Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)

Funding Opportunity Title
Consortium for Design of TB Drug Regimens (UM1 Clinical Trial Not Allowed)
Activity Code

UM1 Research Project with Complex Structure Cooperative Agreement

Announcement Type
New
Related Notices

NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022

Funding Opportunity Announcement (FOA) Number
RFA-AI-22-059
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.855
Funding Opportunity Purpose

The purpose of this FOA is to establish a consortium of tuberculosis (TB) preclinical and clinical experts to systematically refine preclinical models by analyses of relevant pre-clinical and clinical data, and to provide results from optimized models to identify the most efficacious combination regimens for future clinical testing through model-informed research.

Key Dates

Posted Date
September 21, 2022
Open Date (Earliest Submission Date)
January 07, 2023
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
February 07, 2023 Not Applicable Not Applicable July 2023 October 2023 December 2023

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date
February 08, 2023
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in 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 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to establish a Consortium of tuberculosis (TB) preclinical and clinical experts to systematically refine preclinical models by analyses of relevant pre-clinical and clinical data, and to provide results from optimized models to identify the most efficacious combination regimens for future clinical testing through model-informed research.

Background

Globally, TB is a leading cause of death by an infectious disease. The World Health Organization (WHO) estimates that 9.9 million people became ill with TB and 1.5 million died of TB disease in 2020. Annually, approximately 3.3% of new cases and 18% of previously treated cases have had rifampin-resistant TB, but in some countries, resistance in previously treated cases has reached 50%. Around one-quarter of the world’s population has latent TB, and the United States (US) Centers for Disease Control and Prevention (CDC) estimates that as many as 13 million latently infected individuals reside in the US.

To address this longstanding global pandemic, NIAID published a Strategic Plan for TB Research in 2018 that supports the WHO End TB Strategy and outlines a research agenda to accelerate basic, translational, and clinical TB research. The plan supports research to improve treatment for all forms of TB in all populations and age groups, including research to develop less toxic regimens of shorter duration for safe and effective treatment.

In recent years the TB global scientific community has mobilized and focused on applying 21st century science to understanding of the physiology and pathogenesis of Mycobacterium tuberculosis (Mtb) and translating this knowledge into targeted therapy. Recent advances have led to identification of potent individual drug candidates with novel mechanisms of action to add to the armamentarium against both drug-sensitive and -resistant Mtb.

The limited pharmaceutical industry engagement in antimicrobial drug development (and particularly in development of drug combinations) has slowed translation of these discoveries into effective treatment regimens. Advancement of new and more potent regimens with shorter courses by animal model testing requires support from outside of industry. Given the large number of possible combinations, the best candidates must be efficiently identified for advancement to trials. A systematic, analytical approach relying on results from optimized animal models will expedite progress. Communications and coordination of research planning across TB-focused clinical networks is essential for efficiency and effectiveness in development of improved combination regimens.

Specific Objectives of the Consortium

The proposed Consortium would establish a collaborative, multidisciplinary research platform to systematically evaluate new candidate agents in combination. These agents may originate from academic, public-private partnerships, and pharmaceutical industry research efforts and will be evaluated for their potential for incorporation into new TB drug regimens across the human lifespan including young children. By generating adequate and comparable preclinical data on regimen efficacy, pharmacometrics, toxicities, drug-drug interactions, and other factors essential for human clinical trials, the consortium will increase efficiency, accelerate development of new combinations, and identify the most promising regimens for future clinical testing to effect shorter, relapse-free cures of pulmonary TB in adults, children, and persons being treated for HIV.

The TB Drug Regimen Consortium aims to address this by:

  • Providing an open platform for uniting preclinical and clinical TB experts (U.S. and international) in the systematic analysis of available preclinical and clinical efficacy and safety data to identify preclinical research projects, scientific needs/gaps and set an agenda of cooperative goals and research priorities.
  • Optimizing preclinical models with back-translation of clinical data from recent trials into animal and other model development.
  • Facilitating communication, coordination and planning of preclinical research to inform NIH-supported clinical trial networks (both adult and pediatric focused) and other sponsors/investigators by review and discussion of all available information on new agents/combinations, and ongoing and anticipated research. These discussions will guide plans for optimized drug combinations, eliminate duplication, and ensure efficiency by identification and, when appropriate, performance of key preclinical experiments by the Consortium's Preclinical Laboratories.
  • Incorporating pediatric-focused research to stimulate pre-clinical, translational activities that can enable accelerated clinical testing and earlier introduction of new TB drugs and regimens in pediatric populations, with an emphasis on young children (aged 6 years or younger).
  • Performing preclinical evaluations of mechanisms of action of individual and combination drug candidates. Performing preclinical animal model studies (with emphasis on new drug combination efficacy comparisons) identified as needed by the Consortium leadership executive committee after review and approval by NIAID.
  • Providing compiled data and analyses on evaluated combination regimens with priority ranking assessment for consideration by clinical trial networks to guide optimized and coordinated choices of new regimens for phase 2 and 3 trials.
  • Assessing evolving clinical research challenges and opportunities for potential inclusion of special populations, new technologies (including biomarkers), and the broader spectrum of TB disease into the Consortium research agenda.

Expected Characteristics of the Consortium

Scientific and Fiscal Flexibility

The Consortium will use a strategic planning process for its scientific and translational activities and is expected to actively engage major sponsors, researchers, and communities within and outside of the Consortium in establishing and refining the research agenda for treatment of TB diseases. The Consortium Scientific Leadership Group Executive Committee (SLG Ex Com) will work to ensure that the research remains coordinated and complementary to other TB drug research enterprises.

The SLG Ex Com will have the authority to re-prioritize and re-allocate resources/funds according to operating policies and procedures proposed in the application, as long as these changes are within the scope of the original application. Applicants are encouraged to develop creative, synergistic collaborations and to make the most efficient use of existing global resources.

Collaborative Projects (subject to availability of supplemental funds): NIAID or other NIH Institutes/Centers may support additional collaborative projects, which are expected to be initiated in year 2 or during later years of the award and not to exceed the duration of the overall grant award. The purpose of these collaborative projects is to leverage expertise to address challenging scientific studies related to the goals of this FOA as the field evolves.

The TB Consortium Organizational Structure

The overall Consortium structure is intended to facilitate coordinated and efficient TB drug regimen development. The Consortium must include a Scientific Leadership Group (SLG) including a Pediatric Focus Committee led by a SLG Executive Committee, a Preclinical Laboratory Group (PLG), a Data Science and Modelling Group (DSMG), and an Administrative Group (AG). These functional areas will be integrally connected to all aspects of the research agenda for the treatment of TB diseases, focusing primarily on pulmonary TB in both adults and young children.

The Scientific Leadership Group (SLG), led by the PD(s)/PI(s) of the Consortium, is responsible for review and discussion of scientific direction, oversight, and evaluation of consortium activities. The SLG will include the Leaders of all Groups and Laboratories, the Pediatric Focus Committee, representatives of participating TB clinical research networks (both adult and pediatric), pharmacology modelling experts in adult and pediatric research, product development partnerships, the pharmaceutical industry involved with new TB therapeutics, and NIAID staff, as well as other experts identified and recommended by the Consortium PD(s)/PI(s). It will function as a collaborative platform for discussion and prioritization of research concepts deriving input from key project personnel, consulting expert advisors, and the scientific literature. The SLG will prepare target regimen product profiles to guide research endeavors and to identify research gaps and priorities across the human lifespan including younger children. The SLG will develop, coordinate, and periodically update a translational research agenda to inform choices among candidate TB drug regimens for evaluation and make evidence-based recommendations on testing priorities.

The SLG Executive Committee (SLG Ex Com) will include the Consortium PD(s)/PI(s), the Leaders of Preclinical Laboratories and the Data Science and Modelling Group, the Chair of the Pediatric Focus Committee, NIAID clinical trial network representatives, and NIAID scientific representatives. This group will be responsible for final decisions on prioritized research to be performed, ensuring progress, and providing administrative oversight.

The Pediatric Focus Committee (PFC) will work to ensure that pediatric populations benefit from the research undertaken by the Consortium, including suggesting additional research needed to extend the impact of Consortium activities towards pediatric populations (especially related to pediatric pulmonary TB). The Chair of this committee will be identified as key personnel in the application. The PFC will formulate plans to initiate relevant key pediatric translational/pre-clinical activities early during clinical testing of TB drug/combination drug regimens in adults, including those prioritized by SLG or by the WHO-convened Pediatric Antituberculosis Drug Optimization (PADO-TB) priority list. Appropriate research towards this end may include development/optimization of in vivo/ex vivo models and pharmacometrics studies as well as focused research to assess end user preferences to guide product/formulation development.

The Preclinical Laboratory Group (PLG) will consist of Preclinical Laboratories (PLs) and will be responsible for designing and implementing in vitro and in vivo studies of efficacy, mechanisms of action, safety, and pharmacometrics of drugs/combinations approved by the SLG Ex Com. At least two PLs will operate mouse models of TB pulmonary disease with pharmacology/pharmacodynamic capabilities for each drug tested and will have experience in successfully informing clinical trial design. Additional PLs may focus on other small animal models of disease, lesion-centric evaluations and rankings, pharmacology/pharmacodynamics, hollow fiber simulations, pathology, novel quantitative measures of mycobacterial burden/response to therapy, biomarkers, drug effects on mycobacterial metabolism, or other areas supportive of drug regimen evaluation. At least one PL in coordination with the PFC must have capacity to address translational research appropriate for children with TB pulmonary disease.

The Data Science and Modelling Group (DSMG) will summarize and model data for the Consortium to review. The DSMG will be responsible for collecting, organizing, validating, and analyzing existing preclinical and clinical data from completed studies and trials, from across the published literature, and from clinical trial meta data provided by associated networks/sponsors of adult and pediatric studies. The DSMG will define common data elements, conduct integration, harmonization, analysis, and modeling of data generated externally or by the PLG, including translational PK-PD or antiretroviral (ARV) drug-drug interactions modeling approaches, that can enable pediatric dose selection and formulation development. The DSMG will work with the Administrative Group to compile reports for the SLG including assembly of dossiers on candidate drugs' history, chemistry, manufacturing and controls, preclinical efficacy and toxicity data, and clinical trial data across the human lifespan including young children. At least one member of the DSMG should have pediatric pharmacology modeling expertise with TB drugs. The DSMG will maintain a public chemical structure-based database of known drugs and new candidate compounds with links to public chemical databases and PubMed abstracts.

The Administrative Group (AG) provides administrative support for the group, organizes meetings, compiles summaries, facilitates communications, and prepares reports. The AG will coordinate research and data sharing agreements and organize experimental results into formats suitable for regulatory filings. The AG will develop and prepare effective legal agreements between participating parties for maximum disclosure of data to protect intellectual property. The AG will prepare material transfer agreements and other agreements with external entities.

An External Advisory Board (EAB) will be formed by the NIAID after award, to evaluate and comment on scientific progress to the SLG Ex Com of the Consortium.

Applications proposing the following will be considered non-responsive and will not be reviewed:

  • Studies in non-human primates (NHP), unless used solely as an in vivo assay to assess the NHP pharmacometrics of candidate drugs/regimens or in developing models of childhood TB disease.
  • Human subjects research, although use of human specimens in confirmatory or comparative assays is allowed.
  • Applications proposing clinical trials.

Applicants are advised to contact the Scientific/Research Contact with any questions they may have regarding the responsiveness of their application.

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

Section II. Award Information

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 scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

NIAID intends to commit $7.2 million in FY 2024 to fund one award.

Award Budget
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Award Project Period

The total project period may not exceed five years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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)

Local 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)

Federal Government

  • 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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

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.

  • 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.
    • 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.
    • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
  • eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; 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 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.

Eligible Individuals (Program Director/Principal Investigator)

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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women 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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in 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.

Letter of Intent

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:

Yong Gao, PhD
Telephone: 240-669-5048
Email: yong.gao@nih.gov

Page Limitations

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

The Research Strategy must consist of the following subsections with the indicated page limits:

Subsection A: Overview of the TB Drug Consortium; one required; 12 pages

Subsection B: Scientific Leadership Group; one required; 12 pages

Subsection C: Preclinical Laboratory Group; minimum of two laboratories required, no maximum; 12 pages for each laboratory

Subsection D: Data Science and Modeling Group: one required; 12 pages

Subsection E: Administrative Group: one required; 12 pages

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Facilities & Other Resources

  • Data Management Facilities: Describe the unique facilities and features of the data management section to support the processes for the reliable and accurate collection and recording of the data, and the features of the facilities that will enable rapid and secure transfer of data types within the consortium and from collaborating clinical networks. Describe data management, key outcome measures, statistical approaches, overall data management, and plans for information transfer to and interactions with the Data Science and Modelling Group.
  • Laboratory Resources and Facilities: Describe the unique aspects of the facilities supporting Preclinical Laboratories and the existing models for estimating therapeutic efficacy of single drugs and combination regimens.
  • Sample Repository Facilities: Describe the unique and necessary aspects of the facilities needed for the receipt, identification, handling (e.g., aliquot, sample-specific preparation), labeling and storage of the biological and chemical samples/reagents. Describe the storage facilities appropriate for various specimens or reagents, and how the facilities will be monitored and secured based on the nature of the data.

Equipment

Describe any special equipment available to be used for working with Mtb, biohazards or other potentially dangerous substances.

SF424(R&R) Senior/Key Person Profile

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

In line with the interdisciplinary collaborative nature of this initiative, it may be appropriate to have one PD/PI with preclinical and one with clinical expertise.

R&R Budget

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

Applicants must budget for the following:
 

  • In the budget justification provide a detailed apportionment of the PD(s)/PI(s) time to oversee management and research activities associated with the TB Drug Consortium functions.
  • In line with the interdisciplinary collaborative nature of this initiative, it may be appropriate to have one PD/PI with preclinical and one with clinical trial expertise, and for the PFC, a chairperson with pediatric trial expertise.
  • One day initial Kick-Off Meeting within the first 6 months of the award in the Bethesda MD area for the PD(s)/PI(s) and key personnel.
  • Annual Programmatic meetings, to be held annually beginning in Year 2, in the Bethesda MD area (2 days per annual meeting) for the PD(s)/PI(s) and key personnel to update NIAID on progress and future directions. Include travel funds for four to-be-named External Advisory Board members to attend.

    The budget justification should include a breakdown of the apportionment of funds for each of the proposed Groups for the first year. The amount for the laboratory research activities of the Pediatric Focus Committee should not exceed $750k in total costs. The budgets for out-years should represent best estimates for the general research plan. Resource allocations are expected to change over time from what is initially proposed.
R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy: The Research Strategy section must consist of a single attachment consisting of subsections A-E, as designated below.

Subsection A. Overview of the TB Drug Consortium

Provide an overview of the approach to identifying research gaps, opportunities, and prioritizing research that will be incorporated into the agenda, centering on optimal combination therapy, and scientific opportunities relevant to the clinical application of prioritized regimens. Describe the approach to optimizing preclinical models with back-translation of clinical data from recent trials into animal and other model development for improving reliability of predictions of clinical outcomes based on model-informed research. Describe the criteria for selection of drug or drug candidates to be included in potential new regimens for adults and children. Describe the innovative elements of the consortium program and the potential to advance scientific knowledge or clinical practice. Without duplicating information in the biosketches, discuss the suitability of the PD(s)/PI(s) to develop, manage, and direct an integrated and focused consortium, and manage collaborations. Describe how pediatric drug regimen development will be integrated into the Consortium.

Subsection B. Scientific Leadership Group (SLG)

In this subsection, describe the organization of the SLG and discuss how the structure promotes effective leadership of overall SLG activities, including establishing the SLG research agenda, the PFC, and a SLG Ex Com. Include the following:

  • Describe the organization and membership of the SLG and discuss how the organizational structure promotes effective leadership and inclusion of the necessary range of TB preclinical research expertise and representation of major TB adult and pediatric clinical research networks. Describe plans for communications and outreach to drug sponsors/manufacturers for pharmaceutical substance supply.
     
  • Describe approaches to communication within and among Consortium functional areas (SLG Ex Com, SLG, PFC, AG, PLG, and the DSMG).
     
  • Describe decision-making in the proposed organization toward the ability to select, prioritize, and recommend novel TB drug regimens for preclinical testing and recommendations for priority ranking of combinations to be studied in clinical trials across the human lifespan and in those on treatment for HIV. The use of organizational charts, diagrams, or other tools to represent the consortium are encouraged.
  • Identify one or more combination regimens that are likely candidates for the Consortium during the first funding period and describe the available data, studies, and experiments that each Group will undertake in contributing to its evaluation.
  • Discuss process, procedure, and plans, including frequency, of the SLG to convene scientific and programmatic meetings to communicate scientific progress, and to identify new research opportunities and potential avenues of collaboration, both within the Consortium and with other stakeholders.
     
  • Describe how the SLG will coordinate and collaborate effectively beyond the Consortium with other Federal, private sector, and international TB research organizations/programs. Describe proposed plans to identify opportunities for such collaborations and to establish joint sponsorship arrangements to capitalize on non-Consortium clinical research data and resources in specific scientific areas. Describe how the SLG will communicate with the scientific community, patient advocacy groups, and the public.
     
  • Discuss the potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the aims. Summarize the special features in the collaborative arrangements that make this application strong or unique. Provide a tentative sequence or timetable for the overall program.
     
  • Describe how the Pediatric Focus Committee (PFC), within the SLG, will be incorporated to ensure that pediatric populations benefit from the research undertaken by the Consortium. Describe the overall approach to pediatric TB drug development within the Consortium and outline plans to align pediatric development to adult TB drug development in order to accelerate translation to pediatric clinical testing.


Subsection C: Preclinical Laboratory (PL) Group

  • Describe each PL in a separate 12-page section that address their research approaches and contributions to the field. Describe the model systems available, the outcome measures, and processes for communication and coordination with the SLG. Describe how new/innovative assays will be assessed and implemented for use, including how decisions will be made on their use.
  • For animal model PLs, describe the Laboratory leader(s) experience in evaluating single drugs and combinations, and in predicting clinical trial outcomes. Animal model laboratory assessments must include: minimal inhibitory concentrations, Mtb growth curve assays, confirmation of chemical identity with mass spectrometry, ability to confirm candidate drugs' mechanisms of action, performing bactericidal and relapse studies of regimens, determination of Mtb colony forming units per gram of lung tissue, concentration of candidate drug concentrations in tissue, and ability to adapt experimental processes to include newer biomarkers of Mtb infection.
  • Describe plans for obtaining and analyzing standardized data on drug candidates under evaluation regarding in vitro potency, bactericidal potential, mechanisms of action, pharmacometrics in animals, achievable concentrations in tissues, and other important aspects of drug candidacy leading to dose selection and schedule.
     
  • Each PL whether focused on in vitro or in vivo studies should provide its protocols for evaluating the SLG's example combination regimens that are likely candidates for the consortium during the first year of funding. Describe approaches to quantifying the contribution of each drug component to a successful regimen.
  • Describe specific plans to effect improvements in model systems, especially back-translation to infected animal model research, to define optimized regimens for human testing. Describe assessments of experimental quality and comparability with human clinical experience. Provide a plan for obtaining additional expertise, engaging new laboratory programs, and integrating state-of-the-art procedures into the PLG as the science progresses.
     
  • Describe the pediatric pre-clinical evaluation strategy of at least one PL including models planned to be used and discuss plans to overcome their limitation regarding pediatric populations, optimize their ability to recapitulate TB/granuloma pathogenesis in children and inform on lesion and compartment specific TB drug uptake. Outline specific tools and approaches to be used including imaging approaches if appropriate. Describe a strategy to use pharmacokinetic-pharmacodynamic (PK-PD) modeling or other approaches to integrate data across different model systems to better predict behavior of new TB drugs and regimens in children.
     
  • If new animal models for pediatric studies are proposed, describe specific plans for their use as coordinated by the PFC. Describe how model features (age, maturity) and disease lesions recapitulate disease course and drug behavior expected in target pediatric populations, particularly young children. Describe study design features and anticipated outcomes and approaches to optimizing pharmacometrics of combination regimens and determining dose selection, frequency, and duration.
     

Subsection D: Data Science and Modeling Group (DSMG)
 

  • Describe the research experience of the DSMG's proposed group leader. Describe the planned approaches to select and design new TB drug regimens using appropriate translational pharmacology and modeling methods to integrate preclinical and early clinical data including back-translation of clinical findings into predictive preclinical approaches. Provide plans for interacting with investigators for development, review and implementation of proposed preclinical studies and possible clinical simulations.
     
  • Describe the communication processes within the DSMG and among the DSMG and other consortium functional areas, and NIAID and TB clinical trial networks. Discuss the development of data standards, data exchange formats, data quality assurance methods, and data security and privacy management tools. Provide the process envisioned for obtaining de-identified patient data from completed or ongoing treatment clinical trials; describe the data elements required.
     
  • Describe the specific considerations, analyses, and approaches to be used in the example combination regimens identified in the SLG section as possible first projects.
     
  • Describe the strategy to use PK-PD modeling or other mathematical and computational approaches to integrate data across different model systems or platforms to better predict behavior of new TB drugs and regimens in adults and children. Describe in detail plans to model drug-drug interaction with antiretroviral drugs (ARVs), outlining approaches to select ARVs for testing.
  • Describe how the DSMG will develop and incorporate new technologies for data analyses, data visualization, and developing and optimizing translational modeling tools. Outline the system procedures and workflows for the collection, storage, access, backup, archiving, and exchange of data from animal model and laboratory studies.
     
  • Describe system security and plans for long-term maintenance and survival of data and the data systems.

Subsection E: Administrative Group (AG)

  • Describe the AG Leader's experience in similar TB research efforts and in technology transfer.
  • Describe the organizational structure, proposed staffing plans, and lines of authority for the AG. Discuss the processes and procedures to establish effective project management of AG activities.
  • Describe the fiscal management plan for the consortium to administer and track the Consortium budget and associated expenditures and reports.
  • Demonstrate how the AG will support and report to the SLG Ex Com including the PFC, assist in implementing the Research Agenda for the consortium and provide fiscal oversight of the Consortium research.
  • Describe the facilities and processes for receiving, handling, storing, inventorying, shipping, monitoring, preserving, and validating chemical identity of candidate drugs and drug products obtained for evaluations by the consortium. Describe the storage facilities appropriate for various specimens or reagents, and how the facilities will be monitored and secured.
  • Describe plans to coordinate with the DSMG on an inventory of proposed investigational products and approved drugs including chemical properties, availability and quantity required to complete PLG studies; ability to meet FDA and International Conference on Harmonization (ICH) regulatory document requirements related to the products including the proposed chemical entity’s Investigational New Drug (IND) Sponsor requirements; ability to identify characteristics and chemical identify of products sourced from various entities. Describe the approach to record-keeping, storage and retrieval of documents and associated data.
  • Discuss the procedures and processes required to address dissemination of results to the research community through the SLB Ex Com.

Letters of Support:

The Letters of Support attachment should begin with a table of letter authors, their institutions, and the type of each letter (institutional commitment, supply of study drugs, or resources; collaboration or role in the project; potential or current user of a resource or service proposed in the application).
 

Provide all appropriate letters of support, including any letter necessary to demonstrate the support of consortium participants, laboratories, and other collaborators. If parts of the research costs are to be borne by sources other than NIH, these contributions must be presented in detail as part of supporting letters signed by an Authorized Organization Representative. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget.

To document their commitment, include letters of support from the following:

Clinical trial networks; product development partnerships; laboratories; and sources for the availability of study reagents, candidate compounds and pharmaceutical products
 

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.

Applications must address an Intellectual Property plan. Since this research will include several institutions, including the private sector, complex IP situations may arise. To avoid delays in implementing new combination therapies, the Consortium is required to provide a plan as part of the application, detailing (1) the approach to be used for obtaining patent coverage and for licensing, where appropriate; (2) a statement demonstrating acceptance of the approach, signed by all parties; (3) a description of procedures to be followed for the resolution of legal problems that potentially may develop; and (4) a list of existing patents/licenses related to the proposed research.

The agreement among the institutions comprising the Consortium, signed and dated by the organizational officials authorized to enter into such arrangements for each Group member and member institution, must be submitted with the application.If the Group wishes to place all inventions and discoveries resulting from these studies within the public domain, a letter to that effect must be submitted in lieu of the agreement. The letter must be co-signed by the PD/PI(s), each of the Group Leaders, and each of the business officials representing the respective institutions.

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • If applicable, all investigators funded under this FOA will be expected to share their data publicly through NIAID supported Bioinformatics Center(s) or the STOP TB Partnership or other public portals approved by NIAID. Therefore, if needed, the Data Sharing plan should include a summary of how the applicant will manage data submission and interactions.
  • It is NIH policy that the results and accomplishments of the activities that it funds should be made available to the public. PD/PIs and recipient organizations are expected to make the results and accomplishments of their activities available to the research community and the public at large. Investigators conducting biomedical research frequently develop unique research resources. NIH considers the sharing of such unique research resources (also called research tools) an important means to enhance the value of NIH-sponsored research. Restricting the availability of unique resources can impede the advancement of further research. At the same time, NIH recognizes the rights of recipients to elect and retain title to subject inventions developed with federal funding pursuant to the Bayh-Dole Act. See the Office of Extramural Research, Division of Extramural Inventions & Technology Resources (DEITR), Intellectual Property Policy page: http://grants.nih.gov/grants/intell-property.htm.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined 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.

PHS Assignment Request Form

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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 fieldof the Senior/Key Person Profile form. 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 unique entity identifier provided on the application is the same identifier 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 NIAID, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

 

Post Submission Materials

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.

Section V. Application Review Information

1. Criteria

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.

Overall Impact

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). While each application will be evaluated in its entirety based on one overall impact score per application, each proposed preclinical research laboratory within the Preclinical Laboratory Group and the Data Science and Modelling Group within each application will also receive separate impact scores.

Scored Review Criteria

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? 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?

Specific to this FOA: To what extent will this program, as proposed, advance tuberculosis treatment research including that in pediatric populations? What is the likelihood that the results of the proposed studies will contribute to new approaches and knowledge that will inform future studies in clinical trials?

Investigator(s)

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: Is the proposed commitment and level of effort of the PD/PI sufficient to ensure the success of the projects? Are the expertise and level of effort of those with clinical trial experience and translational preclinical experience appropriate to the work proposed?

Are the proposed Preclinical Laboratory researchers (PLs) experienced in evaluating single drugs and combinations, and in predicting clinical trial outcomes? Are the approaches proposed by the laboratory investigators based on experience in translational and drug development research?

Are the proposed pediatric TB research experts experienced in TB treatment research for young children?

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?

Specific to this FOA: Are the proposed improvements to preclinical models likely to result in more reliable predictions of clinical success?

Approach

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?

Specific to this FOA: Are the proposed studies relating to the example combination regimens proposed by the SLG appropriately evaluated by the laboratories and by the DSMG? Will the critical resources, reagents or therapeutics needed be available for the study within the proposed time-frame? Are the proposed approaches of each Group (including those specific to pediatric populations) appropriate?

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?

Additional Review Criteria

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 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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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.

Vertebrate Animals

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.

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

Additional Review Considerations

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

Not Applicable.

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)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

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.

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.

2. Review and Selection Process

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, 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 will receive a written critique.

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.

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 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.

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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 recipient's business official.

Recipients 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.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

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, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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.

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.

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 and 2 CFR Part 200.206 “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 2 CFR Part 200, 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 recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

  • Determining and coordinating the scientific and administrative activities of the approved projects; setting project goals and timelines; accepting and implementing common guidelines approved by the Scientific Leadership Group Executive Committee (SLG Ex Com).
  • Serving as a voting member on the SLG Ex Com; participating in SLG Ex Com activities, and accepting and implementing the policies and procedures developed by majority vote of the SLG ExCom.
  • Working closely with NIAID Program Official and Project Scientist(s) in the scientific, technical, and administrative management of this program; ensuring that all members adhere to the rules and guidelines established by the SLG Ex Com.
  • Timely submission of manuscripts for publication that are (co)authored by members of the award and supported in part or in total by the Consortium and for adherence to all aspects of the collaborative group’s Publications Policy, to be determined by the SLG Ex Com and NIAID.
  • Making new information and materials, including research samples, tools, methods, reagents, and data developed under these awards known and available to the broader research community and members of this program through publications, presentations, web announcements, submission to public resources or databases, and reports to NIAID and/or the SLG Ex Com.

Note: Recipients 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 DHHS, PHS, and NIH policies.

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

A program staff from the NIAID Division of Microbiology and Infectious Diseases (DMID) will serve as the NIAID Program Official for programmatic stewardship of the award. The role of the Program Official will be to facilitate and not to direct Consortium activities. The Program Official will:
 

  • Serve as a member(s) of the SLG Ex Com and ensure coordination of SLG activities and implementation of its recommendations, decisions, and policies.
  • Assist the SLG in scheduling meetings of the SLG and subcommittees and actively participate in agenda development as well as the organization and planning of a consortium-hosted workshop/meeting.
  • Support project activities through technical assistance, advice, and coordination.
  • Advise in the selection of sources or resources (e.g., determining where a particular reagent may be found) and identification of potential collaborations to further the goals of the Consortium.
  • Coordinate NIH staff assistance and serve as a resource for scientific information related to the goals of the recipient's research.

In addition, an NIAID Project Scientist will be assigned to participate in the scientific direction of the Consortium and will be a voting member of the SLG Ex Com. The NIAID program staff will select an External Advisory Board (EAB) after award with input from the PD/PI(s) to evaluate and comment to the SLG Ex Com on scientific progress within the Consortium. Additional NIAID staff may join the SLG as advisors.

Areas of Joint Responsibility include:
 

  • The NIAID Project Scientist and the PD(s)/PI(s) will coordinate the scientific objectives and progress to facilitate the achievement of program goals. This may include pre-approved redirection of research aims within the scope of the original award, as needed, to ensure consistent progress.
  • The NIAID Program Official and the PD(s)/PI(s) will collaborate to revise project milestones prior to initial or annual awards, based on peer review of the originally proposed milestones and/or the PD(s)/PI(s) and/or the NIAID Project Scientist assessment of the proposed yearly milestones.

Dispute Resolution:
 

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between 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 Steering 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 recipient. This special dispute resolution procedure does not alter the recipient'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.

3. Reporting

When multiple years are involved, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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.

Section VII. Agency Contacts

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

Application Submission Contacts

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

Scientific/Research Contact(s)

Barbara Laughon, PhD
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3302
Email: blaughon@mail.nih.gov

Tania Lombo, PhD (for pediatric component)
Division of AIDS
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7612
Email: tania.lombo@nih.gov

Peer Review Contact(s)

Yong Gao, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5048
Email: yong.gao@nih.gov

Financial/Grants Management Contact(s)

Liz Sihombing
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5530
Email: elizabeth.sihombing@nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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.

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