[Federal Register: August 4, 2004 (Volume 69, Number 149)]
[Notices]
[Page 47158-47159]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr04au04-82]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Office of Public Health and Science and Food and Drug
Administration
[Docket No. 2004N-0337]
Solicitation of Public Review and Comment on Research Protocol:
Effects of a Single Dose of Dextroamphetamine in Attention Deficit
Hyperactivity Disorder; A Functional Magnetic Resonance Study
AGENCY: Office of Public Health and Science and Food and Drug
Administration, HHS.
ACTION: Notice.
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SUMMARY: The Office for Human Research Protections (OHRP), Office of
Public Health and Science, Department of Health and Human Services
(HHS) and the Food and Drug Administration (FDA), HHS are soliciting
public review and comment on a proposed research protocol entitled
``Effects of a Single Dose of Dextroamphetamine in Attention Deficit
Hyperactivity Disorder (ADHD); A Functional Magnetic Resonance Study.''
The proposed research would be conducted at the National Institutes of
Health (NIH) and supported by NIH's National Institute of Mental Health
(NIMH). Public review and comment are solicited regarding the proposed
research protocol under the requirements of HHS and FDA regulations.
DATES: To be considered, written or electronic comments on the proposed
research must be received on or before 4:30 p.m. on August 20, 2004.
ADDRESSES: Electronic copies of the documents for public review can be
viewed at the Pediatric Advisory Committee (PAC) Docket site at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/ac/acmenu.htm.
(Click on the year 2004 and
scroll down to PAC meetings.) Submit written comments to the Division
of Dockets Management (HFA-305), Docket No. 2004N-0337, Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
Submit electronic comments to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. All
comments should be identified with the docket number found in brackets
in the heading of this document. Received comments may be viewed on the
FDA Web site at: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/dockets/04n0337/04n0337.htm
, or may be seen in the Division of Dockets Management
between 9 a.m. and 4 p.m., Monday through Friday.
FOR FURTHER INFORMATION CONTACT: Julia Gorey, Office for Human Research
Protections, The Tower Building, 1101 Wootton Pkwy., suite 200,
Rockville, MD 20852, 301-496-7005, FAX: 301-402-2071, e-mail:
Jgorey@osophs.dhhs.gov; or Jan N. Johannessen, Office of the
Commissioner (HF-33), Food and Drug Administration, 5600 Fishers Lane
(for express delivery, rm. 17-51), Rockville, MD 20857, 301-827-3340,
or by e-mail: jjohannessen@fda.gov.
SUPPLEMENTARY INFORMATION: All studies conducted or supported by HHS
which are not otherwise exempt and which propose to involve children as
subjects require Institutional Review Board (IRB) review in accordance
with the provisions of HHS regulations for the protection of human
subjects at 45 CFR part 46, subpart D. Under FDA's interim final rule
effective April 30, 2001 (21 CFR part 50, subpart D), FDA adopted
similar regulations to provide safeguards for children enrolled in
clinical investigations of FDA-regulated products. Because the proposed
research, ``Effects of a Single Dose of Dextroamphetamine in Attention
Deficit Hyperactivity Disorder; A Functional Magnetic Resonance
Study,'' would be
[[Page 47159]]
conducted and supported by NIH, a component of HHS, and would be
regulated by FDA, both HHS and FDA regulations apply to this proposed
research.
Under HHS regulations at 45 CFR 46.407, and FDA regulations at 21
CFR 50.54, if an IRB reviewing a protocol to be conducted or supported
by HHS for a clinical investigation regulated by FDA does not believe
that the proposed research involving children as subjects meets the
requirements of HHS regulations at 45 CFR 46.404, 46.405, or 46.406,
and FDA regulations at 21 CFR 50.51, 50.52, or 50.53, respectively, the
research may proceed only if the following conditions are met: (1) The
IRB finds that the research presents a reasonable opportunity to
further the understanding, prevention, or alleviation of a serious
problem affecting the health or welfare of children; and (2) the
Secretary (HHS) and the Commissioner (FDA), respectively, after
consultation with experts in pertinent disciplines (e.g., science,
medicine, education, ethics, law) and following opportunity for public
review and comment, determine either: (a) That the research in fact
satisfies the conditions of 45 CFR 46.404, 46.405, or 46.406 under HHS
regulations, and 21 CFR 50.51, 50.52, or 50.53 under FDA regulations,
or (b) that the following conditions are met: (i) The research or
clinical investigation presents a reasonable opportunity to further the
understanding, prevention, or alleviation of a serious problem
affecting the health or welfare of children; (ii) the research or
clinical investigation will be conducted in accordance with sound
ethical principles; and (iii) adequate provisions are made for
soliciting the assent of children and the permission of their parents
or guardians, as set forth in 45 CFR 46.408 and 21 CFR 50.55.
HHS has received a request on behalf of the IRB of NIMH, to review
under 45 CFR 46.407 the protocol entitled ``Effects of a Single Dose of
Dextroamphetamine in Attention Deficit Hyperactivity Disorder; A
Functional Magnetic Resonance Study.'' The principal investigator
proposes to administer a single 10-milligram dose of dextroamphetamine
in conjunction with functional magnetic resonance imaging (fMRI) in
healthy children and children with attention deficit hyperactivity
disorder (ADHD), all between 9 and 18 years of age. Subjects of the
study would include 10 children for piloting tasks; 14 healthy control
children; 14 children with ADHD; 24 monozygotic twins (12 pairs),
discordant for ADHD; and 24 dizygotic twins (12 pairs), discordant for
ADHD.
The overall goal of the proposed study is to better understand the
pathophysiology of ADHD. The three specific aims of the study are to:
(1) Study brain activation patterns during response inhibition tasks in
children with ADHD and in healthy controls; (2) simultaneously examine
the central and behavioral effects of a single-dose of amphetamine
versus placebo in the two groups; and (3) examine (using monozygotic
and dizygotic twins) brain activation patterns in relation to clinical
state and the degree of genetic relatedness.
The NIMH IRB determined that although the protocol was not
approvable under 45 CFR 46.404, 46.405, or 46.406 because the
administration of dextroamphetamine posed more than minimal risks to
healthy children, the protocol was suitable for review under 45 CFR
46.407. Accordingly, the NIMH IRB forwarded the protocol to OHRP under
45 CFR 46.407. Because this clinical investigation is regulated by FDA,
FDA's regulations at 21 CFR part 50, subpart D, specifically 21 CFR
50.54, apply as well.
In accordance with 45 CFR 46.407(b) and 21 CFR 50.54(b), OHRP and
FDA are soliciting public review and comment on this proposed clinical
investigation. In particular, comments are solicited on the following
questions: (1) What are the potential benefits, if any, to the subjects
and to children in general; (2) what are the types and degrees of risk
that this research presents to the subjects; (3) are the risks to the
subjects reasonable in relation to the anticipated benefits, and is the
research likely to result in generalizable knowledge about the subjects
disorder or condition; and (4) does the research present a reasonable
opportunity to further the understanding, prevention, or alleviation of
a serious problem affecting the health or welfare of children.
To facilitate the public review and comment process, FDA has
established a public docket and placed in that docket the following
information relating to the proposed clinical investigation, including:
Correspondence from NIH referring the proposed research protocol to HHS
for consideration under 45 CFR 46.407; correspondence from FDA to NIH
regarding the proposed protocol; the NIMH research protocol; the IRB
deliberations on the proposed research; the parental permission
documents; and the assent documents. Electronic copies of these
documents can be viewed at the Pediatric Advisory Committee (PAC)
Docket site at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/ac/acmenu.htm. (Click
on the year 2004 and scroll down to PAC meetings.) These materials are
also available on OHRP's website at: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://hhs.gov/ohrp/children/.
All written comments concerning this proposed research should be
submitted to FDA's Division of Dockets Management under 21 CFR 10.20,
no later than 4:30 p.m. on August 20, 2004. The background materials
and received comments may be viewed on the FDA Web site at: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/dockets/04n0337/04n0337.htm
or may be seen in
the Division of Dockets Management between 9 a.m. and 4 p.m. Monday
through Friday. The background materials may also be viewed on OHRP's
website at: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://hhs.gov/ohrp/children/.
Dated: July 29, 2004.
Lester M. Crawford,
Acting Commissioner for Food and Drugs.
Dated: July 29, 2004.
Cristina V. Beato,
Acting Assistant Secretary for Health.
[FR Doc. 04-17825 Filed 7-30-04; 3:42 pm]
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