Community Preparation for Tuberculosis (TB) Vaccine Trials

Announcement Type: New.

Funding Opportunity Number: 04086.

Catalog of Federal Domestic Assistance Number: 93.947.

Key Dates:

Application Deadline: June 28, 2004.

I. Funding Opportunity Description

Authority: This program is authorized under Sections 301 and 317E (b) of the Public Health Service Act, [42 U.S.C. Sections 241 and 247(b)(6)], as amended.

Purpose: The purpose of the program is for CDC to test new Tuberculosis (TB) vaccines that have implemented a large-scale community-based TB vaccine field trial. CDC plans to award cooperative agreements to ensure that the agency has the opportunity to provide technical assistance and guidance to this important partnership, especially with regard to the design and conduct of epidemiologic studies leading to field trials of new TB vaccines. This program addresses the “Healthy People 2010” focus areas of HIV testing in TB patients (aged 25 to 44 years); TB—new cases (per 100,000 population); and curative therapy for TB.

Measurable outcomes of the program will be in alignment with the following performance goal for the National Center for HIV, STD and TB Prevention (NCHSTP): Eliminate TB in the United States.

Project and Research Objectives: Prepare communities for large (over 5,000 subjects) community-based clinical trials for the evaluation of new vaccine candidates for TB in multiple, diverse, global locations.

Activities

To assist in the categorization of the activities as human subjects research (HSR) and not HSR, activities will be divided into two phases, which do not necessarily have chronological significance.

Awardee activities for this program are as follows:

Phase I

• Develop clinical trials training programs and materials, including Good Clinical Practice procedures for the full range of staff needed in a large, community-based TB vaccine trial. This will also include specialized training for establishing local human subjects review capacity according to international standards.
• Develop laboratory capacity for advanced TB diagnosis and immunologic assays required for TB vaccine trials.
• Develop the logistics and systems needed to conduct a randomized, controlled TB vaccine trial that will meet regulatory standards.
• Develop capacity or referral systems to treat and cure patients with TB.

Phase II

• Conduct epidemiologic studies to characterize the TB prevalence and incidence in the proposed study area.
• Conduct observational cohort studies that will mimic the conduct of a vaccine trial.
• Develop and refine information on TB prevalence and incidence in neonatal and adolescent cohorts in the proposed vaccine trials site.

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:

Phase I

• Collaborate in providing epidemiologic and technical assistance in developing infrastructure by assisting training, hiring personnel, provision of laboratory equipment, and protocol development for the observational cohort studies.
• Collaborate to provide epidemiologic and technical assistance in the development of clinical trials training programs that include good clinical practice (GCP) guidelines and ethical standards in HSR.
• Assist in the development of a research protocol for Human Subjects Research review by all cooperating institutions participating in the research project.
• Facilitate collaboration among international partners such as, but not limited to, World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease, the Royal Netherlands Tuberculosis Association (KNCV), Ministries of Health (MOH), and other relevant governmental and nongovernmental organizations doing TB control and public health activities.

Phase II

• Collaborate to provide epidemiologic and other technical assistance (e.g. consultation in operations research methodology, assistance with training and capacity building) in conducting the epidemiologic and cohort studies.
• Assist in developing and refining information on TB prevalence and incidence in neonatal and adolescent cohorts in the vaccine trials sites.

According to U.S. Federal regulations Title 45 CFR Part 46, project activities fall into three basic categories: Not HSR, HSR requiring Institutional Review Board (IRB) review, and HSR exempt from IRB review. Participation by any Federal employee in project activities as specified by the above CDC activities requires either a determination that a component activity of the project is not HSR, or if HSR then approval from either a full CDC IRB or appropriate CDC Official for IRB exemption from full review. Approvals are required prior to fund disbursement for that particular component of the project. IRB approved components of the project must be reviewed annually for continuation until project completion (which often extends beyond subject enrollment). Any change to planned project activities as specified in application for various HSR approvals may necessitate a redetermination of not HSR status (in consultation with CDC HSR contacts), whereas IRB approved HSR components of the project require approved IRB amendments.

II. Award Information

Type of Award: Cooperative Agreement CDC involvement in this program is listed in the Activities Section above.

Fiscal Year Funds: FY 2004.

Approximate Total Funding: $750,000 to $1,000,000 .

Approximate Number of Awards: One.

Approximate Average Award: $750,000 to $1,000,000 (This amount is for the first 12-month budget period, and includes both direct and indirect costs.)

Floor of Award Range: None, award is dependent upon availability of funds.

Ceiling of Award Range: $1,000,000.

Anticipated Award Date: August 1, 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 all foundations uniquely qualified to test new TB vaccines, as demonstrated by the implementation and conduct of a large-scale community-based TB vaccine field trial.

Eligibility is limited in response to Congressional appropriation language. Funds are available to both International and domestic applicants. The limitation of the announcement was restricted by Congressional directive appropriation language. While the Congressional intent is not clearly described, it is CDC's understanding that this is in response to success by foundations in this type of vaccine research, especially in high-burden, endemically impacted countries. It is necessary to find a foundation with a proven history of experience because vaccine development for human use is an extremely difficult process and must be handled with precision.

III.2. Cost Sharing or Matching

Matching funds are not required for this program.

III.3. Other

If you request a funding amount greater than the ceiling of the award range, your application will be considered non-responsive, and will not be entered into the review process. You will be notified that your application did not meet the submission requirements.

If your application is incomplete or non-responsive to the requirements listed below, it will not be entered into the review process. You will be notified that your application did not meet submission requirements.

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

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 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.

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 Date and Time

Application Deadline Date: June 28, 2004.

Explanation of Deadlines: Applications must be received in the CDC 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: None.

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

Application Submission Address: Submit the original and five copies of your application by mail or express delivery service to: Technical Information Management-PA# 04086, 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 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 (which will include non-Federal experts) 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?

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: Are the investigators 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? Are diverse, geographic locations and populations being considered?

Additional Review Criteria

In addition to the above criteria, the following items will be considered in the determination of scientific merit and priority score:

Protection of Human Subjects From Research Risks

Does the application adequately address the requirements of 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 NCHSTP. 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 NCHSTP 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 the CDC/NCHSTP/DTBE 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

V.3. Anticipated Announcement and Award Dates

Award Date: August 1, 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 Parts 74 and 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-4 HIV/AIDS Confidentiality Provisions
• AR-5 HIV Program Review Panel Requirements
• AR-6 Patient Care
• AR-7 Executive Order 12372
• AR-8 Public Health System Reporting Requirements
• AR-10 Smoke-Free Workplace Requirements
• AR-11 Healthy People 2010
• AR-12 Lobbying Restrictions
• AR-14 Accounting System Requirements
• AR-16 Security Clearance Requirement
• AR-22 Research Integrity
• 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 copies of the following reports:

1. Interim progress report, (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 sent 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: Elsa Villarino, Extramural Project Officer, CDC, National Center for HIV, STD and TB Prevention, Division of Tuberculosis Elimination, 1600 Clifton Road, Mail stop E10, Telephone: 404-639-5340, E-mail: evillarino@cdc.gov.

For questions about peer review, contact: Andrew Vernon, Scientific Review Administrator, CDC, National Center for HIV, STD and TB Prevention, Office of the Director, Associate Director for Science Office, Telephone: 404-639-8000, E-mail: avernon@cdc.gov.

For financial, grants management, or budget assistance, contact: Jesse Robertson, Grants Management Specialist, CDC Procurement and Grants Office, 2920 Brandywine Road, Atlanta, GA 30341, Telephone: 770-488-2747, E-mail: jtr4@cdc.gov.