Subpart D Review of Research Protocol Entitled
"HIV Replication and Thymopoiesis in Adolescents"

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.

The University of California at Los Angeles (UCLA) forwarded the above-referenced protocol to the Secretary of HHS for consideration under 45 CFR 46.407, following the determination by the UCLA IRB that a substudy of this research could not be approved under 45 CFR 46.404, 46.405, or 46.406, but was suitable for review under 45 CFR 46.407.  The principal investigator proposes a longitudinal study evaluating the pathogenic properties of Human Immunodeficiency Virus (HIV), the suppressive and selective power of antiretroviral therapy, and the regenerative capacity of the immune system in adolescents and young adults ages 13 to 24 years with perinatally-acquired HIV infection, compared with two age-matched control groups: adolescents who acquired HIV infection via adult behaviors (sexual contact and illicit drug use), and seronegative adolescents.  The proposed substudy would be funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under grant number R01 AI 051996.  Additional information on the proposed research protocol can be accessed through links below.

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, September 2, 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: 407panel04@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 Institute of Allergy and Infectious Diseases, 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. 136, pages 42061, dated July 16, 2003, available at  http://ohrp.osophs.dhhs.gov/references/fr07-16.pdf  [PDF document]: Solicitation of Public Review and Comment
    2. PDF document, see bottom of page to obtain free reader] 
  2. Correspondence from UCLA to OHRP requesting HHS review pursuant to 45 CFR 46.407   [PDF Format  PDF document, see bottom of page to obtain free reader]   [HTML Format]
  3. Original IRB protocol application   [PDF Format  PDF document, see bottom of page to obtain free reader]   [HTML Format]
  4. Correspondence between the UCLA IRB and the principal investigator;
  5. Parental permission and assent documents
  6. Relevant excerpts from the NIH grant application for the above cited protocol  [PDF Format PDF document, see bottom of page to obtain free reader]
  7. Other pertinent information
  8. Individual expert reports solicited pursuant to HHS Regulations at 45 CFR 46.407;

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Updated July 16, 2003