose toxicity studies of appropriate duration in adult animals.
- The standard safety pharmacology information must be determined, and;
- The standard range of genotoxicity tests – studies that look at the effect on genes.
In line with the EU paediatric regulation (EC) No 1901/2006, as amended, a paediatric investigation plan (PIP) should be submitted early in the development of new medicines to make sure that the appropriate development in children is included.
The design of efficacy studies in the paediatric population is essentially similar to that required in adults. Depending on the type of medicinal product, a deferral (postponement) of the studies in children until efficacy and safety data are obtained in adults might be envisaged by the Paediatric Committee (PDCO), part of the European Medicines Agency (EMA).
For products not likely to be
used in children (e.g. medicines for Alzheimer patients) the PDCO may grant
a waiver so paediatric studies need not be performed.