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

Atopic Dermatitis Research Network (ADRN) (U19)

Activity Code

U19 Research Program – Cooperative Agreements

Announcement Type

New

Related Notices
  • June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
Funding Opportunity Announcement (FOA) Number

RFA-AI-14-033

Companion Funding Opportunity

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 

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) solicits applications from institutions to administer a multi-project, multi-institution program to conduct clinical research and provide the leadership and administrative responsibilities for the Atopic Dermatitis Research Network (ADRN). The ADRN conducts clinical research studies to better understand host defense mechanisms in the skin, by comparing responses to infections and vaccines, and underlying mechanisms, in healthy, non-atopic individuals vs. those with atopic dermatitis (AD). Such effects include skin barrier and adaptive and innate immune system responses to viral and bacterial infections, and genetic and epigenetic studies. The scope of research supported under this FOA will include the role of the microbiome in regulating host defense, and the development of clinical interventions to enhance host defense. The FOA will also support the conduct of longitudinal studies aiming at the identification of AD phenotypes pertaining to clinical presentation, skin and peripheral blood immunologic responses and patterns of cutaneous host defense. 

Key Dates
Posted Date

March 20, 2014

Open Date (Earliest Submission Date)

June 8, 2014  

Letter of Intent Due Date(s)

June 8, 2014  

Application Due Date(s)

July 8, 2014, by 5:00 PM local time of applicant organization.

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

October 2014  

Advisory Council Review

January 2015  

Earliest Start Date

April 2015 

Expiration Date

July 9, 2014  

Due Dates for E.O. 12372

Not Applicable

** ELECTRONIC APPLICATION SUBMISSION REQUIRED**

NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the 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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Table of Contents

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

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description


Background

Atopic Dermatitis (AD) is a chronic inflammatory skin disease that affects many children and adults and has an estimated prevalence in the United States of 12% in children under age 18. AD is associated with reduced cutaneous immune responses, defective skin barrier function and increased susceptibility to cutaneous infections. In a subset of AD patients, defective skin barrier function is associated with genetic defects in the skin barrier proteins filaggrin and claudin. AD is also associated with several cutaneous immune abnormalities such as increased Th2 cytokine expression, decreased expression of antimicrobial peptides, and low numbers of plasmacytoid dendritic cells. The interrelationship between immune and skin barrier function in AD is complex. For example, patients with a deficiency of filaggrin have increased IgE sensitization to allergens. Th2 cytokines themselves can decrease cutaneous levels of filaggrin. Furthermore, the precise relationship of the skin barrier defects and immune abnormalities to increased susceptibility to infections is not known.

One potentially important problem with host defense in the skin of AD patients is increased risk of a serious complication to classical smallpox vaccination, a potentially life-threatening dissemination of vaccinia, called eczema vaccinatum (EV). In the 1960s and 1970s, EV occurred in approximately 10-40 per million vaccinees, and EV appeared to occur almost exclusively in patients with AD. Mortality in untreated EV has been reported to vary from 1% to 6%, and up to 30% in children under the age of 2 years. Between 50 and 66% of cases of EV, and almost all the deaths, were associated not with exposure by vaccination, but rather with exposure to vaccinated household contacts. Because of the limited use of “standard” smallpox vaccines, EV has been very rare in recent years. However, sporadic severe cases do occur: in 2007, an infant with a history of AD developed severe EV after his service member father received the smallpox vaccine and then had physical contact with his child. Thus, EV remains a risk, and protection against EV is an important element for our national biodefense program.

Patients with AD are susceptible not only to cutaneous viral infections, but also to Staphylococcus aureus (SA) skin colonization and infections. Such infections often result in exacerbations of AD. It has been suggested that certain components of SA, e.g., enterotoxin, can function as superantigens resulting in polyclonal T cell activation and an inflammatory cascade. The skin of SA colonized AD patients improves more after treatment with topical steroid and antibiotic therapy, than after topical steroid use alone; it is, therefore, likely that SA contributes to the pathophysiology of AD. SA colonization is estimated to occur in 76-100% of AD patients and 2-25% of healthy individuals. Because of the very high rate of SA colonization of AD patients, AD may be an important source of community acquired methicillin-resistant Staphylococcus aureus (MRSA), a significant health concern. However, the relative contribution of MRSA vs. methicillin-sensitive SA in the pathogenesis of AD is currently unknown.

It is postulated that host defense abnormalities in AD subjects are primarily defects in the skin, although systemic defects may also exist, and that the defects are due to dysfunction of the innate and adaptive immune system and of the skin barrier. Previous NIAID-sponsored atopic dermatitis related research activities include the Atopic Dermatitis Vaccinia Network (ADVN, 2004-2010) and the Atopic Dermatitis Network (ADRN, 2010-2015). The current ADRN consists of 8 clinical centers plus 3 additional sites, which support genetics and other mechanistic studies. It also includes 3 centers performing animal studies.

The ADRN is conducting, or has completed, the following human interventional clinical trials and clinical studies:

The ADRN is conducting, or has completed, the following animal studies:

Previous studies have evaluated immune responses in subsets of AD subjects, with these subsets being based mostly on clinical manifestations. These studies demonstrated that ADEH subjects have a more profound defect in innate immune response than AD subjects without EH, suggesting that the innate immune defect correlates with susceptibility to EH. In addition, compared to the total population of AD, subjects with ADEH have higher levels of serum total and specific IgE, suggesting that there are also adaptive immune system abnormalities in ADEH. Additional ADRN data show that AD subjects with SA colonization and/or infections also have elevated total and specific IgE. These clinical subsets (e.g., AD subjects with a history of EH or colonized with SA), may identify subjects whose genetic and epigenetic profiles differ from those of AD subjects who do not have a history of EH or SA colonization.

Other ADRN studies have focused on responses to vaccines that are administered by a cutaneous vs. a non-cutaneous route. In a trial of yellow fever vaccine (http://clinicaltrials.gov/ct2/show/NCT00723489), there were no differences in antibody or T cell responses between AD and non-atopic subjects following subcutaneous vaccination. However, in response to transcutaneous vaccine, AD subjects had a reduced T cell response compared to non-atopics. With the transcutaneous route, both T cell and antibody response correlated inversely with total serum IgE levels. In a trial of trivalent influenza vaccine (http://clinicaltrials.gov/ct2/show/NCT01737710), there were no differences in antibody or T cell responses between AD and non-atopic subjects following intramuscular vaccination. However, following intradermal vaccine, the antibody response was reduced in the subset of AD subjects whose skin was colonized with SA.

Research Studies and Objectives

The ADRN organization will comprise multiple components to carry out the broad scope of research delineated below. These are:

Administrative Core – The Administrative Core will be responsible for the overall scientific leadership and administrative functions as well as for establishing and maintaining the following committees/groups: ADRN Investigator Committee, ADRN Steering Committee and External Scientific Advisory Group

Clinical Projects –In this FOA, clinical projects are divided into two categories: Interventional Clinical Trials with associated mechanistic studies and Clinical Studies with associated mechanistic studies. Applicants are required to propose 2 Interventional Clinical Trials Projects and 2 Clinical Studies Projects, and may propose up to 2 other, optional clinical projects, either interventional clinical trials or clinical studies, with no more than 6 total clinical projects proposed.

The two required Interventional Clinical Trials should be aimed at modulating viral or bacterial colonization/infection of the skin and/or the immune response to these infectious agents. Interventional Clinical Trials aiming at improving the clinical course of AD are acceptable as required Interventional Clinical Trials as long as improvement of the cutaneous host defense is included as a secondary objective.

In addition to the required Interventional Clinical Trials, optional Interventional Clinical Trials may also be proposed that either have the same focus as the required Interventional Clinical Trials, or have a broader focus: compare cutaneous and non-cutaneous vaccination approaches to examine the host defenses of the skin in various AD phenotypes.

Clinical Studies may include, but are not limited to, observational studies, genetic and/or epigenetic studies, studies of the skin microbiome or longitudinal studies to identify and characterize AD phenotypes pertaining to clinical presentation, skin and peripheral blood immunologic responses and patterns of cutaneous host defense. The objectives and scope of the Optional Clinical Studies are identical to those of the required Clinical Studies.

Both Interventional Clinical Trials and Clinical Studies projects should include mechanistic studies. Mechanistic studies should involve human subjects and are defined as aiming at 1) understanding the mechanisms of cutaneous host defense in AD, and/or 2) understanding the mechanisms of action of a treatment modality, and/or 3) identifying biomarkers that predict the ability of a treatment modality to affect host defense or safety. The mechanistic studies should take advantage of new mechanistic research developments and should introduce and integrate cutting edge technologies and state-of-the-art assays into the ADRN.

The majority of research to be conducted by the ADRN should involve human subjects.

Animal Projects - Animal studies are not required. They are optional and will be supported only if they provide information that cannot be obtained by human studies and only if they are directly linked to ongoing or planned human studies.

General areas of research interest that are responsive to this FOA include, but are not limited to, the following:

ADRN Resources

The ADRN maintains several resources. As of early November 2013, an ADRN registry included 2,132 subjects. The ADRN maintains the following repositories from registry subjects: (a) serum repository of 61,000 samples; (b) DNA sample repository of 15,000 samples; and (c) SA repository of 7,800 samples. The ADRN grantee is expected to maintain all current ADRN resources.

Areas of research not responsive to this FOA:

Committees and Advisory Groups:

The Administrative Core will have responsibility for establishing and maintaining several committees/groups.  Descriptions of the committees/groups include:

Network Investigator Committee: The investigator committee includes the Program Director/Principal Investigator (PD/PI) of the ADRN, the PD/PI of the Statistical and Clinical Coordinating Center (SACCC), both clinical and mechanistic investigators at all study sites, and NIAID staff.

Network Steering Committee: The voting members of the Steering Committee include the PD/PI of the ADRN, the PD/PI of the SACCC, three Clinical Project Investigators (either Clinical Site and/or Mechanistic Studies Site Project Leaders) appointed by the PD/PI, and up to two designated NIAID project scientists. The Steering Committee responsibilities include: (i) making decisions regarding overall scientific direction, recommending specific studies for NIAID approval, and coordinating and managing approved studies; (ii) developing and implementing policies to ensure the efficient operation and effective management of Network functions, including enforcement of Network Steering Committee decisions and resolution of disputes and differences of opinion within the Network Steering Committee and between the Network Steering Committee and the Network External Scientific Advisory Group; (iii) establishing and implementing policies and procedures for publications, presentations at scientific meetings, potential collaborations with external investigators, and other forms of information dissemination pertaining to Network-supported studies and study data; (iv) developing and implementing policies and procedures for the identification, disclosure, reporting and management of potential and actual conflicts of interest for members of the Network and the External Scientific Advisory Group; and (v) approving policies and procedures for the secure transfer of clinical and laboratory data to the central databases of the SACCC.

External Scientific Advisory Group (ESAG): The members of the ESAG should be selected from institutions that do not include members of the ADRN. The ESAG will be composed of no less than 3 and no more than 5 clinical and basic science investigators. The ESAG should include expertise in the areas: dermatology, skin pathophysiology, genetics and epigenetics, molecular biology, mucosal immunology, basic immunology, immunotherapeutics, human microbiome, interventional clinical trials, and mechanistic studies in human immunologic diseases. Applicants should not contact or name potential members. ESAG appointments should be for one year but may be renewed throughout the duration of the ADRN.

Responsibilities of the ESAG will include:

NIAID Resources: Certain resources for the ADRN will be provided by NIAID.  These include:

The Atopic Dermatitis Research Network will be supported by a SACCC through an independent NIAID award. The SACCC will provide a broad range of clinical research support services, including support for the design and organization of each ADRN protocol, development of protocol-related materials, assistance in activities related to review and approval of final clinical study protocols, interim statistical analyses, progress reports, safety updates and final safety reports for the NIAID DSMB or SMC, data collection, data management and quality control, clinical site monitoring, safety monitoring and reporting, data analysis and manuscript development support.

NIAID will serve as the Sponsor for any ADRN interventional clinical trials conducted under Investigational New Drug (IND) Applications and Investigational Device Exemptions (IDEs) with full responsibility for carrying out sponsor regulatory requirements.

All clinical trial and mechanistic data produced by this Network will be made publicly available by NIAID, through the SACCC, within 18 months after database lock. NIAID will provide the resource for public access, either through ImmPort (https://immport.niaid.nih.gov/immportWeb/home/home.do?loginType=full) or through another NIAID resource.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

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

Funds Available and Anticipated Number of Awards

NIAID intends to commit $6 million total costs in FY 2015 to fund 1 award.

Award Budget

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

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 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

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.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility


Number of Applications

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

Section IV. Application and Submission Information


1. Requesting an Application Package

Applicants can access the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

2. Content and Form of Application Submission

It is critical that applicants follow the 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.

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

Letter of Intent

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

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

The letter of intent should be sent to:

Zhuqing (Charlie) Li, Ph.D. 
National Institute of Allergy and Infectious Diseases (NIAID)
6700B Rockledge Drive Room 3136
Bethesda, MD 20817
Telephone: 301-402-9523
Fax: 301-480-2408
Email: liz@niaid.nih.gov

Page Limitations

Component Types Available in ASSIST

Research Strategy/Program Plan Page Limits

Overall

30

Admin Core

12

Project (use for required and optional Interventional Clinical Trials, Clinical Studies, and Animal Studies Projects)

12


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

Instructions for the Submission of Multi-Component Applications

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:

Optional Clinical Projects: up to 2; these may be either Interventional Clinical Trials Projects or Clinical Studies Projects

Note: no more than 6 total Clinical Projects (required and optional combined) may be proposed.

Overall Component

When preparing your application in ASSIST, use Component Type ‘Overall’.

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

SF424 (R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement  (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Location(s) (Overall)

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.

Research & Related Senior/Key Person Profile (Overall)

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.

Budget (Overall)

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.

PHS 398 Research Plan          (Overall)

Specific Aims: List the Specific Aims of the ADRN focusing on the overall research agenda and strategic plan.

Research Strategy: In this narrative section, the applicant should provide their overall Strategic Plan, Vision, and Research Agenda for the ADRN. The multi-component application should be viewed as a confederation of interrelated clinical projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section as 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 and timeline for attacking the problems. The applicant’s Strategic Plan, Vision, and Research Agenda should identify gaps in current knowledge, address current challenges in human subjects research (e.g. include new approaches in the design of interventional clinical trials aiming at reducing trial duration), and discuss approaches to move the field in new directions. Include an overview of previous clinical trials and studies in AD pertinent to the proposed Research Agenda (these can include trials and studies performed by the applicant, including preliminary data, or those performed by other investigators, indicating what has been learned from previous studies). Applications responding to this FOA should explain how the proposed Clinical Projects (Interventional Clinical Projects, Clinical Studies Projects) and Mechanistic Studies are synergistic and fit under the overarching program theme and how the Research Agenda can evolve to incorporate new scientific discoveries in the field. Highlight accomplishments of the PD(s)/PI(s) and proposed key personnel and collaborators in the research areas proposed and describe the synergy and collaborations that will be possible within the framework of the ADRN.

In addition, applicants should provide a general overview of the processes that will be employed in the conduct of the Interventional Clinical Trials Projects, Clinical Studies Projects, and Mechanistic Studies proposed under the ADRN. Include a discussion of how clinical sites will be identified and established and how the protocol team will be formed. This description should include a Clinical Project Implementation and Management plan that establishes the policies and procedures for the Network. The overall section will also include a detailed summary of how the Network plans to conduct protocol-specific training for the participating investigators and the relevant clinical and technical Clinical Study Site and Mechanistic Study Site staff. Summarize any special features in the environment and/or resources that make this application strong or unique. Include a timeline for the milestones, timelines and performance guidelines for both the protocol development process and for study initiation, execution, completion and analysis of final data.

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 SF424 (R&R) Application Guide, with the following modification: 

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

Administrative Core

When preparing your application in ASSIST, use Component Type ‘Admin Core .’

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

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. 

Project /Performance Site Location(s) (Administrative Core)

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.

Research & Related Senior/Key Person Profile (Administrative Core)

Budget (Administrative Core)

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

The PDs/PIs (identified as the Core Lead in this component) will be required to commit a minimum of 3 person months effort per year to the project

Applicants are requested to budget for: (1) centralized operational, administrative and fiscal support of the ADRN; (2) maintenance of the ADRN Registry and the three ADRN Repositories (serum repository 61,000 samples, DNA repository 15,000 samples, SA repository 7,800) and (3) travel to ADRN Network meetings for ESAG members).

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.

PHS 398 Research Plan          (Administrative Core)

Specific Aims: List the Specific Aims of the Administrative Core.

Research Strategy: In this section describe the fiscal, administrative and management responsibilities of the Administrative Core

Applicants should describe plans, processes, and procedures for the following activities:

Within the governance and management structure, the Administrative Core will have responsibility for establishing and maintaining the following committees/groups:

Network Investigator Committee: Describe plans, processes or procedures for this committee to fulfill its role in reviewing the details of planned, ongoing or completed trials.

Network Steering Committee: Applicants should provide plans, processes and procedures for the following:

External Scientific Advisory Group: Applicants should describe plans, processes, and procedures for the following activities:

Note: Proposed ESAG members should not be named in the application or contacted prior to IRG review of the application.

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 SF424 (R&R) Application Guide, with the following modification:

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

Planned Enrollment Report  (Administrative Core)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

PHS 398 Cumulative Inclusion Enrollment Report (Administrative Core)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. 

Interventional Clinical Trial Projects

When preparing your application in ASSIST, use Component Type ‘Project.’

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

SF424 (R&R) Cover (Interventional Clinical Trials Projects)

Complete only the following fields:

PHS 398 Cover Page Supplement (Interventional Clinical Trials Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Interventional Clinical Trials Projects)

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.

Facilities and Other Resources: Applicants should demonstrate:

Project /Performance Site Location(s) (Interventional Clinical Trials Projects)

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.

Research & Related Senior/Key Person Profile (Interventional Clinical Trials Projects)

Budget (Interventional Clinical Trials Projects)

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

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.

The project must include a full budget for the entire proposed period of support. Budgets should be based on per patient costs and include the other costs of performing the study (clinical research tests, coordinator and Project Leader time, drug costs if applicable, pharmacy costs, etc.). The costs for mechanistic studies should be included. The costs for data collection and management, statistical support and monitoring and other costs associated with study management will be covered by the SACCC. Full development will begin soon after award, with the help of NIAID staff and the SACCC.

PHS 398 Research Plan          (Interventional Clinical Trials Projects)

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

Research Strategy:  Use this section to describe how the proposed research will contribute to meeting the ADRN goals and explain the approach and rationale for selecting the methods to achieve 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 and its role in the overall research strategy of the ADRN.

Note that all clinical projects must have integrated mechanistic studies. The mechanistic studies must be described within the context of the interventional clinical trial or clinical studies project. More details about the mechanistic studies can be found below in the section on Mechanistic Investigations.

The clinical and mechanistic studies should not duplicate the applicants’ ongoing or previously completed studies, or ongoing or completed ADRN studies listed on clinicaltrials.govclinicaltrials.gov, and should provide new insights into atopic dermatitis. The number of Clinical Sites participating in a clinical or mechanistic study can range from 1 to all Clinical Sites that will participate in the ADRN. It is expected that multiple studies will be performed concurrently.

All interventional clinical trial projects must provide a single synopsis addressing the following aspects of the proposed trial.  The synopsis should be presented in sufficient detail to allow reviewers to judge significance, approach, innovation and environment.  Do not submit a detailed, final clinical protocol because the protocols from the application that is funded will be developed collaboratively as a result of initial peer review, external scientific advisory review, DAIT/NIAID CRC review, DSMB or SMC review, and NIAID priorities.

This Research Strategy section should include the following:

Mechanistic Investigations:

Each interventional clinical trial must include corresponding mechanistic components aiming at 1) understanding the mechanisms of cutaneous host defense in AD, and/or 2) understanding the mechanisms, including immunologic, genetic and epigenetic mechanisms, of action of a treatment modality, and/or 3) identifying biomarkers that predict the ability of a treatment modality to affect host defense or safety. 

It is expected that state-of-the-art technologies that accommodate small blood volumes will be used wherever possible for the proposed studies. For interventional clinical trials involving multiple sites, it is expected that state-of-the-art laboratory assays (e.g., skin barrier function, assays of immune function, immune profiling, etc.) will be performed at a well-equipped central facility at one of the ADRN sites.

The proposed mechanistic studies must not exceed the clinical and scientific resources of the applicant’s team of institutions (e.g., the applicant group must be able to recruit the required number of study subjects from within their collaborating institutions).

For each Project include the following:

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 SF424 (R&R) Application Guide, with the following modification:

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

Planned Enrollment Report  (Interventional Clinical Trials Projects)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

PHS 398 Cumulative Inclusion Enrollment Report (Interventional Clinical Trials Projects)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. 

Clinical Studies Projects

When preparing your application in ASSIST, use Component Type ‘Project.’

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

SF424 (R&R) Cover (Clinical Studies Projects)

Complete only the following fields:

PHS 398 Cover Page Supplement (Clinical Studies Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Studies Projects)

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.

Facilities and Other Resources: Applicants should demonstrate:

Project /Performance Site Location(s) (Clinical Studies Projects)

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.

Research & Related Senior/Key Person Profile (Clinical Studies Projects)

Budget (Clinical Studies Projects)

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

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.

The project must include a full budget for the entire proposed period of support. Budgets should be based on per patient costs and include the other costs of performing the study (clinical research tests, coordinator and Project Leader time, drug costs if applicable, pharmacy costs, etc.). The costs for mechanistic studies also should be included. The costs for data collection and management, statistical support and monitoring and other costs associated with study management will be covered by the SACCC. Full development of the protocols will begin soon after award, with the help of NIAID staff and the SACCC.

PHS 398 Research Plan (Clinical Studies Projects)

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

Research Strategy:  Use this section to describe how the proposed research will contribute to meeting the ADRN goals and explain the approach and rationale for selecting the methods to achieve 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 and its role in the overall research strategy of the ADRN.

Clinical Studies Projects may include: observational/natural history studies, genetics/epigenetic studies, studies focused on the skin microbiome or microbiome of other tissues, and/or vaccine administration where the focus is on the mechanisms underlying the response to the vaccine.

Note that all clinical projects must have integrated mechanistic studies. The mechanistic studies must be described within the context of the clinical studies project. More details about the mechanistic studies can be found below in the section on Mechanistic Investigations.

The clinical and mechanistic studies should not duplicate ongoing or previously completed studies, including ADRN studies, and should provide new insights into atopic dermatitis. The number of Clinical Sites participating in a clinical or mechanistic study can range from 1 to all Clinical Sites that will participate in the ADRN. It is expected that multiple studies will be performed concurrently.

Use this section to describe how the proposed research will contribute to meeting the ADRN goals and explain the approach and rationale for selecting the methods to achieve the specific aims. In addition to stating the biological significance of the research, indicate its relevance to the primary theme of the application.  

Clinical Studies:

All clinical study projects must provide a clinical study synopsis addressing the following aspects of the proposed clinical study. 

Mechanistic Investigations:

Applicants should propose mechanistic studies involving human subjects for each clinical studies project in the description of the project. Potential areas for mechanistic studies research are described above in Part 2. Section I: Purpose.

It is expected that state-of-the-art technologies that accommodate small blood volumes will be used wherever possible for the proposed studies. For clinical studies involving multiple sites, it is expected that state-of-the-art laboratory assays (e.g., skin barrier function, assays of immune function, immune profiling, etc.) will be performed at a well-equipped central facility at one of the ADRN sites.

Study plans should be submitted with the understanding that the studies to be conducted by the ADRN may be different as a result of initial peer review, external scientific advisory review, and/or the priorities of NIAID.

The proposed mechanistic studies must not exceed the clinical and scientific resources of the applicant’s team of institutions (e.g., the applicant group must be able to recruit the required number of study subjects from within their collaborating institutions).

For each Project include the following:

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 SF424 (R&R) Application Guide, with the following modification:

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

Planned Enrollment Report (Clinical Studies Projects)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

PHS 398 Cumulative Inclusion Enrollment Report (Clinical Studies Projects)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. 

Animal Study Projects

When preparing your application in ASSIST, use Component Type ‘Project.’

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

SF424 (R&R) Cover (Animal Study Projects)

Complete only the following fields:

PHS 398 Cover Page Supplement (Animal Study Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Animal Study Projects)

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.

Project /Performance Site Location(s) (Animal Study Projects)

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.

Research & Related Senior/Key Person Profile (Animal Study Projects)

Budget (Animal Study Projects)

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

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.

PHS 398 Research Plan (Animal Study Projects)

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

Research Strategy: Use this section to describe how the proposed research will contribute to meeting the ADRN goals and explain the approach and rationale for selecting the methods to achieve 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 and its role in the overall research strategy of the ADRN.

Animal Study Investigations:

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 SF424 (R&R) Application Guide, with the following modification:

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

Planned Enrollment Report  (Animal Study Projects)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

PHS 398 Cumulative Inclusion Enrollment Report (Animal Study Projects)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. 

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 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.

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.

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.

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 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 Applying Electronically.

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 by the Center for Scientific Review and responsiveness by components of participating organizations, 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-13-030.

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 score to reflect their assessment of the likelihood for the Network  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 Network proposed).

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 score, but will not give separate scores for these items.

Does the proposed overall research strategic plan address important areas and will it advance knowledge and provide evidence for therapeutic approaches in cutaneous host defenses relevant to atopic dermatitis?

Is the ADRN as a whole scientifically compelling?  Are there coordination and synergy of the individual research projects with the core towards the achievements of the central objectives of the ADRN?  Will the integration of the individual projects into a single Network be more beneficial than pursuing each project independently?

Does the PD(s)/PI(s) have the leadership and scientific ability to develop an integrated and focused research network?  Will the PD(s)/PI(s) devote adequate time and effort to the ADRN?  Is there evidence of adequate institutional support in terms of space, equipment and other resources?  Are plans adequate and appropriate to ensure sufficient communication and coordination among the investigators?

Is the administrative and organizational structure appropriate and adequate for the attainment of the objectives?

Are the clinical and mechanistic sites suitable to perform the proposed work?

Have the applicants assembled a team of investigators capable of conducting state-of-the-art clinical and mechanistic studies of the immunopathogenesis of atopic dermatitis, including severe systemic viral and bacterial reactions, and skin barrier function?  

Scored Review Criteria - Interventional Clinical Trials, Clinical Studies, and Animal Studies 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? Do the interventional clinical trials, clinical studies, animal studies and associated mechanistic studies conform to the overall strategic plan outlined in the Research Plan and Administrative Core?

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/PI , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Do the Clinical Project leaders, Clinical Site leaders and Mechanistic Study Site leaders have a strong history and experience in successfully designing and conducting interventional clinical trials, clinical studies and technologically advanced mechanistic studies in AD? Do key personnel involved in Clinical Projects have experience in executing clinical and mechanistic study protocols and appropriate experience and GCP/IHC training? 

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 human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed? Are plans for development, review, implementation, execution and management of interventional clinical trials and clinical studies and associated mechanistic studies adequate including protocol development, selection and management of clinical and mechanistic study sites, and management of laboratory quality assurance and control? Are the applicants looking at the appropriate populations of interest? Are the proposed mechanistic studies feasible and would they contribute to the understanding the etiopathogenesis of AD or its treatment? Are state-of-the-art technologies and assays used in the mechanistic studies?

For any proposed animal studies: Do the animal studies propose work that cannot be obtained by human studies? Are the animal models used relevant to human disease? Do the proposed studies demonstrate a direct link to ongoing or planned human studies?

For each proposed interventional clinical trial, clinical study, mechanistic study and animal study, are adequate statistical analysis plans described, including sample size justification and power calculation? Are the proposed milestones and timelines appropriate? For multi-center trials, does the application adequately address standardization/quality control of, and adherence to, the clinical protocol and data collection or distribution guidelines?   

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?   

Overall Impact – Administrative Core

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Administrative Core 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 proposed).

Review Criteria – Administrative Core

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

Are the plans for management (including fiscal) and planning, initiation, implementation, tracking, and monitoring adequate and timely for completion of planned activities?

Are plans for establishing and implementing collaborations with other Federal and non-Federal organizations/institutions for the co-sponsorship of research in areas of mutual interest and collaborations with industry for the evaluation of specific products/approaches adequate?

Are plans for reducing start-up time of multi-site studies by increasing the efficiency of IRB review and for reducing redundancy, delays and excess due to duplicated infrastructure associated with a Network of clinical sites adequate?

Are plans for establishing and maintaining the functions of committees responsible for governance and management adequate?

Are adequate plans in place for training of investigators and staff at interventional clinical trials, clinical studies and mechanistic studies sites?

Does the application adequately address Good Clinical Practices (GCP), Good Laboratory Practices (GLP), and Good Manufacturing Practices (GMP) compliance as appropriate?

Additional Review Criteria - Interventional Clinical Trials, Clinical Studies, and Animal Studies Projects

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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

Not Applicable

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 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.

2. Review and Selection Process

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

As part of the scientific peer review, all applications:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA . Following initial peer review, recommended applications will receive a second level of review by the 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/PI 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, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

Prior Approval of Pilot Projects

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.

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:

The PD/PI will provide for the overall management, integration and coordination of all activities. The PD/PI will establish an Administrative Center composed of the PD/PI and financial and administrative personnel to carry out the following functions:

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

NIAID will assign one or more Project Scientists to the grant. Project Scientists will provide guidance and support in the design of research activities, will serve as a resource for protocol design and development, will provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, will advise in the selection of sources or resources, and will advise in management and technical performance. The role of 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. In various matters related to clinical study approval and oversight, NIAID Project Scientists will have final decision authority, as described below. Up to two NIAID Project Scientists will be designated voting members of the Steering Committee.

ADRN Investigator Committee

The investigator committee includes the PD/PI of the ADRN, the PD/PI of the SACCC, both clinical and mechanistic investigators at all study sites, and the NIAID staff. 

ADRN Steering Committee

The voting members of the Steering Committee will include the PD/PI of the U19, the PD/PI of the SACCC, three investigators chosen by the PD/PI of the U19 who are either Clinical Site PD/PIs and/or Mechanistic study site leaders, and up to two NIAID-designated Project Scientists.

External Scientific Advisory Group (ESAG)

The members of the ESAG should be selected from institutions that do not include members of the ADRN. The ESAG shall be composed of no less than 3 and no more than 5 clinical and basic science investigators.

Responsibilities of the ESAG will include:

Publications and Communications Policy

After the grant award, the Steering Committee will develop and implement policies and procedures for planning, authorship, preparation, review and final approval of manuscripts resulting from Consortium-supported studies and for submission of manuscripts for publication in peer-reviewed journals. All final manuscripts must be submitted to the NIAID for review in advance of journal submission. The respective roles, rights and responsibilities of pharmaceutical and medical device companies providing investigational materials for Consortium-sponsored studies in the publication review process will be specified in Clinical Trial Agreements (CTAs) between NIAID and the company.

In addition, the Steering Committee will develop and implement policies and procedures for publicizing the accomplishments and the data resulting from Consortium sponsored studies to the scientific and lay communities and other relevant audiences. This includes policies for presentations at scientific meetings and for communications with the press. The PD/PI will ensure that the NIAID Project Scientist has received an advance copy of any press release related to the grant prior to the issuance of the press release.

Public Access to Data Generated by the ADRN

All clinical trial and mechanistic data produced by this Network will be made publicly available by NIAID, through the SACCC, within 18 months after database lock. NIAID will provide the resource for public access, either through ImmPort (https://immport.niaid.nih.gov/immportWeb/home/home.do?loginType=full) or through another NIAID resource.

Protocol-specific Training

Prior to the initiation of any clinical study, the Protocol Chair will organize and conduct, with the support of the SACCC, protocol-specific training for the participating investigators and the relevant clinical and technical clinical study site and mechanistic site staff. Training will include face-to-face meetings and teleconferences.

Clinical Study Implementation and Management

The PD/PI will work in coordination with the SACCC to execute the following tasks:

All policies and procedures delineated above will be approved by the Network Steering Committee prior to implementation.

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 or RPPR) 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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)

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

TTY: 301-451-5939
Email: commons@od.nih.gov

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

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

Scientific/Research Contact(s)

Michael Minnicozzi, Ph.D.
National Institute of Allergy and Infectious Diseases  (NIAID)
Telephone: 240-627-3532
Email: minnicozzim@mail.nih.gov 

Peer Review Contact(s)

Zhuqing (Charlie) Li, Ph.D. 
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-9523
Email: liz@niaid.nih.gov

Financial/Grants Management Contact(s)

Maggie Wells
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-594-9847
Email: wellsmaggie@niaid.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.


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NIH Funding Opportunities and Notices



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