[Federal Register Volume 64, Number 102 (Thursday, May 27, 1999)]
[Notices]
[Pages 28822-28824]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-13493]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
[Announcement Number 99105]
Research Studies to Characterize the Clinical Relevance of HIV
Superinfection Notice of Availability of Funds
A. Purpose
The Centers for Disease Control and Prevention (CDC) announces the
availability of fiscal year (FY) 1999 funds for a cooperative agreement
program for epidemiologic and laboratory research studies to
characterize reinfection with Human Immunodeficiency Virus Type 1 (HIV-
1.) This program addresses the ``Healthy People 2000'' priority area of
HIV Infection.
The purpose of this program is to characterize the occurrence of
reinfection with a second strain of HIV and determine whether
reinfection has clinical relevance for the pathogenesis of HIV disease.
Specific questions must at least include:
1. Can naturally-occurring reinfection with a second, genotypically
distinct strain of HIV-1 be documented after initial infection has been
established?
2. (How often?) Does reinfection result in the emergence of a new
predominant strain of HIV-1?
3. Is reinfection with a second strain of HIV-1 associated with
clinical disease progression, emergence of resistance to antiviral
drugs, or other adverse consequences?
B. Eligible Applicants
Applications may be submitted by public and private nonprofit and
for-profit organizations and by governments and their agencies; that
is, universities, colleges, research institutions, hospitals, other
public and private nonprofit and for-profit organizations, State and
local governments or their bona fide agents, and federally recognized
Indian tribal governments, Indian tribes, or Indian tribal
organizations.
Because studies to date suggest that reinfection with a second HIV-
1 strain may be rare or difficult to detect, a case-control study
design may be most likely to yield expeditious answers to study
questions. Funds under this announcement may not be used to establish a
prospective cohort. Therefore, successful applicants must demonstrate
access to an existing cohort for recruitment of appropriate study
subjects for whom stored specimens are available to conduct the
necessary retrospective analysis.
C. Availability of Funds
Approximately $500,000 will be available in FY 1999 to fund
approximately 2 awards. It is expected that the average new award will
be approximately $250,000. It is expected that awards will begin on or
about September 30, 1999. Awards will be funded for a 12-month budget
period within a project period of up to 3 years. Funding estimates may
vary. Continuation awards within the project period will be made on the
basis of satisfactory progress as evidenced by required reports and the
availability of funds.
D. Program Requirements
In conducting activities to achieve the purpose of this program,
the recipient will be responsible for the activities listed under
Recipient Activities, and CDC will be responsible for conducting
activities listed under CDC Activities.
1. Recipient Activities
a. Develop Study Protocol: Design an appropriate study to answer
the specific research questions related to HIV-1 reinfection.
b. Identify Study Cohort: Identify a cohort of HIV-infected persons
from which eligible study subjects can be recruited, for whom (1)
sufficient information is available to document a known or likely re-
exposure to a second strain of HIV-1; (2) a clinically significant
event such as disease progression or emergence of antiviral drug
resistance has been recognized; and (3) suitable stored specimens are
available for genotypic analysis of viral strains of HIV-1 before and
after occurrence of the clinical event.
c. Conduct Productive and Scientifically Sound Studies: Identify,
recruit, obtain informed consent, and enroll study participants as
determined by the study protocol and the program requirements. Perform
the laboratory tests necessary to characterize viral strains as
determined by the study protocol. Ideally, recipients would be able to
characterize the HIV-1 strain in the source partner epidemiologically
associated with reinfection.
d. Publish the Results of the Study: Upon completion, publish the
results of the study. At the completion of the funding period,
recipients should optimally prepare at least one manuscript based on
the funded research for a peer-reviewed journal. All recipients will
provide copies of relevant publications and other significant documents
to CDC project co-investigators, and any other local agencies or
individuals with a special interest in the research project.
e. Share Data and Specimens: Share data and specimens (when
appropriate) with other collaborators to answer the project's specific
research questions.
2. CDC Activities
a. Assist in Protocol Development: CDC staff will assist in the
development
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of a research protocol for Institutional Review Board (IRB) review by
all cooperating institutions participating in the research project. The
CDC IRB will review and approve the protocol initially and on at least
an annual basis until the research project is completed.
b. Provide Technical Assistance: CDC staff will assist in the
design of the research and quality assurance of laboratory methods.
c. Provide Scientific Expertise: CDC staff will provide current
scientific and programmatic information relevant to the studies, and
will provide technical advice throughout the study, including study
design, data analysis and publication.
d. Share Data and Specimens: CDC staff will assist in the
dissemination of study results and distribution of specimens.
E. Application Content
Use the information in the Program Requirements, Other
Requirements, and Evaluation Criteria sections to develop the
application content. Your application will be evaluated on the criteria
listed, so it is important to follow them in laying out your program
plan. Applications must not be more than 25 double-spaced pages,
printed on one side, with one inch margins and 12 point font (exclusive
of official PHS application pages and relevant attachments.)
Applications will not be reviewed if the narrative is more than 25
pages, not counting PHS forms and appendices. In the narrative, address
the following:
1. Background: Briefly describe your research questions.
2. Study design: Describe: (a) the proposed study design and (b)
how this study design will address the specific research questions.
3. Study cohort: Describe: (a) the study cohort from which eligible
study subjects will be recruited; (b) how this study cohort was
selected; (c) specific clinical and epidemiologic information available
for potential study subjects related to the study objectives; and (d)
the availability, quality, and condition of stored specimens necessary
for the laboratory analysis as determined by the study design. Also
provide evidence that the necessary information and specimens from this
cohort will be accessible for the purposes of this study.
4. Laboratory methods: Describe the laboratory methods that will be
used to characterize the viral strains, and provide evidence that these
are adequate to distinguish between different strains of HIV-1 with the
same envelope subtype.
5. Organization: Describe: (a) the existing relationship between
the proposed study staff, managers of the proposed study cohort, and
the laboratory which will perform the study analyses; (b) the proposed
organization structure, with lines of authority, for implementing the
proposed study; (c) the current working relationship with any research,
academic, scientific groups, community-based organizations or other
affiliated organizations; and (d) strategy for identification and
recruitment of study participants.
6. Capacities: Describe your capacity and experience in: (a)
performing previous clinical or laboratory research involving the
recruitment of HIV-positive persons and collection of clinical or
epidemiologic data; (b) performing genotypic analysis of viral strains
of HIV-1; (c) ensuring the hiring of staff for implementing the study
in a timely manner; and (d) participating in collaborative research
with other research organizations.
7. Personnel: Describe (a) personnel proposed for implementing the
research study; (b) roles and responsibilities for each proposed staff;
and (c) evidence of qualifications for the responsibilities proposed.
8. Budget and Line-Item Justification: Provide an annualized budget
that anticipates the organizational and operational needs to carry out
the proposed study.
F. Submission and Deadline
Submit the original and five copies of PHS-398 (OMB Number 0925-
0001) (adhere to the instructions on the Errata Instruction Sheet for
PHS 398). Forms are in the application kit. On or before August 1, 1999
submit the application to: Kevin Moore, Grants Management Specialist,
Grants Management Branch, Procurement and Grants Office, Centers for
Disease Control and Prevention (CDC), 2920 Brandywine Road, Room 3000,
Mail Stop E-15, Atlanta, GA 30341, Email KGM1@cdc.gov.
Deadline: Applications shall be considered as meeting the deadline
if they are either received on or before the stated deadline date or
sent on or before the deadline date and received in time for submission
to the independent review group. (Applicants must request a legibly
dated U.S. Postal Service postmark or obtain a legibly dated receipt
from a commercial carrier or U.S. Postal Service. Private metered
postmarks are not acceptable proof of timely mailing. Applications that
do not meet these criteria are considered late applications, will not
be considered, and will be returned to the applicant.
G. Evaluation Criteria
Each application will be evaluated individually based on the
evidence submitted against the following criteria by an independent
review group appointed by CDC (Note: total possible point value is
110):
1. Demonstration of the applicant's understanding of the research
objectives and the ability, willingness, and need to collaborate in the
study design and analysis, and (when appropriate) sharing of data and
specimens. Evidence should include a brief review of previous studies
related to HIV-1 infection, and laboratory methods for characterizing
viral strains of HIV-1. (15 points)
2. Quality of an explicit research plan adequate to address the
study questions. The research plan should include a specific study
design (e.g., case series, case-control analysis) and describe how HIV-
infected study subjects will be identified and how their re-exposure to
infection with another strain of HIV-1 will be documented. The research
plan should specify the anticipated number of subjects, and demonstrate
how this study design and subject selection will resolve the study
questions. Preference will be given to applicants who propose to
evaluate reinfection in persons whose initial infection and possible
reinfection are both due to group M, subtype B strains of HIV-1. (25
points)
3.a. Capacity to access a cohort of HIV-infected persons with
sufficient epidemiologic information to document re-exposure to HIV-1,
adequate descriptive clinical information to identify significant
clinical events such as disease progression or emergence of antiviral
drug resistance, and the availability of adequate stored specimens to
implement the study. (15 points)
b. The degree to which the applicant has met the CDC policy
requirements regarding the inclusion of women, ethnic, and racial
groups in the proposed research. This includes:
(1) The proposed plan for the inclusion of both sexes and racial
and ethnic minority populations for appropriate representation.
(2) The proposed justification when representation is limited or
absent.
(3) A statement as to whether the design of the study is adequate
to measure differences when warranted.
(4) A statement as to whether the plans for recruitment and
outreach for study participants include the process of establishing
partnerships with communities and recognition of mutual benefits. (5
points)
4. Capability to employ laboratory methods sufficient to
differentiate
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among viral strains of HIV-1 with the same envelope subtype. Evidence
should include a justification for the laboratory techniques selected,
documentation of either proficiency with these methods or specific
plans and commitments to access services from a laboratory which has
demonstrated this proficiency, and assurance that capacity is adequate
to accomplish the analyses necessary for the proposed research. Letters
of support from collaborating institutions or organizations should be
included. (15 points)
5. Demonstration of a history of conducting comparable research
studies. Research studies related to the molecular biology, genetic
diversity, or genetic evolution of HIV-1 are of greatest interest. (10
points)
6. The capacity to effectively manage the study as evidenced by the
proposed organizational structure, the quality and experience of
proposed personnel with realistic and sufficient percentage-time
commitments; clarity of the described duties and responsibilities of
project personnel; adequacy of the facilities; and plans for
administration of the project including project oversight and data
management. Evidence should document qualifications of a prospective PI
and other key personnel, and, if indicated, support arrangements with a
university, community-based or other affiliated organization, etc. (15
points)
7. A comprehensive schedule, including a time line, for
accomplishing the activities of the research and an evaluation plan
that identifies methods and instruments for evaluating progress in
designing and implementing the research objectives. (10 points)
8. Other (Not Scored).
a. Budget: The budget will be reviewed to determine the extent to
which it is reasonable, clearly justified, consistent with the intended
use of funds, and allowable. All budget categories should be itemized.
b. Human Subjects: Whether or not exempt from the Department of
Health and Human Services (DHHS) regulations, are procedures adequate
for the protection of human subjects?
H. Other Requirements
Technical Reporting Requirements
Provide CDC with original plus two copies of
1. Annual progress reports;
2. Financial status report, no more than 90 days after the end of
the budget period; and
3. Final financial status and performance reports, no more than 90
days after the end of the project period. Send all reports to the
Grants Management Specialist identified in the paragraph Where to
Obtain Additional Information.
The following additional requirements are applicable to this
program. For a complete description of each, see Attachment I in the
application kit.
AR-1 Human Subjects Requirements
AR-2 Requirements for Inclusion of Women and Racial and Ethnic
Minorities in Research
AR-4 HIV/AIDS Confidentiality Provisions
AR-6 Patient Care
AR-7 Executive Order 12372 Review
AR-9 Paperwork Reduction Act Requirements
AR-10 Smoke-Free Workplace Requirements
AR-11 Healthy People 2000
I. Authority and Catalog of Federal Domestic Assistance Number
This program is authorized under Sections 301 and 311 of the Public
Health Service Act, [42 U.S.C. 241 and 243], as amended. The Catalog of
Federal Domestic Assistance number is 93.943.
J. Where To Obtain Additional Information
To receive additional written information and to request an
application kit, call 1-888-GRANTS4 (1-888-472-6874). You will be asked
to leave your name and address and to identify the Announcement number,
99105. If you have questions after reviewing the contents of all the
documents, business management technical assistance may be obtained
from: Kevin Moore, Grants Management Specialist, Grants Management
Branch, Procurement and Grants Office, Centers for Disease Control and
Prevention (CDC), 2920 Brandywine Road, Room 3000, Mail Stop E-15,
Atlanta, GA 30341, Telephone (770) 488-2737, E-mail address
KGM1@cdc.gov.
For a detailed description of the additional requirements in
Attachment 1, to download forms required by this announcement, and to
review other CDC program announcements, see the CDC home page on the
Internet: www.cdc.gov.
For program technical assistance, contact Kay Lawton, Division of
HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention,
Centers for Disease Control and Prevention (CDC), 1600 Clifton Road,
NE., Mail Stop E-46, Atlanta, Georgia 30333, telephone (404) 639-6131,
E-mail address KEL1@cdc.gov.
Dated: May 21, 1999.
John L. Williams,
Director, Procurement and Grants Office, Centers for Disease Control
and Prevention (CDC).
[FR Doc. 99-13493 Filed 5-26-99; 8:45 am]
BILLING CODE 4163-18-P
