[Federal Register Volume 70, Number 194 (Friday, October 7, 2005)]
[Notices]
[Pages 58713-58714]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-20301]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2005N-0404]


Solicitation of Public Review and Comment on Research Protocol: 
Gonadotropin-releasing Hormone Agonist Test in Disorders of Puberty

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), are soliciting 
public review and comment on a proposed research protocol entitled 
``Gonadotropin-releasing Hormone (GnRH) Agonist Test in Disorders of 
Puberty.'' The proposed research would be conducted at the University 
of Chicago Hospitals General Clinical Research Facility and supported 
by the National Center for Research Resources of the National 
Institutes of Health (NIH). 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 Tuesday, November 
1, 2005.

ADDRESSES: Electronic copies of the documents for public review can be 
viewed at the Pediatric Advisory Committee (PAC) Docket Web site at 
http://www.fda.gov/ohrms/dockets/ac/acmenu.htm. (Click on the year 2005 
and scroll down to Pediatric Ethics Subcommittee meetings.) Submit 
written comments to the Division of Dockets Management (HFA-305), 
Docket No. 2005N-0404, Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852. Submit electronic comments 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 FDA's Web site at http://www.fda.gov/ohrms/dockets/05n0404/05n0404.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: Kevin Prohaska, Office for Human 
Research Protections, The Tower Building, 1101 Wootton Pkwy., suite 
200, Rockville, MD 20852, 240-453-6900, FAX: 240-453-6909, e-mail: 
[email protected]; or Jan N. Johannessen, Office of the 
Commissioner (HF-33), Food and Drug Administration, 5600 Fishers Lane 
(for express delivery, rm. 14C-06), Rockville, MD 20857, 301-827-6687, 
or by e-mail: [email protected].

SUPPLEMENTARY INFORMATION: All studies conducted or supported by HHS 
that are not otherwise exempt and that 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 in 45 CFR part 46, subpart D. Under FDA's interim final rule 
effective April 30, 2001, FDA adopted similar regulations in part 50, 
subpart D (21 CFR part 50, subpart D) to provide safeguards for 
children enrolled in clinical investigations of products regulated by 
FDA. Because the proposed research, ``Gonadotropin-releasing Hormone 
(GnRH) Agonist Test in Disorders of Puberty,'' would be 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 in 45 CFR 46.407, and FDA regulations in 
Sec.  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 in 45 CFR 46.404, 46.405, or 
46.406, and FDA regulations in Sec. Sec.  50.51, 50.52, or 50.53, 
respectively, the research may proceed only if the following conditions 
are met: (1) 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), 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 Sec. Sec.  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 Sec.  50.55.
    HHS has received a request on behalf of the University of Chicago 
Hospitals' IRB to review under 45 CFR 46.407 the protocol entitled 
``Gonadotropin-releasing Hormone (GnRH) Agonist Test in Disorders of 
Puberty.'' The principal investigator proposes to administer leuprolide 
10 micrograms/kilogram to approximately 300 subjects with and without a 
disorder of puberty followed by serial blood determinations of 
endogenous sex-related hormones. Serial blood draws will be done 
through an indwelling venous catheter using an automated pump. Children 
will be closely supervised in the research facility for two overnight 
stays. The specific aim of the study is to test the hypothesis that the 
response to the injection of the GnRH agonist, leuprolide acetate, will 
distinguish among the causes of precocious puberty and delayed puberty.
    The University of Chicago Hospitals IRB determined that the full 
protocol was not approvable under 45 CFR 46.404, 46.405, or 46.406 
because the proposed administration of leuprolide acetate poses more 
than minimal risks to the control subjects, there is no prospect of 
direct benefit to the individual control subjects, the interventions or 
procedures do not present an experience to the control group that is 
reasonably commensurate with those inherent in their expected medical 
situation, and the control group does not have the condition or 
disorder under study. However, the IRB did find that this research 
presents a reasonable opportunity to understand, prevent, or alleviate 
a serious problem affecting the health or welfare of children. 
Accordingly, the University of Chicago Hospitals IRB forwarded the 
protocol to OHRP under 45 CFR 46.407 for consideration. Because this 
clinical investigation is regulated by FDA, FDA's regulations at part 
50, subpart D, specifically Sec.  50.54, apply as well.
    In accordance with 45 CFR 46.407(b) and Sec.  50.54(b), OHRP and 
FDA are soliciting public review and comment

[[Page 58714]]

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 
knowledge that can be generalized 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 information 
relating to the proposed clinical investigation, including the 
following items: Correspondence from the University of Chicago 
referring the proposed research protocol to HHS for consideration under 
45 CFR 46.407, correspondence from FDA and OHRP to the University of 
Chicago regarding the proposed protocol, the research protocol, NIH's 
grant funding the protocol, IRB's deliberations on the proposed 
research, and the parental permission documents. Electronic copies of 
these documents can be viewed at PAC's Docket Web site at http://www.fda.gov/ohrms/dockets/ac/acmenu.htm. (Click on the year 2005 and 
scroll down to Pediatric Ethics Subcommittee of PAC meetings.) These 
materials are also available on OHRP's Web site at http://www.hhs.gov/ohrp/children/. (FDA has verified the Web site address but is not 
responsible for subsequent changes to the Web site after this document 
publishes in the Federal Register.)
    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 Tuesday, November 1, 2005. The background 
materials and received comments may be viewed on FDA's Web site at 
http://www.fda.gov/ohrms/dockets/05n0404/05n0404.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 
Web site at http://www.hhs.gov/ohrp/children/. (FDA has verified the 
Web site address but is not responsible for subsequent changes to the 
Web site after this document publishes in the Federal Register.)

    Dated: October 3, 2005.
Jason D. Brodsky,
Acting Associate Commissioner for External Relations.
[FR Doc. 05-20301 Filed 10-5-05; 11:25 am]
BILLING CODE 4160-01-S