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 using ASSIST or an institutional system-to-system solution; paper applications will not be accepted.

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

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

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

Background

The NIH Common Fund Extracellular RNA Communication program (https://commonfund.nih.gov/exrna) was established in 2012 to uncover fundamental principles of exRNA generation, secretion, and transport; identify and develop a catalog of exRNA found in normal human body fluids; and investigate the potential for using exRNAs in the clinic as therapeutic molecules and/or biomarkers of disease. The Common Fund supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for transformation of research processes.

ExRNAs can act as endocrine signaling molecules, both locally and systemically, representing a novel paradigm in intercellular communication. ExRNAs are transported in body fluids in association with an array of carrier vehicles of varying complexity including extracellular vesicles (EVs), ribonucleoproteins (RNPs), and lipoproteins (LPPs). While these carriers (EVs, RBPs, and LPPs) share the functional attribute of protecting exRNAs from degradation by ubiquitous extracellular RNAses, their respective contributions to biodistribution, uptake, and/or function of their respective exRNA cargo in target cells is less clear. In humans, exRNAs have been found in virtually all body fluids examined, including blood, saliva, urine, breast milk, cerebral spinal fluid (CSF), amniotic fluid, semen, ascites, and pleural effusions. Reports in the literature suggest that exRNAs can have both protective and pathogenic roles in a variety of human diseases, and concomitantly serve as biomarkers for disease states. Taken together, the above findings highlight the important role secreted exRNAs have in regulating human health and disease.

While significant strides have been made in the field of exRNA biology, specific technological challenges remain. For example, RNA concentrations in biofluids are significantly lower than in tissues, necessitating the development of improved methods for their isolation and analysis. Currently available separation approaches are time-consuming and do not adequately discriminate exRNAs encapsulated in EVs from exRNAs associated with non-vesicular RNPs or LPPs. Ultimately, this can lead to unintended biases in exRNA population profiling based upon the specific isolation method used. Further, little is known about the normal physiology of exRNAs, the functional consequences of exRNA uptake, or deficiency of uptake, by recipient cells, and the level of variation existing at the subpopulation level in both normal and disease states. These technological impediments limit the utility and impact of current efforts to catalog exRNAs and assess their contribution(s) to human health and disease.

These technology challenges will be addressed in the second stage of the NIH Common Fund exRNA Communication Program Advancing Extracellular RNA (exRNA) Communication Research. Three FOAs will focus on the development of tools, technologies, and resources to catalyze the field of exRNA communication research.

• RFA-RM-18-026: Limited Competition: Data Management and Resource Repository (DMRR) on Extracellular RNA (U54 Clinical Trial Not Allowed).  This FOA will support the DMRR to curate and disseminate information regarding critical reagents and resources, as well as facilitate cross-project collaborations.
• RFA-RM-18-027: Advancing Extracellular RNA (exRNA) Communication Research: Improved Isolation and Analysis of exRNA-Carrier Subclasses (UG3/UH3 Clinical Trial Not Allowed). This companion FOA will specifically focus on improved separation technologies to rapidly and reproducibly sort exRNA carrier vehicles (EVs, RBPs, and LPPs) and identify their respective exRNAomes and associated molecular cargo.
• RFA-RM-18-028: Advancing Extracellular RNA (exRNA) Communication Research: Single Extracellular Vesicle (EV) Sorting, Isolation, and Analysis of Cargo (UG3/UH3 Clinical Trial Not Allowed). This companion FOA will specifically focus on single EV isolation and analysis tools to assess exRNA heterogeneity and enable mapping exRNAs to their cell or tissue of origin.

Development of these tools, technologies, and resources will complement Stage 1 deliverables and fill remaining knowledge and technology gaps. A consortium-structured grant mechanism is being used to support this research initiative to facilitate the generation of community accepted standards. Meeting the goals of the Stage 2 Initiatives will have a transformative effect on the field of exRNA biology as this will enable a greater understanding of the fundamental role of exRNAs in intercellular signaling and the translational potential to diagnose and treat diseases.

Purpose:

This Limited Competition Funding Opportunity Announcement (FOA) invites an application from the currently funded NIH Common Fund-supported Extracellular RNA Communication Consortium (ERCC) Data Management and Resource Repository (DMRR) to support Stage 2 efforts of this program. The overall programmatic goal of the DMRR is to integrate the efforts of all funded components of the ERCC and serve as a community-wide resource for exRNA standards, protocols, and data through the exRNA portal (exRNA.org).

High-level Summary of the Anticipated Activities. During the first year of Stage 2 funding, the DMRR will complete all remaining data coordination and data analysis activities related to Stage 1 of the Common Fund exRNA Communication Program as stated in detail in RFA-RM-12-010. In all years of funding, the DMRR will work with the ERCC to carry out scientific outreach activities, support and update the exRNA portal with newly developed protocols, data, and technologies, and also provide an administrative core support vital for ERCC functions including in-person and virtual meetings.

The U54 will consist of 4 components during year 1 of this project: 1. The DMRR Data Coordination Component (DMRR DCC), 2. The DMRR Data Integration and Analysis Component (DMRR DIAC), 3. The DMRR Scientific Outreach Component (DMRR SOC), and 4. The DMRR Administrative Core. After year 1, we anticipate that only 2 components, the DMRR SOC and DMRR Administrative Core, will have significant activities, although it is possible that limited amounts of data generated by Stage 2 PD(s)/PI(s) could require coordination and analysis.

DMRR Data Coordination Component (DMRR DCC). The DMRR DCC will work with Stage 1 and Stage 2 consortium PD(s)/PI(s), especially those generating reference profiles of exRNAs in normal conditions (RFA-RM-13-014) to provide the scientific community with user-friendly, publicly accessible exRNA information generated by the consortium.  The DMRR applicant should plan to:

• Complete coordination activities for Stage 1 ERCC data by ensuring the accuracy of metadata, data formats, and data quality metrics
• Deposit ERCC data in publicly accessible data archives
• Ensure that data generated in Stage 1 or Stage 2 will adhere to FAIR data principles (Findable, Accessible, Interoperable, and Reusable), data standards and processes to be determined by the NIH Data Commons, and evolving NIH data policies
• Package, export, and analyze Stage 1 and Stage 2 data

DMRR Data Integration and Analysis Component (DMRR DIAC). The DMRR DIAC will work with Stage 1 and Stage 2 consortium PD(s)/PI(s), especially those generating reference profiles of exRNAs in normal conditions (RFA-RM-13-014) to complete analysis of the data obtained by PD(s)/PI(s) within the project.  The applicant should plan to:

• Complete analysis of exRNA data and make the catalog of processed data available to the scientific community
• Work with Stage 1 ERCC members to publish the results of the data analysis efforts
• Ensure the scientific community has access to the most up to date exRNA data pipeline(s)

DMRR Scientific Outreach Component (DMRR SOC). The DMRR will work closely with the consortium PD(s)/PI(s) to 1. provide the scientific community with user-friendly, publicly accessible exRNA information, and 2. make the scientific community aware that this information is available for their use.  The applicant should plan to:

• Maintain and further update the exRNA portal with Stage 2 technology advances
• Ensure that Stage 1 protocols, data, etc., remain available to the scientific community
• Support outreach activities (e.g. seminar series, satellite symposia, social media efforts) to promulgate the use of Stage 1 and 2 technologies and data
• Quantitatively measure scientific outreach effectiveness

DMRR Administrative Core. The DMRR Administrative Core will collaborate closely with the DMRR Director(s), NIH staff, and ERCC PD(s)/PI(s). Applicants should plan to : 

• Facilitate communication and interaction between DMRR DCC, DIAC, and SOC components
• Facilitate communication across the ERCC including setting up teleconferences/ steering committee/workgroup meetings and providing internet-based resources to share data and enable discussions within the consortium
• Organize and support in person domestic meetings bringing together Stage 2 investigators and repeating every 6 months until a final close out meeting around March 2022. All non-DMRR attendees will support their own travel and lodging through their funded grants
• Provide NIH staff with quantitative updates regarding the data and resources generated by the Consortium and how they are being used by the scientific community

Applicants should refer to Section IV 2 for detailed application instructions. After award selection but prior to funding, the prospective awardee(s) for the DMRR components will be asked to submit revised budgets and research plans for all proposed DMRR components and the administrative core. 

Program Formation and Governance

The awards funded under this FOA will be cooperative agreements (see Section VI. 2. Cooperative Agreement Terms and Conditions of Award). Close interactions among the awardees and NIH will be required to maintain this complex program. The exRNA Communication Consortium (ERCC) governance will rest with the ERCC Program Steering Committee in collaboration with NIH Program Officials, with advice from a group of External Program Consultants (EPC) providing critical scientific and managerial insights, and subject to oversight by the NIH ERCC Working Group. The NIH ERCC Working Group consists of NIH programmatic staff from multiple Institutes and Centers of the NIH and the NIH Office of the Director. This group will be primarily responsible for the stewardship of the ERCC program. The NIH ERCC Working Group is chaired by the Director of the National Center for Advancing Translational Science (NCATS) and Director for the Division of Cancer Biology, National Cancer Institute (NCI). It reports to the Directors of the Office of Strategic Coordination/Common Fund and the Division of Program Coordination, Planning, and Strategic Initiatives for final funding decisions.

By participating in the exRNA Communication Consortium, the awardees are expected to agree to:

• Communication Plan
• Participate in regular (monthly) conference calls with all consortium members
• Coordinate efforts with other awardees, in particular with the DMRR
• Participate and present findings at meetings convened by the NIH through the DMRR twice a year in the DC area
• Jointly publish findings in a timely manner
• Performance Requirements

Meet yearly milestones as defined by investigators and NIH Program Official at the time of award

• Work with, cooperatively interact with, and actively seek input from NIH
• Sharing Plan
• Broad sharing of data and biological specimens with academic, industry, and government researchers is a critical feature of this program that is consistent with applicable laws, regulations, and policies. All subjects must be properly consented to allow appropriate sample and data distribution to researchers in academia and industry.

The DMRR and designated NIH databases will be utilized for the banking and distribution of biological and clinical data. Project PD(s)/PI(s) will be expected to harmonize all data and resource generation with the Data Management and Resource Repository (DMRR). The DMRR is expected to curate and disseminate information regarding critical reagents, and resources and promote and facilitate cross-project collaborations (see RFA-RM-18-026).

Technical Assistance Webinar

All applicants are strongly encouraged to contact NIH staff to discuss the alignment of their proposed work with the goals of this FOA and the ERCC program. A technical assistance webinar will be held for potential applicants. NIH staff will be available to answer questions related to this and companion FOAs.  Participation in the webinar is optional. No pre-registration is required, but participants are asked to submit questions ahead of time to exrnacommunication@mail.nih.gov. The slides as well as some frequently asked questions will be available at https://commonfund.nih.gov/exrna following the webinar.

Webinar Information:

The webinar will be held on August 24, 2018 from 2-3:30 PM, EST.

Join us via WebEx using this link:
https://nih.webex.com/nih/onstage/g.php?MTID=ef29317fb2d940f2f6f0c3c410e5df5ff

Call in toll number (US/Canada): 1-650-479-3208

Event number: 629 822 206

Event password: exRNA

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

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

Eligibility is limited to the awardees of RFA-RM-12-010

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 not allowed.

Applicant Organizations

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

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

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

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

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.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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

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

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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.

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

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

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

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

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

The letter of intent should be sent to:

John Satterlee, Ph.D.  on behalf of the NIH Common Fund Extracellular RNA Working Group

Telephone: 301-435-1020

Email: satterleej@nida.nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core (use for Administrative Core)	6 pages
SOC (use for Scientific Outreach Component)	12 pages
DCC (use for Data Coordination Component)	12 pages
DIAC (use for Data Integration and Analysis Component)	12 pages

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

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

The application should consist of the following components:

Overall: required

Administrative Core: required, maximum of 1

Scientific Outreach Component (SOC): required, maximum of 1

Data Coordination Component (DCC): required, maximum of 1

Data Integration and Analysis Component (DIAC): required, maximum of 1

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.

Complete entire form.

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

Follow standard instructions.

Enter primary site only.

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

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

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

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

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

Specific Aims: Describe the overall goals of the DMRR for the performance period of this project.

Research Strategy: Applicants should:

• Describe the major themes of the overall DMRR, its goals and objectives, background information and the overall importance of the research to the objectives of this program.  
• Explain the strategy for achieving the goals defined for the overall program and how each project and core relate to that strategy.  
• Describe their vision for 1. How the different DMRR components will interact with each other and the administrative core, and 2. How the DMRR will interact with other funded components of the exRNA program, and the scientific community.
• Explain how the different aspects of the organization, including Senior/Key Personnel, will coordinate and communicate, why they are essential to accomplishing the overall goal of the research, and how the combined resources create an overall program that is more than the sum of its parts.
• In addition, a timeline (Gantt chart) including milestones is required for all studies.  Milestones are intermediate steps towards the completion of concrete goals.  They must include clear and quantitative criteria for success.  Yearly quantitative milestones are required in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. The application should include clearly-specified, well-defined milestones, quantitative go/no go decision points, and timelines for assessing progress.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should include a Data Sharing Plan.

• Applicants should indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the exRNA Program Steering Committee and approved by NIH staff.  A primary goal of the exRNA program is to facilitate discoveries by the broad scientific community. Restrictive licensing terms and sharing practices for exRNA-generated data, tools, and resources could substantially diminish their value and public benefit. Accordingly, awardees should manage data, resources, protocols, tools, and software in a way that achieves this goal. Sharing practices that would hinder, prevent or block access to or use of exRNA program data, tools, and resources for research purposes will be considered to be hindering the goals of the exRNA program. The development of policies, methods, and standards for such sharing is critically important.  The NIH expects that the awardees, through the exRNA Program Steering Committee, will develop such policies, methods, and standards in concert with the NIH.  These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing.
• Specific Plan for Data Sharing: Consistent with achieving the goals of this program, the NIH expects that information such as collected data (e.g. metabolomic, lipidomic, proteomic, etc.), technical protocols, and any other data or metadata collected under this FOA is to be deposited as appropriate into existing, publicly available data repositories that are easily accessible, and in machine readable format. Where appropriate, applicants should identify such repositories and plans for deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution that is consistent with achieving the goals of the program. Data should also be made available as appropriate via the exRNA Portal that will serve as the central access point for information regarding data, critical tools, protocols and reagents being developed by the exRNA program. Data should also have the ability to be formatted and exported to the NIH Data Commons.
• Genomic Data Sharing Plan:  If applicants propose to generate transcriptomic or other types of genomic data, they must indicate their willingness to abide by the NIH Genomic Data Sharing Policy (https://gds.nih.gov/) and should indicate their agreement to it in the data sharing plan.
• Specific Plan for Protocol, Tool, and Reagent Sharing: As one of the primary goals of this program is to advance research through development, establishment, broad dissemination and use of community resources across the research community, NIH intends that protocols, tools, and reagents generated by the exRNA program be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible for research purposes by the larger scientific community.  For all applications and where otherwise applicable, the applicant should discuss plans for sharing and distribution of non-data resources that will be generated by the proposed project, including protocols, instrument design specifications, animal strains, plasmids, viruses, antibodies, chemical compounds, biomaterials, and other reagents. 
• The exRNA DMRR will work with all exRNA program investigators to collect, curate, and disseminate information regarding tools and reagents being developed by the program and to disseminate this information through the exRNA Portal and other sources as appropriate and consistent with achieving the goals of the program.
• Specific Plan for Sharing Software:  A software dissemination plan, with appropriate timelines, is expected in applications that are developing software.  There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact. A dissemination plan guided by the following principles is thought to promote the largest impact:
• The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.
• The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
• To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.
• The terms of software availability should include the ability of researchers outside the project and its collaborating projects to modify the source code and to share modifications with other colleagues.  An applicant should take responsibility for creating the original and subsequent "official" versions of a piece of software.
• Applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others.  This proposal may include a plan to incorporate the enhancements into the "official" core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution.
• Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan.
• Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov).

Sharing within the ERCC

The ERC program aims to maximize the benefits of sharing, while protecting the intellectual property of the data generators. Prepublication sharing of data within the consortium will allow collaboration across initiatives and further the progress of the ERC Program towards its goals and objectives. Therefore, the ERC program requires that data, metadata, and resources generated from ERC funding be made available to other ERCC members immediately upon being considered "shareable". When ERC-generated material under embargo is shared within the ERCC, it will be considered confidential with the understanding that the information will not be used or disclosed by ERCC members unless explicitly agreed upon by the originator of the data under mutually acceptable terms. That is, Consortium members may not publish using material generated by other consortium members without a collaboration or other agreement, or until the material in question has been made available to the public. As such, ERCC investigators accessing embargoed material only available to members of the ERCC must sign a non-disclosure form agreeing to these terms.

Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Overall)

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

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

When preparing your application, use Component Type 'DCC.'

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Project Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

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.

Specific Aims: Describe the overall goals of the DMRR DCC for the performance period of the grant.

Research Strategy: The DMRR applicant should:

• Describe how they will complete coordination activities for Stage 1 ERCC data by ensuring the accuracy of metadata, data formats, and data quality metrics
• Describe their plans and timeframe for depositing this data in publicly accessible data archives
• Describe how they will ensure that data generated in Stage 1 or Stage 2 will adhere to FAIR data principles (Findable, Accessible, Interoperable, and Reusable), data standards and processes to be determined by the NIH Data Commons, and evolving NIH data policies
• Describe how Stage 1 and Stage 2 data could be packaged, exported, and integrated in a user-friendly manner with other diverse datasets

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Data Coordination Component (DCC))

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type 'DIAC'

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

SF424 (R&R) Cover (Data Integration and Analysis Component (DIAC))

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Data Integration and Analysis Component (DIAC))

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Integration and Analysis Component (DIAC))

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) (Data Integration and Analysis Component (DIAC))

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 (Data Integration and Analysis Component (DIAC))

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Project Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Data Integration and Analysis Component (DIAC))

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 (Data Integration and Analysis Component (DIAC))

Specific Aims: Describe the overall goals of the DMRR DIAC for the performance period of the grant.

Research Strategy: The DMRR applicant should:

• Describe how they will complete integration and analysis of exRNA data and make the catalog of processed data available to the scientific community
• Describe how they will work with Stage 1 ERCC members to publish the results of the data analysis efforts
• Describe how they will ensure the scientific community has access to the most up to date exRNA data pipeline(s)
• Describe how they will serve as a community-wide resource for exRNA standards, protocols, and data through the development of an exRNA Atlas

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Data Integration and Analysis Component (DIAC))

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type 'SOC'

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

SF424 (R&R) Cover (Scientific Outreach Component (SOC))

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Scientific Outreach Component (SOC))

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific Outreach Component (SOC))

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) (Scientific Outreach Component (SOC))

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 (Scientific Outreach Component (SOC))

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Project Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Scientific Outreach Component (SOC))

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 (Scientific Outreach Component (SOC))

Specific Aims: Describe the overall goals of the DMRR SOC for the performance period of the grant.

Research Strategy: The applicant should describe how they will:

• Maintain and further update the exRNA portal with Stage 2 technology advances
• Ensure that Stage 1 protocols, data, etc., remain available to the scientific community
• Support outreach activities (e.g. seminar series, satellite symposia, social media efforts) to promulgate the use of Stage 1 and 2 technologies and data
• Quantitatively measure scientific outreach effectiveness

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Scientific Outreach Component (SOC))

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type 'Admin Core'

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

SF424 (R&R) Cover Administrative Core (Admin Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Admin Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Admin 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) (Admin 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 (Admin Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Project Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Admin Core)

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 (Admin Core)

Specific Aims: Describe the overall goals of the DMRR Administrative Core for the Performance period of the grant.

Research Strategy: Applicants should describe how they will: 

• Facilitate communication and interaction between DMRR DCC, DIAC, and SOC components
• Facilitate communication across the ERCC including setting up teleconferences/ steering committee/workgroup meetings and providing internet-based resources to share data and enable discussions within the consortium
• Organize and support in person domestic meetings bringing together Stage 2 investigators and repeating every 6 months until a final close out meeting around March 2022. All non-DMRR attendees will support their own travel and lodging through their funded grants
• Provide NIH staff with quantitative updates regarding the data and resources generated by the Consortium and how they are being used by the scientific community

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Admin Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization's profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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

Only the review criteria described below will be considered in the review process. 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.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the DMRR 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? If the proposed DMRR is fully successful in carrying out its plans, will it have a transformative effect on this scientific field?  

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the DMRR? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the DMRR 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 DMRR? Do DMRR team members and/or associated collaborators have prior experience and/or necessary qualifications to successfully execute and implement the proposed DMRR components including, where appropriate, the ability to partner and collaborate with other scientists or organizations? Do the PD(s)/PI(s) and/or key personnel have demonstrated expertise or prior experience in successfully leading the coordination or analysis of intensive activities and high-throughput datasets? 

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

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

If the DMRR 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? How well do the proposed plans of the DMRR DCC, DIAC, SOC, and administrative core align with the anticipated critical activities of the DMRR?  How well will the approach proposed by the applicant enable the DMRR components to integrate the efforts of all of the funded components of the ERCC and serve as a community-wide resource for exRNA standards, protocols, and data through the development of an exRNA Atlas?  How well thought out are the plans for each component?  Does the DMRR overall plan allow for data transportability and data interoperability in the future?  How well does the management structure support achievement of the proposed goals and milestones?

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 proposed DMRR? Will the DMRR benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the DMRR 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.

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.

When the proposed DMRR 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.

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

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

Not Applicable

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

Not Applicable

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

Not Applicable

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

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

For a DMRR involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

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

As part of the scientific peer review, all applications:

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

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

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

•         Scientific and technical merit of the proposed project as determined by scientific peer review.
•         Availability of funds.
•         Relevance of the proposed project to program priorities.

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

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

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

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

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

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

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

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

Definitions

NIH exRNA Communication Working Group (WG): Consists of NIH programmatic staff from multiple Institutes and Centers of the NIH. This group will be primarily responsible for the stewardship of the exRNA Communication Program.

Steering Committee (SC): The SC will provide coordination activities for the exRNA Communication Program. The SC will include PDs/PIs of each of the awards and NIH exRNA Communication WG members. The SC will be chaired by two PD/PIs that are nominated by the SC and approved by the NIH. The SC will establish subcommittees to oversee the development and implementation of consortium policies including data release.  The number of NIH votes may not exceed one third of the total number of votes on the SC. The number of votes from a multiple PI award will be one. Votes will inform recommendations to the NIH.

External Scientific Consultants (ESC): The NIH exRNA Communication WG will recruit outside experts (4-6 senior scientists; non-awardees) of relevance to the exRNA Communication Program. The ESC will be responsible for reviewing and evaluating the progress of the exRNA Communications Consortium toward meeting their individual and collective goals. The ESC will be appointed by and provide recommendations to the NIH about continued support of the components of the Consortium. The membership of the ESC may be enlarged permanently, or on an ad hoc basis, as needed. The ESC will meet at least once a year. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the ESC to interact directly with the awardees. Annually, the ESC will provide comments regarding progress of the Consortium and on any changes that may be necessary to the NIH.

ExRNA Communication Consortium (ERCC): The ERCC will be made up of exRNA Communication awardees, the NIH exRNA Communication WG and other scientists and groups the SC agrees to include within the Consortium. The Consortium structure is meant to enable the overall goals of the exRNA Communication Program.

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

•         Determining experimental approaches, designing protocols, setting project milestones and conducting experiments;
•         Adhering to the NIH policies regarding intellectual property, data release and other policies that might be established during the course of this activity;
•         Accepting and implementing any other common guidelines and procedures developed for the NIH exRNA Communication WG and approved by the exRNA Communication SC;
•         Accepting and participating in the cooperative nature of the ERCC;
•         Attending bi-annual workshops organized by the NIH and the Data Management and Resource Repository (DMRR).

Publications

The Program Director/Principal Investigator (PD/PI) will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The PD/PI and Project Leaders are requested to submit manuscripts to the NIH Project Scientist within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the Principal Investigator and appropriate Project Leaders and will require appropriate acknowledgement of NIH support. Timely publication of major findings is encouraged.

Intellectual Property

•         The awardee is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the applicant to perform the project.
•         Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.
•         The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act).
•         Awardees will retain custody of and have primary rights to the data and resources developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards.

NIH Project Scientists:

•         Participate (with the other Steering Committee members) in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols, project milestones or approaches as warranted. The Project Scientists will assist and facilitate the group process but not direct it;
•         Serve as a liaison between the awardees, the Advisory Councils for those Institutes that plan to administer elements of the NIH Common Fund Extracellular RNA Communication Program and the larger scientific community;
•         Coordinate the efforts of the awardee with others engaged in exRNA research, including other awardees under this FOA and those awardees involved in related NIH programs;
•         Attend all Steering Committee meetings and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action;
•         Periodically report progress to the Directors, NIH Institutes involved in the NIH Common Fund Extracellular RNA Communication Program and the Directors of the Division of Program Coordination, Planning, and Strategic Initiatives and Office of Strategic Coordination;
•         Lend relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions who are to serve as Program Consultants.
•         Serve as liaison between the Steering Committee and the Program Consultants;
•         Serve on subcommittees/working groups of the Steering Committee as appropriate;
•         Provide advice in the management and technical performance of the investigation;
•         Assist in promoting the availability of data and resources developed in the course of this project to the scientific community at large;
•         Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
•         Retain the option to recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals according to the milestones agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award.

Areas of Joint Responsibility include:

A SC will serve as the main governing board of the ERCC. The SC membership will include NIH Project Scientists and the PD/PI of each awarded cooperative agreement. The PD/PI of each award (or designee) will have one vote on the SC. The Project Scientists may vote, but the total votes will count as a maximum of one-third of the total number of votes. The SC Chairs will not be NIH staff members. Additional members may be added by action of the SC. Other government staff may attend the SC meetings, if their expertise is required for specific discussions. The SC will:

•         Discuss progress in meeting the goals of various exRNA projects;
•         Develop recommendations for uniform procedures and policies necessary to meet the goals of the Research Network, for example for data quality measures and assessment, conventions for data deposition, or measuring costs and throughput. Adoption of procedures and policies developed by the SC will require concurrence by ESC.
•         The SC will also serve as a venue for coordination on the improvement of exRNA scientific methods, for example by disseminating best practices and collectively evaluating new procedures, resources, and technologies.
•         The SC will consider collective goals for the ERCC, will determine how joint publication of results will contribute toward the goals of the exRNA Program, and will coordinate joint publication as needed to demonstrate overarching principles of exRNAs. It will schedule the time for, and prepare concise (2 to 4 pages) summaries of, the SC meetings, which will be delivered to members of the group within 10 business days after each meeting.
•         Each full member will have one vote. Awardee members of the SC will be required to accept and implement policies approved by the SC.

Communication Plan

•         Participating in regular (monthly) conference calls with all NIH exRNA Communication WG members.
•         Coordinating efforts with other awardees, especially in circumstances where synergy of efforts and resources is beneficial to the overall goals of the exRNA Communication program.
•         Participating and presenting findings at the semi-annual workshops convened by the NIH.
•         Coordinating or jointly publishing findings in a timely manner, and as to have the broadest impact.
•         Making new information and materials known to the research community in a timely manner through publications, web announcements, reports to the NIH exRNA Communication WG, and other mechanisms.

Performance Requirements

•         Meeting yearly milestones as defined by investigators and NIH program at the time of award.
•         Working with, cooperatively interacting with, and actively seeking input from NIH.
•         Sharing broadly data and biological specimens within the Consortium and with the broader scientific community, using established data sharing guidelines as appropriate and consistent with achieving the goals of the program.
•         Attending one in-person "kickoff meeting" at the beginning of the award period; this meeting will serve as an organizing workshop together with NIH staff, including representatives from the institutes supporting the awards. The workshop will go over Terms and Conditions of Award for the UG3/UH3 and DMRR, ERCC responsibilities and duties, and provide an opportunity for awardees to describe their project to the consortium.
•         Attending semi-annual consortium meetings to be held in the Washington, DC area.
•         Attending one in-person "closeout meeting" at the end of the award period; this meeting will serve as a summary of accomplishments completed in the project period.
•         The NIH will enlist additional scientific experts as necessary from within the NIH, other government agencies, such as the FDA and NIST whose function will be to assist the NIH exRNA Communication WG in carrying out the goals and aims of the approved studies.

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.

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

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, and post-submission issues)

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John Satterlee, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1020
Email: satterleej@nida.nih.gov

Maqsood Wani
Center for Scientific Review (CSR)
Telephone: 301-435-2270
Email: wanimaqs@csr.nih.gov

Aida Vasquez 
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-2154  
Email: vasquez@mail.nih.gov

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

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