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

Leadership Group for a Clinical Research Network on Antibacterial Resistance (UM1 Clinical Trial Required)

Activity Code

UM1 Research Project with Complex Structure Cooperative Agreement

Announcement Type

Reissue of RFA-AI-12-019

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-AI-18-036

Companion Funding Opportunity

None

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.855

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications to support a Leadership Group (LG) for a Clinical Research Network on Antibacterial Resistance (AR), which was initiated to develop, implement, and manage a clinical research program to address key clinical research questions in AR. The LG is a cohesive program dependent on the highly integrated and complementary activities of the four centers that comprise the network: Scientific Leadership Center (SLC), Clinical Operations Center (COC), Laboratory Center (LC) and Statistics and Data Management Center (SDMC).

Key Dates
Posted Date

July 9, 2018

Open Date (Earliest Submission Date)

December 3, 2018

Letter of Intent Due Date(s)

December 3, 2018

Application Due Date(s)

January 3, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

May 2019

Advisory Council Review

October 2019

Earliest Start Date

December 2019

Expiration Date

January 4, 2019

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.


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 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

    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

    Background and Purpose

    Antibacterial resistance (AR) is a growing, multifactorial, global public health threat that has recently garnered increased national attention as the subject of the United States (US) Government’s Combatting Antibiotic Resistant Bacteria (CARB) National Strategy, Action Plan, Task Force, and Presidential Advisory Council. Internationally, AR has recently been the focus of key meetings of the United Nations General Assembly, of the G7 and the G20, and has also received extensive attention from the World Health Organization (WHO). These national and international efforts have consistently recognized the need for sustained support for AR research and product development in general, and clinical research specifically. An integrated clinical research program that both explores ways to reduce the overall risk of antimicrobial resistance and tests new approaches to diagnose, prevent, and treat AR infections is a critical component of the response to the AR problem.

    The Leadership Group for the Clinical Research Network on Antibacterial Resistance (LG) was initiated by the National Institute of Allergy and Infectious Diseases (NIAID) in 2013 in response to the growing public health threat of AR. Their charge was to design, prioritize, implement and manage an integrated, clinical research program targeting the most important clinical questions in AR. The objective of the current FOA is to continue support for a Clinical Research Network composed of an LG and affiliated clinical sites that will develop, implement, and manage a research agenda that can adjust and react to the evolving clinical priorities in AR. The LG is complementary to NIAID’s other preclinical and clinical AR activities, as well as AR programs at other government agencies.

    Since its inception in 2013, the Antibacterial Resistance Leadership Group (ARLG)’s clinical research agenda has focused on studies to address gram-negative and where appropriate gram-positive infections, as well as studies to support the development and use of diagnostic tests and to inform antibiotic stewardship efforts. They have solicited studies from their network of expert clinician scientists, as well as from the external research community, industry, and NIAID. Key achievements include: expansion of an observational study of patients infected with gram-negative pathogens to collect data on patient characteristics, treatments, and outcomes, as well as the genotypes and phenotypes of their infecting organisms; clinical validation of a host gene expression-based diagnostic test that rapidly determines whether a patient’s respiratory symptoms are viral, bacterial or non-infectious in nature; a strategy trial to evaluate whether a short course of antibiotics is superior to the standard course in children with community-acquired pneumonia; a collaboration with multiple diagnostics companies to implement a master diagnostic protocol to allow for the evaluation of multiple diagnostic tests simultaneously using specimens from the same patients; mentoring the next generation of clinician-scientists focused on addressing AR; and statistical innovations, including novel tools for assessing strategy trials and diagnostic evaluation studies.

    While progress has been made to further our understanding of and ability to manage AR infections, the AR problem continues to grow, and numerous significant clinical research gaps remain. These include the development of better therapeutic and prophylactic approaches for resistant infections, including non-antibiotic approaches like vaccines, monoclonal antibodies, microbial ecology approaches, and bacteriophage; strategy trials to study optimal treatment of bacterial infections using existing drugs; and the development and deployment of novel, rapid diagnostic strategies. This FOA places a priority on studies that address these gaps and that cannot be done by other NIH programs, government funders, or private industry.

    Research Objectives and Scientific Scope:

    The LG is designed to conduct clinical research studies and clinical trials that will impact the prevention, diagnosis and treatment of AR infections. The LG research agenda is expected to give the highest priority to the top AR threats identified by US and international expert bodies, such as the CDC and the WHO. Efforts should be generalizable to the US experience and could include, but are not limited to:

    • Early clinical evaluation of new antibacterial therapeutic and prophylactic products, including small molecule antibiotics, monoclonal antibodies, applications of microbial ecology approaches, bacteriophage-based products, and vaccines.
    • Comparative effectiveness trials.
    • Strategy trials to optimize currently licensed antibacterials (e.g. dose, duration, clinical algorithms, need for drug, combinations) to reduce the risk of resistance.
    • Validation studies of new diagnostic tests using clinical isolates or specimens, including to support regulatory submissions.
    • Clinical utility studies of diagnostic tests to determine the impact of approved tests on patient- and facilities-level outcomes and prescribing behavior.
    • Molecular epidemiological studies to provide data on the associations between patient characteristics, clinical outcomes, and resistant genotypes/phenotypes, and to inform future interventional trials.
    • Pharmacokinetic (PK) and pharmacodynamic (PD) studies.
    • Strategies to better manage the consequences of broad spectrum antimicrobial use, e.g. Clostridium difficile infections.
    • Collaborations with industry and academic groups as needed, both domestically and internationally, to guide optimal clinical trial designs, answer key questions that cannot be addressed alone, and strengthen a community of AR researchers that can contribute to the US government’s response to emerging resistant threats.

    The following types of studies are beyond the scope of the FOA:

    • Studies of infection control programs and broad antimicrobial stewardship interventions, which are supported by other government agencies. However, innovative statistical analyses of ongoing stewardship efforts are permitted.
    • Studies focused on parasites, viruses, and mycobacteria, which are supported by other NIAID programs.

    Leadership Group Structure

    The LG is collectively comprised of a Scientific Leadership Center (SLC), Clinical Operations Center (COC), Laboratory Center (LC) and Statistics and Data Management Center (SDMC). The activities and synergies of these centers will support the large-scale, complex LG and carry out the essential functions necessary for achieving the network’s clinical research agenda.

    Scientific Leadership Center (SLC) 

    The SLC will be responsible for overall administrative and scientific leadership for the network, as well as oversight and evaluation of all network activities, including developing and refining the research agenda, prioritizing research concepts, and ensuring timely publication and communication of results.

    The SLC is also responsible for the following:

    Governance. Integral to the success of the LG is establishing clear governance structures, including effective communication and decision-making plans, lines of authority, plans for coordinating and collaborating effectively with external collaborators and NIAID, and resource distribution policies. The SLC may establish committees to achieve the work of the LG.

    Research Agenda/Scientific Priorities.  The LG research agenda articulates the network’s scientific priorities and establishes a framework for the initial project portfolio and future studies and trials envisioned. The SLC is expected to actively engage researchers and AR communities within and outside of the network in establishing and refining the research agenda.

    Innovation. The LG is encouraged to explore innovative types of countermeasures, study/trial designs, approaches to public-private partnerships, and statistical techniques that will have a broad impact on the overall field of AR clinical research.

    Mentoring. The LG should make every effort to provide clinical research training opportunities for early stage clinical investigators. This may take the form of small clinical research projects, classroom training in clinical research and statistical analysis, participation in network committees, participation as junior investigators on studies and trials, and exposure to other aspects of clinical research in AR.

    Collaborative Responsibilities.  The LG is encouraged to collaborate with other NIH-supported networks and other Federal and private sector clinical research programs. Such collaborations and interactions are essential for the development and implementation of a comprehensive research agenda that utilizes the strengths, experience and expertise of the various collaborating organizations.  Sharing of expertise, resources and procedures is expected in key areas, including:  harmonization of laboratory resources and specimen management and harmonization of common data elements and data entry interfaces.

    Clinical Operations Center (COC)

    The COC provides operational support, management, and oversight for the network’s clinical studies and trials. This requires close coordination with the SLC, LC, SDMC, network-affiliated clinical research sites, and NIAID’s Project Scientist and clinical research support programs. The COC provides leadership on protocol development and implementation and is responsible for protocol-specific site selection, qualification, and management. The COC is responsible for effective management and oversight of protocol teams and all LG center activities and must establish efficient systems for resource distribution and re-allocation in response to evolving priorities identified by the SLC. Finally, the COC is expected to provide specialized training for clinical trials, applicable laboratory procedures and data management for network and site staff in support of LG activities.

    The COC is also responsible for the following:

    Management. The COC is expected to employ strong project management practices for management, oversight and coordination of long-term and day-to-day activities associated with LG studies and trials, including: development of project plans that establish realistic milestones and timelines; ongoing evaluation and adjustments; and implementation of contingency plans. The COC should work synergistically and seamlessly with NIAID and the clinical research sites in driving protocols through to completion. Other responsibilities of the COC include development of policies, by-laws, standard operating procedures (SOPs), budgets, and communication plans.

    Clinical Research Sites. Due to the diverse nature of LG studies and required patient populations, it is expected that performance sites for implementation of the research agenda may be located at the applicants’ institutions, subcontracted to protocol-specific clinical research sites, or provided by other NIAID clinical sites. A major activity of the COC is establishing efficient processes for identifying, qualifying, and approving protocol-specific sites to address specific clinical research network needs.

    Laboratory Center (LC)

    The LC contributes to the development of the network’s research agenda, and leads the development, implementation and evaluation of the laboratory research that is essential to the successful execution of that research agenda.  The LC manages and oversees relevant laboratory services, including any necessary PK services, bioanalysis, and network specimen characterization; laboratory quality management programs; the monitoring and evaluation of all specialized laboratories in the network; sharing of specimens outside the network, as necessary; and provides adequate storage facilities necessary to accomplish the network’s clinical research agenda.  LC leadership fosters collaboration and harmonization of laboratory activities within the network, including clinical research site-affiliated laboratories.

    Statistics and Data Management Center (SDMC)

    The SDMC provides leadership and services for biostatistics, study design, analysis, interpretation and publication of results, including innovative statistical methods in the field of AR, along with state-of-the-art clinical and laboratory data management systems to ensure complete, high-quality data. The SDMC must ensure the integrity of study design and statistical analysis for all LG studies and trials, as well as training and education for protocol-specific site and laboratory staff on data management and specimen shipping/tracking systems. The SDMC will also provide comprehensive data management and data analyses for LG studies and trials not conducted under an Investigational New Drug or Device Exemption (IND/IDE). The SDMC has a central role in standardizing and harmonizing statistics and data management activities within the network and coordinating with other NIAID-sponsored programs, as necessary. 

    External Advisory Board (EAB)

    An External Advisory Board (EAB) will be established by NIAID in collaboration with the awardees to review the progress in meeting the goals of the LG and NIAID and will make recommendations for the continuation or re-direction of all projects and activities of the LG on an ongoing basis. In addition, the EAB may make recommendations about areas needing intensified attention by the LG’s research agenda. The EAB is expected to consist of investigators who are not current collaborators of the funded programs.

    Additional resources provided by NIAID:

    • Safety Oversight Committees. NIAID oversees the safety of all participants in clinical trials funded by NIAID. NIAID monitors Phase II, Phase III and Phase IV multicenter, randomized clinical trials primarily through Data and Safety Monitoring Boards (DSMBs).  NIAID monitors Phase I and small Phase II clinical trials primarily through Safety Monitoring Committees (SMCs) in conjunction with Independent Safety Monitors (ISMs). (https://www.niaid.nih.gov/research/safety-oversight-clinical-research).
    • Other Support Services. NIAID will provide additional support services for LG trials that must be conducted under an Investigational New Drug (IND) or Investigational Device Exemption (IDE). These services may include domestic regulatory sponsorship, data management and statistical support, management of clinical agents and specimens, and clinical site monitoring. Each study will be evaluated for the need for an IND/IDE by NIAID and support services to be provided will be determined on an individual study basis. For clinical trials that do not require an IND/IDE, the LG should be prepared to provide all support services other than safety oversight. For clinical studies that do not meet the NIH definition of a clinical trial, the LG will need to provide all resources and expertise necessary for the conduct of the study.

    Note: For further information on the Leadership Group for a Clinical Research Network on Antibacterial Resistance please visit the following website for general information and questions and answers.

    https://www.niaid.nih.gov/grants-contracts/questions-answers-rfa-ai-18-036

    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
    Renewal

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

    Required: Only accepting applications that propose clinical trial(s)

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NIAID intends to commit $15 million in FY 2020 to fund 1-2 awards.

    Award Budget

    Budgets for directs costs of up to $10,000,000 per year may be requested.

    Award Project Period

    The scope of the proposed project should determine the project period. The maximum project period is 7 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)

    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
    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.

    • 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) (formerly CCR) – 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. 
    • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

    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 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.

    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.  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).
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    Buttons to access the online ASSIST system or to download application forms 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 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.

    For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

    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:

    Brenda Lange-Gustafson, PhD
    Telephone: 240 669-5047
    Fax: 301 480-2408
    Email: bgustafson@niaid.nih.gov

    Page Limitations

    All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

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

    Subsection A. Overview of the proposed Leadership Group for a Clinical Research Network on Antibacterial Resistance; one required 6 pages

    Subsection B: Scientific Leadership Center; one required 30 pages

    Subsection C: Clinical Operations Center; one required 30 pages

    Subsection D: Laboratory Center; one required 12 pages

    Subsection E: Statistics and Data Management Center; 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.  

    SF424(R&R) Senior/Key Person Profile

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

    R&R Budget

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

    In the budget justification, provide a budget breakout for all activities under one of two major headings: 1. Core Funds, which covers all costs NOT related to clinical trials, and 2. Protocol Funds to cover all costs associated with conduct of clinical trials. Budgetary requests should align with activities in the research agenda and are expected to vary in the proportion of funds going to activities in any given year. For example, Protocol Funds may start at 10% direct costs in year one and fluctuate between 25% and 75% direct cost per year based on trial implementation.

    Requested budgets must include funds for travel by the PD(s)/PI(s), key personnel, and up to five External Advisory Board Members to a kickoff meeting and annual meetings in the Bethesda, MD area.

    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:

    Specific Aims: Describe the specific scientific aims of the network.

    Research Strategy: The Research Strategy section should consist of subsections A-E, as designated below.

    Subsection A. Overview

    Provide a high-level overview of the key clinical research questions in AR and explain how the LG’s research agenda will address them. The Overview should contain a coherent, coordinated and synergistic vision of AR clinical research and include the overall goals of the LG and a discussion of the multi-disciplinary approaches to be taken. Without repeating information in biosketches, explain how the composition of the SLC, COC, LC and SDMC team leaders will be integrated and leveraged to meet the goals of the LG.

    Subsection B. Scientific Leadership Center

    In this subsection, the applicant should describe the organization of the LG and discuss how the structure promotes effective leadership of overall LG activities, including establishing the LG research agenda. Include the following:

    • LG Structure and Governance
    • Describe the overall LG structure. Tables, diagrams, flow charts and organizational charts are strongly recommended.
    • Describe the approach to governance of the LG, including establishment of decision making committees and their composition, roles, responsibilities and decision-making authorities. Do not name or contact potential committee members that are not already key personnel in the application.
    • Discuss how the proposed governance structure capitalizes on the individual strengths of the key personnel to achieve the scientific goals of the LG.
    • Discuss plans, including frequency, of the LG to meet to share scientific and programmatic information, to assess scientific progress, and to identify new research opportunities and potential avenues of collaboration. 
    • Describe plans to establish effective project management for high-level scientific and administrative decisions for the LG, including research prioritization, reassessment, and redirection. Include a discussion of the involvement of key stakeholders.
    • Describe plans for LG communications, including communications among and between the SLC, COC, LC, and SDMC, and specifically address how NIAID Program Staff will be integrated into LG activities. Describe plans for how abstracts and manuscripts describing LG studies will be prepared and reviewed within the LG.
    • Describe in detail the plans for management and administration of the business and scientific activities and how the composition of staff (e.g. PD(s)/PI(s), project manager, COC, LC, SDMC leaders, administrative staff etc.) and their responsibilities will coordinate for efficient project management to achieve the scientific goals, timelines, and milestones; redirect efforts; and link to cost-effective management of LG resources. Plans should address innovative scientific or administrative approaches and how they will benefit the LG.
    • Describe the network’s policy for mitigating scientific conflict of interest.
    • Describe any established collaborations and provide proposed LG collaboration plans, including plans for collaborating with pharmaceutical and medical device companies and other government-funded programs that will advance the LG research agenda. Do not name or contact potential collaborators that are not already key personnel in the application.
    • Research Agenda and initial project portfolio
    • In detail, clearly describe the comprehensive AR clinical research agenda for the LG. Address how current efforts by others in the field were considered in developing the research agenda, how the research agenda will address key knowledge gaps and future opportunities in the field of AR clinical research, and any innovative aspects of the agenda. In addition, include descriptions of high-priority concept areas to be included as part of the initial project portfolio. For human subjects and clinical trials information associated with a specific study (ies) of the initial project portfolio, including delayed onset, applicants are required to address within the Study Record.
    • Provide milestones and timelines for completing key goals of the research agenda. For clinical trials, applicants will provide specific clinical trials timelines under the PHS Human Subjects and Clinical Trials Information and these should not be duplicated under the Research Strategy.   
    • Describe how the proposed LG structure will facilitate achievement of the goals of the research agenda and how to ensure flexibility in responding to new AR-related scientific opportunities.
    • Provide preliminary data/information supporting the feasibility of the research agenda.
    • Continuous refinement of research agenda and project portfolio
    • Describe how additional research concepts representing the most promising ideas addressing the research agenda will be solicited from investigators within and outside the LG and evaluated.
    • Describe how ancillary studies will be considered, approved, and integrated into approved research concepts.
    • Describe the process and frequency for assessing the research agenda, including plans to obtain external assessments of research plans and priorities.  Discuss the processes for instituting major adjustments to the agenda in response to assessments. Describe how the utility of and continued need for decision-making committees will be evaluated and, if necessary, modified to best meet the needs of the LG.
    • Describe the process and frequency for assessing the scientific merit and feasibility of approved research concepts throughout the life of the project.
    • Provide plans for initiating and fostering relationships with representatives from relevant pharmaceutical and medical device companies to ensure access to the most promising countermeasures to be studied.
    • Training and Mentoring
    • Describe how the training needs of LG scientific staff will be determined and provided, how the value and effectiveness of training conducted will be reviewed and evaluated periodically, and how necessary changes in training programs/approaches will be decided and implemented.
    • Provide plans to incorporate clinical research training opportunities for early stage clinical investigators into the LG. This may take the form of small clinical research projects, classroom training in clinical research and statistical analysis, participation in LG committees, participation as junior investigators on studies and trials, and exposure to other aspects of clinical research in AR.
    • LG Evaluation and Improvement
    • Describe how the overall performance of the LG will be evaluated and improved over the course of the award period. 
    • Describe proposed policies, methods, and approaches for evaluating the operational performance of the overall LG and each LG center (SLC, COC, LC and SDMC) in the conduct of LG activities, including the financial management of network resources. Include a discussion of metrics that may be used to determine both productivity and quality of the results generated by the LG (including individual centers) over the duration of the award. Include information on how findings will impact adjustments to LG activities and follow up evaluations.
    • Describe proposed processes for the resolution of performance problems for LG centers and proposed processes for the development of remediation/improvement plans to avoid future shortcomings.

    Subsection C: Clinical Operations Center (COC)

    In this subsection, the applicant should describe the structure and function of the COC in implementing the clinical studies and clinical trials of LG’s research agenda. Include the following:

    • COC Structure and Management Plan:
    • Describe the organizational structure of the COC. Include provisions for the fiscal management of LG resources. Tables, diagrams, flow charts and organizational charts are strongly recommended.
    • Describe the lines of authority and decision-making processes by which the day-to-day operations of the COC will be managed.
    • Describe the processes and procedures to establish effective project management of COC activities. Discuss the composition of staff (e.g. clinical research site investigators, protocol investigators, project managers, scientific, administrative, business support staff etc.) and how their responsibilities will coordinate for efficient practices to meet clinical study and trial timelines and milestones; develop contingency plans and redirect efforts, as needed; link to cost-effective use of LG resources and as applicable solicit, evaluate, award, and manage subcontracts. Refer to section 3.5 of the PHS Human Subjects and Clinical Trials Information form for details of staff composition.  For clinical trials, applicants will provide specific clinical trials timelines under the PHS Human Subjects and Clinical Trials Information and these should not be duplicated under the Research Strategy.   
    • Describe any innovative approaches taken in the organization, oversight and/or management of a complex clinical research effort. Discuss approaches to identify obstacles or delays in study start up and to assess subcontractor performance. Include examples of specific metrics and, as applicable, examples for achieving study and trial goals (e.g. site selection, initiation). Highlight structures that demonstrate how the proposed approach will facilitate efficient decision-making and the ability to effectively drive protocols through to completion, on time and on budget (e.g. approaches to budget management and subcontracting) as appropriate and consistent with achieving the goals of the program.
    • Discuss how decisions will be made for setting and adhering to timelines and plans for remediation and follow up for failure to meet established timelines.
    • Describe the systems for tracking COC activities, including subcontracting activities and monitoring study progress, timelines and budgets. Discuss how plans will support timely expenditure of funds, time savings/cost savings.
    • Provide plans for communicating and coordinating with the clinical research sites and affiliated laboratories, as well as NIAID clinical research support programs. Discuss how plans will translate to ensuring synergy among the clinical research sites and a flexible structure capable of responding to new scientific opportunities.
    • Include plans for evaluating the operational performance of the protocol teams, clinical research sites and affiliated laboratories, and proposed processes for the development of remediation/improvement plans to avoid the identified shortcomings in the future.
    • Protocol Development
    • Describe the proposed approach to developing clinical research concepts approved by the SLC into protocols and associated documents, ensuring adherence to NIAID clinical research policies and SOPs. Describe how decisions at each step in the protocol development process will be made. Include a discussion of the process for fast tracking development of high priority concepts.   
    • Provide the criteria upon which protocol investigators, protocol project managers, and protocol teams will be selected and assembled to ensure strong scientific, clinical, and operational leadership. Describe how protocol teams will access expertise in clinical site management, study product management, regulatory support (including for non-US regulatory agencies, where applicable), and industry liaisons, as appropriate. Indicate criteria for selecting junior investigators on protocol teams.
    • Discuss how project management plans will be developed, tracked, and monitored. Include a discussion of establishing realistic milestones and go/no go criteria, evaluation of established plans, actual data, and future projections. Include discussion on the development of contingency plans and the processes to adjust project plans.  For specific clinical trials, applicants will provide specific clinical trials timelines under the PHS Human Subjects and Clinical Trials Information and these should not be duplicated under the Research Strategy.   
    • Discuss the process for developing essential documents to support the protocol, such as regulatory documents, the Manual of Operating Procedures, and Informed Consent Forms.
    • Clinical Research Site Selection and Management

    Describe the general thought process and overall approach for the activities below:

    • conducting feasibility assessments, including how site capacity, capabilities, and needs will be assessed; 
    • soliciting, reviewing, and selecting clinical research sites to implement specific protocols based on objective data on the presence of the desired patient population and the ability to recruit, enroll, and retain research participants;
    • 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;
    • classification, labeling, documentation, shipping and tracking of clinical specimens;
    • ensuring access to an affiliated laboratory capable of protocol-specified testing, as well as specimen processing, laboratory data management capabilities, shipment and storage of samples collected at the site;
    • ensuring access to a secure pharmacy facility; and
    • ensuring the ability to collect, process, analyze (if appropriate) and transmit data to the SDMC and/or NIAID clinical support programs.
    • Protocol Implementation:
    • Discuss plans for implementation of approved protocols, including how the COC will identify and ensure adherence to critical milestones and adjustments based on evaluation of projections against actual data. List the expected critical milestones for protocol implementation. For specific clinical trials, applicants will provide specific clinical trials timelines under the PHS Human Subjects and Clinical Trials Information and these should not be duplicated under the Research Strategy.   
    • Provide approaches for integration with NIAID clinical research support programs.
    • Describe the process for fast tracking implementation of high priority protocols.
    • Describe plans and procedures to identify and provide protocol-specific training. Include the source(s) of training; general format; plans for monitoring training needs; and how the need for retraining will be identified and implemented, if required.

    Subsection D: Laboratory Center

    In this subsection, the applicant should provide an overview of the anticipated scientific contributions of the LC towards implementing the research agenda of the LG. Include the following:

    • Organizational Structure.
    • Describe the overall LC structure, identifying the number and types of laboratories that will comprise the LC.  Tables, diagrams, flow charts and organizational charts are strongly recommended. Refer to section 3.5 of the PHS Human Subject and Clinical Trials Information form for details of staff composition.
    • Describe the roles and significance of each laboratory, pointing out any synergisms, how the composition will contribute to the success of the LC, and any innovative aspects of the proposed structure. Discuss how the LC will be integrated into the LG and synergize with the other centers to achieve the goals of the research agenda.
    • Research Strategy and Methodologies.
    • Describe the types of services to be provided, identifying any proposed innovations. Highlight any novel or innovative assays or capabilities that are in place.
    • Discuss the approach to making decisions on the selection of specialized assays, procedures (e.g. specimen characterization), and analyses (e.g. PK and other bioanalyses) for performance of protocol-specified testing. 
    • Describe plans for development of any new/innovative assays that further the goals of the research agenda.
    • Describe the general nature and type of biological samples that are projected to be collected during the course of network studies, and how the samples will be processed according to standardized procedures appropriate to sample type and stored until needed. Describe the quality control procedures for the biological specimens, and how to identify and resolve issues with quality control to maintain the integrity of specimens.
    • Describe the LC’s approaches for conducting ancillary studies using pre-existing stored samples when available from LG clinical trials.
    • Describe the LC’s approach to distributing specimens outside the network.
    • Quality Management
    • Describe laboratory quality management procedures. Include general quality assurance (QA) and quality control (QC) procedures, as well as LC requirements for external quality assurance (EQA), validations, reference range studies and laboratory audits.
    • Clinical Research Site-Affiliated Laboratories 
    • Describe the procedures and interactions among laboratories, LG centers and clinical sites for performing routine non-specialized testing, collecting and processing specimens, and shipping to one of more laboratories within the LC for specialized testing or to a repository for storage. 

    Subsection E: Statistics and Data Management Center

    In this subsection, the applicant should provide an overview of the SDMC toward implementing the research agenda of the LG and providing statistics and data management support to proposed clinical studies and trials. Include the following:

    • Organizational Structure. 
    • Describe the overall SDMC structure, including statistics, data management and IT elements. Provide a detailed description of the lines of authority. Tables, diagrams, flow charts and organizational charts are strongly recommended.
    • Discuss how the composition of the SDMC will facilitate the achievement of the goals of the LG in connection with designing and implementing cutting edge statistical analysis and the development, validation and utilization of data systems designed to support research on AR.
    • Discuss how the statistics and data management staff will interface in a synergistic manner within the SDMC, with other LG centers, and clinical research sites to provide general support for network activities, including, but not limited to:  protocol design and development, data analysis, preparation of data summaries (within and across protocols), and publication of results.
    • Research Strategy and Technical Capabilities
    • Discuss any innovations in statistical methodologies, e.g. study design, control/comparison groups, sample size/power estimates, endpoints, stratification/blocking methods, that may broadly impact the field of AR clinical research and improve the ability to study difficult-to-study infections.
    • Describe the development of data collection systems, forms and formats, and identify any innovations in adapting database systems and structures to accommodate LG and collaborator needs.
    • Describe the process for preparation of materials for the implementation of clinical trials and studies (Case Report Form (CRF), Laboratory Manual, Pharmacy Manual, electronic CRF instructions).
    • Explain the processes for planning and conducting interim and final analyses (including safety analyses) of clinical studies and clinical trials, including the development of Statistical Analysis Plans.
    • Describe plans for a centralized system for participant randomization and procedures for strict maintenance of blinding throughout studies.
    • Data Management Plans and Systems. 
    • Describe the nature and type of data to be collected, and how these data taken together will address the overall goals and objectives of LG studies. Provide a plan for managing data generated in the context of research studies carried out by the LG. 
    • Describe the data system and its components, their individual and integrated functional capabilities, and the method(s), requirements and procedures for compliance with NIAID policies, regulations and procedures. Describe procedures used to guide software development including project planning, requirements definition, system design, implementation, integration and testing, deployment, maintenance, and system retirement.
    • Describe procedures used for study randomization, randomization systems supported (web-based allocation, touch tone allocation, permuted block allocation, etc.), procedures for verification and validation of eligibility prior to randomization.
    • Describe the processes (e.g., paper and/or electronic) that will be used to collect and manage data generated at clinical research sites, clinical laboratories and central LG laboratories, including a description of how datasets will be transmitted, collated, reconciled and merged for purposes of efficient and valid analysis.
    • Describe the day-to-day procedures that will be used to ensure data quality and validity (QA/QC), including the processes and proposed timelines for querying and resolving data discrepancies or irregularities or acquiring missing data.
    • Describe the SDMC policies and plans to ensure the security, confidentiality, and integrity of data and data systems at the SDMC and during the transmission of data from and to external systems, including NIAID clinical research support programs.
    • Describe measures used to ensure compliance with US regulatory authority and or public laws (e.g. Clinical Data Interchange Standards Consortium (CDISC), 508 compliant, privacy impact assessment, title 21 CFR part 11, etc.) of data coding activities.
    • Describe plans for data retrieval, including timely provision of reports (data sets, tables and figures), and statistical support for LG publications. 
    • Describe plans for the provision of an electronic specimen tracking system.  
    • Describe plans for training site personnel on the use of data systems.
    • Describe how the SDMC will interact with NIAID-held safety oversight committees.  Provide SDMC policies and procedures in the timely provision of confidential closed and/or open data sets and presenting data to the Safety Oversight Committee (SOC).

    Letters of Support: Include all appropriate letters of support, including any letters necessary to demonstrate the support of consortium/site participants, centers, laboratories, pharmacies, and any industry and academic collaborators.

    Include a letter from the applicant organization(s) in support of the following:

    • 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.

    PHS Human Subjects and Clinical Trials Information

    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, with the following additional instructions:

    Section 2 – Study Population Characteristics

    2.5 Recruitment and Retention Plan

    Please limit responses to no more than one page.

    Section 3 -Protection and Monitoring Plans

    3.3 Data and Safety Monitoring Plan

    For clinical trials, upload an attachment that states: NIAID monitors the conduct of all clinical trials and will convene the Safety Oversight Committee and develop the monitoring plan. No other information should be provided.

    3.5 Overall Structure of the Study Team

    Please limit responses to no more than one half page.

    Section 4 – Protocol Synopsis

    4.2 Study Design

    Significant development will be conducted with NIAID after award. Please keep your responses brief.

    4.4 Statistical Design and Power

    Please limit responses to no more than one page.

    4.6 Will the study use an FDA-regulated intervention?

    4.6.a If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status

    Please limit responses to no more than one half page.

    4.7 Dissemination Plan

    Please limit responses to no more than one half page.

    Delayed Onset Study

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

    If no trials or studies are proposed as part of the application requiring a study record, then the applicant must upload a minimum of one (1) delayed onset clinical trial record.

    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.

    • Awards issued under this FOA will be incrementally funded awards for project periods of up to 7 years.  Multi-year funded grants will not be awarded.      
    • Grants awarded under this FOA will be excluded from automatic carryover – all carryover requests must be approved. 
    • Grants awarded under this FOA will not be provided the authority to automatically extend the final budget period one time for up to 12 months beyond the original expiration date shown in the Notice of Award – all extensions, including the first extension, will require approval. 
    • Progress and financial reporting will be required and reviewed annually.
    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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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.

    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. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

    A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

    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).

    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 there a strong scientific premise for the project? 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 scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy?  For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

    Specific to this FOA: Is the overall research agenda significant, does it adequately address the scientific objectives of the FOA and how well does it address key clinical questions in AR research? Is the proposed initial portfolio of research projects appropriate to address the top priorities of the research agenda? Are the network structure and governance adequate to ensure that the LG continues to respond to the most significant needs and opportunities in AR clinical research?

    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?

    With regard to the proposed leadership, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

    Specific to this FOA: Do the PD/PI(s), leadership of each center, and other key personnel have documented experience in directing clinical research projects of comparable size and scope required to address the objectives and scope of the FOA?     

    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?

    Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

    Specific to this FOA: Do the research agenda and initial project portfolio provide highly innovative projects to advance the understanding and management of AR infections? Are novel clinical trial designs and statistical approaches proposed that could improve our ability to study difficult to study infections? Is there evidence that innovative countermeasures will be evaluated? Will the network structure allow for optimal innovation in AR clinical research?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 children, justified in terms of the scientific goals and research strategy proposed?

    Does the application adequately address the following, if applicable?

    Study Design:

    Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

    Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

    Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

    Data Management and Statistical Analysis:

    Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

    Specific to this FOA:

    • Scientific Leadership Center
    • Is there an appropriate and clear organizational structure for the LG?
    • Are there adequate lines of authority and strong, feasible and fair governance plans for the LG?  
    • Are plans for engaging academic and industry researchers to identify the most promising ideas and countermeasures to be tested sound?
    • Are there appropriate and feasible procedures to measure and assess the productivity and quality of the LG overall and each center individually and to make adjustments, as needed?
    • Are there appropriate plans for continuous refinement of the clinical research agenda?
    • Are training and mentoring plans appropriate?
    • Are the plans and approaches for LG Evaluation and Improvement appropriate?
    • Clinical Operations Center
    • Are the management and communication plans adequate to manage, support and track protocol development and implementation, communicate with NIAID, and achieve the goals of the LG?
    • Are plans to apply key principles of program management to protocol development and implementation in place? 
    • Has the applicant proposed appropriate approaches to identify, select and manage clinical research sites?
    • Has the applicant proposed appropriate plans to manage all aspects of clinical trials, including suitability of systems for tracking clinical trial activities?
    • Has the applicant proposed adequate plans for: a) soliciting, evaluating, awarding and managing subcontracts; b) assessing subcontractor performance, identifying performance problems and approaches for their remediation; and c) plans for financial management of network resources?
    • Are contingency plans and ability to re-direct efforts in response to direction from the SLC clear?
    • Laboratory Center
    • Are there strong, meritorious and appropriate plans for the assessment and implementation of new assays and technologies? Are the proposed number, type and location of laboratories adequate and appropriate to meet network research agenda and will they allow for the sharing of specimens outside the network if it becomes scientifically necessary?
    • Do the proposed laboratory services demonstrate scientific and technical merit, appropriateness and feasibility especially with respect to the facilities, staff, standard operating procedures, plans for laboratory data management, and specimen tracking?
    • Statistics and Data Management Center
    • Are there strong, meritorious, appropriate and feasible plans and procedures for providing data management services required by the LG, including database design, security, confidentiality and administration, participant randomization/registration, data collection, quality control, data retrieval, report generation, and site training? 
    • Are there strong, meritorious, appropriate and feasible plans and procedures for planning and conducting interim and final analyses of clinical studies and for strict maintenance of blinding throughout the study?
    • Are the plans, procedures and systems sufficient to ensure data quality and integrity and ensure compliance with US regulatory authority/public laws?  
    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?

    If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

    Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

    If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

    If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

    Specific to this FOA: Is there evidence, including in the letters of support, of adequate institutional commitment and capacity to provide effective administrative, financial, and managerial support for a highly complex clinical research network? 

    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.

    Study Timeline

    Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

    Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

    Protections for Human Subjects

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

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

    Inclusion of Women, Minorities, and Children 

    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 children 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

    For Renewals, the committee will consider the progress made in the last funding period.

    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:

    • 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 on the basis of established PHS referral guidelines 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 appropriate 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. e.g. therapeutics and diagnostics for the management of multi-drug resistant gram-negative pathogens.
    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 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.

    Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. 

    ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/   

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

    Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

    Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE). 

    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, 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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies. 

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

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

    • Identifying and implementing a clinical research agenda that addresses AR scientific priorities;
    • Facilitating collaboration and communication, to accomplish the objectives of the LG;
    • Overseeing all aspects of studies supported through this award, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The PD(s)/PI(s) agrees to accept close coordination, cooperation, and participation of NIAID staff in those aspects of scientific and technical management of studies supported by this award as stated in these terms and conditions;
    • Adhering to NIAID policy for the conduct of clinical trials. Website: https://www.niaid.nih.gov/research/dmid-clinical-research-policies;
    • Managing involvement of industry or any other third party in studies supported by this award;
    • Establishing policies and procedures for decision-making to adapt to evolving research priorities over time;
    • Establishing and providing by-laws, policies and standard operating procedures to NIAID Program Staff within 90 days of issuance of an award, to include, at a minimum, the following:
    • Assure compliance with NIAID Clinical Research Policies and Standard procedures and to ensure adequate protection of the rights and safety of subjects involved in the research;
    • Detailed lines of authority and communication within the network and with NIAID program staff;
    • Identifying, qualifying, and approving protocol-specific sites to address specific clinical research network needs after award;
    • Clinical Quality Management Plan, developed in accordance with DMID CQMP policy and to be approved by DMID; and
    • Coordinate and collaborate with NIAID and NIAID clinical research support programs to facilitate collection of site essential regulatory documents, activation of study sites, clinical site monitoring and quality assurance services, pharmacovigilance (SAE reporting) and safety oversight, in adherence with NIAID standards and processes.
    • Providing a protocol to NIAID Program Staff for each study/trial prior to study start;
    • Determine the distribution of core and protocol funds, monitor expenditures and communicate with the clinical research sites;
    • Ensuring the following are provided to NIAID Program Staff for each clinical trial;
    • Project Management and communication plans;
    • Composition of the study team, including roles and responsibilities;
    • Timelines and budgets; and
    • Recruitment and Retention plan.
    • Providing input on potential members of the EAB;
    • Participating in the activities of the EAB, as needed; and
    • The SLC will also work closely with NIAID Program Staff to ensure the research agenda is consistent with NIAID’s AR research priorities.

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

    • The NIAID Project Scientist will coordinate the activities listed below. NIAID staff (NIAID Program Officer, Clinical Project Manager(s), and Medical Officer(s)) will provide assistance to the NIAID Project Scientist. These staff will be identified at the time of award.
    • Provide specific guidance on expectations for clinical studies and clinical trials;
    • Ensure that network research efforts are consistent with NIAID priorities for AR clinical research and complement other NIH and NIAID programs;
    • Facilitate coordination among the NIAID- and other NIH-supported clinical trials networks and research groups, clinical research support programs, and other U.S. Government agencies, promoting collaborations and facilitating information exchange;
    • Review and accept processes for identifying, qualifying, and approving protocol-specific sites to address specific clinical research network needs after award;
    • Serve as members of study teams;
    • Track protocol development, implementation, and study conduct;
    • Participate in meetings, training activities, and conference calls;
    • Serve as resources for scientific and policy information;
    • Share information regarding promising new agents, strategies, and developments when appropriate;
    • Identify scientific gaps and organize meetings to facilitate exchange of scientific and regulatory information, including during network meetings;
    • Periodically conduct an independent review of the constituent parts of the network for reliability and compliance with clinical and regulatory requirements;
    • Coordinate contract resources that facilitate the provision of support services for clinical trials;
    • Participate on scientific committees as a voting member;
    • Participate in the presentation of research results, including publications; and
    • Serve as a non-voting member of the EAB and assist in developing the operating guidelines for the EAB.
    • Clinical Trials Agreements. For trials requiring IND/IDE, NIAID will lead the negotiation of Clinical Trials Agreements (CTAs) with pharmaceutical companies (or other providers of investigational agents). The LG is not expected to be a party to CTAs for IND/IDE studies. NIAID will provide copies of signed CTAs to the LG. The LG will need to coordinate any necessary agreements for trials not conducted under IND/IDE and will provide copies of the signed agreements to NIAID.
    • Trial Sponsorship. NIAID will have the option to independently file an IND on investigational agents or an IDE on investigational devices evaluated in NIAID-supported clinical studies.  NIAID will advise the investigators on the specific regulatory requirements for IND/IDE sponsorship.  In situations where NIAID is the IND sponsor, NIAID through its contractors will also assemble, review, and submit the required regulatory documents to the FDA.  When holding an IND or IDE, NIAID has responsibility for the data management and reporting of safety information in accordance with FDA requirements and preferences.  In order to provide for consistent reporting of serious adverse experiences across the NIAID-supported clinical trial networks, NIAID will provide current policies and procedures that govern the reporting of adverse events in NIAID-supported trials.
    • Pharmaceutical Support.  For studies in which NIAID is the IND or IDE sponsor, NIAID staff and/or contractors will provide consultation on study treatment-related issues, including manufacturing, preparation, administration and availability of active dosage forms and placebo. NIAID staff and/or contractors may also interact with pharmaceutical company collaborators to facilitate adequate and timely supply of study product; and oversee the distribution of study product to the clinical research sites.
    • Trial Monitoring. NIAID will oversee an external clinical site monitoring contract that evaluates GCP, regulatory compliance, protocol implementation, internal quality assurance, and test article accountability at the clinical research sites for clinical trials conducted under IND/IDE.  The monitoring contractor, with or without accompanying NIAID staff, will visit the clinical research sites periodically to review selected protocols, provide training on general protocol conduct, review internal QA/QC plans, and audit pharmacies.
    • Laboratory Oversight. NIAID staff and NIAID contract resources will provide oversight and monitoring of clinical research sites for GCLP and for the quality of subject diagnosis and safety tests (e.g. hematology, chemistry, liver function), as well as the quality of pharmacological tests (e.g. drug levels, drug interactions), end point tests and blood processing. 
    • Training.  NIAID staff will provide a variety of training activities to appropriate network personnel to help the network ensure that consistent standards for protection of human subjects and clinical trial conduct and documentation are achieved across the NIAID-supported clinical trials networks.  Training areas include, but are not limited to, regulatory requirements, GCP, adverse event reporting, human subject protections, informed consent, and NIAID and NIH policies and procedures.
    • Protocol approval. NIAID will review all protocols and must approve all clinical trial protocols.  The Clinical Project Manager or designee will return comments and recommendations to the network after review.  The network must address in writing all safety, regulatory, ethical, and conflict of interest concerns raised by NIAID to the satisfaction of NIAID before participant enrollment can begin.  If a protocol is disapproved, NIAID will not provide investigational products or permit expenditure of NIH funds for the proposed investigation.  If a protocol is not initiated within twelve months of NIAID approval, re-review and approval by NIAID will be required.
    • Safety Monitoring. NIAID will oversee an external contract that will develop appropriate safety monitoring plans for all planned clinical trials. NIAID must approve the plan for all trials involving investigational drugs, devices, or biologics.  The frequency and intensity of safety monitoring will be based on individual study characteristics and experience with study products and may require review by an Independent Safety Monitor, Safety Monitoring Committee (SMC) or Data and Safety Monitoring Board (DSMB).  NIAID Medical Monitors will be part of network-organized protocol safety review teams to monitor the safety and efficacy of the intervention(s) for ongoing studies and will be provided with appropriate reports.  Medical Monitors will be responsible for the disposition of Serious Adverse Events. Approval of the final monitoring plan, including the composition of the review committee, by NIAID is required prior to study initiation.  NIAID independently supports Data and Safety Monitoring Boards (DSMB) that oversee Phase IIb/III and other select clinical trials at the discretion of NIAID.
    • Study Termination.  NIAID reserves the right to terminate or curtail a clinical study for any of the following reasons:
    • risk to subject safety
    • the scientific question is no longer relevant, or the objectives will not be met (i.e. slow accrual)
    • failure to comply with GCP, U.S. Federal regulations, or Terms and Conditions of Award
    • occurrence of unforeseen drug safety issues or data from preclinical studies indicate a presence of unanticipated toxicity
    • risks that cannot be adequately quantified
    • ethical concerns raised by the community or medical care/health care authorities
    • failure to remedy deficiencies identified through site monitoring
    • substandard data
    • reaching a major study endpoint substantially before schedule with persuasive statistical significance
    • External Advisory Board
      An External Advisory Board (EAB) will be established by NIAID to review the progress in meeting the goals of the LG. The EAB is expected to consist of individuals who are not key personnel or collaborators of the key personnel of any of the awardees. The EAB will make recommendations for the continuation or re-direction of all LG projects and activities on an ongoing basis in consultation with NIAID staff.
    • The EAB will prepare concise summaries of the EAB meetings, which will be delivered in a timely manner to members of the EAB and NIAID. The EAB will meet on an annual basis in conjunction with the Annual Network Meeting and on an ad-hoc basis by conference calls, as needed. The EAB's meetings will include NIAID staff, PD(s)/PI(s) and other members of the LG, as necessary.
    • The EAB will select one member to be the Chair of the Committee and the Chair will not be a NIAID staff member.
    • Data Access. The awardees retain the rights to the data, consistent with current DHHS, PHS, NIH and NIAID policies; however, NIH will have access to all data generated (raw and analyzed) and may periodically review it.  This includes a review of data as recorded on the case report forms or in the central database, and external checking against the original source documentation as required by federal regulation and NIAID as the IND/IDE sponsor.  NIAID may request from the network specific data analysis needed for programmatic activities or for issues related to NIAID plans with other partners.  The NIH may provide public access to selected data sets generated with the use of public funds within a reasonable time after primary analysis and publication. Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

    Areas of Joint Responsibility include:

    • Research Plans. Implementing, monitoring, and updating the clinical research agenda for the network to ensure consistency and relevance with the AR scientific priorities.
    • Research Activities. Reviewing the network's research activities and goals on an agreed upon schedule (but no less than once every year).
    • Protocol Development. The COC will assemble and manage study teams, but NIAID staff and support contractors, as required, will participate in these teams.
    • Oversight of Clinical Trials. On an ongoing basis, the SLC, COC, and NIAID staff will jointly evaluate the progress of clinical trials, including enrollment milestones, site quality, and data quality. NIAID and NIAID contractors may audit sites, SDMC, and laboratories to assess GCP and data quality and integrity.
    • Performance Assessment.  NIAID, in conjunction with the EAB will assess the performance of all LG centers and clinical research sites in an ongoing manner.  The LG will develop an evaluation plan with defined goals and measurable objectives linked to specific performance metrics and include remedial actions for sites failing to meet acceptable standards. Clinical research sites that fail to meet performance standards may be subject to withdrawal of funding.
    • Network Meetings. A kickoff meeting will be held in the vicinity of Bethesda, Maryland soon after award in which expectations for the conduct of clinical studies and trials, roles and responsibilities will be discussed. The LG will hold an annual meeting to share recent findings and facilitate collaborations. All key personnel and NIAID program staff are expected to attend and participate. External Advisory Board members may also attend the program update portion of the meeting. The highlights from each project’s recent findings should be presented. 

    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 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 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.

    3. Reporting

    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.

    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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

    Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

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

    Scientific/Research Contact(s)

    Jane Knisely, PhD
    National Institute of Allergy and Infectious Diseases (NIAID)
    Telephone: 240-627-3289
    Email: Jane.Knisely@nih.gov

    Peer Review Contact(s)

    Brenda Lange-Gustafson, PhD
    National Institute of Health (NIAID)
    Telephone: 240 669-5047
    Email: bgustafson@niaid.nih.gov

    Financial/Grants Management Contact(s)

    Chernay Rogers
    National Institute of Health (NIAID)
    Telephone: 240-669-2992
    Email: masoncl@od.nig.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.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.