February 2024 SOCRA Source Journal - Journal - Page 8
and to optimize the sample
sizes for both the pediatric
and adult study populations.
Further, while every effort
should be made to gather data
that adequately address each
targeted pediatric subgroup for
the proposed indication for use,
in some cases, the expected
benefit and safety can be
determined without separate
studies in each subgroup. That
is, it may be extrapolated from
one age group to another.38
In other cases, such as with
neonates, clinical data gathered
specifically in that subgroup will
likely be needed.39
C. Study Procedures
in Pediatric Clinical
Investigations
In the context of a clinical
investigation, procedures
that are carried out as part of
routine clinical care of a child
generally are considered to
offer a clinical benefit and do
not require evaluation as a
research intervention under the
regulations. Procedures that are
carried out solely for research
purposes and do not offer
prospect of direct benefit must
meet the minimal risk criteria
(21 CFR 50.51) or no more than
a minor increase over minimal
risk criteria (21 CFR 50.53) in
order to be included in a clinical
investigation unless referred for
review under 21 CFR 50.54 (see
section III.F).
The potential for harm and the
invasiveness and frequency of
the planned procedures should
be considered when assessing
the risk. A single lumbar
puncture or a single muscle
biopsy have been considered,
in many circumstances, to
constitute a minor increase over
minimal risk.40
8
However, large organ
biopsies—such as liver or
kidney biopsies—when done
for research purposes only have
generally been considered to
exceed a minor increase over
minimal risk, and should not
be done in children unless
the procedure is performed
as part of the routine clinical
care for that child in the
treatment of their condition.
When considering the risk
of a procedure, the risk of
any sedation not needed for
the child’s clinical care (i.e.,
non-therapeutic procedural
sedation, see section
IV.C.1) or the risk of use of a
contrast agent should also be
considered. For example, a
single MRI without contrast
could be considered minimal
risk, but the addition of contrast
or sedation to the procedure
is likely to constitute at least
a minor increase over minimal
risk, depending on the type of
contrast being used and the risk
of the sedation.
1. Procedural Sedation in
Pediatric Clinical Investigations
Procedures in children in
a clinical trial may require
sedation and the risks of
sedation needed for nonbeneficial “research-only” (nontherapeutic) procedures should
be considered. The Pediatric
Ethics Subcommittee of FDA’s
Pediatric Advisory Committee
met in March 2015 to discuss
the use of non-therapeutic
procedural sedation and
came to the following areas of
agreement when considering
the use of sedation for a nontherapeutic procedure:41
• Procedures should be
performed at a high-volume
center with a dedicated
pediatric
SOCRA SOURCE © May 2023
•
•
•
•
•
•
•
There should be rigorous
scientific justification for
the need for the nontherapeutic procedures;
The approach to procedural
sedation and risk
minimization procedures
should be described in the
protocol;
Children with chronic
conditions that may place
them at higher risk from
procedural sedation should
be carefully evaluated and
potentially excluded from
the protocol;
The non-therapeutic
procedure should be
terminated if complications
of sedation arise or the level
of sedation is inadequate,
as it would be inappropriate
to escalate the approach to
procedural sedation beyond
what would be considered a
minor increase over minimal
risk rather than to stop the
procedure;
If a particular procedure in a
particular patient population
is normally accompanied by
sedation when performed
for clinical reasons, sedation
should not be withheld
in the non-therapeutic
research setting to avoid its
risks and thereby attempt
to enhance the procedure’s
approvability under federal
research regulations; and
There should be clear
communication with
potential subjects
(and their parents/
guardians) regarding the
non-therapeutic nature
of the procedures and
procedural sedation in
child assent and parental
permission documents.