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.

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: kprohaska@osophs.dhhs.gov; 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: jjohannessen@fda.gov.

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 § 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 §§ 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 §§ 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 § 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 § 50.54, apply as well.

In accordance with 45 CFR 46.407(b) and § 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 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.)