Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)

Funding Opportunity Title

Asthma and Allergic Diseases Cooperative Research Centers (U19)

Activity Code

U19 Research Program – Cooperative Agreements

Announcement Type

Reissue of RFA-AI-10-013

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-AI-12-006

Companion FOA

None

Number of Applications

Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.

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

 93.855, 93.856 

FOA Purpose

The National Institute of Allergy and Infectious Diseases (NIAID) invites new or renewal applications from single institutions and consortia of institutions to participate in the Asthma and Allergic Diseases Cooperative Research Centers (AADCRC) program. The purpose of this AADCRC Funding Opportunity Announcement (FOA) is to support basic and clinical research on the immunological basis, pathobiology, diagnosis, treatment and prevention of asthma and allergic diseases and to accelerate the application of fundamental knowledge of immune function to the investigation, prevention, and treatment of asthma and allergic diseases.

Key Dates
Posted Date

November 28, 2011

Letter of Intent Due Date

March 24, 2012

Application Due Date(s)

April 24, 2012   

AIDS Application Due Date(s)

Not Applicable 

Scientific Merit Review

October, 2012  

Advisory Council Review

January, 2013

Earliest Start Date(s)

April, 2013 

Expiration Date

April 25, 2012

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) invites new or renewal applications from single institutions and 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 basic research to conduct studies on the mechanisms underlying the onset and progression of asthma and allergic diseases including allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy. The overarching goal of the program is to improve the understanding of the pathogenesis and diagnosis and treatment of asthma and allergic diseases, and to provide a rational foundation for the development of effective treatment and prevention strategies.

Background

Asthma and allergic diseases are among the major causes of illness and disability in the United States for all ages; the trend of the diseases is still on the rise. A recent nationwide survey found that more than half (54.6%) of all U.S. citizens test positive to one or more allergens, which is thought to be a predictor for eventual development of allergic conditions. Major allergic disease types include asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis, and food allergy. Asthma affects 8.2% of the U.S. population (almost 25 million people) and 9.6% of children. The prevalence of asthma in the U.S. continues to increase and the number of people with asthma worldwide is predicted to increase by more than 100 million by 2025. Allergic rhinitis is estimated to affect approximately 60 million people in the U.S. Chronic rhinosinusitis is one of the leading forms of chronic disease in the U.S. Thirty-one million people suffer from chronic rhinosinusitis, leading to roughly 15 million doctor visits and 200,000 sinus surgical procedures each year. Atopic dermatitis affects 10% to 20% of children and 1% to 3% of adults in the U.S. Food allergy affects about 6 to 8% of children under the age of four, and more than 3.7% of adults in the U.S. More significantly, food allergy is the most frequent single cause of emergency room visits for anaphylaxis and accounts for 34 to 52% of these visits. As the adverse impact of asthma and allergic diseases on public health continues to grow, there is an urgent need for the development of novel approaches to treat and, eventually, prevent these diseases.

Research during the past decades has increased our understanding of the pathogenesis of asthma and allergic diseases. A Th2-dominant immune response was long considered as the underlying mechanism of many allergic diseases. Evidence now also supports the idea that the innate immune system plays a central role in these diseases. Additional types of T cell responses (e.g. Th17) may also contribute to these diseases. Other disease triggers such as viral infections, environmental pollutants, and/or other stimuli, interact with various susceptibility factors involved in innate immunity and epithelial/mucosal functions and together contribute to the pathogenesis of asthma and allergic diseases. It is widely believed that specific environmental exposures lead to the expression of allergic phenotypes in previously unaffected, but genetically predisposed individuals.

Despite the importance of these research findings, only modest advances on the therapy of asthma and allergic diseases have materialized.  Currently, the management of asthma is complex and treatment regimens for rhinitis and chronic rhinosinusitis are aimed at controlling inflammation and alleviating symptoms.  Effective control of asthma poses stringent compliance requirements, and severe asthma is still difficult to control. In addition, most of the drugs currently used to treat asthma and allergic diseases have a number of undesirable side effects and, in some cases, overuse can actually lead to worsening of the disease. This underlines the need for the development of new therapeutic approaches, particularly those that involve immunomodulation.

The NIAID AADCRC program, established more than three decades ago as the first targeted research program in the field of asthma and allergic disease, is the cornerstone of NIAID's efforts to promote innovative, multidisciplinary clinical and basic research on asthma and allergic diseases. Supported by a multi-project grant mechanism, the program aims to leverage expertise provided by centers around the U.S. through collaborations among researchers. The program currently supports 12 AADCRC U19 grants, 4 of them will end by early 2013.

Research Objectives and Scope

Consistent with overall goals of the AADCRC program, the objective of this FOA is to support multidisciplinary and multi-project research programs with the focus on pathogenesis of asthma and allergic diseases in humans. Applications considered to be responsive to this FOA must be composed of a minimum of three interrelated research projects structured around a central scientific theme that is clearly relevant to the pathogenesis of, and intervention strategies for asthma and allergic diseases.

This FOA will focus on diseases with high public health impact. These include asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy. In order to stress the integration and focus of the applications on human disease-related mechanisms, NIAID requires that the majority of the proposed research in each application be defined as NIH human subjects research. (For the NIH definition of human subjects research, please see the NIH Office of Extramural Research Human Subjects website http://grants.nih.gov/grants/policy/hs/index.htm)

The NIAID solicits applications under this FOA that are highly integrated and synergistic. Component projects within a single U19 application should not only relate to a central theme relevant to asthma or other allergic diseases, but also relate to the other component projects within the same application. In order to achieve this objective, NIAID highly recommends applications be drafted using one of the two models provided below. 

MODEL A

The grant application focuses on the role of an immunologic mechanism/pathway that is hypothesized to be an important pathobiologic process in asthma or other allergic diseases.  This mechanism/pathway may involve a single 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, adjuvants and pollutants).  The grant application should include projects that address this pathway from various perspectives including clinical studies or clinical trials, genetics, systems biology approaches, mathematical modeling, in vitro work, and animal models.  The majority of the proposed research should utilize human material (including primary human cells, biologic samples, and clinical data). Any proposed animal studies must be of relevance to human asthma and allergic diseases and the rationale for using animal studies should be based on a sound scientific need and on inability to address the hypothesis using human material.  

MODEL B

The grant 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 or a novel mechanistic hypothesis in asthma or other allergic diseases. The clinical trial(s) or study(ies) constitute the source of material that supports the conduct of a series of associated in vitro studies that test the central hypothesis of the grant in a comprehensive manner.  The grant application should include projects built around the clinical trial(s) or study(ies) including mechanistic studies, genetics, systems biology approaches, and mathematical modeling.  Animal models may be utilized in parallel to the clinical trial(s) or study(ies), only if they provide more in-depth hypothesis testing on outcomes that cannot be assessed in human trials or studies. Such animal studies should represent a minor component of the overall U19 application.

Examples of research relevant to both models include, but are not limited to, the following areas:

This FOA will not support:

Applications proposing such studies will be considered non-responsive and will not be reviewed. 

Clinical Research Projects (required)

The majority of research proposed must meet the NIH definition of clinical research (http://grants.nih.gov/grants/policy/hs/index.htm) and should involve individuals with clinically defined asthma and/or allergic diseases, or should involve 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. See Section IV.B.5 Specific Instructions for Individual Research Projects, “Clinical trial projects”, for detailed NIH definition of clinical trials. Studies using human specimens obtained from relevant ongoing or completed clinical studies or clinical trials may be proposed.

Core Facilities

A separate Administrative Core is not allowed under this FOA. Instead all administrative aspects of the program should be described in the Overall Research Strategy section of the Center Program Overview.

Scientific Core(s), Clinical Trial Implementation Core, Data Management and Analysis Core (optional):  Such cores may be proposed if they support the multi-project grant as a whole and directly support at least two of the proposed research projects.  The application must indicate which specific projects each Core will support.  If the application proposes to conduct more than one clinical trial or clinical study, a Clinical Trial Core may be proposed.  This Core will be responsible for the organizational and regulatory aspects of the clinical trials and studies and may include data administration and analysis functions; alternatively, data management and analysis may be conducted under a separate Data Management and Analysis Core.

The Cores should present a clear picture of the facilities, techniques, and skills these cores will provide and describe the role of the Scientific Core Leader and each of the key participants.  The apportionment of dollars or percentage of dollars that will be required to support each component research project that will utilize each scientific core should be included in the Core budget.

Statistical Design, Analysis and Data Management and Safety Monitoring for Clinical Trials and Studies

This FOA will not support a separately funded, centralized, stand-alone statistical and clinical coordinating center.

The applicant is responsible for including the costs of all support for statistical design, data collection, analysis and management, as well as the costs for clinical site monitoring, medical monitoring, project management and quality assurance of the proposed clinical trials or interventional clinical studies in the application budget. For responsibilities associated with Investigational New Drug (IND) or Investigational Device Exemption (IDE) sponsorship, the awardee is required to comply with NIH and U.S. Food and Drug Administration (FDA) regulatory requirements for data and clinical monitoring, reporting, and the protection of human subjects. See Section VI.2. - Cooperative Agreement Terms and Conditions of Award below. The NIAID retains the right to be the IND/IDE sponsor in selected clinical trials.

Steering Committee

NIAID, in conjunction with the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) of all AADCRC grants will establish a Steering Committee to serve as the governing body for all AADCRC activities. All Program Director(s)/Principal Investigator(s) must serve on the Steering Committee. For multi-PD(s)/PI(s) applications only one PD/PI per AADCRC grant will be allowed to serve on the Steering Committee at a time. Members of the Steering Committee will be required to accept and implement common guidelines and procedures approved by the Steering Committee. Steering Committee components and responsibilities are further described under Section VI.2.  Cooperative Agreement Terms and Conditions of Award - Areas of Joint Responsibility

Infrastructure and Opportunity Fund

Under previous FOA, NIAID established a single Infrastructure and Opportunity Fund (IOF) of up to $500,000 per year to support new clinical research projects and resource development projects, led by or through collaborations with AADCRC investigators, to capitalize on emerging opportunities in the pathophysiology and therapy of target illnesses, which include asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy. The Infrastructure and Opportunity Fund will support new research opportunities not proposed at the time of the awards. The Steering Committee has established goals, priorities, and evaluation criteria for use of the funds. Post award, Program Director(s)/Principal Investigator(s) funded under this FOA will have an opportunity to compete for IOF and will be provided with details regarding IOF management and the application process, as well as the scope of research supported by the funds. 

Potential applicants are strongly encouraged to consult with the appropriate NIAID program contact listed in Section VII.  Agency Contacts during the early stages of preparation of the application. 

See Section VIII Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

New
Renewal

The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIAID intends to commit $6.5 million per year under this FOA, and anticipates approximately 3-4 awards will be made.

Award Budget

Direct costs for each AADCRC award are expected to be approximately $1,000,000 per year.

Award Project Period

The total project period for an application submitted in response to this FOA may not exceed five years.  

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

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

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

Note that the multiple PD(s)/PI(s) option may be used only for the Overall Program.  The multiple PD(s)/PI(s) option is not available for the leadership roles of the individual research projects or cores within the multi-project application.

An investigator can serve as a PD(s)/PI(s) on only one AADCRC award or application. This includes all PD(s)/PI(s) of a multiple-PD(s)/PI(s) application. In addition, the PD(s)/PI(s) of each AADCRC U19 application (and every PD(s)/PI(s) of a multi-PD(s)/PI(s) application) must also serve as a Project Leader, and is required to commit a minimum of 3 person months in AADCRC activities.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed. NIAID will not award more than one AADCRC grant to an applicant institution and NIAID will not make an award to institutions that are currently funded under RFA AI-10-013.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Section IV. Application and Submission Information

1. Address to Request Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

The letter of intent should be sent to:

Paul Amstad, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3121, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service Express or regular mail)  
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: 301-402-7098
FAX:  301-480-2408
Email:  pamstad@mail.nih.gov

Application Submission

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

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

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

Paul Amstad, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3121, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service Express or regular mail)  
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: 301-402-7098
FAX:  301-480-2408
Email:  pamstad@mail.nih.gov

Page Limitations

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed.

Research Plan

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Supplemental Instruction for the Preparation of Multi-Project Applications

The following section supplements the instructions found in Form PHS 398 for preparing a multi-project grant application. Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme. 

The supplemental instructions for multi-project applications below are divided as follows:

A. General Instructions – addresses collaborative efforts among research projects, the administrative and organizational structure as well as the overall facilities and environment, and the overall budget.

B. Specific Instructions for Individual Research Projects – describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the Project.

C. Specific Instructions for Cores – Describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the Core.

A. General Instructions

All applications must be submitted on Form PHS 398.  The multi-project grant application should be assembled and paginated as one complete document.

1. Face Page

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

2. Description

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

Project/Performance Sites

List the performance sites where the research will be conducted.

Key Personnel

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

3. Table of Contents

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

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

4. Composite Budget

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

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

Component

Year 1

Year 2

Year 3

Year 4

Year 5

All Years

Project 1. Invest.

125,000

130,000

135,200

140,608

146,232

677,040

Project 2. Study

125,000

130,000

135,200

140,608

146,232

677,040

Project 3. Develop.

100,000

104,000

108,160

112,486

116,985

541,631

Core A. Clinical Core.

50,000

52,000

54,080

56,243

58,493

270,816

Core B. DNA

25,000

50,000

52,000

54,080

56,243

237,323

Totals

425,000

466,000

484,640

504,025

524,185

2,403,850













5. Total Direct Costs for the Entire Budget Period

Complete the Total Direct Cost line entries for all requested budget periods (years) and the Total Direct Cost for Entire Period of Support entry. Detailed budgets are required within the descriptions of each project and core (see below). Assume a standard 2% escalation from the initial to the future year(s) of support.

6. Biographical Sketch

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

7. Resources

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

8. Center Program Overview (Research Objectives and Strategic Plan)

Specific Aims (Limited to 1 page.)

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

Overall Research Strategy (Limited to 12 pages)

This narrative section summarizes the overall research plan for the multi-project application and is limited to twelve (12) pages.  The multi-project application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another.  This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program – by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems.  As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme.  Summarize the special features in the environment and/or resources that make this application strong or unique.

If you choose to appoint a Program Advisory Committee (optional), describe the expertise and responsibilities of your potential Program Advisory Committee 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.

Do not propose an administrative core. All administrative aspects should be described in the overall research strategy. Describe the organizational and administrative structure of the proposed multi-project application.  Include plans on how the PD(s)/PI(s) will interact with Project 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 training and experience of proposed staff and the functions to be performed; how fiscal and other resources will be prioritized, allocated and managed; how communications will be facilitated; and how research related travel and training will be budgeted.  Funding for the overall administrative efforts, including administrative services, expenses for publications demonstrating collaborative efforts, and communication expenses, should be requested in the PD(s)/PI(s)’project.

If the application is a renewal, this section should also highlight past performance and the major accomplishments from the prior funding period as described in the PHS 398 Instructions.  In addition to discussing results from individual projects, describe the synergy and collaborations that occurred within the Program.  For individual research projects and cores that will be continued as part of a renewal application, additional details should be provided in the progress report section of the Research Strategy within each research project and core.

9. Checklist

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

10. Appendix Materials

Refer to Section IV.6. “Appendix Materials” below, for instructions on submitting appendix materials.

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

B. Specific Instructions for Individual Research Projects

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each research project.

For each individual Research Project, include:

Face page (see special instructions, below)

Description & Key personnel (PHS 398 Form Page 2)

Table of Contents (PHS 398 Form Page 3)

Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications

Research Plan

Resources

1. Cover Page

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

2. Description

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

Project/Performance Sites

List the performance sites where the research will be conducted.

Key Personnel

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

3. Table of Contents

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

4. Detailed Budget for Initial Budget Period

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

Budget request should also include travel funds for the Principal Investigator to participate in annual Steering Committee meetings, and PD(s)/PI(s) and subproject PD(s)/PI(s) to attend annual two-day AADCRC scientific meetings to be held in conjunction with the Steering Committee meeting in Bethesda, Maryland (see the Section VI. Award Administration Information, Cooperative Agreement Terms and Conditions of Award, Meetings).

5. Individual Research Project Research Plan

(A minimum of three individual research projects are required)

Specific Aims (Limited to 1 page.)

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

Research Strategy (Limited to 12 pages.)

Use this section to 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.

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

Non-clinical research projects

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

Clinical research projects

Clinical trial projects: The NIH defines a clinical trial as a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (such as drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective. Behavioral human subjects research involving an intervention to modify behavior (such as diet, physical activity, cognitive therapy, etc.) fits this definition. Research with human subjects to develop or evaluate clinical laboratory tests (imaging or molecular diagnostic tests) might be considered as 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. In general, a clinical trial should be presented as an individual project of the U19 application. If two trials are highly related and share most aspects of study design, they can be presented within the same individual project.

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

In addition, the following information is required and should be presented in the Research Plan under “Section 6. Protections for Human Subjects” (not included in the 12 page limit for the Research Strategy):

Clinical study projects

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

For clinical study applications that plan to obtain human samples derived from parent 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:

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. This documentation should be supplied in the form of letter(s) of support. 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 been consented and the material they have provided can be used by the AADCRC project.

6. Resources

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

7. Biographical Sketch

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

C. Specific Instructions for Core(s)

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each proposed core.

For each individual Core, include:

Cover page (see special instructions, below)

Description & Key personnel (PHS 398 Form Page 2)

Table of Contents (PHS 398 Form Page 3)

Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications

Core Services Plan

Resources Format Page

1. Cover Page

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

The following are specific instructions for sections of the PHS 398 application form that are to be completed differently than usual.  For all other items in the core application, follow the usual PHS 398 instructions.

2. Description

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

Project/Performance Sites

List the performance sites where the core activities and services will be conducted.

Key Personnel

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

3. Table of Contents

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

4. Budget Pages

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

5. Individual Core Services Plan

Specific Aims (Limited to 1 page.)

List in priority order, the broad, long-range objectives and goals of the proposed core. In addition, state the core’s relationship to the Center’s goals and how it relates to the individual research projects or other cores in the application.

Core Services (limited to 6 pages)

Use this section to describe how the proposed core activities will contribute to meeting the Center's goals and objectives and explain the rationale for selection of the general methods and approaches proposed to accomplish the specific aims.  In addition, this section should indicate the relevance of the core to the primary theme of the application.

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

6. Resources

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

7. Biographical Sketches

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

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies; GWAS) as provided in the PHS398 Application Guide, with the following modification:

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide..

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS398 Application Guide.

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

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. Other Submission Requirements and Information

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

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Overall Impact - Overall

Reviewers will provide an overall impact/priority 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 Center proposed).

Is the Center as a whole scientifically compelling? Are there coordination and synergy of the individual research projects and cores towards the achievement of the central objectives of the Center? Are the overall Center goals significant and focused on studies that meet the objectives of the FOA? Will the integration of the individual projects into a single Center be more beneficial than pursuing each project independently? Do(es) the PD(s)/PI(s) have the leadership and scientific ability to develop an integrated and focused research Center? Will the PD(s)/PI(s) and other Project/Core Leaders devote adequate time and effort to the Center? Is there adequate evidence of sufficient institutional support for the PD(s)/PI(s) in terms of laboratory space, equipment and other resources? For applications designated multiple PD(s)/PI(s), is the Leadership Plan both adequate and appropriate to ensure that there will be sufficient coordination and communication among the PD(s)/PI(s)? Is the administrative and organizational structure appropriate and adequate to the attainment of the objective(s) of the proposed Center? Is the management plan for fiscal accountability and communication within the Center appropriate?  Are the plans for coordination, communications, problem identification and resolution, and the establishment of a strong collaborative environment for the Center appropriate? For renewal applications, have the Center's accomplishments made a major impact on the field or successfully achieved their original goals?

Overall Impact– Individual Research Projects

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

Scored Review Criteria - Individual Research Projects

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  Is the rationale for the relevance of the proposed animal models to human asthma and/or allergic diseases sound and with high scientific merit? If a clinical trial(s) is proposed, is there potential for the clinical trial to significantly advance the prevention and/or treatment of asthma and/or allergic diseases or to provide mechanistic information that will facilitate the development of new therapeutic approaches? 

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the clinical project leader have both the expertise/capabilities and demonstrated experience to support the clinical research activities proposed in the U19 applications as a whole? Does the clinical project leader 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?  Do the investigators commit adequate effort to successfully fulfill the proposed projects’ needs? 

Innovation

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

Approach

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

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? If a clinical trial(s) is proposed, are the selection of the study population, the applicant’s plans for managing the proposed trial, including management and reporting of study data and monitoring safety, and the timeline for protocol development and implementation, plans for preparation of an Investigational New Drug or Investigational Device Exemption application, and plans for recruitment and retention of study participants sound and feasible? Are the applicant’s overall approaches to overcoming obstacles and limitations sound and feasible?  If animal studies are included, is the choice of animal model justified in relation to what can be achieved using human data?  

Environment

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

Additional Review Criteria - Overall

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable.  

Renewals

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

Revisions

Not Applicable. .

Additional Review Considerations - Overall

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

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

Scored Review Criteria – Cores

Is provision of resources and core services to two or more of the Research Projects critical and justified? Is the relationship of a scientific and/or clinical core to the central focus of the overall Center strong? Are the quality of the relevant facilities or services provided and criteria for prioritization and usage appropriate? Are the qualifications, competence, and commitment of the Core Leader and key personnel appropriate? Does the clinical core leader have both the expertise/capabilities and demonstrated experience to support the clinical research activities proposed in the U19 applications? Does the core leader 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?

2. Review and Selection Process

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

As part of the scientific peer review, all applications:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

PD(s)/PI(s) will be responsible for defining the research objectives, approaches and details of the projects within the guidelines of the FOA and for performing the scientific activity. PIs shall ensure compliance with NIH clinical research policy and NIAID Clinical Terms of the Award in all AADCRC U19 supported research activities.

Principal Investigators must agree to Documentation of Commitment to the Collaborative Group. This is a written commitment, signed by the Principal Investigator and the applicant institution, to participate in the cooperative research program, including serving on the Steering Committee, adhering to Steering Committee policies and decisions, and accepting the participation and assistance of NIH staff in accordance with the guidelines described in the NIH staff responsibilities in these Terms and Conditions of Award.

Clinical Research Responsibilities

The PD(s)/PI(s) is responsible for ensuring that, in accordance with NIH policy, all clinical trials performed through the AADCRC must be conducted in accordance with the International Conference on Harmonization (ICH) Good Clinical Practices and applicable Federal regulations. The PD(s)/PI(s) will ensure that all individuals involved in clinical research projects provide current GCP certification prior to project initiation.

1. Protocol Development, Review and Approval

a. 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.

b. 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 Medical Officer is assigned.

c. Monitoring Boards. The AADCRC PD(s)/PI(s) will cooperate with and will abide by the decisions of the NIAID Data and Safety Monitoring Board (DSMB) or any other monitoring body that the NIAID will assign to the study.

2. Investigational New Drug Applications (IND)

It is the responsibility of the PD(s)/PI(s) to contact Regulatory Authorities and obtain guidance as to the need for an IND or IDE (Investigational Device Exemptions) for interventions (whether to be used for therapeutic or mechanistic purposes) that are planned to be employed in any clinical study or trial, 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. In most cases of clinical trials under the FOA where an IND/IDE is required, 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. This includes but is not limited to all communications with the FDA (or other regulatory authority) and the IRB. In rare cases, NIAID retains the right to become the IND/IDE sponsor. If the 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.

3. 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.  Additional responsibilities to regulatory authorities that arise as a result of the PD(s)/PI(s) or another scientist of the Center being the IND/IDE sponsor of clinical trials supported by this FOA also belong to the PD(s)/PI(s) of the Center.

For all clinical trials and some clinical studies (to be identified by NIAID post-award), the PI is responsible for ensuring independent monitoring through a clinical monitoring plan and for obtaining NIAID approval of the plan. This plan should include site monitoring by experienced professionals who are independent from the Center PD(s)/PI(s) or the trial or study investigators.  In addition, 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. 

4. Safety Reports

If the PD(s)/PI(s) is the IND/IDE sponsor in any clinical trial supported by this FOA she/he is responsible for submitting complete safety reports to the FDA, per FDA regulations.  The PD(s)/PI(s) will submit these reports to NIAID for review prior to submission to the FDA.  For all clinical trials that are under a DSMB (or any other monitoring body) review, even if no IND/IDE is involved, the PD(s)/PI(s) has the responsibility for preparing and presenting annual safety reports.

Access to Data

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

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, per policies established by the AADCRC steering committee.

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 grant.  Project Scientists may provide guidance and support in the design of research activities, may serve as a resource for protocol design and development, may provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, may advise in the selection of sources or resources, and may 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 addition, two NIAID Project Scientists will be non-voting members of the Steering Committee and participate in all Steering Committee activities, including conference calls, subcommittees and special committees. However, 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

1. 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.

2. 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 all 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.

3. 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.

4. Safety Reports

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.

5. Study Termination

NIAID reserves the right to terminate or curtail a clinical study for any of the following reasons: (1) risk to subject safety; (2) the scientific question is no longer relevant or the objectives will not be met; (3) failure to comply with Good Clinical Practices, federal regulations, or Terms and Conditions of Award; (4) occurrence of unforeseen drug safety issues or data from preclinical studies indicate a presence of unanticipated toxicity; (5) risks that cannot be adequately quantified; (6) failure to remedy deficiencies identified through site monitoring; (7) substandard data; (8) inadequate progress in fulfilling the research agenda; (9) slow accrual; or (10) reaching a major study endpoint substantially before schedule with persuasive statistical significance.

6. Access to Data

The NIH Project Scientists 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. The NIH may provide public access to selected data sets generated with the use of public funds within a reasonable time after the primary analysis and publication.

7. 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 a review of progress. The Government, via the NIAID program official, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies.

Areas of Joint Responsibility include:

Steering Committee

A Steering Committee will serve as the governing board for AADCRC grantees. 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. The Steering Committee meetings will be organized by the Chair of the Steering Committee. Each U19 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.

Steering Committee responsibilities will include:

Meetings

NIAID will arrange quarterly Steering Committee teleconferences, and annual face-to-face meetings in conjunction with the annual AADCRC scientific meeting. The annual AADCRC scientific meeting is open to the members of AADCRC. The annual scientific meeting is a forum for members of AADCRC to provide the latest update on their research, exchange ideas and information, and discuss collaborations among members of AADCRC. Meeting participants will identify the group's tangible resources, capabilities, and needs to advance the AADCRC's overall goals. The PD(s)/PI(s) of each AADCRC (or a designated representative for multiple PD(s)/PI(s) awards) is required to make an oral presentation on current and planned activities and projects.

The two-day scientific meeting will be held each year in Bethesda, Maryland. 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.

Dispute Resolution:

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

3. Reporting

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Gang Dong, M.D., Ph.D.
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
Room 6605, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Telephone: (301) 496-8973
FAX: (301) 480-5824
Email: gdong@niaid.nih.gov 

Peer Review Contact(s)

 Paul Amstad, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3121, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service Express or regular mail)  
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: 301-402-7098
FAX:  301-480-2408
Email: pamstad@niaid.nih.gov

Financial/Grants Management Contact(s)

Leslie Boggs
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2111, MSC-7614
6700B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 402-6450
FAX: (301) 493-0597
Email: boggsl@mail.nih.gov  

Section VIII. Other Information

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

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
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