[Federal Register Volume 68, Number 136 (Wednesday, July 16, 2003)]
[Notices]
[Pages 42061-42062]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 03-17916]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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: 407panel04@osophs.dhhs.gov.
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 LBall@osophs.dhhs.gov.
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: 407panel04@osophs.dhhs.gov.
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]
BILLING CODE 4150-36-P