[Federal Register Volume 68, Number 136 (Wednesday, July 16, 2003)]
[Notices]
[Pages 42061-42062]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-17916]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Solicitation of Public Review and Comment on Research Protocol: 
HIV Replication and Thymopoiesis in Adolescents

AGENCY: Department of Health and Human Services, Office of the 
Secretary, Office of Public Health and Science, Office for Human 
Research Protections.

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) is soliciting public review and comment on a proposed research 
protocol entitled ``HIV Replication and Thymopoiesis in Adolescents.'' 
The proposed research would be supported by a grant awarded by the 
National Institute of Allergy and Infectious Diseases, National 
Institutes of Health. Public review and comment are solicited regarding 
the proposed research protocol pursuant to the requirements of HHS 
regulations at 45 CFR 46.407.

DATES: To be considered, written or electronic comments on the proposed 
research must be received on or before 4:30 p.m. EST September 2, 2003.

ADDRESSES: Submit written comments to: Ms. Kelley Booher, Division of 
Policy, Planning, and Special Projects, Office for Human Research 
Protections, 1101 Wootton Parkway, Suite 200, The Tower Building, 
Rockville, MD 20852, telephone number (301) 402-5942 (not a toll-free 
number). Comments also may be sent via facsimile at (301) 402-0527 or 
by e-mail to: [email protected].

FOR FURTHER INFORMATION CONTACT: Dr. Leslie K. Ball, Office for Human 
Research Protections, The Tower Building, 1101 Wootton Parkway, Suite 
200, Rockville, MD 20852; telephone (301) 496-7005; fax (301) 402-0527; 
e-mail [email protected].

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. Pursuant to HHS regulations at 
45 CFR 46.407, if an IRB reviewing a protocol to be conducted or 
supported by HHS 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, the research may proceed only if the 
following conditions are met: (a) 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 (b) the Secretary (HHS), after consultation 
with a panel of experts in pertinent disciplines (for example: science, 
medicine, education, ethics, and law) and following opportunity for 
public review and comment, determines either: (1) That the research in 
fact satisfies the conditions of 45 CFR 46.404, 46.405, or 46.406, or 
(2) that the following conditions are met: (i) The research 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 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.
    HHS received a request from the University of California, Los 
Angeles (UCLA) pursuant to the provisions of HHS regulations at 45 CFR 
46.407. The principal investigator of the above-referenced research 
protocol, Dr. Paul Krogstad, 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:

[[Page 42062]]

adolescents who acquired HIV infection via adult behaviors (sexual 
contact and illicit drug use), and seronegative adolescents. The 
proposed research protocol would be funded by the National Institute of 
Allergy and Infectious Diseases, National Institutes of Health (NIH), 
under grant number R01 AI 051996.
    The specific aims of the study are: (1) To compare quantitative 
parameters of thymopoiesis and T cell turnover in adolescents and young 
adults with perinatal HIV infection with those from age-matched 
individuals with HIV acquired via recent adult behaviors and 
seronegative control subjects; (2) to evaluate the impact of viral 
factors on thymopoiesis of HIV infected adolescents; and (3) to examine 
the cellular immune responses of perinatally-infected adolescents. The 
long term aims of the study are to better understand the immunological 
status and prognosis of long-term survivors of perinatal HIV, and to 
identify possible therapeutic strategies to promote a normal, healthy 
lifespan for these individuals. The proposed study would enroll a total 
of 60 to 90 adolescents and young adults (20-30 subjects in each group) 
and would involve approximately six clinic visits at six month 
intervals (four visits for control subjects) over a 30-month period, 
during which medical histories will be obtained and physical exams, 
blood drawing and CT exams will be performed. At the second visit (six 
months following initial enrollment), approximately 5-10 subjects from 
each group (15 to 30 total) will be asked to participate in a substudy 
of this research protocol. During this substudy, subjects would be 
admitted to the General Clinical Research Center (GCRC) and be infused 
intravenously over a 24-hour period with a deuterium-labeled glucose 
solution, and would have blood drawn at several intervals thereafter. 
Under the protocol, if the glucose infusion does not permit adequate 
labeling of immune cells, subjects would receive 70% deuterium-labeled 
water orally over 24 hours in the GCRC. Subjects would be sent home 
with additional aliquots 70% deuterium-labeled water to be consumed 2 
to 3 times per week for four weeks, and additional blood drawing would 
be performed during that period.
    In July 2002, UCLA forwarded this protocol to the Secretary of HHS 
for consideration under 45 CFR 46.407, following the determination by 
the UCLA IRB that the substudy of the proposed research described above 
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 IRB found that the 
substudy was not designed to provide direct benefit to any of the 
subjects. The IRB also found that the administration of deuterium-
labeled glucose in healthy adolescents did not address a disorder or 
condition in that specific subject population. The IRB found, however, 
that the proposed research presented a reasonable opportunity to 
further the understanding, prevention, or alleviation of a serious 
problem affecting the health or welfare of children.
    Experts in relevant disciplines have reviewed this protocol and 
each have provided recommendations to the Secretary of HHS. In this 
Federal Register Notice, HHS solicits public review and comment 
pursuant to the requirements of 45 CFR 46.407. The Secretary of HHS 
will consider the experts' recommendations and the public comments in 
making a final determination regarding whether or not HHS should 
support this research.
    In particular, comments are solicited on the following questions: 
(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; and (5) have adequate provisions been made for soliciting 
the assent of children and the permission of their parents or 
guardians? In formulating a response to question (4), 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).
    All written comments concerning this matter should be submitted to 
Ms. Kelley Booher, Division of Policy, Planning, and Special Projects, 
Office for Human Research Protections, 1101 Wootton Parkway, Suite 200, 
The Tower Building, Rockville, MD 20852, telephone number (301) 402-
5942 (not a toll-free number). Comments also may be sent via facsimile 
at (301) 402-2071 or by e-mail to: [email protected].
    Materials to be available for public review on the OHRP Web page 
(available at: http://ohrp.osophs.dhhs.gov/panels/407-04pnl/pindex.htm) 
will include correspondence from UCLA referring the proposed research 
protocol to the Secretary of HHS for consideration under 45 CFR 46.407; 
the original IRB protocol application; correspondence between the UCLA 
IRB and the principal investigator; relevant excerpts of the NIH grant 
application, the parental permission and assent documents; and reports 
from each of experts pursuant to 45 CFR 46.407. A paper copy of the 
information referenced here is available upon request.

    Dated: July 9, 2003.
Arthur J. Lawrence,
Acting Principal Deputy Assistant Secretary for Health.
[FR Doc. 03-17916 Filed 7-15-03; 8:45 am]
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