[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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