February 2024 SOCRA Source Journal - Journal - Page 7
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in older subjects, or that
is expected based on
other clinical or nonclinical
investigations; and
Likely duration of drug
or device use and its
impact on the growth and
development of the child,
including behavioral and
psychosocial effects.
The following sections provide
additional design considerations
for clinical investigations of
drugs and clinical investigations
of medical devices.
1. Clinical Investigations of
Drugs
To offer a prospect of direct
benefit, any dose planned
for use in a pediatric clinical
investigation should have the
potential to have a therapeutic
effect based on available
scientific information.32 If there
are adults with the disease,
pharmacokinetic (PK) and
pharmacodynamic (PD) data
in adults may provide useful
information to help establish
a potentially effective dose for
use in children.
If there are a limited number of
adults with the condition, PK
and PD data from clinical trials
in healthy adult volunteers33
or in adults or children
using the product for other
indications may be informative
in helping to establish initial
dosing for children with the
condition under study. Such
information may also provide
some evidence of drug
activity to support prospect
of direct benefit if the activity
assessment is relevant to the
pediatric population of interest.
Extending a dose for a product
from another patient population
(or different indication) to the
new pediatric population should
be based on a sound scientific
assessment, particularly
addressing how the exposureresponse for effectiveness and
safety in the other population
was used to predict the
exposure-response relationship
in the pediatric population of
interest.
Nonclinical studies in diseasespecific animal models of a
pediatric condition or in vitro
data could be used to support
an initial pediatric dose if the
PD effect on important aspects
of the condition in question can
be translated into an equivalent
human dose that is anticipated
to be effective and offers
prospect of direct benefit. This
should be based on scientific
criteria that estimate the
relationship between the PD
effect in the nonclinical model
and human physiology.
Clinical investigations should be
of sufficient duration to offer a
potential clinical benefit to the
individual child. This judgement
is similar to that made when
exposing children to a
treatment in clinical practice. Of
note, most single-dose studies
intended to collect PK data in
children do not offer prospect
of direct benefit because the
study duration is too short to
offer a clinical benefit. A study
intended to collect single-dose
PK data might be considered
under 21 CFR 50.53 as a
minor increase over minimal
risk if there is adequate safety
information to characterize
the risk from exposure to the
investigational drug and any
additional study procedures as
no more than a minor increase
over minimal risk.34, 35 In this
case, the study intervention
does not offer benefit but may
contribute to generalizable
knowledge about the child’s
disorder or condition.
Multiple-dose studies36
intended to collect PK data
may offer prospect of direct
benefit, but the dose and
duration of exposure to the
study intervention should be
sufficient to have the potential
to result in a clinical benefit
or to effect some change in a
surrogate of clinical benefit. To
provide studies of adequate
duration to offer prospect of
direct benefit, adaptive study
designs should be considered
when additional dose finding
is required within the context
of the clinical investigation.
Such adaptive designs could
combine prospectively planned
dose ranging or dose titration
with continued dosing after a
dose is established.37
2. Clinical Investigations of
Medical Devices
Compared to drugs, devices
present different challenges due
to the range of technology they
incorporate and their varying
applications. The available
clinical data for the device (e.g.,
published studies and reports
and actual use information)
should be considered when
designing the clinical trial
to maximize the amount
of information gained
and minimize the number
of subjects involved. For
indications involving both adults
and children, it may be possible
to design a single pivotal study
that includes both pediatric
and adult subjects to reduce
the burden of multiple studies
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