It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) invites applications from single institutions or consortia of institutions to participate in the Asthma and Allergic Diseases Cooperative Research Centers (AADCRC) program. The program will support centers that integrate clinical and translational research to conduct studies on the mechanisms underlying the onset and progression of diseases of interest including asthma, rhinitis (allergic and non-allergic), chronic rhinosinusitis, atopic dermatitis, food allergy, and drug allergy. The overarching goal of the program is to improve the understanding of the pathogenesis of these conditions and to provide a rational foundation for new, effective treatments and prevention strategies.

Asthma and allergic diseases are major causes of illness and disability in the United States and the prevalence of these conditions is still on the rise. Also of high prevalence and morbidity are chronic rhinosinusitis and non-allergic rhinitis, which share pathophysiologic and clinical characteristics with allergic diseases. In all these conditions, major gaps exist in our understanding of their immunopathophysiology and, for most of them, management is either based on avoidance of allergens or pharmacologic interventions that offer either only symptomatic relief or have nonspecific anti-inflammatory activities that do not alter the natural history of the disease. Allergen immunotherapy for food and aeroallergens or early dietary introduction of food allergens offer promise in disease modification and prevention, but require further study.

• Asthma affects 8-9% of the U.S. population including more than 6 million children and is one of the major causes of missed school days and hospitalization in children and adolescents. Severe asthma affects 5-10% of all patients with asthma, but is responsible for a much higher social and economic burden when compared with mild and moderate disease. Despite advances in understanding asthma endotypes, large gaps remain in determining the immunologic pathways that lead to the inflammatory presentations of severe disease.
• Allergic rhinitis is estimated to affect approximately 60 million people in the U.S. and non-allergic rhinitis at least another 30 million. Large numbers of patients with these conditions do not achieve adequate relief with available medications, resulting in substantial social and economic burdens. Non-allergic rhinitis presumably includes a number of distinct syndromes, but no systematic research has been conducted to determine phenotypes and endotypes, a necessary step towards rational development of novel therapeutic approaches.
• Chronic rhinosinusitis, which probably affects more than 10% of the US population and results in roughly 15 million physician visits and 200,000 sinus surgical procedures each year, manifests as persistent inflammation of the nasal and sinus mucosa and is highly heterogeneous and difficult to manage pharmacologically. Research to elucidate endotypes and define the early events in the development of the disease is needed. Recent studies with biologic agents suggest that some forms of chronic rhinosinusitis may be manageable, but predictors of highly responsive patients are needed.
• Atopic dermatitis affects approximately 12% of children under age 18 and up to 7-8% of adults in the U.S. Despite the known scientific associations between atopic dermatitis and allergic disease, the role of allergy in atopic dermatitis and the etiologic and pathophysiologic interactions between atopic dermatitis and food or respiratory allergy are incompletely understood.
• Food allergy affects approximately 8% of children and, as recently suggested, 10% of adults. Food allergy is the most frequent cause of emergency department visits for anaphylaxis and the number of food allergy-related anaphylaxis visits to U.S. emergency departments has steadily increased in the past 2 decades. The mechanisms of food allergy development are not fully understood and require further investigation. Recent studies indicate that prevention and management of food allergy with early allergen exposure or with allergen immunotherapy, respectively, may provide therapeutic benefit, but much remains to be learned regarding optimal timing for early food introduction or treatment initiation, dosing, duration of treatment, transition to natural food intake and improved safety.
• Allergic drug reactions are defined for the purpose of this FOA as reactions that have an immunologic component. These reactions result in excess morbidity, particularly in patients who are in need of the drug in question and have underlying serious conditions. The mechanisms of many allergic drug reactions have not been determined. Better understanding of the pathogenesis of these reactions may facilitate prediction and prevention or may guide the development of drugs with less allergenicity.

Both innate and adaptive immune responses participate in the pathogenesis of allergic diseases. It is well established that environmental exposures in early childhood influence the expression of many of these diseases later in life. These exposures involve not only allergens, but other immunologically active agents that may include bacteria, viruses, and various environmental substances. Some of these exposures may be protective against allergic disease, but much remains to be learned as to the mechanisms of protection. Interactions of early exposure to these factors plus an individual's genetic makeup shape the development of the immune system and together determine the risk for allergic disease. Recent insights raise the possibility that epigenetic modifications also play a role in controlling the function of the immune system and that these modifications are also influenced by environmental exposures.

Allergen-specific immunotherapy trials with food and aeroallergens have demonstrated reduced responsiveness to the allergens in question, a protective effect that also can be sustained after discontinuation of treatment. A recent large trial has shown substantial reduction in the development of peanut allergy with early introduction and maintained exposure of peanut-containing food in high-risk infants. Earlier studies have suggested that allergen immunotherapy in children with allergic rhinitis can prevent the development of asthma. Thus, evidence exists that allergy prevention is possible. However, improvements in allergen immunotherapy are necessary to increase its tolerogenic effectiveness and reduce the duration of treatment while further improving its safety profile. In addition, new forms of immunotherapy are under development and require testing.

The NIAID AADCRC program, established almost 5 decades ago as the first targeted research program in the field of asthma and allergic diseases, is the cornerstone of NIAID's efforts to promote innovative, multidisciplinary clinical and basic research on these diseases. Supported by a multi-project mechanism, the program aims to leverage expertise provided by centers around the U.S. through collaborations among researchers. The program currently supports 11 AADCRC research centers.

The objective of this FOA is to support multidisciplinary research on the following conditions of interest: immunopathophysiology of asthma, rhinitis (allergic and non-allergic), chronic rhinosinusitis, atopic dermatitis, food allergy, and drug allergy. The overall goal of the AADCRC program is to improve the understanding of the pathogenesis of these conditions and to provide a rational foundation for new, effective treatments and prevention strategies.

NIAID programmatic priorities for this FOA are:

• The role of innate and adaptive immune functions in the development and pathogenesis of asthma and allergic diseases with a focus on severe asthma, chronic rhinosinusitis, atopic dermatitis, and drug allergy;
• The impact of the microbiome and pollution on immune responses as they pertain to the development, prevention and management of asthma, allergic rhinitis, food allergy and atopic dermatitis;
• The interaction between infections and atopy and the role of immune responses to infections in the development and exacerbations of asthma, allergic rhinitis, chronic rhinosinusitis, and atopic dermatitis;
• Induction of and understanding of the mechanisms of desensitization and sustained tolerance for the treatment and prevention of asthma, allergic rhinitis, food allergy, and drug allergy;
• Genetic variations and epigenetic alterations affecting host immune responses to aeroallergens, food allergens and drug allergens and host response to therapeutic interventions;
• Clinical, immunologic and physiologic phenotyping and endotyping of drug allergy, atopic dermatitis, chronic rhinosinusitis and non-allergic rhinitis syndromes that provide mechanistic insights for disease etiology or management.

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

• Research on autoimmunity and autoimmune diseases;
• Research on primary immune deficiency diseases;
• Demonstration and Education Research Projects;
• Phase III clinical trials;
• Clinical trials at foreign sites;
• Continuation of ongoing (active) clinical trials. The applicant may only propose new clinical trials. For the purpose of this FOA, a new trial is defined as one that has not previously recruited any subjects and will not be recruiting any subjects prior to award;
• Applications in which human research is not the focus;
• Research on HIV or AIDS.

In order to ensure the focus of the applications is on human disease, the proposed research within each application should be defined as human subjects research (for the HHS definition of human subjects research, please see the NIH Office of Extramural Research Human Subjects) or utilize human material (including primary human cells, biologic samples, and clinical data). Studies using only transformed human cell lines will not count toward this requirement. Very limited animal research may be included based on the need for experimentation that is not possible in humans or with human materials and the animal studies must be clearly integrated into an overall experimental plan that will translate animal findings to human disease.

Highly integrated and synergistic research programs are encouraged for the AADCRC program. This includes multi-institutional applications for conditions of interest to this FOA, especially where research resources are limited (e.g., non-allergic rhinitis or drug allergy). AADCRC Research Programs funded under this FOA will be comprised of multiple components to carry out the broad scope of research delineated above. Component projects and cores within a single application should not only relate to a central theme relevant to the specified diseases of interest, but also relate to the other components within the same application. Research programs could be organized around either:

• One or more immunologic mechanism/pathway that is hypothesized to be an important pathobiologic process in a condition of interest to this FOA, or
• One or more clinical trials or clinical studies that test a novel therapeutic or preventive approach, a mechanistic hypothesis, or aim at elucidating disease phenotypes and endotypes in a condition of interest to this FOA.

Applicants are advised that, in the event their application is selected for NIAID funding, any proposed clinical trials will be reviewed by various review bodies per NIAID clinical trial policies and final clinical protocols will be developed collaboratively. This will include reviews by the Medical Monitor and Project Scientist that the NIAID will assign to the study; review by the NIAID Division of Allergy, Immunology and Transplantation (DAIT) Clinical Research Committee; and review by the DAIT Asthma and Allergy Data and Safety Monitoring Board (DSMB).

It is the responsibility of the PD(s)/PI(s) to contact Regulatory Authorities and obtain guidance as to the need for an Investigational New Drug (IND) or Investigational Device Exemptions (IDE) for interventions (whether to be used for therapeutic or mechanistic purposes) that are planned to be employed in any clinical trial or study, if these interventions are not approved for the specific indication (including medical condition, age range, dose range) for which they will be used in the research project. If an IND is required, it is expected that, in most instances, either an awardee or the organization supplying the investigational agent or device will serve as the IND/IDE Sponsor. The Sponsor of an IND/IDE is responsible for the development, assembly, and submission of all required regulatory documents, and will provide NIAID all required information following NIH clinical research guidance and complying with NIH Grants Policy. This includes but is not limited to all communications with the FDA (or other regulatory authority) and the IRB. However, NIAID reserves the right to decide whether it will be the Sponsor of this trial and hold the IND. If NIAID is the IND/IDE Sponsor, then the NIAID is responsible for the development, assembly, and submission of all required regulatory documents, unless this responsibility is otherwise delegated by the NIAID. If NIAID is the Sponsor, the PD(s)/PI(s) is responsible for providing all information to NIAID that is needed for compliance with FDA regulations.

Administrative Core: Each application must contain an Administrative Core that is responsible for the overall management, communication, coordination, and supervision of the Program. Duties of the administrative core must include a plan of administering the AADCRC Infrastructure and Opportunity Fund (IOF).

A single Infrastructure and Opportunity Fund of up to $500,000 total costs per year will be established under this FOA to support new and pilot research projects led by investigators within the AADCRCs, as well as for the development of resources that the AADCRC Steering Committee may deem necessary. After awards have been made, one AADCRC awardee institution will be selected by the NIAID to manage the IOF for the entire AADCRC program. This institution must agree to take responsibility for managing the IOF, including fund disbursement, administration, and reports. Management of the IOF will involve:

• Establishing an administrative structure to manage the IOF;
• Disbursing and tracking IOF funds under the direction of the Steering Committee;
• Implementing plans for interacting with the institutions that will receive IOF funds, including establishing consortium agreements, when applicable;
• Establishing procedures, formats, and timelines for reporting on the status of IOF projects and expenditures to the NIAID and the AADCRC Steering Committee.

Research Projects: Each application must contain at least two research projects organized around a common theme or hypothesis. Research should meet the NIH definition of Human Subjects research or utilize human material.

Service Core(s): Each application may propose Service Cores, as necessary to ensure the success of the supported Research Projects and the overall goal(s) of the Center. Examples of Service Cores include, but are not limited to, a Clinical Core or a Data Management Core.

Resources Provided by NIAID: For all clinical trials (but not clinical studies) that will be conducted, NIAID will provide a Data and Safety Monitoring Board (DSMB).

Steering Committee

Program Directors/Principal Investigators (PDs/PIs) funded under this program will form a Steering Committee after award. The Steering Committee will serve as the main governing body for the cooperative group. The Steering Committee will meet by teleconference twice-a-year and in a face-to-face meeting once-a-year. Among other responsibilities, it will discuss collaborative research projects and develop guidelines for the publication of collaborative project results, organize the yearly competition for the IOF funds, discuss and propose funding plans for the IOF funds, set the agenda for an annual face-to-face AADCRC scientific meeting (to be held in or near Rockville, MD) and propose AADCRC-centered sessions for national and international scientific meetings. NIAID staff members will also be non-voting members of the Steering Committee and participate in all Steering Committee activities.

Potential applicants are strongly encouraged to consult with the Scientific/Research Contact listed in Section VII during the early stages of preparation of the application.

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

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.

Applicant Organizations

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

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

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

Note that the multiple PD(s)/PI(s) option may be used only for the Overall Program. Projects are limited to a single project lead per project and a single core lead per core within the multi-component application.

An investigator can serve as a PD/PI on only one AADCRC award or application. This includes all PD(s)/PI(s) of a multiple-PD/PI application.

Note that the current FOA will not allow foreign clinical trial sites. However, foreign components that will be allowed include mechanistic projects, observational studies, specialized assay, etc.

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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

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

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

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

The letter of intent should be sent to:

Thomas Conway, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5075
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Core (use for Service Core)	6 each
Project (use for Research Projects)	12 each

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required, 1
• Service Cores: optional, no maximum, but each core must support at least two Research Projects
• Research Projects: required; minimum of 2

When preparing your application, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

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

Research Strategy: This narrative section summarizes the overall research strategy for the multi-component application. The multi-component application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problem. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique. To highlight program synergy, applicants may describe in the Overview section how the individual components will be coordinated and work together to address the overall goals and aims of the program. Include a schematic overview of the interactions and collaborations among the components and indicate collaborations among members and relevant publications co-authored by members of the program. Program synergy may also be addressed in other sections of the application, as appropriate.

As part of the Overall Research Strategy, describe the focus of the research program in this application. In order to achieve this FOA’s objective of supporting highly integrated and synergistic research programs focused on a central theme relevant to the specified diseases of interest, it is recommended, but not required, that applications be drafted along the lines of either of the two models provided below.

• MODEL A Pathway Focus

The application focuses on the role of one or more immunologic mechanism(s)/pathway(s) that are hypothesized to be important pathobiologic processes in a condition of interest, as specified in this FOA, or in allergy, in general. This mechanism(s)/pathway(s) may involve a single cellular molecular species or several interrelated species, selected genes, a cell type, a micro-organism or a group of micro-organisms, an environmental factor or a group of environmental factors (such as allergens, microbes or pollutants). The application should include projects that examine such pathways from various perspectives including clinical studies or clinical trials, genetics, systems biology approaches, in vitro work, or, if necessary, animal models. The proposed research should utilize human material (including primary human cells, biologic samples, and clinical data). Very limited research using animal models may be proposed in parallel to human subjects research, only if it provides more in-depth hypothesis testing on outcomes that cannot be assessed with human research.

• MODEL B Clinical Intervention/Observation Focus

The application is centered around one or more clinical trials (interventions) or clinical studies (cross-sectional or short-term longitudinal observational studies, genetic studies) that test a novel therapeutic approach, a novel mechanistic hypothesis, or aim at elucidating disease phenotypes and endotypes in a condition of interest to this FOA. The clinical trial(s) or study(ies) constitute the source of material that supports the conduct of a series of associated studies that test the central hypothesis of the application in a comprehensive manner. The application should include projects built around the clinical trial(s) or observational study(ies) including mechanistic studies, systems biology approaches (including genomics, epigenomics, metabolomics, etc.), microbiome studies or genetics.

If the application is a renewal, this section should also highlight progress made and the major accomplishments from the prior funding period. For individual research projects and cores that will be continued as part of a renewal application, additional details of progress made during the prior funding period should be provided in the Research Strategy within each research project and core.

If an External Advisory Group is proposed, then describe the expertise and responsibilities of your potential members. For a new application, if applicable, do not contact, recruit, or name potential members. For a renewal application, provide the names only of current members.

Letters of Support: Provide any institutional letters of support specific to the Overall Component.

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 items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

When preparing your application, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• For institutions/organizations proposing a single PD/PI, the PD/PI will serve as the Administrative Core Lead. For institutions/organizations proposing multiple PD(s)/PI(s), the Contact PD/PI must serve as the Administrative Core Lead. Through the required Administrative Core functions indicated below, the Administrative Core Lead provides leadership and guidance in fulfilling the stated objectives of his or her Center, and is responsible for generating, within the Administrative Core, an infrastructure that promotes cross-discipline interactions among all of the Cores and Research Projects, and provides oversight and governance over fiscal and resource management.

Budget forms appropriate for the specific component will be included in the application package.

Funding for the overall administrative efforts, including administrative services, expenses for publications demonstrating collaborative efforts, and communication expenses, should be requested in this core.

Infrastructure and Opportunity Fund (IOF): All applicants should propose funds for the IOF. The IOF budget of $500K Total Costs will be awarded to one recipient organization which will be selected by NIAID post-award to manage the fund. Each applicant should propose Direct Costs as a single line item in the Other Direct Costs Category of the Administrative Core Budget. A part of the IOF budget, Direct Costs proposed for an IOF administrator may be requested in the Personnel Category for a maximum of 0.5 calendar months and must comply with NIH Grants Policy. F&A Costs will be applied in accordance with NIH Grants Policy.

All applications should include travel funds for the PD(s)/PI(s) to participate in annual Steering Committee meetings, and PD(s)/PI(s) and subproject PD(s)/PI(s) to attend the annual AADCRC scientific meetings. The two-day scientific meeting will be held each year in Bethesda, Maryland.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: List in priority order the proposed activities and services of the Administrative Core. Concisely describe the work to be completed to address issues of program coordination, communication, management, and administering IOF.

Research Strategy: A fully-developed and well-described Administrative Core plan is required. Duties of the administrative core must include a plan of administering the AADCRC Infrastructure and Opportunity Fund (IOF) as described in this FOA.

Describe the organizational and administrative structure of the proposed multi-component application. Include plans on how the PD(s)/PI(s) will interact with Project/Core Leaders and whether and how the Center research projects will be supported by external consultants. Provide an administrative plan that includes a discussion of the structure and roles of administrative staff, including the functions to be performed; how fiscal and other resources will be prioritized, allocated and managed; how communications will be facilitated; how conflict resolution will be attained; how research related travel and training will be managed. Present a leadership succession plan. No research data management and data analysis should be included in the Administrative Core.

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 items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Core.

Service Cores may include, but are not limited to, a Clinical Core, or a Data Management (e.g., database establishment, data collection and cleaning) Core. Each Core must support at least two projects. A Clinical Core may be proposed if the application proposes to conduct a clinical trial or clinical study. This Core will be responsible for the organizational and regulatory aspects of the clinical trial(s) and study(ies) and may include data management. Alternatively, data management may be conducted under a separate Data Management Core.

Depending on the intention of the trial and/or study, the proposed clinical trial and/or study can be presented within a research project or in a service core. If the proposed clinical trials and/or studies are not to test a hypothesis (non-hypothesis generating) but are meant only to collect and provide samples for at least two research projects, details of the trials or studies may be incorporated into a Clinical Core. However, these trials or studies should also be summarized in each of the research projects that the Core will serve. If the proposed clinical trials and/or studies are intended to test a novel therapeutic approach or a novel mechanistic hypothesis, the clinical trial must be proposed as a project and not be presented in a service core.

If proposed, the activities of the Service Cores must not overlap with each other or with the activities of a Research Project.

Additional service cores (e.g. genetics/genomics, research laboratory services) can also be proposed.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• NIAID highly recommends inclusion of Core personnel whose role will be to ensure timely submission of data and data analysis obtained under this award to the ImmPort database or to other public portals designated by NIAID.

Budget forms appropriate for the specific component will be included in the application package.

The percentage of total funds that will be required to support each component research project that will utilize the core should also be presented. This information should be included in the core’s budget justification for Year 1.

For all clinical trials, NIAID will provide a Data and Safety Monitoring Board (DSMB). Therefore, the applicant does not need to include or budget for DSMB expenses.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: List in priority order the broad, long-range activities and services of the proposed Core. In addition, state the Core’s relationship to the program’s goals and how the Core relates to two or more individual research projects in the application.

Research Strategy: Describe how the proposed Core activities will contribute to meeting the Program’s goals and objectives, and explain why the Core resources are not otherwise available. In addition, this section should indicate the relevance of the Core to the primary theme of the application. The application must indicate the specific projects to be served by the Service Core. Describe the interactions of the Core Lead and each of the Scientific Projects.

If the Service Core proposes clinical trials and/or studies designed only to collect and provide samples for two or more research projects, this section must describe the following aspects of the proposed trial(s)/study(ies):

• Discuss the role of the trial/study in the overall research strategy of the application. Outline the objective and concisely describe the design of the proposed trial/study, include rationale and process for the selection of the participant population, choice of intervention (if applicable), duration and schedule of events. Discuss the trial/study's feasibility, difficulties that may be encountered, and offer alternative approaches to be implemented, if needed, include general concepts for sample size determinations and statistical methodologies, but, particularly for clinical trials, provide study-specific details in the PHS Human Subjects and Clinical Trial Information Forms.

Note: Specific details for trials and studies will be captured using the PHS Human Subjects and Clinical Trials Information Form. Do not duplicate information requested under the PHS Human Subjects and Clinical Trials Information Forms.

If the service core proposes a Data Management Core, this section should describe the Data Management infrastructure to support the proposed activities and sufficient effort and expertise dedicated to data management and data transfer to ImmPort or other public portals designated by NIAID.

Letters of Support: Provide any letters of support from collaborators that are specific to the Service Core.

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 items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Project.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• If a Data Management Core is not proposed, Senior/Key persons in the Research Project section should include a data manager whose role will be to ensure timely submission of data and data analysis obtained under this award to the ImmPort database or to other public portals designated by NIAID.

Budget forms appropriate for the specific component will be included in the application package.

In single PD/PI applications, the PD/PI must also serve as a Project Leader, and is required to commit an overall minimum of 3 person months in AADCRC activities. In multi-PD/PI applications, every PD/PI must serve as a Project or Core Leader with at least one of the PD(s)/PI(s) serving as a Project Leader and committing an overall minimum of three person months in AADCRC activities.

If the project involves a clinical trial or a clinical observational study, the applicant is responsible for including the costs of all support for statistical design, data collection, analysis and management, data deposition into ImmPort (https://immport.niaid.nih.gov) or other public portals designated by NIAID and ClinicalTrials.gov if required, as well as the costs for clinical site monitoring, project management and quality assurance of the proposed clinical trials or observational clinical studies in the application budget. Alternatively, these costs can be incorporated into the budget of relevant Service Core(s), provided that specific cross-references are made to clarify how these necessary functions will be supported.

For all clinical trials, NIAID will provide a Data and Safety Monitoring Board (DSMB). Therefore, the applicant does not need to include or budget for DSMB expenses.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

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

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

Clinical research

The research proposed should meet the HHS definition of human subjects research or utilize human material and should involve individuals with one or more of the conditions of interest named in this FOA, or clinical specimens from such individuals. Healthy volunteers may be included in proposed clinical studies only as controls. Clinical trials, if proposed, are limited to Phase I or Phase II trials. Studies using human specimens obtained from relevant ongoing or completed clinical studies or clinical trials may also be proposed.

Clinical trials

The NIH defines a clinical trial as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes (https://grants.nih.gov/grants/glossary.htm#ClinicalTrial). Research with human subjects to develop or evaluate clinical laboratory tests (imaging or molecular diagnostic tests) might be considered a clinical trial if the test will be used for medical decision-making, or if the test itself imposes more than minimal risk for subjects.

In the spirit of the above definition, any study that involves interventions aiming at understanding mechanisms of disease (e.g. allergen challenges, experimental exposure of humans to an inflammatory mediator or to a rhinovirus), or any study that involves an intervention for which the FDA will require an IND/IDE application, will be considered a clinical trial.

A clinical trial can be proposed as an individual project of the U19 application. However, depending on the intention of the trial and/or study, the proposed clinical trial and/or study can be presented within a research project or in a service core. If the proposed clinical trials and/or studies are intended to test a novel therapeutic approach or a novel mechanistic hypothesis, the clinical trial must be proposed as a project and applicants must follow the instructions for the clinical trial below. If two trials are highly related and share most aspects of study design, they can be presented within the same project.

The Approach section of the clinical trial project must address the following aspects of the proposed trial(s):

• Discuss the overall significance of the problems being studied, their role in the overall research strategy of the application and the potential impact of the proposed work. Indicate how the trial(s) will improve the clinical outcome of interest. Describe earlier studies that led to the proposed clinical trial and provide the rationale and pertinent information and/or data from preliminary studies which address the need for and the feasibility of the project. Outline the hypothesis, objective and how the proposed outcomes will adequately address the hypothesis. Concisely describe the design of the proposed trial, include rationale and process for the selection of the participant population, choice of intervention (if applicable), duration and schedule of events. Discuss each trial's feasibility, difficulties that may be encountered, and offer alternative approaches to be implemented, if needed. Include a plan for the management of the clinical trial that offers description of personnel involved in conducting the trial, personnel involved in data entry and management, and the personnel involved in statistical analysis; the interactions between these teams should be described. Include general concepts for sample size determinations and statistical methodologies, but provide study-specific details in the PHS Human Subjects and Clinical Trial Information Forms.

Note: Specific details for each trial will be captured using the PHS Human Subjects and Clinical Trials Information Forms. Do not duplicate information requested under the PHS Human Subjects and Clinical Trials Information Forms.

Clinical studies

For applications proposing one or more clinical studies (observational studies with no-interventions and involving only minimal risk procedures), the Approach section of the clinical study project must address the following aspects of the study:

• Discuss the overall significance of the problem(s) being studied, their role in the overall research strategy of the application and the potential impact of the proposed work. Describe earlier research that led to the proposed study and provide the rationale and pertinent information and/or data from preliminary studies which address the need for and the feasibility of the project. Outline the hypothesis, objective and how the proposed outcomes will adequately address the hypothesis. Concisely describe the design of the proposed study, include rationale and process for the selection of the participant population, choice of outcomes, duration and schedule of events. Discuss each study's feasibility, difficulties that may be encountered, and offer alternative approaches to be implemented, if needed. Include a plan for the management of the clinical study that offers description of personnel involved in conducting the study, personnel involved in data entry and management, and the personnel involved in statistical analysis; the interactions between these teams should be described. Include general concepts for sample size determinations and statistical methodologies, but provide study-specific details in the PHS Human Subjects Information Forms.

Note: Specific details for each study will be captured using the PHS Human Subjects Information Form. Do not duplicate information requested under the PHS Human Subjects Information Forms.

Projects obtaining human samples from non-AADCRC-supported clinical studies or trials

For projects that plan to obtain human samples derived from clinical studies or clinical trials that are planned, ongoing or completed and are or have been sponsored by sources other than the AADCRC, the information in the Approach section should include the following:

• Study title
• Study objectives (primary and secondary)
• Study population(s) with clear description of clinical phenotypes
• Key design features, including primary and secondary endpoints, comparison/control groups
• Sample size calculations and statistical analysis plans as they pertain to the questions posed by the AADCRC study that will utilize the parent study/trial samples
• Study duration and timeline (if a planned or an ongoing study)

Non-clinical research

Describe the research design conceptual procedures, and analyses to be used to accomplish the specific aims of the project. Describe any new methodology and its advantage over existing methodologies. Describe any novel concepts, approaches, tools, or technologies for the proposed studies. In the rare instances where animal models are proposed, justify the models and describe how the findings could be translated into human research and how they associate with the proposed clinical project(s). Discuss the potential difficulties and limitations of the proposed research and alternative approaches to achieve the aims. Provide a tentative timetable for the project.

Letters of Support: Provide letters of support from collaborators that are specific to the research projects.

For Projects obtaining human samples from non-AADCRC-supported clinical studies or trials, include documentation of the ability to acquire human samples, including written agreements between the PD(s)/PI(s), the applicant institution, the clinical study/trial sponsor(s), including drug companies, if applicable, and the IND/IDE sponsor (if not one of the above) to be used in the studies proposed by the application is required. A statement is required that the subjects from whom samples were obtained from the parent clinical study/trial not supported by the proposed AADCRC project have given informed consent/assent and the material they have provided can be used by the AADCRC project.

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 items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Describe actions to be taken to address problems with recruitment or retention of study participants.

Please note: Sections 4 and 5 of the PHS Human Subjects and Clinical Trials Information form are only available to clinical trials.

Section 4 - Protocol Synopsis

4.2 Study Design

4.2.a Narrative Study Description

Additional instructions

For multi-visit studies, provide a description of the study design including the procedures and activities that can occur at each visit (schedule of events).

Section 5.1 - Other Clinical Trial-related Attachments

Describe the plan to obtain required investigational agent(s).

Delayed Onset Study

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

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads 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.

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 (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

In addition, for applications involving clinical trials:

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.

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

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

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

Specific to this FOA

Are there coordination and synergy of the individual research projects and cores towards the achievement of the central objectives of the Center? Will the integration of the individual projects into a single Center be more beneficial than pursuing each project independently? For renewal applications, have the Center's accomplishments made a major impact on the field or successfully achieved their original goals?

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

Specific to this FOA

Do(es) the PD(s)/PI(s) have the leadership and scientific ability to develop an integrated and focused research Center? Will the PD(s)/PI(s) and other Project/Core Leaders devote adequate time and effort to the Center? For applications designated multiple PD(s)/PI(s), is the Leadership Plan both adequate and appropriate to ensure that there will be sufficient coordination and communication among the PD(s)/PI(s)?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the Center involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

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

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

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

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

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypotheses and intervention(s) well supported by preliminary data, clinical and/or preclinical studies, 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?

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

Specific for this FOA

Do the investigators commit adequate effort to successfully fulfill the proposed projects needs? If applicable, do the Project Leaders and key personnel have the experience and expertise with regulatory activities, including IND/IDE submissions and safety oversight and reporting?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, 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?

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?

In addition, for applications involving clinical trials

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?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA

For proposed observational or cross-sectional clinical studies, are the timeline for protocol development and implementation, plans for recruitment and retention of study participants, proposed study site(s), safety monitoring and plans for management and analysis of study data appropriate and feasible?

If animal studies are included, is the relevance of the proposed animal models to human asthma and/or allergic diseases sound and with high scientific merit? Is there strong scientific potential for findings in animals to translate to human disease? Could similar data have been obtained from human study participants instead of animal models?

In addition, for applications involving clinical trials

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?

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?

In addition, for applications involving clinical trials

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

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

Reviewers will consider each of the review criteria below, as appropriate for the individual core, in the determination of scientific merit and provide an overall impact score for each Core, but will not give separate scores for these items.

• Are the staffing and administrative plan appropriate to facilitate attainment of the objectives of the proposed program? Are the experience, level of commitment, and availability of the Core Leader adequate to manage the core and the overall program?
• Is the plan to organize communications, group meetings, and teleconferences adequate and appropriate? Are the plans for coordination, problem identification and resolution, and establishment of a strong collaborative environment for the program appropriate?
• Are the plans for resource allocation within the program adequate and appropriate?
• Is the management plan for fiscal accountability and communication within the program appropriate?
• Does the administrative core include a plan of administering the AADCRC Infrastructure and Opportunity Fund (IOF) as described in this FOA and is this plan appropriate?
• Are the plans for conflict resolution and leadership succession appropriate?

• Is provision of the proposed core services to two or more Research Projects critical and justified?
• Is the relationship of the core to the central scientific theme of the overall program strong?
• Are the quality of the relevant facilities or services provided (including procedures, techniques, quality control) and criteria for prioritization of usage appropriate?
• Are the proposed personnel appropriate to lead and staff the core? Is the commitment of the Core Leader and other staff sufficient? Are the experience, level of commitment, and availability of the Core Leader adequate to manage the core?
• Does the Clinical Core leader, if applicable, have both the expertise/capabilities and demonstrated experience to support the clinical research activities proposed in the application?
• Does the Clinical Core leader, if applicable, have the experience and expertise to guide and/or assist in the development and preparation of documentation required for clinical research as well as experience with regulatory activities, including IND/IDE submissions, recruitment and retention of study participants, medical monitoring, and safety oversight and reporting?
• Is there sufficient Data Management infrastructure to support the proposed activities?
• Is there sufficient effort and expertise dedicated to data management and data transfer to ImmPort or other public portals designated by NIAID?
• If a non-hypothesis driven clinical trial(s) is proposed, are the selection of the study population, proposed study site(s), study design, plans for recruitment and retention of study participants and plans for trial management sound and feasible?

As applicable for the project or core 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

Specific to applications involving clinical trials

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)?

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

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

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

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

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

Not Applicable

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

Not Applicable

As applicable for the project or core 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.

Not Applicable

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

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

Are sufficient effort and expertise dedicated to data transfer to ImmPort or other public portals designated by NIAID?

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.

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National 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.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

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 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).

Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

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

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

Determine and coordinate the scientific and administrative activities of the approved projects; set project goals and timelines; accept and implement common guidelines approved by the Steering Committee.

To promote rapid public access to AADCRC-supported data, NIAID expects that all AADCRC investigators will share their AADCRC-supported data publicly through ImmPort (https://immport.niaid.nih.gov) or other public portals designated by NIAID. The privacy of participants will be safeguarded and confidential and proprietary information will be protected. The PD(s)/PI(s) are responsible for developing data sharing plans to be presented to the NIAID Program Official assigned to the grant for approval. Sharing plans represent a commitment by the applicant institution (and its sub-contractors, if any) to support and abide by the plan. The PD/PI will establish procedures within the center to ensure that all members of that center, including any scientists added via IOF support, conform to the data-sharing plan.

Protocol Development, Review and Approval

• Protocol Development. After awards are made, AADCRC Principal Investigators will fully develop the clinical research protocols for projects supported by this FOA with the participation of the NIAID Division of Allergy, Immunology, and Transplantation (DAIT) staff. AADCRC protocols will utilize the protocol templates provided by NIAID.
• Protocol Review and Approval. The AADCRC PD(s)/PI(s) will provide all clinical research protocols to NIAID for review and will not implement the protocol until all NIAID approvals are obtained and a NIAID DAIT Project Scientist is assigned.
• Monitoring Boards. The AADCRC PD(s)/PI(s) will adhere to the decisions of the NIAID Data and Safety Monitoring Board (DSMB) or any other monitoring body that the NIAID will assign to the study.

Clinical Trial Monitoring

In all AADCRC clinical trials and studies, the PD(s)/PI(s) of the Center has the financial and organizational responsibilities for data and safety site monitoring and medical monitoring. These include monitoring compliance with good clinical research practices, regulatory compliance, accurate protocol implementation, internal quality assurance, and test agent accountability at the clinical research sites.

In all clinical trials and in some clinical studies (to be identified by NIAID post-award), the Center PD(s)/PI(s) is responsible for including an Independent Safety Monitor (ISM) in the clinical monitoring plan. The ISM is a licensed physician with clinical research experience, administratively independent from the PD(s)/PI(s) team. The ISM will conduct safety monitoring by reviewing all serious adverse events, protocol deviations, individual and study stopping rules. In some studies (to be identified by NIAID post-award), the ISM may also be required to conduct pre-study initiation protocol and consent document review, as well as periodic post-initiation safety and data review.

Access to Data

The PD(s)/PI(s) is responsible for making data available for external checking against the original source documentation.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. However, awardees must be committed to making the biological samples, diagnostic products, and other research tools, methods, data, and materials that they develop under AADCRC awards available to the AADCRC and the research community. This includes timely submission of all data and data analysis obtained under this award to the ImmPort database or to other public portals designated by NIAID per policies established by the AADCRC Steering Committee. Informed consent/assent forms utilized in AADCRC-supported clinical trials or studies should reflect this commitment.

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

NIAID may assign a Project Scientist to an AADCRC Center. The Project Scientist will

• provide guidance and support in the design of research activities
• serve as a resource for protocol design and development
• provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities
• advise in the selection of sources or resources
• advise in management and technical performance.

In AADCRC Centers that include clinical trials and, in some cases, clinical studies, the NIAID-assigned Project Scientist will be a Medical Officer. In those studies, NIAID may also assign a Project Manager who will provide guidance and support for clinical research to be conducted per guidelines.

Two NIAID Project Scientists will be non-voting members of the Steering Committee and participate in all Steering Committee activities.

Overall, the role of the NIAID Project Scientists will be to facilitate and not direct activities. It is anticipated that decisions in all activities will be reached by consensus and that the NIAID Project Scientists will participate in this process.

Clinical Research Oversight

Protocol Development, Review and Approval

NIAID staff will participate with AADCRC PD(s)/PI(s) in the development, review, and approval (as mentioned above) of all clinical trial and some non-trial, clinical study protocols for projects supported by this FOA. All clinical research protocols will be reviewed by NIAID and, depending on their level of complexity and risk, will be further reviewed by the NIAID DAIT Clinical Research Committee and by the NIAID DAIT Data and Safety Monitoring Board (DSMB) or another monitoring body. Prior to initiation, all clinical research protocols must be approved by an assigned NIAID Medical Officer.

IND/IDE

For clinical trials under this FOA where NIAID is not the IND/IDE sponsor, NIAID will provide guidance on the development and submission of required regulatory documents, e.g., those regarding the use of investigational drugs, to the FDA or other applicable health authorities. NIAID retains the right to have NIAID serve as the IND/IDE sponsor.

Clinical Trial Monitoring

If NIAID holds the IND/IDE for a clinical trial supported by this FOA, NIAID will be responsible for monitoring compliance with good clinical research practices, regulatory compliance, accurate protocol implementation, internal quality assurance, and test agent accountability at the clinical research sites. In studies where NIAID does not serve as the IND/IDE sponsor, NIAID will review and approve the clinical monitoring plan, review the recruitment status of the trial on an ongoing basis, review the results of clinical trials, and provide oversight of data and safety monitoring.

Monitoring Boards and Safety Reporting

NIAID will convene an independent NIAID Data and Safety Monitoring Board (DSMB) or another monitoring body to review and monitor any protocols deemed to possess more than minimal risks.

If NIAID holds the IND/IDE for clinical trials supported by this FOA, NIAID will be responsible for reporting safety information in accordance with FDA requirements. An NIAID Medical Officer or NIAID designated contractor will monitor the clinical trials and serve as the Medical Monitor.

Study Termination

NIAID reserves the right to terminate or curtail a clinical study or clinical trial for any of the following reasons:

• risk to subject safety;
• the scientific question is no longer relevant or the objectives will not be met;
• failure to comply with Good Clinical Practices, 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;
• failure to remedy deficiencies identified through site monitoring;
• substandard data; inadequate progress in fulfilling the research agenda;
• slow accrual; or
• reaching a major study endpoint substantially before schedule with persuasive statistical significance.

Access to Data

The NIAID Project Scientist or designee will have access to all data generated under this cooperative agreement, and may review the data as recorded on the case report forms or in a database. Data must be available for external checking against the original source documentation. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study.

The Project Scientist will negotiate data deposition timelines with each awardees post award, and facilitate data deposition to either ImmPort (https://immport.niaid.nih.gov) or to another NIAID resource.

Performance Monitoring

The NIH Project Scientists will review the performance of each participating AADCRC through consideration of annual reports, site visits, and compliance with NIH procedures.

Scientific and Programmatic Oversight

An NIAID program official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. This stewardship includes monitoring program progress, approving changes and concurring in proceeding into study implementation stage. Release of each yearly funding increment for AADCRC U19s will be based on satisfactory progress.

Areas of Joint Responsibility include:

Steering Committee

A Steering Committee will serve as the governing board for AADCRC awardees. All participants in the AADCRC program are bound by the policies and procedures developed by the Steering Committee; adoption of such policies and procedures requires a majority vote. Awardees under this FOA will be required to accept and implement policies approved by the Steering Committee.

Membership in the Steering Committee will include the PD(s)/PI(s) of each AADCRC U19 award, a designated representative in the case of Multiple PD(s)/PI(s) award, and two NIH Project Scientists. The chair will be chosen by a majority vote of the Steering Committee, with terms determined by the committee. Each AADCRC center will have one vote. The two NIH Project Scientists will be non-voting members and will not serve as the Chair of the Steering Committee.

For multi-PD(s)/PI(s) applications, only one PD/PI per AADCRC U19 will be allowed to serve on the Steering Committee at a time. For these multi-PD/PI U19s, the representing PD/PI should be declared by notification sent to the NIAID Steering Committee Project Scientist and the Steering Committee Chair. Such notification must be signed by all PD(s)/PI(s) of the U19 in question. The same process will be followed if a change in the PD/PI representing the multi-PD/PI U19 at the Steering Committee is to be made.

Steering Committee responsibilities will include:

• Evaluating and recommending new collaborations and resource allocations among AADCRC members;
• Establishing goals and priorities for the use of the Infrastructure and Opportunity Funds; developing policies, procedures, and instructions for the solicitation, submission and approval of proposals to use these funds.
• Coordinating research resource sharing among AADCRC, including reagents and samples.
• Setting the scientific agendas for the AADCRC yearly face-to-face scientific meeting.
• Proposing AADCRC-centered sessions for national and international scientific meetings

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 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.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

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

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Gang Dong, MD, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3508
Email: [email protected]

Thomas Conway, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5075
Email: [email protected]

Jordan A. Kindbom
National Institute of Allergy and Infectious Disease (NIAID)
Telephone: 240-669-2983
Email: [email protected]

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

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