Subpart D Review of Pending NHLBI Grant Entitled "Sleep Mechanisms in Children: Role of Metabolism"

The Office for Human Research Protections (OHRP) is soliciting public review and comment pursuant to Department of Health and Human Services (HHS) regulations at 45 CFR 46.407 on the above-referenced research protocol.

HHS regulations at 45 CFR part 46, subpart D, provide additional protections to children involved in research.  Under the requirements of subpart D, if an institutional review board (IRB) reviewing a protocol to be conducted or supported by HHS does not believe that the proposed research involving children meets requirements for approval under 45 CFR 46.404 (research not involving greater than minimal risk), 46.405 (research involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects), or 46.406 (research involving greater than minimal risk and no prospect of direct benefit to the individual subjects but likely to yield generalizable knowledge about the subject's disorder or condition), but 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, the IRB may refer the proposed research to the Secretary of HHS for a determination regarding whether the research is otherwise approvable under subpart D.  Under the process outlined in 45 CFR 46.407, the Secretary must consult with experts in relevant disciplines, and provide the opportunity for public review and comment, before determining whether the proposed research may be conducted or supported by HHS.

This research protocol proposes to measure glycogen, glutamate turnover rate, and glutamate-glutamine cycling in wakefulness and sleep in adolescent children ages 13 to 17 years.  The investigator also proposes to study a subset of children in a similar manner following sleep deprivation.  The study would involve three visits to the Children's Hospital at Montefiore Medical Center.  Measurements will be made using magnetic resonance spectroscopy following intravenous infusion of 13C-acetate and 13C-glucose.  The long term aims of the study are to better understand (a) sleep; (b) the diseases afflicting children and adults that impact on their sleep; and (c) sleep-related diseases that impact on neurocognitive, cardiovascular, behavioral, and other functions.

OHRP is requesting comments on the following questions related to the study:

1.  What are the types and degrees of risk that this research presents to the subjects?

2.  What are the potential benefits, if any, to the subjects and to children in general?

3.  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?

4.  If conducted as proposed in the above-cited protocol, would the research be conducted in accordance with sound ethical principles?  In formulating a response, commenters may wish to consider whether the proposed protocol satisfies all the requirements under HHS regulations at 45 CFR 46.111 (criteria for IRB approval of research).

5.  Have adequate provisions been made for soliciting the assent of children and the permission of their parents or guardians?

To be considered, comments on this proposed research protocol must be submitted on or before 4:30 PM, EST July 28, 2003.  Written comments should be submitted to Ms. Kelley Booher, Division of Policy, Planning, and Special Projects, OHRP, 1101 Wootton Parkway, Suite 200, The Tower Building, Rockville, MD 20852.  Comments may also be submitted via facsimile at 301-402-2071 or by email to: 407panel03@osophs.dhhs.gov .  Following public review and comment, the Secretary of HHS will make a final determination on whether HHS may support this research protocol.  If approved, this research would be supported by a grant awarded by the National Heart, Lung, and Blood Institute, National Institutes of Health.

Please note that some of the information in the following documents is exempt from disclosure under existing Federal statutes and has been redacted.
  1. Federal Register Notice Vol. 68, No. 114, pages 35415-6, dated June 13,2003: Solicitation of Public Review and Comment, available at  http://www.hhs.gov/ohrp/references/fr06-13h.pdf  [PDF document].
  2. Correspondence from the IRB referring the proposed research protocol to the Secretary of HHS for consideration under 45 CFR Part 46.407   [PDF Format  PDF document, see bottom of page to obtain free reader]   [HTML Format]
  3. IRB protocol application   [PDF Format  PDF document, see bottom of page to obtain free reader] 
  4. IRB deliberations on the proposed research   [PDF Format  PDF document, see bottom of page to obtain free reader] 
  5. Parental permission and assent forms  [PDF Format PDF document, see bottom of page to obtain free reader]   [HTML Format]
  6. Relevant excerpts of the NIH grant application  [PDF Format PDF document, see bottom of page to obtain free reader]
  7. Individual expert reports solicited pursuant to HHS Regulations at 45 CFR 46.407;

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Updated June 13, 2003