February 2024 SOCRA Source Journal - Journal - Page 9
FDA recommends that sponsors
use these recommendations
for minimizing risk in designing
and implementing protocols
that include non-therapeutic
procedural sedation. These
recommendations will also aid
IRBs when assessing the risk to
children. The IRB should
consider the cumulative risk if
more than one procedure with
non-therapeutic procedural
sedation is planned. If the
IRB determines that the
procedure(s) is integral to
answering the scientific
question and ethical to perform,
but that it constitutes more than
a minor increase over minimal
risk, review under 21 CFR
50.54 will be required before
the clinical investigation may
proceed.
CITATIONS
31 See the Federal Register of January 13, 1978 (43 FR 2084 at 2110).
32 These considerations also apply to investigational gene therapies. For these trials, a single dose
of vector is generally administered, with the possibility of a long-lasting duration of action and
resulting benefit; the study dose will need to be in the potentially therapeutic range.
33 Testing in adult normal, healthy volunteers is generally not acceptable for gene therapy trials. See
the guidance for industry Human Gene Therapy for Rare Diseases (January 2020).
34 See the draft guidance for industry General Clinical Pharmacology Considerations for Pediatric
Studies of Drugs, Including Biological Products (September 2022). When final, this guidance will
represent the FDA’s current thinking on this topic.
35 Roth-Cline M, Nelson RM. Microdosing Studies in Children: A US Regulatory Perspective. Clinical
Pharmacology and Therapeutics. 2015; 98(3): 232-233.
36 Given the complexity of gene therapy products, multiple dose PK studies are unlikely to be
conducted. Please contact CBER for additional considerations that may apply.
37 Guidance for industry Adaptive Designs for Clinical Trials of Drugs and Biologics (November
2019).
38 See footnote 20.
39 For additional information, see the guidance for industry and FDA staff Premarket Assessment of
Pediatric Medical Devices (March 2014).
40 Snyder D, Lee C, and Nelson R. (2018). Invasive Placebos, Patient Burdens and Community
Advocacy: A Federal Ethics Panel Protocol Review. In Kodish, E and Nelson, R. (Eds). Ethics and
Research with Children, A Case-Based Approach (2nd ed.). New York, NY: Oxford University Press.
41 Minutes of the Pediatric Ethics Subcommittee of FDA’s Pediatric Advisory Committee, March
23, 2015. http://wayback.archive- it.org/7993/20180127092544/https://www.fda.gov/downloads/
AdvisoryCommittees/CommitteesMeetingMaterials/P ediatricAdvisoryCommittee/UCM510177.pdf
(accessed September 19, 2022).
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