numbering 13 units. There are other non-govern-
mental specialized units also available for pediatric
PK work.
An alternative method of getting PK data is
to take a small extra sample of blood (and urine)
at a child’s regular scheduled visit when blood is
drawn for routine blood work. The time of day of
this sample is predetermined by the time of the
administration of the medicine. If samples
are obtained from many children, a weight–age-
corrected, scatter-plot graph can be constructed
and a PK profile be calculated. This is the ‘phar-
macokinetic screen’ method. A version of this
method is also utilized to gather ethnic data for
labeling in adults as well as children, and is called
‘population pharmacokinetics’.
Recruitment
One of the major problems in running pediatric
clinical trials is the availability of pediatric
patients, who tend to be scattered, because they
are numerically less likely to have diseases (other
than asthma and the usual childhood illnesses).
This affects the logistics of screening and subse-
quent clinicvisits. Another hurdleis findingtrained
pediatric investigators or pediatric pharmacolo-
gists, and overseas they are even harder to find. In
Europe, there is collaboration between the US-
based Pediatric Pharmacology Research Units
(PPRU), the European Society of Developmental
Pharmacology and the European Network for Drug
Investigation in Children (ENDIC). For diseases of
children, there are often self-help organizations
that can prove invaluable in recruiting children
and in reassuring their parents.
A large package of data, and two well-con-
trolled pivotal studies of safety and efficacy are
rarely required, with the exception of diseases
specific to childhood, such as surfactant studies
in respiratory distress syndrome. This is espe-
cially the case if the drug has similar effects in
both adult and pediatric populations, for example
antihistamines.
However, if a disease or drug behaves in differ-
ent ways in children compared with adults but a
large body of safety data exists in adults, then
usually only a single efficacy and safety study is
required.Ethical concerns
The American Academy of Pediatrics formed
a Committee on Drugs to examine ethical issues
of pediatric studies for its members and for the
guidance of IRBs dealing with pediatric studies.
The Committee released its report in 1995. This
report (Committee Drugs, American Academy of
Pediatrics) is very comprehensive, but amongst its
many recommendations the following areas are
highlighted.Vulnerability
In this special population, there is a special duty to
avoid (unintended) coercion of the patient, parent
or guardian. This coercion may arise because the
investigator is usually also the treating physician. It
would be better to have a colleague explain and
obtain the informed consent. There are varying
degrees of vulnerability. Patients handicapped
either mentally, emotionally or physically are fre-
quently institutionalized and may be supervised as
Wards of Court or by a social welfare agency.
These patients should be rarely used, unless the
treatment is for serious disease specific to institu-
tional settings and no other treatment is available.
Emergency situations can arise where it may be
impossible to obtain written informed consent
from a parent or guardian. Medications for this
type of problem will require intense IRB review
and overview; only in special circumstances will
informed consent be waived, and then it must ‘not
adversely affect the rights and welfare of the sub-
ject’. (Abramsonet al., 1986). The last category is
the use of a research medicine in a child close to
dying who has either no response to standard ther-
apy or where no alternative therapy exists. The
agent to be considered must have some evidence
of efficacy (animal proof of concept or clinical data
and a good chance of a beneficial result). The risk
of unintended coercion of desperate parents is
especially to be guarded against.17.5 CLINICAL STUDIES 227