It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) 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. 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.

Part 1. Overview Information
Part 2. Full Text of the 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

Tuberculosis (TB) now ranks as the leading infectious disease cause of mortality in the world. About 1.7 billion people are currently infected with Mycobacterium tuberculosis (Mtb) and are at risk of developing active TB disease. Increasing rates of multi-drug and extensively drug-resistant TB (MDR-TB and XDR-TB) pose a growing threat. Early diagnosis of TB and universal drug-susceptibility testing (DST) are critical to identifying the most appropriate treatment for individual patients and to preventing the spread of disease. Despite major advances in recent years, critical diagnostic needs are still unmet. There remains an urgent need for true point of care (POC) diagnostics, including rapid drug susceptibility testing (DST) in decentralized settings, pediatric targeted diagnostics that include non-sputum based diagnosis/technologies, and technologies to improve diagnosis of disseminated and paucibacillary TB.

The purpose of this Funding Opportunity Announcement (FOA) is to support proof-of principle studies to evaluate novel, early stage TB diagnostic tests, assays and strategies, and to provide feedback to diagnostic developers on the performance of the technology and potential strategies for use in endemic settings. For the purpose of this initiative, an "early stage" diagnostic refers to a diagnostic that has advanced to the stage where a prototype is ready and available to be evaluated but is not currently used in clinical care and treatment decisions for tuberculosis. Funding under this FOA will establish a partnership of investigators and existing clinical study sites in TB endemic countries, coordinated and led by a leadership team. Clinical sites are encouraged to provide access to both adult and pediatric study populations with drug susceptible and drug resistant TB, populations including HIV-negative and HIV/TB co-infected individuals, and subjects who received childhood vaccination with BCG. Additionally, applicants are encouraged to include sites that can demonstrate access to study populations with other common co-morbidities such as type II diabetes, and subjects with exposure to mycobacteria other than Mtb, such as Mycobacterium leprae and environmental non-tuberculous mycobacteria (NTMs).

Attaining the goals of the FOA will require coordination with local and country TB programs and a demonstrated capacity to perform state of the art diagnostic capabilities for TB including smear, culture and Xpert methods to allow comparison of new diagnostics to the standard of care in these settings.

Successful awardee(s) will have one or more early stage diagnostics ready for initial testing in the first year of performance and have detailed plans to evaluate additional diagnostics in subsequent years. Plans are anticipated to include mechanisms to identify and solicit novel diagnostics for testing and provide for requests from third party developers. Of particular interest are applications addressing: 1) true point of care (POC) tests; 2) diagnostics for use in underserved populations, including children and persons with disseminated and/or paucibacillary TB disease; 3) product candidates that identify TB using specimens other than sputum (e.g. serum, urine or stool) allowing identification of paucibacillary or extrapulmonary TB in adult and pediatric patients; 4) diagnostics that may overcome limitations such as cost and infrastructure associated with current molecular diagnostic approaches; 5) diagnostics that provide expanded rapid drug susceptibility testing, including at the POC, and 6) diagnostics that distinguish between vaccinated individuals and those who are infected. Diagnostics may be targeted to any stage of TB disease, including identification of incipient disease. Also, of interest is the evaluation of novel diagnostic strategies for TB in the context of existing clinical algorithms in TB endemic countries. This may include, for example, testing the use of multiple diagnostics in combination to address a limitation in TB diagnosis, e.g. by testing an inexpensive triage test in combination with a more expensive definitive test.

Information from experimental diagnostics may not be used to inform treatment decisions. Clinical trials are not allowed.

Applications proposing any of the following topic areas will be considered nonresponsive and will not be reviewed:

• Applications that propose establishment of new clinical infrastructure.
• Applications that propose to establish a biorepository (i.e. a repository to distribute samples to requesting parties, samples may be stored and used in studies by the study team).
• Applications that propose the development of a new diagnostic.
• Applications that propose to conduct a clinical trial.

Administration and Leadership Team

The members of the Administration and Leadership Team, led by the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)), will be responsible for organizing, coordinating, and providing oversight for the implementation of studies to evaluate TB diagnostics. This team will provide administrative oversight, coordinate the entire study, and serve to connect technology holders with clinicians in TB endemic countries to ensure diagnostic developers understand the needs of the primary users and patients.

Clinical Study Sites

The Clinical Study Site(s) should have established clinical facilities and laboratories capable of conducting clinical research studies to evaluate new TB diagnostics. It is expected that sites will have established relationships with local clinicians familiar with the current clinical algorithms for the diagnosis of TB. The Clinical Study Sites should include the facilities and personnel required to carry out study-specific laboratory testing in accordance with Good Laboratory Practice (GLP) guidelines, storage of patient samples under appropriate conditions, as well as the ability to diagnose TB according to the current standard of care.

Clinical Study Sites must include at least one foreign clinical study site located in a TB-endemic country (as identified by the WHO annual Global Report, http://www.who.int/tb/publications/global_report/en/, updated yearly). The program is expected to be flexible and to incorporate new clinical sites as needed to conduct the most effective studies.

Clinical Support Team

The members of the Clinical Support Team will be responsible for coordinating the functions at individual enrollment sites to facilitate multiple study procedures related to recruitment, enrollment, data and biological sample collection.

Data Management and Analysis Team

The members of the Data Management and Analysis Team will be responsible for developing and implementing procedures for the collection, oversight and inventory of data and biological samples, including, for example, harmonization, quality control, and uniformity of data collection processes, troubleshooting data system problems and developing solutions. Team members will also work with key personnel to provide statistical support for the study design and data analyses for the study. This team will be responsible for sharing data, as well as providing expertise on study design planning and data analysis.

External Advisory Committee (EAC)

An External Advisory Committee will be established to review progress and share recommendations with NIAID as part of the annual programmatic meeting. The EAC will also make recommendations regarding the continuation or re-direction of the research program on an ongoing basis and in consultation with NIAID staff. The EAC will be established after award. Prioritization of requests for evaluation of novel diagnostics will be made in a collaboration between the EAC, NIAID and the PD(s)/PI(s) in the partnership.

Annual Programmatic Meetings

A kick-off meeting and annual program meetings will be held to articulate and establish the major roles and functions of the program and to facilitate collaborations, provide progress reporting, seek new research directions and ideas, and update NIAID on issues of need. These meetings will be attended by the PD(s)/PI(s), Key personnel, NIAID staff, and the EAC membership.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

o   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

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• o   NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 SF424 (R&R) Application Guide.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) 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 activity
• 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:

Lynn Rust, Ph.D.
Telephone: 240 669 5069
Email: lrust@niaid.nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exception:

For this specific FOA, the Research Strategy is limited to 30 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. with the following additional instructions:

Facilities and Other Resources:

In separate sections using the suggested titles below include the following:

Biological Sample Storage and Access: describe the facilities available to store, manage and retrieve biological specimens for use by the PD(s)/PI(s) and key personnel. 

Clinical Sites: Describe the unique facilities and features of the clinical sites to recruit, screen, and enroll patients in a timely manner as well as to follow and retain patients as required for the proposed and potential studies. Describe the laboratory capabilities of the sites to diagnose TB using the standard of care (e.g. culture, smear and Xpert).

Data Management:  Describe the unique facilities and features of the data management center that will support the reliable and accurate collection and recording of the data, rapid and secure transfer of all data between the clinical sites, and data analysis.

All instructions in the SF424 (R&R) Application Guide must be followed. with the following additional instructions:

Within the Biosketch under Personal Statement, describe the leadership approach and experience of the PD(s)/PI(s) with respect to managing multi-site international clinical studies, including any experience managing TB diagnostics studies.

Within the Biosketch under Personal Statement, all Key Personnel should demonstrate strong administrative, technical, and management ability in areas critical to the success of the application, including experience working productively in collaborative environments. Demonstrate how specific abilities support the multi-disciplinary approach to guarantee a successful, integrated effort towards the goals of the research project.

All instructions in the SF424 (R&R) Application Guide must be followed. with the following additional instructions:

In Year 1, include funds in the budget for the PD(s)/PI(s), collaborators, site-specific personnel, and other Key Personnel and up to five members of the EAC to travel and attend a kickoff meeting to be held shortly after the award over 1 full day in the Bethesda, MD area.

In Year 1, include funds in the budget for at least one clinical research study.  

Beginning in Year 2, include funds in the budget for an annual program meeting to be held over two full days in the Bethesda, MD area.  Do not include costs associated with organizing and holding the kickoff or annual program meetings.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: with the following additional instructions: 

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed research, and indicate how these goals will be accomplished using the proposed structure and available clinical research sites.  Concisely describe the hypothesis or hypotheses to be tested. Indicate how the work proposed dovetails to address the overall goals and objectives of the research. 

Research Strategy:

• Identify and clearly describe one or more novel, early stage diagnostic tests that will be studied in the first year of performance.
• Provide a plan as to how additional diagnostics will be identified from third party diagnostic developers for testing during the later years of the grant period, including a process to submit a request for evaluation of an early stage diagnostic, and the criteria and process by which these requests will be prioritized for testing by clinical sites.
• Discuss how the proposed initial study(ies) will be conducted to evaluate novel diagnostic tests and strategies, and how feedback will be provided to diagnostic developers on the performance of the technology(ies).
• Describe a strategy for how to use the diagnostics identified for the initial evaluation in an endemic setting and discuss the potential for novel diagnostics to improve the care cascade for both drug resistant and drug susceptible TB.
• Describe how additional diagnostic studies will be developed and implemented for future studies.
• Describe the current TB diagnostic capabilities and technologies at the clinical sites to be used as a benchmark for comparison including smear, culture and Xpert methods.
• Note: if the proposed research includes clinical studies, specific information for that study will be entered using the PHS Human Subjects and Clinical Trials Information Section and should not be duplicated in the Research Strategy.

In separate sections, using the suggested titles below, include the following:

Administration and Leadership Team Plan

• Describe the administrative and organizational structure of the research study and the unique features of the organizational structure that serve to facilitate accomplishment of the long-range goals and objectives.  Describe the overall management plan, including how resources will be managed, organized, and prioritized, and how subcontracts and consultants, if applicable, will be selected/funded and monitored. Describe how communications will be planned, implemented, and provided to collaborators, teams, or sites.
• Describe strategies for oversight and implementation of standardized approaches to ensure efficient cooperation, communication and coordination across the multiple sites and team structure. 
• Describe how the training needs of scientific staff will be determined and provided.
• Provide plans for communicating and coordinating with the clinical research sites and affiliated laboratories. Discuss plans to both ensure synergy among the clinical research sites and a flexible structure capable of responding to new scientific opportunities.
• Describe any existing relationships with the local TB control programs or ministry of health associated with the proposed clinical sites, including any established collaborations and provide proposed collaboration plans. Highlight collaborations with, plans for and process when coordinating with local and in country TB experts. Do not name or contact potential collaborators that are not already key personnel in the application.

Clinical Study Sites Plan

• Discuss general plans to include clinical study site(s) with established clinical facilities and laboratories capable of conducting clinical studies to evaluate new TB diagnostics, as well as established, collaborative relationships with local clinicians familiar with the current clinical algorithms for the diagnosis of TB.
• Describe the overall approach and strategies for the Clinical Research Site Selection and Management activities below:
• conducting feasibility assessments, including how site capacity, capabilities, and needs will be assessed; 
• soliciting, reviewing, and selecting clinical research sites;
• safety oversight for study participants and compliance with all safety guidelines and regulations at all clinical research sites;
• receiving, labeling, storing, and tracking study products and for monitoring storage conditions, and inventory control; and
• classification, labeling, documentation, shipping, and tracking of clinical specimens.
• Discuss general plans for access to adequate numbers of relevant patient populations to ensure the prompt screening, enrollment, and completion of clinical studies.  Include overall plans to ensure access to adult and pediatric patient populations: TB patients with drug susceptible and/or drug resistant disease; adult and pediatric subjects presenting with TB related co-infections and co-morbid conditions, such as HIV/AIDS or Type II diabetes; underserved populations including children and persons with disseminated and/or paucibacillary TB disease and controls; subjects with exposure to mycobacteria other than Mtb, such as Mycobacterium leprae and environmental NTMs; and subjects who have received childhood vaccination with BCG.

Clinical Support Team Plan

• Without repeating information from individual biosketches, describe the team's experience with developing and testing diagnostics and past relevant accomplishments. Include staffing plans with diagrams and charts as needed.

Data Management and Analysis Team Plan

• Describe the overall plan and approach for biostatistical support systems; for example: 1) preliminary data analyses, 2) estimates of power and sample size, 3) research study design and protocol development.  Describe plans to estimate and achieve adequate sample size to achieve the needs of the research program. Describe the plan to support the data analytics and design features unique to the research study.
• Describe internal and external data acquisition strategies to achieve harmonization of systems and procedures for data management, data quality, data analyses, and dissemination for all the data and data-related materials generated by the research studies. 
• Within the plan, indicate the extent to which dedicated systems or procedures will be utilized to harmonize the acquisition, curation, management, inventory and storage of data and samples. Describe how training for the data and sample collection, in terms of the use of electronic data capture systems, will be provided to all staff including those at enrollment sites.
• Describe the quality control procedures for the data and biological specimens and how to identify and resolve issues with quality control that maintains integrity of data and specimens.

External Advisory Committee Plans

• Describe an overall plan for nominating, vetting, and inviting membership on the EAC and for including the EAC recommendations in the overall research direction and progress towards milestones of the award. The EAC will be developed in collaboration with NIAID after an award is made.  Note that applicants should not name or contact potential EAC members in their application.

 Project Milestones and Timelines

• Describe specific quantifiable milestones by annum and include annual projections for the overall research study and for tracking progress from individual sites, collaborators, and Teams.  Milestones must specify the outcome(s) for each activity. Milestones should be quantifiable and scientifically justified and include the completion of major research study activities. Milestone criteria should not simply be a restatement of the specific aims.  Using a Gantt chart or equivalent tool, describe the associated timelines and identified outcomes for the research study. 

Note: if the proposed research includes clinical studies, specific Milestone and Timeline information for that study will be entered using the PHS Human Subjects and Clinical Trials Information and should not be duplicated in the Research Strategy section.

Letters of Support: Provide a letter signed by the appropriate institutional official(s) from the applicant institution documenting specifics of institutional commitment for the duration of the award.

• Provide letters of support from clinicians, collaborators, or contractors named as Key Personnel or whose support is necessary for the successful conduct of the scope of research.
• Provide a letter of support, if needed, to demonstrate access and permission to utilize any proprietary diagnostics in the research plan.
• Provide a letter from the applicant organization(s) in support of efficient and effective processes for the negotiation and execution of subcontracts and other legal agreements.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) 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.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

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 submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process.

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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.

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

Specific to this FOA

Do the investigators have established relationships with local TB control programs, and experience in conducting clinical studies of human TB diagnosis? Do the investigators have the knowledge of TB diagnosis and diagnostic algorithms to be able to serve as a resource to the TB research community to provide advice and support for moving TB diagnostics forward in the clinical setting? Do the data management personnel have the appropriate experience in providing database management services, particularly for projects involving multi-national collaborations and foreign sites in resource-limited countries? Do the investigators have experience in designing and developing protocols for clinical studies of human TB, including statistical design and analysis studies of human TB, particularly for TB diagnostics, and for multi-national collaborative studies involving foreign sites in resource-limited countries? Do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed research plan and meet milestones and timelines?

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?

Specific to this FOA

Are the diagnostics proposed for evaluation during the initial phase of the award novel and appropriate for evaluation in a TB endemic country?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

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?

Specific to this FOA

Do the clinical sites proposed provide access to sufficient numbers of appropriate adult and pediatric study populations, including individuals with co-infections and co-morbid conditions, individuals with exposure to other mycobacterial diseases, and individuals who have received childhood vaccination with BCG?

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.

Project Milestones and Timelines

Are the proposed milestones and timelines appropriate for the proposed work and is it feasible to meet these milestones?

Solicitation, Review and Prioritization of Proposals for Future

Diagnostic Studies

Are the plans for the solicitation, review and prioritization adequate and appropriate to ensure that the most relevant diagnostics will be tested during the time of the award?

For research that involves human subjects but does not involve one of the 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 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 Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

Not Applicable

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.

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.

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).

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) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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 the National Institute of Allergy and Infectious Diseases (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 in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications 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 Institute of Allergy and Infectious Diseases Advisory 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.

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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 terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this 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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

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 Part 75, 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:

• Maintaining a website or location where all documentation is archived and accessible to all scientific staff (protocols, approvals, case report forms (CRF s), informed consents (IC s), standard operating procedures (SOP s), meeting or conference call minutes, reports, presentations, etc.);
• Organizing an Annual Programmatic/EAC meetings, Annual Workshops, teleconferences, and other activities to be defined over the course of the award period;
• Organizing, planning and coordinating the activities of the EAC to include:
• Choosing the EAC Chair and up to 4 additional experts, in consultation with NIAID, representing the scientific areas of expertise relevant to the Research Projects;
• Planning, organizing and conducting the Annual Programmatic/EAC meetings and preparing reports of the meeting content, relevant discussions and EAC recommendations;
• In addition to following the NIH Genomic Data Sharing Policy, following the requirements and timelines described in the NIAID Data and Reagents Sharing and Release Guidelines (https://www.niaid.nih.gov/research/data-sharing-and-release-guidelines). Project-generated data and software should be made available through a publicly accessible project website and other publicly accessible resources, including those at the NIAID funded Bioinformatics Resource Centers  (https://www.niaid.nih.gov/research/bioinformatics-resource-centers), at NCBI (http://www.ncbi.nlm.nih.gov/) and/or other repositories to be determined. 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);
• Data analysis tools, models and algorithms generated under this grant, including model parameters and source code, complete use documentation and tutorials;
• Data set definitions and timelines will be negotiated with NIAID as part of the data-sharing plan for the program.

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

• The NIAID Project Scientist will work closely with the PD(s)/PI(s) and other member scientists to facilitate collaborations and to leverage the resources available to the study and establish possible collaborations with other NIH supported prospective longitudinal cohort studies and investigators.
• The NIAID Project Scientist will monitor the progress of the projects, help coordinate research approaches, and contribute to the shaping of research projects or approaches as warranted, including negotiating with the PI on annual updates to project milestones. The NIAID Project Scientist will support and facilitate this process but will not direct it.
• The NIAID Project Scientist will keep the study 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 study to other NIAID resources, as well as assist the research efforts of the study 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 Scientists will serve as a non-voting member of the EAC and will assist in developing the operating guidelines and consistent policies for dealing with situations that require coordinated action.
• The NIAID Project Scientists will provide advice to the PI in the selection of the EAC chair and up to four additional Federal and non-Federal experts to participate in EAC activities in an advisory capacity when appropriate.
• The NIAID Project Scientist will assist with the determination of the site for the Annual Workshop and EAC meetings.

Areas of Joint Responsibility include:

• The NIAID Project Scientist and the PD(s)/PI(s) will coordinate the scientific objectives and progress at the annual meeting to facilitate the achievement of program goals.
• Meeting: The meeting participants will include the PD(s)/PI(s) for each project, key scientific staff for each project, the NIAID Project Scientist, and other NIAID scientific staff, as well as members of the EAC. 

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 Committee 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 Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Karen Lacourciere, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3297
Email: lacourcierek@niaid.nih.gov

Lynn Rust, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240 669 5069
Email: lrust@niaid.nih.gov

Sufiyan Saeed
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3761
Email: Sufiyan.saeed@nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.