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 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.

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: 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 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 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.
• 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.