[Federal Register: April 26, 2004 (Volume 69, Number 80)]
[Notices]               
[Page 22531-22535]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26ap04-74]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

 
Annual Influenza Vaccine Effectiveness Estimates in Healthy and 
High-risk Populations

    Announcement Type: New.
    Funding Opportunity Number: 04109.
    Catalog of Federal Domestic Assistance Number: 93.283.
    Key Dates:
    Letter of Intent Deadline: May 11, 2004.
    Application Deadline: June 10, 2004.
    Executive Summary: Annual estimates of influenza vaccine 
effectiveness are important to assess the protection against influenza 
provided by vaccination. These studies will help determine the degree 
of protective immunity provided by the vaccine in years when the 
vaccine contains a virus that is antigenically different from the 
predominantly circulating strain as well as in years where the vaccine 
and circulating viruses are well-matched. The results will provide 
information that is beneficial to future vaccine strain decisions and 
help guide policy development for influenza vaccination 
recommendations. This cooperative agreement seeks to support 
researchers with access to pediatric and adult populations to conduct 
vaccine efficacy studies each year beginning in the fall of 2004.

I. Funding Opportunity Description

    Authority: This program is authorized under sections 301(a) and 
317(k)(1) of the Public Health Service Act, [42 U.S.C. sections 
241(a) and 247b(k)(1)], as amended.

    Purpose: Each year, on average, influenza results in 36,000 deaths 
in the United States. Influenza vaccination is the best way to prevent 
influenza and its severe complications. Each year the Advisory 
Committee for Immunization Practices (ACIP) reviews the annual 
recommendations for influenza vaccination and uses new studies or other 
evidence gained over the previous years to decide if there should be 
new target groups for immunization. The current target groups for 
immunization include groups that are at increased risk for influenza 
related complications, such as the elderly (i.e., persons 65 years of 
age and older) and persons with certain chronic medical conditions. 
Persons aged 50 to 64, because of the likelihood of chronic medical 
conditions, and caretakers (health-care workers and household contacts) 
who have frequent contact with people who have high-risk conditions are 
also recommended for vaccination to reduce the likelihood of 
transmitting influenza to high-risk groups.
    Over the years, the results from studies on the effectiveness and 
efficacy of influenza vaccination in preventing influenza-like illness 
or laboratory-confirmed influenza infection have varied. In addition, 
vaccine effectiveness or efficacy is dependent on the age group and 
health care status of the group being studied. Vaccine effectiveness 
and efficacy estimates tend to be higher in healthy, immunocompentent 
people, whereas, studies have shown lower effectiveness in the elderly. 
In years when the vaccine match is suboptimal, estimates of

[[Page 22532]]

vaccine effectiveness tend to be even lower and in some cases the 
vaccine has had zero effectiveness against preventing influenza-like 
illness. Because of the simplicity of design and availability of 
existing data, many more studies of vaccine effectiveness using 
influenza-like illness as the outcome of interest have been conducted 
than have studies using laboratory-confirmed influenza as the outcome. 
Studies which measure effectiveness of the vaccine in preventing 
influenza-like illness can underestimate efficacy because other 
respiratory pathogens co-circulate during influenza season and often 
present as influenza-like illness, thus lowering the effectiveness 
estimates for influenza vaccine. In contrast studies that measure 
effectiveness among persons with laboratory-confirmed influenza 
infections among those who present with influenza-like illness give a 
better estimate of the vaccine's ability to prevent influenza 
infection.
    This program announcement seeks to support epidemiologic studies, 
(e.g., cohort or case control) designed to provide annual vaccine 
effectiveness, with laboratory confirmation of influenza illness, 
estimates at regular intervals throughout the influenza season, with a 
final estimate at the end of the season. These data will provide better 
estimates of the benefits of influenza vaccine and will be valuable in 
guiding vaccine policy development. In addition, these data are also 
critical in understanding the effectiveness of annual vaccination in 
seasons when the vaccine strain is less well-matched to the strains 
circulating. Over time, such data may provide data to help improve 
vaccine strain selection.
    These studies should be designed to provide estimates of the 
effectiveness of influenza vaccine in reducing laboratory confirmed 
illness among vaccinated persons, both among pediatric and adult age 
groups, on an annual basis, during the influenza season and at the end 
of the influenza season. This program addresses the ``Healthy People 
2010'' focus area of immunization and infectious diseases.
    Measurable outcomes of the program will be in alignment with the 
following performance goal for the National Center for Infectious 
Diseases (NCID): Protect Americans from infectious diseases.
    Research Objectives: Provide annual estimates of influenza vaccine 
effectiveness in reducing lab-confirmed cases of influenza illness 
among pediatric and adult populations both during the influenza season 
and at the end of the influenza season.
    Activities: Awardee activities for this program are as follows:
     Identify populations in which prospective cohort 
or case control studies can be implemented to measure vaccine 
effectiveness in reducing laboratory-confirmed influenza illness among 
pediatric and/or adult groups.
     Develop protocols to address the research 
objective that include collection of appropriate risk factor data, 
vaccination information and other information regarding the study 
participants that will be needed for data analysis. Methods must be 
specified to reduce potential sources of bias (e.g., confounding by 
indication) that may affect studies of vaccination effectiveness.
     Describe the epidemiologic and laboratory 
methodologies that will be used to determine influenza illness.
     Begin enrolling participants for the first year 
of the study prior to vaccination for the 2004 influenza season. 
Describe a timeframe for enrollment, conducting the study, collection 
of specimens and completion of the study.
     Develop a plan that will provide and report 
estimates of vaccine efficacy on an on-going basis to CDC during the 
study, depending on the circulation of influenza, with final results at 
the end of each influenza season. Describe the methodology that will be 
used to determine periodic estimates of vaccine effectiveness 
throughout the season and final results. Describe sample sizes you 
propose to use. Respondents should have experience with the conduct of 
clinical trials, as p-spending methods and other techniques to address 
multiple statistical tests using data from a single individual.
    In a cooperative agreement, CDC staff is substantially involved in 
the program activities, above and beyond routine grant monitoring.
    CDC Activities for this program are as follows:
     Participate in the review of study design, 
interpretation, analysis, dissemination and publication of results 
including co-authorship.
     Characterize select viral isolates obtained from 
the study for determining the antigenic and genetic characteristics of 
virus isolates from study participants.
     Provide surveillance data, such as virologic 
information and influenza-like illness information for the region of 
the country and or state in which the study is taking place during the 
influenza season.

II. Award Information

    Type of Award: Cooperative Agreement.
    CDC involvement in this program is listed in the Activities Section 
above.
    Fiscal Year Funds: 2004.
    Approximate Total Funding: $500,000.
    Approximate Number of Awards: One to two.
    Approximate Average Award: $250,000-$500,000 (This amount is for 
the first 12-month budget period, and includes both direct and indirect 
costs).
    Floor of Award Range: None.
    Ceiling of Award Range: None.
    Anticipated Award Date: August 16, 2004.
    Budget Period Length: 12 months.
    Project Period Length: Three years.
    Throughout the project period, CDC's commitment to continuation of 
awards will be conditioned on the availability of funds, evidence of 
satisfactory progress by the recipient (as documented in required 
reports), and the determination that continued funding is in the best 
interest of the Federal Government.

III. Eligibility Information

III.1. Eligible Applicants

    Applications may be submitted by public and private nonprofit 
organizations and by governments and their agencies, such as:
     Public nonprofit organizations.
     Private nonprofit organizations.
     Universities.
     Colleges.
     Research institutions.
     Hospitals.
     Community-based organizations.
     Faith-based organizations.
     Federally recognized Indian tribal governments.
     Indian tribes.
     Indian tribal organizations.
     State and local governments or their Bona Fide 
Agents (this includes the District of Columbia, the Commonwealth of 
Puerto Rico, the Virgin Islands, the Commonwealth of the Northern 
Marianna Islands, American Samoa, Guam, the Federated States of 
Micronesia, the Republic of the Marshall Islands, and the Republic of 
Palau).
     Political subdivisions of States (in 
consultation with States).

    A Bona Fide Agent is an agency/organization identified by the state 
as eligible to submit an application under the state eligibility in 
lieu of a state application. If you are applying as a bona fide agent 
of a state or local government, you must provide a letter from the 
state or local government as documentation of your status. Place this 
documentation behind the first page of your application form.

[[Page 22533]]

III.2. Cost Sharing or Matching

    Matching funds are not required for this program.

III.3. Other

    If your application is incomplete or non-responsive to the 
requirements listed in this section, it will not be entered into the 
review process. You will be notified that your application did not meet 
submission requirements.
    Your application must:
     Provide evidence that you have access to the 
populations needed for conducting large-scale epidemiologic studies.
     Describe the methods that will be used to 
determine lab confirmation of influenza illness and provide background 
on experience of the entity in conducting the confirmation.
     Describe the time frame for enrollment, 
intermittent assessments and reporting of vaccine effectiveness and a 
final report.
     Provide evidence of support and ability for any 
collaborating partners.
    Individuals Eligible to Become Principal Investigators: Any 
individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support. Individuals from underrepresented 
racial and ethnic groups as well as individuals with disabilities are 
always encouraged to apply for CDC programs.

    Note: Title 2 of the United States Code section 1611 states that 
an organization described in section 501(c)(4) of the Internal 
Revenue Code that engages in lobbying activities is not eligible to 
receive Federal funds constituting an award, grant, or loan.

IV. Application and Submission Information

IV.1. Address To Request Application Package

    To apply for this funding opportunity, use application form PHS 398 
(OMB number 0925-0001 rev. 5/2001). Forms and instructions are 
available in an interactive format on the CDC Web site, at the 
following Internet address: http://www.cdc.gov/od/pgo/forminfo.htm.

    Forms and instructions are also available in an interactive format 
on the National Institutes of Health (NIH) Web site at the following 
Internet address: http://grants.nih.gov/grants/funding/phs398/phs398.html
.

    If you do not have access to the Internet, or if you have 
difficulty accessing the forms on-line, you may contact the CDC 
Procurement and Grants Office Technical Information Management Section 
(PGO-TIM) staff at: 770-488-2700. Application forms can be mailed to 
you.

IV.2. Content and Form of Application Submission

    Letter of Intent (LOI). Your LOI must be written in the following 
format:

     Maximum number of pages: 1.
     Font size: 12-point unreduced.
     Single spaced.
     Paper size: 8.5 by 11 inches.
     Page margin size: One inch.
     Printed only on one side of page.
     Written in plain language, avoid jargon.
    Your LOI must contain the following information:
 Descriptive title of the proposed research.
 Name, address, E-mail address, and telephone number 
of the Principal Investigator.
 Names of other key personnel.
 Participating institutions.
 Number and title of this Program Announcement (PA).
    Application: Follow the PHS 398 application instructions for 
content and formatting of your application. For further assistance with 
the PHS 398 application form, contact PGO-TIM staff at 770-488-2700, or 
contact GrantsInfo, Telephone (301) 435-0714, E-mail: 
GrantsInfo@nih.gov.

    Your research plan should be single spaced and address activities 
to be conducted over the entire project period.
    You are required to have a Dun and Bradstreet Data Universal 
Numbering System (DUNS) number to apply for a grant or cooperative 
agreement from the Federal government. Your DUNS number must be entered 
on line 11 of the face page of the PHS 398 application form. The DUNS 
number is a nine-digit identification number, which uniquely identifies 
business entities. Obtaining a DUNS number is easy and there is no 
charge. To obtain a DUNS number, access http://www.dunandbradstreet.com or 

call 1-866-705-5711.
    For more information, see the CDC Web site at: http://www.cdc.gov/od/pgo/funding/pubcommt.htm
.

    This PA uses just-in-time concepts. It also uses the modular 
budgeting as well as non-modular budgeting formats. See: http://grants.nih.gov/grants/funding/modular/modular.htm
 for additional 

guidance on modular budgets. Specifically, if you are submitting an 
application with direct costs in each year of $250,000 or less, use the 
modular budget format. Otherwise, follow the instructions for non-
modular budget research grant applications.
    Additional requirements that may require you to submit additional 
documentation with your application are listed in section ``VI.2. 
Administrative and National Policy Requirements.''

IV.3. Submission Dates and Times

    LOI Deadline Date: May 11, 2004.
    CDC requests that you send a LOI if you intend to apply for this 
program. Although the LOI is not required, not binding, and does not 
enter into the review of your subsequent application, the LOI will be 
used to gauge the level of interest in this program, and to allow CDC 
to plan the application review.
    Application Deadline Date: June 10, 2004.
    Explanation of Deadlines: Applications must be received in The 
Procurement and Grants Office by 4 p.m. eastern time on the deadline 
date. If you send your application by the United States Postal Service 
or commercial delivery service, you must ensure that the carrier will 
be able to guarantee delivery of the application by the closing date 
and time. If CDC receives your application after closing due to: (1) 
Carrier error, when the carrier accepted the package with a guarantee 
for delivery by the closing date and time, or (2) significant weather 
delays or natural disasters, you will be given the opportunity to 
submit documentation of the carriers guarantee. If the documentation 
verifies a carrier problem, CDC will consider the application as having 
been received by the deadline.
    This announcement is the definitive guide on application submission 
address and deadline. It supersedes information provided in the 
application instructions. If your application does not meet the 
deadline above, it will not be eligible for review, and will be 
discarded. You will be notified that your application did not meet the 
submission requirements.
    CDC will not notify you upon receipt of your application. If you 
have a question about the receipt of your application, first contact 
your courier. If you still have a question, contact the PGO-TIM staff 
at: 770-488-2700. Before calling, please wait two to three days after 
the application deadline. This will allow time for applications to be 
processed and logged.

IV.4. Intergovernmental Review of Applications

    Your application is subject to Intergovernmental Review of Federal 
Programs, as governed by Executive Order (EO) 12372. This order sets up 
a system for state and local governmental review of proposed federal 
assistance applications. You should contact your

[[Page 22534]]

state single point of contact (SPOC) as early as possible to alert the 
SPOC to prospective applications, and to receive instructions on your 
state's process. Click on the following link to get the current SPOC 
list: http://www.whitehouse.gov/omb/grants/spoc.html.


IV.5. Funding Restrictions

    Restrictions, which must be taken into account while writing your 
budget, are as follows:
     There is a restriction on the use of these funds 
for laboratory equipment and construction.
    If you are requesting indirect costs in your budget, you must 
include a copy of your indirect cost rate agreement. If your indirect 
cost rate is a provisional rate, the agreement should be less than 12 
months of age.
    Awards will not allow reimbursement of pre-award costs.

IV.6. Other Submission Requirements

    LOI Submission Address: Submit your LOI by express mail, delivery 
service, fax, or e-mail to: Barbara Stewart, Centers for Disease 
Control and Prevention, National Center for Infectious Diseases, 1600 
Clifton Road, NE., Mail Stop C-19, Atlanta, GA 30333, Phone: 404-639-
0044, Fax: 404-639-2469, E-mail Address: bsg2@cdc.gov.
    Application Submission Address: Submit the original and five hard 
copies of your application by mail or express delivery service to: 
Technical Information Management--PA 04109, CDC Procurement 
and Grants Office, 2920 Brandywine Road, Atlanta, GA 30341.
    Applications may not be submitted electronically at this time.

V. Application Review Information

V.1. Criteria

    You are required to provide measures of effectiveness that will 
demonstrate the accomplishment of the various identified objectives of 
the cooperative agreement. Measures of effectiveness must relate to the 
performance goals stated in the ``Purpose'' section of this 
announcement. Measures must be objective and quantitative, and must 
measure the intended outcome. These measures of effectiveness must be 
submitted with the application and will be an element of evaluation.
    The goals of CDC-supported research are to advance the 
understanding of biological systems, improve the control and prevention 
of disease and injury, and enhance health. In the written comments, 
reviewers will be asked to evaluate the application in order to judge 
the likelihood that the proposed research will have a substantial 
impact on the pursuit of these goals.
    The scientific review group will address and consider each of the 
following criteria in assigning the application's overall score, 
weighting them as appropriate for each application. The application 
does not need to be strong in all categories to be judged likely to 
have major scientific impact and thus deserve a high priority score. 
For example, an investigator may propose to carry out important work 
that by its nature is not innovative, but is essential to move a field 
forward.
    The criteria are as follows:
    Significance: Does this study address an important problem? If the 
aims of the application are achieved, how will scientific knowledge be 
advanced? What will be the effect of these studies on the concepts or 
methods that drive this field?
    Approach: Are the conceptual framework, design, methods, and 
analyses adequately developed, well-integrated, and appropriate to the 
aims of the project? Does the applicant acknowledge potential problem 
areas and consider alternative tactics? Has the applicant outlined a 
reasonable plan for obtaining vaccine effectiveness results at 
reasonable intervals throughout the study and at the end?
    Innovation: Does the project employ novel concepts, approaches or 
methods? Are the aims original and innovative? Does the project 
challenge existing paradigms or develop new methodologies or 
technologies?
    Investigator: Is the investigator appropriately trained and well-
suited to carry out this work? Is the work proposed appropriate to the 
experience level of the principal investigator and other researchers 
(if any)?
    Environment: Does the scientific environment in which the work will 
be done contribute to the probability of success? Do the proposed 
experiments take advantage of unique features of the scientific 
environment or employ useful collaborative arrangements? Is there 
evidence of institutional support?
    Additional Review Criteria: In addition to the above criteria, the 
following items will be considered in the determination of scientific 
merit and priority score:
    Study Populations:
    (1) Has the applicant described the populations to which they will 
have ready access to for conducting this study?
    Laboratory Confirmation:
    (1) Has the applicant described the methods that will be used to 
determine lab confirmation of influenza illness?
    (2) Has the applicant provided background and experience for the 
entity conducting the laboratory testing?
    Study Timeline and Protocol:
    (1) Has the applicant described a timeframe for enrollment, 
conducting the study, assessment, reporting and completion of the 
study?
    Protection of Human Subjects from Research Risks: Does the 
application adequately address the requirements of Title 45 CFR Part 46 
for the protection of human subjects? This will not be scored; however, 
an application can be disapproved if the research risks are 
sufficiently serious and protection against risks is so inadequate as 
to make the entire application unacceptable.
    Inclusion of Women and Minorities in Research: Does the application 
adequately address 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; and (4) a statement as 
to whether the plans for recruitment and outreach for study 
participants include the process of establishing partnerships with 
community(ies) and recognition of mutual benefits.
    Budget: The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

V.2. Review and Selection Process

    Applications will be reviewed for completeness by the Procurement 
and Grants Office (PGO) and for responsiveness by NCID. Incomplete 
applications and applications that are non-responsive to the 
eligibility criteria will not advance through the review process. 
Applicants will be notified that their application did not meet 
submission requirements.
    Applications that are complete and responsive to the PA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group or charter study section convened by NCID in accordance 
with the review criteria listed above. As part of the initial merit 
review, all applications may:
     Undergo a process in which only those 
applications deemed to have the highest scientific merit, generally the 
top half of the applications under review, will be discussed and 
assigned a priority score.
     Receive a written critique.

[[Page 22535]]

     Receive a second level review by CDC senior 
staff.
    Award Criteria: Criteria that will be used to make award decisions 
include:
     Scientific merit (as determined by peer review).
     Availability of funds.
     Programmatic priorities.
     A multiple range of study designs, from database 
studies to prospective cohort studies, will be considered for funding, 
but priority will be given to projects that include analysis of test 
confirmed influenza cases.

V.3. Anticipated Announcement and Award Dates

    Anticipated Award Date: August 16, 2004.

VI. Award Administration Information

VI.1. Award Notices

    Successful applicants will receive a Notice of Grant Award (NGA) 
from the CDC Procurement and Grants Office. The NGA shall be the only 
binding, authorizing document between the recipient and CDC. The NGA 
will be signed by an authorized Grants Management Officer, and mailed 
to the recipient fiscal officer identified in the application.
    Unsuccessful applicants will receive notification of the results of 
the application review by mail.

VI.2. Administrative and National Policy Requirements

45 CFR Part 74 and Part 92
    For more information on the Code of Federal Regulations, see the 
National Archives and Records Administration at the following Internet 
address: http://www.access.gpo.gov/nara/cfr/cfr-table-search.html.

    The following additional requirements apply to this project:

 AR-1 Human Subjects Requirements.
 AR-2 Requirements for Inclusion of Women and Racial 
and Ethnic Minorities in Research.
 AR-3 Animal Subject Requirements.
 AR-7 Executive Order 12372.
 AR-10 Smoke-Free Workplace Requirements.
 AR-11 Healthy People 2010.
 AR-12 Lobbying Restrictions.
 AR-15 Proof of Non-Profit Status.
 AR-22 Research Integrity.
 AR-23 States and Faith-Based Organizations.
 AR-25 Release and Sharing of Data.

    Additional information on these requirements can be found on the 
CDC Web site at the following Internet address: http://www.cdc.gov/od/pgo/funding/ARs.htm
.


VI.3. Reporting

    You must provide CDC with an original, plus two hard copies of the 
following reports:
    1. Interim progress report, (use form PHS 2590, OMB Number 0925-
0001, rev. 5/2001 as posted on the CDC Web site) no less than 90 days 
before the end of the budget period. The progress report will serve as 
your non-competing continuation application, and must contain the 
following elements:
    a. Current Budget Period Activities Objectives.
    b. Current Budget Period Financial Progress.
    c. New Budget Period Program Proposed Activity Objectives.
    d. Budget.
    e. Additional Requested Information.
    f. Measures of Effectiveness.
    2. Financial status report and annual progress report, no more than 
90 days after the end of the budget period.
    3. Final financial and performance reports, no more than 90 days 
after the end of the project period.
    These reports must be mailed to the Grants Management Specialist 
listed in the ``Agency Contacts'' section of this announcement.

VII. Agency Contacts

    For general questions about this announcement, contact: Technical 
Information Management Section, CDC Procurement and Grants Office, 2920 
Brandywine Road, Atlanta, GA 30341, Telephone: 770-488-2700.
    For scientific/research issues, contact: Dr. Mary Lerchen, Acting 
Director, Office of Extramural Research, CDC, National Center for 
Infectious Diseases, 1600 Clifton Road, NE., Mailstop: C-19, Atlanta, 
GA 30333, Telephone: 404-639-0043, E-mail: mll0@cdc.gov.
    For questions about peer review, contact: Barbara Stewart, CDC, 
National Center for Infectious Diseases, 1600 Clifton Road, NE., 
Mailstop: C-19, Atlanta, GA 30333, Telephone: 404-639-0044, E-mail: 
bsg2@cdc.gov.

    For financial, grants management, or budget assistance, contact: 
Lynn Walling, Contract Specialist, CDC Procurement and Grants Office, 
2920 Brandywine Road, Atlanta, GA 30341, Telephone: 770-488-2612, E-
mail: lqw5@cdc.gov.

VIII. Other Information

    None.

    Dated: April 20, 2004.
William P. Nichols,
Acting Director, Procurement and Grants Office, Centers for Disease 
Control and Prevention.
[FR Doc. 04-9371 Filed 4-23-04; 8:45 am]

BILLING CODE 4163-18-P