Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Tuberculosis Research Units (U19)
Activity Code	U19 Research Program Cooperative Agreements
Announcement Type	New
Related Notices	March 30, 2020 - This RFA has been reissued as RFA-AI-20-020. January 8, 2013 - See Notice NOT-AI-13-021. Notice of Revised Application Due Date. November 30, 2012 - See Notice NOT-AI-13-015. The purpose of this Notice is to provide clarity regarding two components: Number of Applications Allowed per Institution and Allowable Budgets.
Funding Opportunity Announcement (FOA) Number	RFA-AI-12-045
Companion Funding Opportunity	None
Number of Applications	Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856
Funding Opportunity Purpose	The purpose of this FOA is to support the establishment of two to three multinational, multidisciplinary Tuberculosis Research Units (TBRUs) that will operate as a collaborative network to study tuberculosis latency and persistence and their relation to active TB disease, in humans and animal models.

Posted Date	November 6, 2012
Letter of Intent Due Date(s)	(Extended to June 1, 2013 per NOT-AI-13-021) January 14, 2013
Application Due Date(s)	(Extended to July 1, 2013 per NOT-AI-13-021) February 13, 2013
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	(Extended to January 2014 per NOT-AI-13-021) June, 2013
Advisory Council Review	(Extended to May 2014 per NOT-AI-13-021) October, 2013
Earliest Start Date	(Extended to October 1, 2014 per NOT-AI-13-021) April, 2014
Expiration Date	(Extended to July 2, 2013 per NOT-AI-13-021) February 14, 2013
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS 398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The purpose of this FOA is to support the establishment of two to three multinational, multidisciplinary Tuberculosis Research Units (TBRUs) that will operate as a collaborative network to study tuberculosis latency and persistence and their relation to active TB disease, in humans and animal models.

The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) supports research related to the basic understanding, treatment and ultimately prevention of infectious, immunologic and allergic diseases that threaten millions of human lives. The NIAID Division of Microbiology and Infectious Diseases (DMID) supports a comprehensive extramural research program focused on the prevention and control of diseases caused by virtually all infectious agents. This includes basic research, such as studies of microbial biology and physiology; applied research, including the development of medical diagnostics, therapeutics and vaccines; and clinical trials to evaluate experimental drugs and vaccines.

NIAID recognizes the importance of biomedical research in tuberculosis (TB), a global disease of epidemic proportion that continues to take the lives of close to 2 million persons each year. NIAID has established an extensive TB research program that facilitates the translation of basic research findings into new drugs, vaccines and other biologics, diagnostics, and scientific tools for TB. A critical component of NIAIDs tuberculosis program has been the Tuberculosis Research Unit (TBRU) which was first established in 1994. The purpose of the TBRU has been to integrate scientific and clinical research disciplines to study aspects of human TB in endemic countries. The current TBRU integrates epidemiology, immunology, microbiology, and clinical studies and trials across a multinational, cross-disciplinary consortium to study the interaction of the causative agent of tuberculosis, Mycobacterium tuberculosis (Mtb), with the human host and its immune system in well characterized cohorts.

During the past 15 years, biomedical research in TB has led to an improved understanding of host/pathogen interactions, and many of these findings translated to a now sizeable pipeline of drug, vaccine and diagnostic candidates. However, a transformation in how this complex disease can be optimally managed continues to be hampered by a limited understanding of the stages of TB infection that precede active pulmonary disease (latency) or are implicated as the reason for prolonged antibiotic treatment (persistence). Latency and persistence are characterized by low levels of bacteria in secretions and likely other sites of infection (paucibacillary stages) which are inherently difficult to study and have also limited our understanding of their transition to active pulmonary or extra-pulmonary disease.

The need to focus research on latency and persistence has been underscored in NIAID’s 2007 Research Agenda for Multidrug-Resistant and Extensively Drug-Resistant TB (http://www.niaid.nih.gov/topics/tuberculosis/research/documents/mdrxdrresearchagenda.pdf) and the recently published International Roadmap for Tuberculosis Research (http://www.stoptb.org/assets/images/global/research/rmcover.jpg).

This initiative will support two to three individual TBRUs that will operate as a collaborative network. This expansion is expected to facilitate 1) pursuit of separate and distinct avenues of investigation; 2) the ability to target different paucibacillary stages; 3) conduct of both hypothesis-generating and hypothesis-confirming studies; and 4) scientific depth and breadth to address paucibacillary stages of TB disease through integration of human studies and animal models.

Each TBRU will be independently established as part of a multi-disciplinary, multinational consortium of investigators and institutions with expertise in clinical research, animal models, microbiology, epidemiology, immunology, as well as data and statistical management. Each TBRU will be overseen by a Project Director/Principal Investigator (PD/PI) who will coordinate and oversee its multidisciplinary research and ensure that the individual research projects synergize to advance the goals of this FOA. Recognizing that new hypotheses to study human paucibacillary stages of TB may have to be initially developed in animal models and validated in human study cohorts, integration of clinical and animal model research will be required for each TBRU. It is expected that studies conducted through the TBRUs will address key questions that will help to re-define the state of the science in this field and contribute to early stage product development efforts.

While animal studies are expected to guide hypotheses for investigation in humans, back-translation of clinical findings into animals may also lead to more predictive, targeted and interpretable animal models of various stages of TB infection and disease. These animal models as well as an improved understanding of host/pathogen interactions during paucibacillary stages of TB have the potential to contribute to the selection and characterization of drug and vaccine candidates during product development. Investigators responding to this FOA are encouraged to focus on principles governing the development of human-relevant animal models, as outlined in the FDA Guidance for Industry on Animal Models Essential Elements to address Efficacy under the Animal Rule (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm078923.pdf) , specifically Section IV Discussion of Essential Data Elements of an Animal Model. While it is understood that this FDA guidance pertains to registration of new medicinal products based on animal efficacy studies, this guidance nevertheless provides important general principles for the establishment of predictive and human-relevant animal models and should be considered.

Of particular interest for this FOA are immunological studies and biomarker/bio-signature discovery projects to improve strategies for therapeutic, vaccine and diagnostic development. Overall, research conducted under this initiative is expected to provide information about HUMAN TB. All research projects must be clinically relevant. This will necessitate intensive collaborations among clinical and non-clinical researchers to advance this challenging scientific area.

To facilitate the understanding of the spectrum of TB infection and disease and facilitate the translation of research findings into product and clinical applications, each U19 application must include at least one clinical project and one animal research project that synergize to answer critical questions in latency or persistence of TB. Applications that do not include these components will be considered non-responsive and the applications will not be reviewed.

Please note that it is expected that some animal models that are developed by the TBRUs will be suitable for product development and evaluation. NIAID may request transfer of the protocols for these animal models to DMID’s preclinical services programs to be made available as a service to the community.

1) TBRU Administrative Core

Each TBRU must include an Administrative Core, to be directed by the PD/PI, which is responsible for managing, coordinating, and supervising all TBRU activities. The Administrative Core must include a Data Management Center for collection, storage, quality control, and evaluation of all study data.

Each TBRU must propose a formal Management Plan that will guide its operations and activities. The Management Plan should outline how the multiple scientific projects will be integrated to answer the proposed scientific questions and hypotheses within the objectives of this FOA, and how projects and studies will be coordinated and scientifically managed. In addition, the Management Plan must provide integrated overall milestones, timelines and performance objectives for each proposed project and, where appropriate, define measureable go/no-go decision criteria for project advancement. The Administrative Core will also interact directly with NIAID staff.

The Administrative Core must address the following elements within each TBRU, and in collaboration with the other TBRUs:

• Data and information sharing;
• Monitoring overall research progress;
• Scientific group meetings and teleconferences throughout each funding period among projects leaders;
• Presentation and publication of data;
• Public dissemination of data and other resources;
• Sharing of models and other resources generated under the program (refer to the Terms and Conditions of the Award); and
• Establishment of any Collaborative Projects beginning no earlier than in year 2 of the award (see below).

The Administrative Core is also responsible for the following administrative activities:

• Development and implementation of a staffing plan;
• Organization and participation in the Annual Programmatic Meetings;
• Organization and participation in the activities of the External Advisory Group and other activities to be defined over the course of the award period; and
• Communication with other TBRUs regarding collaboration.

It is expected that the Data Management Center will serve as a resource to the TBRU investigators, providing data management and statistical support. It should provide for assistance in study design and protocol development and, where appropriate, assist with statistical issues related to laboratory testing and results.

The Data Management Center should operate under a data management implementation plan, employ a full-time data manager, and include an electronic data management system. The data management system must be capable of collecting and managing data from the participating study sites in order to ensure uniformity of procedures and high quality data. The data management system should include but is not limited to:

• security features for controlled access to all project data;
• security features for ensuring data integrity and privacy;
• a tracking system for data forms, activities, and study samples;
• date and time stamping of all data records with electronic signatures;
• audit trails to track all changes made to data records;
• a reporting system that generates error reports and summary information reports; and
• compatibility with the NIAID supported computing infrastructure.

Data should be communicated with the NIAID supported Bioinformatics Center(s) (http://www.niaid.nih.gov/labsandresources/resources/dmid/brc/Pages/default.aspx) or their successors as one of the approaches to make information generated by this program available to the scientific community.

External Advisory Group (EAG): Each PD/PI, in collaboration with NIAID, will appoint a three member EAG to review the progress of each TBRU, and to provide advice to NIAID as part of the annual programmatic meeting of the TBRUs. The EAG may not include investigators who are collaborators of the funded TBRUs. The EAG will meet as part of the annual TBRU meetings and may be accessed ad hoc by each individual TBRU PD/PI if specific advice/perspective is sought. Names of EAG Members will be determined in collaboration with NIAID staff after award.

Collaborative Projects (subject to availability of supplemental funds): NIAID is interested in supporting cross-TBRU collaborative projects, which are expected to be initiated in year 2 or later years of the award and not to exceed the duration of the overall grant award (subject to the availability of funds). The purpose of these collaborative projects is to leverage expertise across all awarded TBRUs to address challenging scientific questions or studies related to the goals of this FOA. These projects must relate to the overall scope of the TBRU’s focus on high-risk, innovative approaches or applications, not duplicate projects already undertaken by any TBRU, and must be completed within one to two years. A detailed research plan, statement of how the proposed science relates and augments the overall scope of the TBRUs, and budget will be required for each collaborative project. Projects will be presented at the annual TBRU meeting for consideration and input by other TBRU PI/PDs and the EAG and will be reviewed by NIAID program staff before considering award.

Applications for a TBRU should not include descriptions of the collaborative projects; these will be discussed with NIAID program staff and the External Advisory Group at the annual TBRU meeting. Selection of the specific collaborative projects to be supported will be at the discretion of the NIAID Program Officer in consultation with the External Advisory Group. Only collaborative projects between 2 or more TBRUs will be accepted for consideration.

2)Research Projects

The following areas of research are examples of questions to be addressed by each TBRU. Research projects should include both animal and humans studies where possible and where appropriate to meet a key goal of the FOA cross disciplinary science engaging both clinical and animal model researchers. Projects may propose using experimental or licensed drugs and vaccines to establish or test hypotheses. Each approach should provide the greatest degree of innovation and possible contribution to the field.

• Define risk factors for progression to TB disease after infection with Mycobacterium tuberculosis (Mtb);
• Determine correlates of transition from latent to active disease;
• Characterize the role of persistent, metabolically diverse Mtb populations for treatment duration and relapse;
• Identify early markers of bacterial clearance in response to chemotherapy and/or the action of vaccine and immunostimulatory agents;
• Characterize the correlation between bacterial burden and likelihood of developing active TB disease or relapse post treatment;
• Identify immunological or other markers that indicate the presence of live Mtb;
• Develop animal models to study paucibacillary disease using endpoints that correlate to human disease/pathology or immunology; and
• Determine correlates of protection from active TB disease.

Each proposed project must include the following:

• Discussion of relevant knowledge gaps and a discussion of those knowledge gaps to be addressed by the clinical and non-clinical study plan;
• Synopses of proposed study protocols and their scientific basis/rationale, study design, justification of sample size and statistical analysis of data;
• A discussion of potential problems or obstacles to addressing these knowledge gaps and proposed approaches to overcoming any such problems and obstacles;
• Discussion of how the clinical/animal research will advance translational TB research; and
• Plans for collection and sharing of human and animal derived specimens and bacterial cultures within the TBRUs and for limited external collaborations that benefit the projects of each TBRU.

3)Clinical Site

Each application must provide expertise and capacity to conduct international clinical studies/trials (either at the awardee site or through collaborations and sub-contracts). This component must include a research site in at least one country outside of the United States (U.S.) in which TB is endemic (see Dye et al.- http://jama.ama-assn.org/cgi/content/full/282/7/677 ). The clinical site(s) must have an established infrastructure, including experienced local investigators capable of conducting multi-disciplinary human clinical studies in TB that meet US regulatory requirements for the protection of human subjects, adequate laboratory facilities and personnel to perform protocol-specific tests, access to patient populations that are suitable to study latency and persistence, as well as their relation to active TB; track record of successful enrollment of volunteers (healthy and infected/presenting with disease) in clinical studies/trials; experience working under US Federal Human Subjects regulations; expertise in epidemiology, immunology, and microbiology; and expertise and infrastructure to model human relevant aspects of paucibacillary TB in animals.

4)Programmatic Meetings

Each year a one to two day meeting will be held in Bethesda, Maryland among all awarded TBRUs, the EAG, and NIAID staff. These meetings are conducted to review progress on scientific projects; highlight recent findings; exchange information about promising technologies, models and methodologies; and encourage collaborations among the TBRUs. These meetings will also serve to review proposed cross-TBRU collaborative projects for NIAID consideration.

Each TBRU should ensure that support for meeting attendance by the PD/PI, the Project Leaders and Cores leaders, and other key personnel is included in the budget. The Project Leaders and key technical and scientific staff shall present an update on progress and a summary of results generated on each project, including a discussion of problems/obstacles encountered and proposed approaches taken or planned to overcome them. Annual meetings shall also address the application of policies and procedures for monitoring the direction of specific projects.

Within 3 months of award, NIAID plans to hold a TBRU kick-off meeting in Bethesda, Maryland to provide opportunities for the awarded TBRUs to present their research plans and initiate discussion with other TBRUs. The PD(s)/PI(s) and all Project Leaders are expected to attend this kick-off meeting and include this in the first year budget.

NOTE: The following activities are not within the scope of this FOA. Applications proposing research in these areas are considered non-responsive and will not be reviewed:

1) Establishment of NEW clinical research infrastructure and capacity in TB endemic countries;

2) Establishment of clinical trial infrastructure and capacity for testing novel diagnostics, drug or vaccine candidates as a service to the community;

3) Evaluation of the safety and efficacy of new vaccine and drug candidates, or animal studies evaluating the efficacy of novel experimental diagnostic tools, therapeutics/regimens or preventive strategies for the purpose of meeting regulatory requirements for new candidate products;

4) Establishment of sample repositories for distribution to the TB research community;

5) Provision of clinical care.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New The OER Glossary and the PHS 398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIAID intends to commit $10 million in FY 2014 to fund two (2) to three (3) TBRUs.
Award Budget	Applicants may propose budgets of up to $3.25 million total costs (direct and indirect combined) in FY 2014.
Award Project Period	7 years

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• System for Award Management (SAM) must maintain an active entity registration (formerly CCR registration), to be renewed at least annually. Use the Sam.gov Manage Entity function to manage your entity registrations. See the Grants Registration User Guide at SAM.gov for additional information.
• eRA Commons

All Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 6 weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization 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 NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS 398 Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS 398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed research
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

L.-Yong Gao, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3127, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Zip code for express couriers: 20817-7616
Phone: 301-443-8115
FAX: 301-480-2408
Email: [email protected]

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

L.-Yong Gao, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3127, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Zip code for express couriers: 20817-7616
Phone: 301-443-8115
FAX: 301-480-2408
Email: [email protected]

All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, with the following exceptions:

• Overall Research Strategy section is limited to 12 pages
• Individual Project Research Strategy is limited to 12 pages
• Administrative Core (required) is limited to 12 Pages
• Other Core Services is limited to 6 pages

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

The following section supplements the instructions found in Form PHS 398 for preparing a multi-project grant application. Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme. All applications must be submitted on Form PHS 398. The multi-project grant application should be assembled and paginated as one complete document. Instructions for the Overall Component are presented first, followed by instructions for Research Projects, followed by instructions for Cores.

Form Page 1. Face Page(Overall)

Items 1 - 14: complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

Form Page 2. Summary, Relevance, Project/Performance Site,Senior/Key Peronnel, Other Signficant Contrbutor, and Human Embroyonic Stem Cells (Overall)

Descripton: Using Page 2 of Form 398; provide a succinct but accurate description (abstract) of the OVERALL multi-project application addressing the major, common theme of the program. Do not exceed the space provided.

Project/Performance Site: List the performance sites where the research will be conducted.

Senior/ Key Personnel:Under "Key Personnel", list the PD/PI of the multi-project application, followed by the Project and Core Leaders of the component research projects and cores, and other key personnel and then other significant contributors.

Form Page 3. Table of Contents (Overall)

Do not use Form Page 3 of the PHS 398; a more comprehensive table of contents is needed for a multi-project application.

Bearing in mind that the application will be scientifically reviewed project by project and core by core, prepare a detailed Table of Contents that will enable reviewers to readily locate specific information pertinent to the overall application as well as to each component research project and core. A page reference should be included for the budget for each project and each core. Further, each research project should be identified by number (e.g. Project 1), title, and responsible Project Leader, and each Core should be identified by letter (e.g. Core A), title, and responsible Core Leader. The page location of a COMPOSITE BUDGET should be indicated in the "Table of Contents."

Form Page 4. Composite Budget (Overall)

Do not use Form Page 4 of PHS Form 398. Instead, using the suggested format presented below, prepare a Composite Budget for All Proposed Years of Support. (Justification for budget elements should not be presented here but in the individual budgets of the projects and cores.)

SAMPLE: Consolidated Direct Cost Budget for All Proposed Years of Support

Component	Year 1	Year 2	Year 3	Year 4	Year 5	Year 6	Year 7	All Years
Project 1. Invest.	125,000	130,000	135,200	140,608	146,232	152,081	158,165	987,286
Project 2. Study	125,000	130,000	135,200	140,608	146,232	152,081	158,165	987,286
Project 3. Develop.	100,000	104,000	108,160	112,486	116,985	121,664	126,531	789,826
Core A. Admin. Core.	50,000	52,000	54,080	56,243	58,493	60,833	63,266	394,915
Core B. DNA	25,000	50,000	52,000	54,080	56,243	58,493	60,832	356,648
Totals	425,000	466,000	484,640	504,025	524,185	545,152	566,958	3,515,961

Form Page 5. Total Direct Costs for the Entire Budget Period

Complete the Total Direct Cost line entries for all requested budget periods (years) and the Total Direct Cost for Entire Period of Support entry. Detailed budgets are required within the descriptions of each project and core (see below).

Biographical Sketch Format Page

Biographical sketches of all professional personnel for all components should be placed at the end of the application with the PD/PI first, followed by those of other key personnel in alphabetical order.

Resources Format Page

Do not complete. Essential information is to be presented in the individual research project and core sections of the application.

Program Overview Research Plan (Research Objectives and Strategic Plan) (Overall)

Specific Aims

List in priority order, the broad, long-range objectives and goals of the proposed Program. Concisely and realistically describe the hypothesis or hypotheses to be tested.

Overall Research Strategy

This narrative section summarizes the overall research plan for the multi-project application and explains how the proposed Program satisfies the purpose and all objectives of this FOA as delineated in Section I. Applications responding to this FOA should describe the central theme of the proposed Program and explain how the proposed Research Projects are synergistic and fit under the overarching Program theme. The multi-project application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for addressing the problems. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Checklist (Overall)

hecklist, placed at the end of the application, is to be submitted for the entire application.

Appendix Materials (Overall)

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide, with the following modification:

• For each project or core in the multi-project application, 3 publications plus other approved material are allowed.

A minimum of two individual research projects are required.

For each individual Research Project, include: Cover page (replaces Face Page), Description & Key personnel (PHS 398 Form Page 2) , Table of Contents (PHS 398 Form Page 3) , Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications , Research Plan, and Resources

Cover Page (Research Projects)

The Face Page of the 398 Form should not be used as a cover page for individual research projects within a multi-project application. Instead, use the PHS 398 continuation page to create a "Cover Page" containing selected data about each individual research project. This Cover Page will demarcate each individual research project and should contain the following information items (these are a subset of the information provided on a PHS 398 Face Page):

• Project Number and Title: (e.g., 1. Preclinical Evaluation of HIV Microbicides)
• Name of Project Leader: (e.g., Jones, Roberta A.)
• Human Subjects: (Yes or No)
• If Yes:
• Exemption number, -or-
• IRB Approval Date (e.g., 12/13/2006,or "Pending"), and Federalwide Assurance (FWA) number
• Vertebrate Animals: (Yes or No)
• If Yes:
• IACUC Approval Date (e.g., 11/17/2006, or Pending) and Animal welfare assurance number:
• Proposed Period of Support:
• From: (mmddyy - e.g., 07/01/2007)
• To: (mmddyy - e.g., 06/30/2112)
• Costs Requested for Initial Budget Period: (e.g. 07/01/2007-06/30/2008)
• Direct Costs: (e.g., $ 150,000)
• Total Costs: (e.g., $162,000)
• Costs Requested for the Entire Budget Period: (e.g., 07/01/2007-06/30/2112)
• Direct Costs: (e.g., $700,000)
• Applicant Organization (full address)

Form Page 2 (Research Projects)

Provide a Description (abstract) of the research proposed in the individual research project according to the instructions on Form Page 2 of PHS Form 398. In addition, the abstract should contain a brief description of how the individual research project will contribute towards attainment of the multi-project objectives.

Project/Performance Sites: List the performance sites where the research will be conducted.

Key Personnel: Under "Key Personnel", list the Project Leader, followed by other key project personnel, and then other significant contributors.

Form Page 3. Table of Contents (Research Projects)

Prepare a Table of Contents for the research project using Form Page 3 of the PHS 398.

Form Page 4 and 5. Detailed Budget for Initial Budget Period (Research Projects)

Prepare a detailed budget and justification for the research project using Form Pages 4 and 5 of the PHS 398.

Individual Research Project Research Plan (Research Projects)

Specific Aims: List, in priority order, the broad long-range objectives and goals of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the individual research project's relationship to the Program’s goals and how it relates to other projects or cores.

Research Strategy : Use this section to describe how the proposed research will contribute to meeting the TBRU’s goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application.

Organize the Research Strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5. Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information. Experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. Preliminary Studies for new projects must be included as part of the approach section, and must be contained within the page limits of the Research Strategy section.

Describe the research design conceptual procedures, and analyses to be used to accomplish the specific aims of the project. Describe any new methodology and its advantage over existing methodologies. Describe any novel concepts, approaches, tools, or technologies for the proposed studies. Discuss associations with clinical project(s). Discuss the potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the aims. As part of this section, provide a tentative sequence or timetable for the project.

Describe the clinical and non-clinical study plan, as well as the rationale for selection of clinical sites. Provide synopses of proposed study protocols and their scientific basis/rationale, study design, sample size and statistical analysis. Discuss potential problems or obstacles to addressing these knowledge gaps and proposed approaches to overcoming any such problems and obstacles. Discuss plans for collection and sharing of human and animal derived specimens and bacterial cultures within the TBRUs.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Resources Format Page (Research Projects)

Provide information on resources available for the project. Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.) For Early Stage Investigators, describe institutional investment in the success of the investigator. If there are multiple performance sites, describe the resources available at each site.

Describe any special facilities used for working with biohazards or other potentially dangerous substances in the US and at non-US sites.

Biographical Sketch Format Page (Research Projects)

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

For each individual Core, include Cover page, Description & Key personnel (PHS 398 Form Page 2), Table of Contents (PHS 398 Form Page 3), Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications , Administrative and Core Services Plan, and Resources Format Page.

Cover Page (Cores)

The Face Page of the 398 Form should not be used as a cover page for cores within a multi-project application. Instead, use the 398 continuation page to create a "Cover Page" containing selected data about each individual core. This Cover Page will demarcate each core and should contain the following information items (which are a subset of the information provided on a Face Page - see PHS 398):

• Core Letter and Core Title: (e.g., A. Monoclonal Antibody Production Core)
• Name of Core Leader: (e.g., Smith, Robert A.)
• Human Subjects (Yes or No)
• If Yes,
• Exemption Number, -or-
• IRB Approval Date (e.g., 5/14/06, or Pending), and Federalwide Assurance (FWA) number
• Vertebrate Animals (Yes or No)
• If Yes,
• IACUC Approval Date (e.g., 4/15/07, or Pending), and Animal welfare assurance number
• Proposed Period of Support
• From: (mmddyy, e.g., 07/01/2007)
• To: (mmddyy, e.g., 06/30/2012)
• Costs Requested for Initial Budget Period
• Direct Costs (e.g. $50,000)
• Total Costs (e.g. $70,000)
• Costs Requested for the Entire Budget Period
• Direct Costs (e.g. $212,323)
• Total Costs (e.g. $297,252)
• Applicant Organization (ABC University; 111 Main Street; Anywhere, Else 99999)

Form Page 2. (Cores)

Description: Provide a Description (abstract) of the core activities and services according to the instructions on Form Page 2 of the PHS 398. In addition, the abstract should contain a brief description of how the core services will contribute towards attainment of the objectives.

Project/Performance Sites: List the performance sites where the core activities and services will be conducted.

Key Personnel: Under "Key Personnel", list the Core Leader, followed by other key core personnel, and then other significant contributors.

Form Page 3. Table of Contents (Cores)

Prepare a Table of Contents for the core using page 3 of Form PHS 398.

Form Page 4 and 5. Budget Pages (Cores)

Prepare a detailed budget and justification for the core using Form Pages 4 and 5 of the PHS 398.

Individual Core Plan (Research Plan for Cores)

Specific Aims: For the required core, as well as for all additional proposed cores, list in priority order the broad, long-range objectives and goals of the proposed core(s). Concisely and realistically describe the methods that will be applied to the cores and any hypotheses that may be addressed through them. In addition, state the core’s relationship to the Program’s goals and how it relates to the individual research projects or other cores in the application.

Administrative Core Research Strategy:

• Provide a Staffing and Administrative Plan that includes a discussion of the structure and roles of administrative and scientific staff, including the committed level of effort, the training and experience of proposed staff and the functions to be performed; how resources will be prioritized, allocated and managed. Provide a plan to establish a Collaborative Projects Program beginning with the second year of the award. In addition, applicants are also required to provide overall Program’s milestones, timelines and performance objectives in a section of the application entitled Milestones and Timelines , which must include also those of the Research Projects and all Core activities. The budget request should also include travel funds for the PI(s)/PD(s), Research Projects and Core Leaders to participate in Annual Programmatic Meetings of all Programs funded under this FOA, including the kick-off meeting. Provide a management plan for fiscal accountability and communication within the Program. Describe the identification and resolution of problems, and engagement of the EAG and NIAID, including details of how to interact with the EAG aside from the required annual review meetings. Names of EAG Members should not be proposed as part of the application since EAG members will be independent, non-affiliated experts and will be selected in collaboration with NIAID.
• Provide details about the Data Management Center and how it will serve as a resource to the TBRU investigators by providing data management and statistical support. Provide details of the data integration, management and tracking activities of the Program and include a Plan for public dissemination of generated resources to the scientific community that is consistent with the guidelines and timelines described in the NIAID Data and Reagents Sharing and Release Guidelines (http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Pages/data.aspxv)

Other Core Services Research Strategy

• Use this section to describe how the proposed core activities will contribute to meeting the Center's goals and objectives and explain the rationale for selection of the general methods and approaches proposed to accomplish the specific aims. In addition, this section should indicate the relevance of the core to the primary theme of the application. Provide details of the services or resources provided by the optional cores to at least two Research Projects and clarify how the optional cores are not duplicative of other services or facilities.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Biographical Sketch Format Page

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

Resources Format Page

Provide information on resources available for the core. Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.) For Early Stage Investigators, describe institutional investment in the success of the investigator. If there are multiple performance sites, describe the resources available at each site. Describe any special facilities used for working with biohazards or other potentially dangerous substances.

Foreign (non-U.S.) Institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the PHS 398 Application Guide.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS 398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact - Overall

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

• Are the individual projects or at least their overall structure synergistic and do they help answer common questions about latency and/or persistence of TB?
• Is the Program as a whole scientifically compelling?
• Are there coordination and synergy of the individual research projects and cores towards the achievement of the central objectives of the Program?
• Are the overall Program goals significant and focused on studies that meet the purpose and objectives of the FOA?
• Will the integration of the individual projects into a single Program be more beneficial than pursuing each project independently?
• Do(es) the PD(s)/PI(s) have the leadership and scientific ability to develop an integrated and focused research Program?
• Is there adequate evidence of sufficient institutional support for the PD(s)/PI(s) in terms of laboratory space, equipment and other resources?
• For applications designated multiple PD(s)/PI(s), is the Leadership Plan both adequate and appropriate to ensure that there will be sufficient coordination and communication among the PD(s)/PI(s)?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the Project Leader have an appropriate track record for network collaborative activities?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Are proposed animal models/studies suitable to create human relevant hypotheses? Are the proposed studies appropriately challenging dogma? Are appropriate state of the art technologies proposed to address this research area?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Are animal models/studies appropriately linked with concurrent human clinical studies?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Are appropriate international research sites proposed? Are appropriate infrastructure and space available to conduct relevant animal studies?

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the core to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria, and additional review criteria (as applicable for the core proposed).

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the core to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria, and additional review criteria (as applicable for the core proposed).

Administrative Core

• Is the Staffing and Administrative Plan appropriate to facilitate attainment of the objectives of the proposed Program?
• Are the experience, level of commitment, and availability of the PD(s)/PI(s), Research Projects and Core Leaders adequate to manage the overall Program?
• Is the plan to establish the Collaborative Projects adequate and appropriate?
• Are the plans for coordination, problem identification and resolution and the establishment of a strong collaborative environment for the program appropriate?
• Are the plans for coordination, problem identification and resolution and the establishment of a strong collaborative environment with other TBRUs appropriate?
• Are the proposed timelines, milestones and performance objectives for the overall Program adequate?
• Is the management plan for fiscal accountability and communication within the Program appropriate?
• Is the proposed management implementation plan feasible and appropriate? Is the Data Management Center appropriately integrated into the administrative core to provide support to all proposed projects?
• Is the data management system adequate, appropriate and capable of collecting and managing data from the participating study sites in order to ensure uniformity of procedures and high quality data?

Other Scientific Cores

• Is provision of resources and core services to the Research Projects critical and justified?
• Is the relationship of the core to the central focus of the overall Program strong?
• Are the quality of the relevant facilities or services provided (including procedures, techniques, quality control) and criteria for prioritization and usage appropriate?
• Are the optional Scientific Cores justified and relevant to the theme of the overall Program? Is adequate justification provided that it will support at least two Research Projects?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIAID , in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted response to this FOA..

Applications will be assigned to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council . The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Compliance of the plan for public dissemination of generated resources to guidelines of the NIAID Data Sharing and Release Guidelines (http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Pages/data.aspx).

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Defining the research objectives, approaches and details of the projects and core within the guidelines of the FOA;
• Performance of the scientific activity;
• Ensuring that studies conducted under this cooperative agreement utilize/employ a multidisciplinary approach that integrates clinical and field aspects with animal, laboratory, molecular and genomic methods;
• Planning, direction, and execution of the proposed collaborative projects;
• Evaluate the changing landscape of tuberculosis research, provide the flexibility necessary to conduct cutting edge research;
• Provide a process for assessing ongoing research projects and modifying, redirecting and/or curtailing ongoing research projects to reflect new findings;
• Attending and presenting at EAG reviews;
• Assuring compliance of all projects within the application with applicable Federal, State, Local, regulations;
• Assuring compliance with all applicable DHHS/NIH/NIAID policies for conduct of animal research and clinical trials;
• Ensuring that on-site administrative structure, scientific capacity and training are available to enable endemic sites to perform the research activities proposed in this grant; and
• Provide semi-annual progress reports in a format to be defined by the NIAID after award.

Federally Mandated Regulatory Requirements for Clinical Research

Each institution participating in clinical research is required to meet DHHS regulations for the protection of human subjects. At a minimum, this includes:

• Methods for assuring that each institution at which Program investigators are conducting clinical studies has registered with the Office of Human Research Protections (OHRP; http://www.hhs.gov/ohrp/) and has a Federal wide Assurance; that study protocols are reviewed and approved by the responsible Institutional Review Board (IRB) prior to participant entry; that active protocols are reviewed at least annually by the IRB, and that amendments are approved by the IRB.
• Methods for assuring or documenting that each participant, or participant’s parent/legal guardian, gives fully informed consent to participation in a research protocol prior to the initiation of the intervention.

Intellectual Property

The awardee is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the awardee to perform the project.

Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.

The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 200-212 (Bayh-Dole Act). It is the responsibility of the Awardee to take appropriate steps, if desired, to obtain intellectual property protection on any such inventions in light of the information disclosures contemplated in this Announcement.

Program Generated Data, Software and Other Resources

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

The Programs funded under this Program are expected to follow the guidelines and timelines described in the NIAID Data and Reagents Sharing and Release Guidelines (http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Pages/data.aspx). Program-generated data and software should be made available through publicly accessible web and database sites, including the Web Portal, the BRCs (http://www.niaid.nih.gov/dmid/genomes/brc/default.htm), the NCBI (http://www.ncbi.nlm.nih.gov/) and/or other public repositories, as identified by the Steering Committee in consultation with the NIAID.

Program-generated data and software include, for example:

• all research data (both experimentally and computationally generated) and associated metadata;
• database schema and specifications;
• experimental protocols and Standard Operating Procedures (SOPs); and
• data analysis tools and algorithms generated under this contract, including and source code, complete use documentation and tutorials. Whenever possible, the Awardee shall provide software certified by the Open Source Initiative (http://www.opensource.org/licenses/), to guarantee the right of others to read, redistribute, modify, and freely use the software.

Program-generated novel reagents (e.g., expression vectors, mutant strains, libraries, protein clones), should be made available through NIAID-supported repositories, such as the NIAID BEI Resources (http://www.beiresources.org/) or in other repositories in consultation with the NIAID.

Publications

The PD(s)/PI(s) will be responsible for the timely submission to the NIAID of all abstracts, manuscripts and reviews (co)authored by members of the grant and supported in whole or in part under this Cooperative Agreement. The PD(s)/PI(s) are requested to provide manuscripts to the NIAID Program staff prior to the submission to the Journal so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the PD(s)/PI(s) and appropriate Research Project and Core Leaders and will require appropriate acknowledgement of NIAID support. Awardees are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, and reports to the NIAID, or other mechanisms.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The role of the NIAID/NIH Project Scientist in the cooperative agreement is to support and encourage the recipient's activities by substantial involvement as partners and facilitators in the process without assuming responsibilities that remain with the PDs/PIs. The NIAID Project Scientist will work closely with the PD(s)/PI(s) and other Program member scientists to facilitate collaborations and to leverage the resources available to the Program.

The NIAID Project Scientist will monitor the progress of the Program, help coordinate research approaches among all Programs funded through the FOA, and contribute to the shaping of research projects or approaches as warranted. The NIAID Project Scientist will support and facilitate this process but will not direct it.

The NIAID Project Scientist will keep the Program informed about other ongoing studies supported by NIAID to avoid duplication of effort and encourage sharing/collaboration in infectious diseases research. The NIAID Project Scientist will coordinate access for the Program to other NIAID resources, as well as assist the research efforts of the Program by facilitating access to fiscal and intellectual resources provided by industry, private foundations, NIH intramural scientists and other federal government agencies as appropriate.

The NIAID Project Scientist will serve as a non-voting member of the External Advisory Group and will assist in developing the operating guidelines and consistent policies for dealing with situations that require coordinated action.

The NIAID Project Scientist will retain the option to recommend, with the advice of the External Advisory Group, the withholding or reduction of support from any cooperative agreement that substantially fails to achieve its goals according to the milestones agreed to at the time of the award or fails to comply with the Terms and Conditions of the award.

Additionally, a NIAID program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program official may also serve as an NIAID Project Scientist.

Areas of Joint Responsibility include:

The NIAID Project Scientist will provide overall coordination across all funded Programs, will coordinate with the PD(s)/PI(s) and hold regular program-wide-discussions to facilitate the achievement of program goals. In the event that some members of the Programs develop common research interests working groups may be formed to pursue collaborative activities.

In addition, PD(s)/PI(s), Research Project and Core Leaders and the NIAID Project Scientist will participate in the External Advisory Group activities as needed.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the External Advisory Group chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Dr. Christine Sizemore
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-435-2857
Email: [email protected]

L.-Yong Gao, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3127, MSC 7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Zip code for express couriers: 20817-7616
Phone: 301-443-8115
FAX: 301-480-2408
Email: [email protected]

Deanna Ingersoll
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 2110, MSC 7614
6700 B Rockledge Drive
Bethesda, Maryland 20892-7614
Phone: (301) 451-2686
FAX: (301) 493-0597
email: [email protected]

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