Part 1. Overview Information

Key Dates

All applications are due 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.

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

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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. Notice of Funding Opportunity Description

 Background:

Down syndrome (DS) is the most common genetic cause of intellectual disability, the most common autosomal trisomy, and one of the most visible and universally recognized genetic syndromes. Each year there are approximately 5300 babies born in the United States with Down syndrome. Within the past 25 years, the average lifespan for a person with Down syndrome has doubled, from 30 to 60 years. Despite this increase in lifespan, individuals with Down syndrome and their families face significant health challenges with age, and they have often been excluded from participation in research that could improve their health outcomes and quality of life. While all people with Down syndrome are connected by the common feature of a complete or partial copy of chromosome 21 (trisomy 21), there are significant physical and cognitive differences among them, indicating that inter-individual variability exists.

Down syndrome is associated with an increased prevalence of autism and epilepsy. About 75% of individuals experience cognitive decline in a syndrome that resembles Alzheimer’s disease but has its onset a decade or two earlier than typical Alzheimer’s disease. Individuals with Down syndrome also have high rates of hearing loss, eye abnormalities, congenital heart defects, sleep apnea, pulmonary hypertension, gastrointestinal malformations, thyroid disease, leukemia, and other autoimmune or immune dysregulation disorders including celiac disease. However, people with Down syndrome infrequently develop solid tumors such as breast or prostate cancer, and despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, they rarely develop atherosclerosis or have myocardial infarctions. Understanding this unique combination of risks and resiliencies will inform medical advances for individuals with Down syndrome, and for individuals who do not have Down syndrome but share these co-occurring conditions.

This limited competition Notice of Funding Opportunity (NOFO) is one of several NIH-wide research initiatives created in response to Fiscal Years 2018-2024 Omnibus Appropriations Reports, which encourage NIH to expand its current efforts on Down syndrome and common co-occurring conditions also seen in the general population, while increasing the number of Down syndrome investigators and the diversity of study populations and researchers. Together, the initiatives are called the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Information about projects that were funded in prior years, as well as the NIH INCLUDE Down Syndrome Research Plan, are available on the INCLUDE Project website at https://www.nih.gov/include-project/. The INCLUDE Project has three components:

• Component 1: Targeted high risk - high reward basic science studies in areas highly relevant to Down syndrome
• Component 2: Assembly of a large cohort of individuals with Down syndrome across the lifespan to perform deep phenotyping and study co-existing conditions
• Component 3: Inclusive clinical trials of existing and future treatments and interventions for co-occurring conditions in individuals with Down syndrome.

This research initiative expands many of the research objectives and opportunities previously highlighted in the 2014 Down Syndrome Directions: NIH Research Plan on Down Syndrome. More recent discoveries have enhanced our understanding of chromosome segregation and chromosome silencing, identified certain proteins and neurotropic factors involved in brain development using mouse models, and uncovered the role of interferons in immune dysregulation, each of which have the potential to lead to development of novel therapies for individuals with Down syndrome, as well as broader applications. People with Down syndrome are often excluded from clinical research, such as trials of potentially beneficial drugs and therapeutics that are used to treat the same condition in the general population. There is great value in connecting people with Down syndrome to therapies that could improve their overall health and quality of life. And there is great interest in the Down syndrome community in participating in clinical research, based on experience from NICHD’s “DS-Connect®: The Down Syndrome Registry®,” an online survey tool that connects individuals with Down syndrome and their families to research opportunities. A comprehensive clinical cohort study with deep phenotyping and exploration of pan-omics will permit identification of biomarkers and outcomes for the co-occurring conditions in Down syndrome. Coupled with development of a clinical trials readiness program, and informed by basic science discoveries, this combination of resources could have a great impact on addressing health disparities that exist for people with Down syndrome and could also lead to the development of therapies to improve outcomes for those with and without the condition. For a list of projects funded from FY2018 to 2023, see https://www.nih.gov/include-project/funding.

This RFA addresses Component 2 of the INCLUDE Project to continually develop the INCLUDE Data Coordinating Center (DCC). The mission of the INCLUDE DCC is to accelerate discoveries that continuously improve and enrich the lives of people with Down syndrome through accessible data resources that enable interdisciplinary collaboration, connected communities, and the expansion of a global Down syndrome knowledge ecosystem. Under the first funding round, the INCLUDE DCC successfully launched the INLCUDE Data Hub on March 21, 2021. The INCLUDE Data Hub is not only a secure data repository for de-identified participant’s data, but also comprises a data portal and a cloud-based platform, Cavatica, for secure cloud computing.

Scope:

The recipient funded by this NOFO will continue their effort on three broad responsibilities: constructing a Data Hub Core, formerly the Data Portal Core, charged with integrating and sharing INCLUDE Project data through the INCLUDE Data Hub which includes a web-based data portal, data repository services, integrated cloud analysis platform(s), and associated infrastructure, serving as a Data Management Core (DMC) and developing and managing an Administrative and Outreach Core (AOC) for the entire DCC. The INCLUDE Data Hub serves as the primary data repository for INCLUDE Project data and provides tools to facilitate access and analyses by the broader research community. The DMC coordinates the collection of data from researchers and data generators and aggregates and harmonizes these data to be shared through the Data Hub. The AOC coordinates administrative logistics as well as training sessions and education on using the Data Hub and works closely with the Steering Committee (see below under Cooperative Agreement Terms and Conditions of Award for a description of the steering committee) on overall implementation of the program goals.

Administrative and Outreach Core (AOC)

The AOC will organize, coordinate, and oversee the administrative and outreach activities of the INCLUDE Program. Administrative activities will include facilitating meetings, conference attendance and communications between the DCC, NIH, and key external stakeholders including but not limited to the Down syndrome community and the external Program Consultants, and developing procedures and policies for the operation of the DCC. Outreach activities will include establishing and maintaining a registry of investigators participating in the INCLUDE program and educating the research community on how to use the Data Hub through user training utilizing all available methods (e.g., in person, by webinar, through YouTube videos). The AOC will create quarterly newsletters to disseminate to the users about the INCLUDE DCC and its activities including future events. Equally important will be engaging users for their feedback in order to improve the functionality of the Data Hub and the overall DCC.

The activities of the DCC comprise areas of computer science, informatics and data management, but also require effective communication with the clinical or basic science communities to achieve its goals. This requires that the DCC have personnel with sufficient knowledge to serve as liaisons and translators among basic scientist, clinicians, and bioinformaticians and the Down syndrome community. The DCC is therefore expected to be composed of teams with expertise sufficient to allow them to function in this way. The areas of expertise included should also cover existing Down syndrome data as well as future Down syndrome datasets to be generated under INCLUDE, including the Down syndrome Cohort Development Program (DS-CDP). Additionally, in an effort to integrate tools and functions amenable to appropriate statistical analyses into the Data Hub, the Center should include data science and statistical epidemiology expertise within their team. The team should also have experience with phenotype ontology and harmonization, as well as experience in linking to a biospecimen repository(ies), for example through collaboration with the Federated Biobanking resource for the Down Syndrome Cohort Study Program (DS-CDP). In general, INCLUDE intends to prioritize the generation and collection of data from cohorts that are approved for broad data sharing and use, but recognizes that cohort data may involve a variety of data use limitations. The team should demonstrate experience handling all kinds of data modalities, including but not limited to clinical data, electronic health records (EHR) data, imaging data, mobile health data, social determinants' data, be aware of international policies and regulations required to store and utilize data collected internationally as well as -omics data, including both short-read and long-read genomics data. In addition, the team should also demonstrate or provide a plan to implement emerging technologies such as Artificial Intelligence (AI) to their data integration and processing process, as well as making AI tools available on integrated cloud platforms.

Data Management Core (DMC)

The DMC will collect, process, harmonize, and facilitate the sharing of phenotypic, genomic and other -omics data generated from Down syndrome cohorts. To that end, it will be necessary to have a detailed understanding of diverse data types and the ability to manage quality control of the data. Integration of data from Down syndrome studies are of top priority; however, the DMC may seek to collect data from other sources with the intention of creating a comprehensive Down syndrome catalog, prioritizing datasets that are approved for broad sharing and use. In conjunction with activities led by NIH, the DMC will work with investigators to define standard data elements and establish a minimal common dataset in order to harmonize existing phenotypic data and organize the collection of prospective cohort data, which may require external collaboration with the new Down Syndrome Clinical Cohort Coordinating Center (DS-4C) and other parties. The data included in the INCLUDE Project are expected to increase as the number of participating cohorts increases, and the DMC will need to be able to adapt to handle different types of data using existing and emerging technologies. The DCC will not be expected to fund the sequencing and other -omics data acquisition related costs itself.

Another major function of the DMC will be to support a centralized Virtual Biorepository resource to coordinate a single online biospecimen repository or a network of DNA, tissue specimen and cell line repositories relevant to Down syndrome research. Working in collaboration with the future Federated Biobanking resource for the Down Syndrome Cohort Study Program (DS-CDP), the DMC is expected to coordinate standardization and indexing of biospecimen metadata to provide an integrated resource to the investigator community.

Data Management and Access Practices Under the Genomic Data Sharing Policy:

Developers who seek access to human genomic data generated and shared under the NIH Genomic Data Sharing (GDS) Policy (NOT-OD-14-124) are expected to request access through the NIH developer access process (see Implementation Update for Data Management and Access Practices Under the Genomic Data Sharing Policy (NOT-OD-24-157). The NIH developer access process sets expectations for the Lead Developer(s) (e.g., the Principal Investigator (PI) who is listed as the Project Director (PD) or PI on the funding application) and those they directly supervise to ensure GDS Policy participant protections, privacy, and oversight are maintained when accessing human genomic data under the GDS Policy.  

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Only current recipients funded under RFA-OD-20-007 are eligible to apply.

Non-domestic (non-U.S.) Entities (Foreign Organization) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2- Definitions of Terms.

3. Additional Information on Eligibility

Number of Applications

Only one application per institution is allowed.

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Page Limitations

All page limitations described in the How to Apply- 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 How to Apply- Application Guide and should be used for preparing a multi-component application.

Overall Component

When preparing the application, use Component Type ‘Overall’.

All instructions in the How to Apply - 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 Locations (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 and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this NOFO) 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: Concisely address the goals of the DCC and how the work proposed supports the overall objectives of the INCLUDE Project and the specific objectives of the DCC and associated components as described in Section I. Funding Opportunity Description.

Research Strategy: Applicants should describe how the DCC will facilitate meeting the specific objectives of the INCLUDE Project. Applicants should describe the proposed overall design and structure of the DCC including any proposed changes to the existing structure, along with a rationale for such changes (adding, expanding, or removing functionalities).

The Research Strategy should address the following points. 

• General considerations that will lead to successful development and coordination of the overall DCC and how the Center will help meet the general objectives of the INCLUDE Project by providing a general overview of the proposed Center.
• Overall design and structure of the Data Coordinating Center including its management structure, integration of components, and any possible subcontracts.
• Organizational chart of the tasks and milestones for what they will accomplish, identify the types of staff associated with each task, and describe their respective roles and responsibilities.
• Strategies in coordinating data flow in a multi-component research project, and managing administrative logistics and outreach activities, as described.
• Strategies to ensure efficient communication with NIH regarding the different DCC Cores and components.
• Strategies to ensure efficient communication and coordination with the DS-4C, the DS-CRS and the DS-Biorepository.
• Strategies to promote interoperability and cross-initiative data sharing and analysis with other NIH Data Repositories and Cloud-based Platforms.

Resource Sharing Plan:
Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Applications are expected to include a software dissemination plan for any development, maintenance, or enhancement of software as requested in the application. The software dissemination plan should address, as appropriate, the following goals:

• Transparent documentation including use cases and system design documentation, as appropriate.
• Software source code developed under this award, including code for the data portal, should be delivered under an open-source model such that it is freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories. Users should be permitted to modify the code and share their modifications with others.
• Transferability of the software supporting the INCLUDE Data Hub such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.

The DCC may use proprietary or commercial services, tools, and platforms only in compelling cases and should provide adequate justification and explanation for how the approach will be consistent with the requirements for maintaining transparency and interoperability in this program. 

For a list of Best Practices for Sharing Research Software, see https://datascience.nih.gov/tools-and-analytics/best-practices-for-sharing-research-software-faq.

After initial review, program staff will conduct an additional administrative review of the plan for resource sharing and may negotiate modifications of this plan with the prospective awardee. The final negotiated version of this plan will become a term and condition of the award.

Other Plan(s): 

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• The Data Hub Core will share INCLUDE Project data through a common web-based interface to provide access to aggregated and harmonized datasets alongside analytical tools, as well as with links to relevant partners. The DHC will facilitate access to large-scale datasets, including genomic datasets. The DHC is charged with data security compliance for data storage and distribution by the INCLUDE Data Hub in collaboration with NHLBI. The goal of the Data Hub is to make these data readily accessible to users with various levels of expertise. To that end, the design of the features and tools are to reflect statistical rigor and valid methods and approaches relevant to the Down syndrome field, serving a wide range of experts from developmental biologists to clinicians to bioinformaticians. While innovative approaches to serve the Down syndrome research community are warranted, applicants are encouraged to use or integrate with existing data platforms, tools, and work-spaces to promote interoperability and cross-initiative data sharing and analysis, wherever possible. The web portal should be based on open-source software and should be developed through an iterative process based on user feedback. The Data Hub should also have the capacity to grow and adapt with the INCLUDE Project. To the extent possible, the Data Hub should link to, interact, and incorporate with other relevant data portals. Data resources created by the DCC should follow interoperable and reusable. In addition to human data, the DHC should also provide a solution for a common web-based interface to provide access to aggregated data generated from animal model and iPSC studies. The goal is to create a seamless connection between the human and animal model interface to enable a smooth transition from testable hypotheses to tested hypotheses.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide; any instructions provided here are in addition to the How to Apply - Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - 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 How to Apply - Application Guide must be followed.

Delayed Onset Study

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

PHS Assignment Request Form (Overall)

All instructions in the How to Apply- Application Guide must be followed.

Administrative and Outreach Core

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

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Administrative and Outreach 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 (Administrative and Outreach Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative and Outreach 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 and Outreach 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 and Outreach 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 (Administrative and Outreach 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 (Administrative and Outreach Core)

Specific Aims: Describe the administrative and outreach requirements of the DCC and how the work proposed supports these activities.

Research Strategy:

Discuss how the activities listed below will be accomplished, staffed, and managed in support of the DCC. Applicants are encouraged to describe how their plans in this section will leverage their experience described in the Biographical Sketch. Applicants are encouraged to propose and justify any other coordination activities that would be useful to the INCLUDE Project, but are not listed explicitly elsewhere in this NOFO.

Describe plans for the following administrative activities, which include, but are not limited to:

• Coordinating the functions of the other components of the INCLUDE DCC.
• Coordinating general communications between the DCC and the Steering Committee which consists of the DCC PI/PD and Core Directors, and NIH program staff involved in this cooperative agreement. This may include leading regular updates with the INCLUDE NIH staff, such as monthly conference calls and/or monthly reports of milestones.
• Coordinating yearly face-to-face meetings for the Steering Committee and  investigators from the other components.
• Hosting annual Program Consultants meeting to evaluate the progress of the program and to provide advice to the NIH and the Steering Committee about scientific direction; Program Consultant membership will be determined by NIH.
• Documenting discussions, decisions, and actions discussed during meetings and conference calls, and following up with relevant stakeholders when necessary.
• Archiving and tracking all materials relevant to the development of the INCLUDE DCC.
• Developing and implementing standard operating procedures and policies for the operation of the DCC and making them readily available to the public.
• Compiling formal progress reports or other reports as directed by the Project Scientist.

Describe plans for the following outreach and communication activities, which include, but are not limited to:

• Developing and implementing an outreach plan to promote the INCLUDE Data Hub (including the data portal, data repository services, integrated cloud platform(s), and associated infrastructure) to Down syndrome research community as well as the broader Down syndrome stakeholder community.
• Continue developing the INCLUDE DCC website and maintaining a registry of investigators participating in the INCLUDE Project's activities.
• Continue developing study pages for relevant INCLUDE projects.
• Coordinating with the NIH INCLUDE program team to promote new funding opportunities and other opportunities through the DCC website.
• Facilitating communication between investigators who wish to recruit using DS-Connect®: The Down Syndrome Registry and the registry coordinators at NIH to ensure maximal recruitment of subjects into the registry.
• Creating events and workshops with current or potential users of the Data Hub to provide hands-on tutorials on how to best use the Data Hub and soliciting feedback on the usability of and desired features for the Portal.
• Creating online tutorials and how-to guides to be integrated in the web-based portal site.
• Providing guidance in the appropriate use of the resource for the breadth of the user community envisioned for the INCLUDE DCC.
• Creating online tutorials, training workshops, office hours, hands-on tutorials and in-person events and workshops with current and potential users of the cloud-based platform(s).
• Developing and implementing an outreach plan to collaborate with the new Down syndrome Cohort Development Program (DS-CDP) including the Down syndrome Cohort Research Sites (CRS), the Down syndrome Clinical Cohort Coordinating Center (DS-4C) and the Down syndrome Biorepository.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide, with the following modification:

Do not include a Resource Sharing Plan for this Component. Any resources to be developed under this component should be included with the Resource Sharing Plan for the Overall Component.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing (DMS) Plan must be provided in the Overall component. 

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions. Do not use the Appendix to circumvent page limits.

PHS Human Subjects and Clinical Trials Information (Administrative and Outreach Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply- Application Guide must be followed.

Delayed Onset Study

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

Data Management Core (DMC)

When preparing your application, use Component Type ‘Data Management Core’

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Data Management 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 (Data Management Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management 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) (Data Management 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 (Data Management Core)

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

Budget (Data Management 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 (Data Management Core)

Specific Aims: Briefly address the Specific Aims for the DMC and how they will be accomplished.

Research Strategy: The applicant should discuss how data management tasks will be accomplished, staffed, and managed. Applicants are encouraged to use or integrate with existing data management systems and biorepositories, wherever possible. Applicants are encouraged to describe how their plans in this section will leverage their experience described in the Biographical Sketch.

Activities of the DMC will include, but may not be limited to:

• Coordinating the submission of existing data from multiple INCLUDE projects and future data generators to the DCC and/or relevant repositories, including possible sequence and other -omics data generated through other mechanisms.
• Providing guidance for data generators who plan to submit data to the INCLUDE Data Hub, so they can incorporate INCLUDE expectations early in the data life cycle, for example prior to designing data collection forms.
• Developing data integration pipelines for all kinds of data modalities as needed.
• Developing data standards and data model that could be applied to integrate data from the DS and the general research community.
• Implementing cutting-edge automation process for data integration, curation and harmonization.
• Facilitating necessary NIH procedures, as needed, for example dbGaP procedures for genetics and other controlled access studies.
• Managing quality control for data from all INCLUDE cohorts and other related cohorts that will be incorporated into the DCC and portal.
• Process and harmonize diverse data types to facilitate analyses across disparate datasets.
• Storing data, when necessary, to support the data processing and harmonization, as well as analysis, to generate summary results that will be shared through the portal.
• Developing and implementing a plan for phenotype harmonization that might include:
  • Working with PIs to obtain and clarify/understand source phenotype data
  • Working with NIH-convened INCLUDE activities to create standard trait definitions, common data elements, and minimum common data elements
  • Documenting standard operating procedures
  • Creating a web-based phenotype inventory
  • Leveraging existing efforts where relevant
• Advising on the collection of new datasets and biospecimens according to these standards and common data elements.
• Implementing and developing strategies for Digital Object Identifiers (DOI) minting and landing page maintenance in coordination with the NIH DataCite Consortium and NIH INCLUDE staff.
• Developing and implementing a plan to receive, annotate, and share the results of secondary analyses of INCLUDE data.
• Describe plans for the support of an integrated Virtual Biorepository resource and to coordinate with the new federated biorepository under the DS-CDP.

PHS Human Subjects and Clinical Trials Information (Data Management Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply- Application Guide must be followed.

Delayed Onset Study

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

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions. Do not use the Appendix to circumvent page limits.

Data Hub Core (DHC)

When preparing your application, use Component Type ‘Data Hub Core'

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Data Hub 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 (Data Hub Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Hub 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) (Data Hub 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 (Data Hub Core)

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

Budget (Data Hub 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 (Data Hub Core)

Specific Aims: Briefly address the Specific Aims for the Data Hub Core and how they will be accomplished.

Research Strategy: The INCLUDE Data Hub is composed of a data repository for the INCLUDE Project, in collaboration with NHLBI staff, a single point-of-entry, web-based portal for community access to the INCLUDE demographic, phenotypic, genomic, and other -omics data, and a cloud-based platform to allow secure cloud computing. Applicants should specify metrics to evaluate usage and usability of the data through the Data Hub.

Describe plans for the following activities to utilize or develop a Data Hub, which include, but are not limited to:

• Web Portal Interface: A web-based portal is to make INCLUDE data accessible to the research community. The web portal should catalog, display, make searchable, and enable summary statistics and basic analyses of all INCLUDE data. The portal should also facilitate access to associated individual level -omics data which may required integration with dbGaP (Database of Genotypes and Phenotypes). In addition to harmonized data, the web portal should also make original raw data available to the research community. The environment should have the ability to become interoperable with the NIH Data Ecosystem in the future.
• Integration of diverse datasets: facilitating access to and integration of diverse datasets (demographic, phenotypic, genomic, other -omics data, etc.) to allow those with unique perspectives on human disease to perform data mining and complex data analyses.
• Datasets that will be integrated include, but are not limited to:
  • Data generated under currently funded INCLUDE projects (see: https://www.nih.gov/include-project/funding)
  • De-identified datasets extracted from INCLUDE-funded clinical trials
  • Clinical trial and clinical study data and EHR data using FHIR standard
  • Existing Down syndrome cohorts in dbGaP/SRA (Sequence Read Archive), and other data repositories
  • Other external repositories or datasets that may exist in the research or clinical community. Some files may exist in outside domestic and international repositories; the data hub team will be tasked with identifying, cataloging, and indexing to outside datasets, while conforming to the various data sharing policies of the outside repositories.
• Data Storage: Hosting summary, metadata, and other data in the portal to facilitate searching and access to datasets that may reside in other data resources. Developing partnerships with other data resources, per the guidance of INCLUDE staff, to build avenues of data exchange, indexing, and interoperability through integration of the NIH Researcher Auth Service (RAS), as well as implementation of standard application program interfaces (e.g., GA4GH Data Repository Service, HL7 FHIR), and other interoperability standards and practices, such as those being tested and implemented in the NIH Cloud Platforms Interoperability effort (https://datascience.nih.gov/nih-cloud-platform-interoperability-effort)   
• Data Analysis: Integrating or developing infrastructure and tools that will enable:
  • Viewing, manipulating, and exporting summary analysis of multiple datasets at the same time.
  • Identifying cohorts through a "free text" search that accepts a broad range of search terms encompassing standard ontology as well as other common vocabulary relevant to gene variant, proteomic, metabolomic, and phenotypic data.
  • User-defined queries to identify cases and/or samples sets, based on variants, other -omics, and phenotypes.
  • Gene-specific or gene-set-specific queries, returning all data across defined project data sets.
  • Queries based on metadata or phenotypic characteristics, returning all data across defined project data sets.
  • Creating virtual cohorts by allowing users to specify phenotypes or custom range of data values which will be applied across multiple studies in the Data Hub.
  • Grouping and exploring queries by consent group or Data Use Limitations. Specifically, when assembling a cohort, filtering out datasets or individuals that cannot be used for further analysis.
  • Other summary-level queries.
  • Making existing data analysis tools easily accessible for researchers to use.
  • Making available analytic tools that were developed through other INCLUDE NOFOs.
  • Developing infrastructure and tools to help facilitate multimodal integrative data analysis using different data modalities including but not limited to genomic, clinical, imaging and other-omics data.
• Data Display: Developing or adapting existing open source or commercially available software utilities to provide online tools for phenotype and -omics data visualization. Providing intuitive and easy-to-understand display of data and query results.
• Creating a dynamic and cross-referenced index of dataset files relevant to the INCLUDE Project, as described above.
• Providing links to access information about these data sources.
• Developing partnerships and links to relevant programs designated by INCLUDE staff. Potential partnerships include, but are not limited to, NCBI, ClinGen, the NIH Common Fund’s Gabriella Miller Kids First Pediatric Research Program, NHLBI's TOPMed program, the Pediatric Cardiac Genomics Consortium, DS-Connect®: The Down Syndrome Registry, FaceBase, the Rare Disease Clinical Research Network Portal, NICHD’s Newborn Screening Translational Research Network, NIA’S Alzheimer Biomarkers Consortium — Down Syndrome (ABC-DS), NIA’s Alzheimer’s Therapeutic Research Institute and National Alzheimer’s Coordinating Center, Matchmaker Exchange, and the Monarch Initiative.
• Creating INCLUDE project study pages for users to contact cohort recruiting sites for collaboration and collection or sharing of further data, such as more detailed phenotype information.
• Creating or leveraging a system for biospecimen request, review, approval, and distribution through partner biorepository(ies).
• Incorporating new findings, i.e. new annotations or minimal common data elements, into INCLUDE or other Down syndrome datasets shared through the portal.
• Working with different users to refine use cases; design, test, and improve the usability of the interface; and solicit and incorporate ongoing feedback. Outline how the Data Portal user interface will be adaptable for future improvements or new data types that might be suggested by the NIH staff as well as the external user community so that the Portal may be improved and refined throughout the project period.
• Developing web-based tutorials and/or video instructions for users, including interactive help pages and FAQs.
• Maintaining and optimizing a system, such as Google Analytics or others, for collecting metrics on portal usage and functionality, including a user login/registration system, to inform future decisions about changes and modifications needed for website improvements.
• Supporting "help desk" or “ticketing system” functionality for handling questions or issues related to data access, data deposition, data analysis, and Data Hub system features etc.
• Facilitating recruitment through the DS-Connect® registry by directing researchers to DS-Connect's professional portal.
• Continue implementing GUIDs to facilitate participant-level linkages between disparate datasets, including DCC data, biorepository specimens, and DS-Connect registry data via unique identifiers in a de-identified manner.
• The web portal should support all major platforms and consider development of mobile apps. The portal should exhibit flexibility to respond to the changing needs of the scientific community in a timely manner.
• Incorporating federation features into the Data Hub, and integration with RAS to ensure user compliance with data access policies associated with each data set.
• Applicants are encouraged to describe their approaches to ensure that the data and analytical resources supported through this NOFO will conform to the Findable, Accessible, Interoperable, and Reusable (FAIR) principles, without duplicating information in the Data Management and Sharing Plan. Activities that should be discussed in this regard include, but are not limited to, alignment of data and metadata standards, indexing of data and other digital resources, and uses of computing platforms that enable better data access, more robust analysis, and interoperability.
• Continue developing Experimental Model Portal to provide access to aggregated data and knowledge assets generated from animal model and iPSC studies, eventually to create a seamless connection between the human and animal model interface to enable a smooth transition from experimental model studies and human studies.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions. Do not use the Appendix to circumvent page limits.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply- Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

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

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. 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 unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in How to Apply - 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.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to NIH in support of the NIH mission 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 Data Coordinating Center to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Data Coordinating Center 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 Data Coordinating Center that by its nature is not innovative may be essential to advance a field.

Significance

Does the DCC 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 DCC 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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the DCC? 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? Are the broad areas of expertise necessary for development of the overall DCC represented?

Specific to this NOFO: 

Are the broad areas of expertise necessary for development of the overall DCC represented? Do the investigators have experience in developing and managing data resources and coordinating data flow in a multi-component research project?

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 DCC? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the DCC 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?

Specific to this NOFO: 

Will the DCC build on existing resources to address the specific needs of the Down syndrome research community; alternatively, will new resources be developed to address these needs and flexibly meet the future needs of building a Down syndrome cohort?

Does the DCC function as a true “Center” rather than a collection of unrelated core services with the sum of the parts being greater than the individual components?

Do coordination and integration between the DCC and the INCLUDE investigator community reflect a cohesive research resource?

Environment

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

Additional Review Criteria - Overall

As applicable for the Data Coordinating Center 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 categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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 or gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

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

Resubmissions

Not applicable 

Renewals

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

Revisions

not applicable

Additional Review Considerations - Overall

As applicable for the Data Coordinating Center 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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For [programs/projects/networks/consortia/resources] involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

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

Scored Review Criteria - Administrative and Outreach Core (AOC)

Reviewers will evaluate the following items while determining the scientific and technical merit, and in providing an Impact Score, but will not give separate scores for these items.

For the Administrative and Outreach Core, the reviewers will evaluate the following:

• Does the Administrative Core Lead have appropriate experience for overseeing the administrative and outreach activities of the Core?
• Are the other Core personnel appropriate? Is the investigative team experienced in working with the Down syndrome patient and research community?
• Is the management plan sufficient and commensurate with the complexity of the overall DCC?
• Will the services provided by the Core enable the other components to achieve their goals?
• Are the Core's plans for outreach and community training to enhance the use and utility of the INCLUDE Data Hub sufficient and likely to be successful?
• Is the Administrative Core leveraging existing resources to support its mission?
• Does the Core have specific outreach plans for the community, including milestones for engagement and data acquisition?

Scored Review Criteria – Data Hub Core (DHC)

Reviewers will evaluate the following items while determining the scientific and technical merit, and in providing an Impact Score, but will not give separate scores for these items.  An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a Data Hub that by its nature is not innovative may be essential to advance a field.

For the Data Hub Core, the reviewers will evaluate the following:

• Does the Data Hub Core Lead have appropriate experience for overseeing the activities of the Core?
• Are the other Core personnel appropriate? Does the investigative team have the experience in Data Hub development?
• Is the management plan sufficient and commensurate with the complexity of the overall DCC?
• Are the Core's plans to enhance the use and utility of the INCLUDE Data Hub sufficient and likely to be successful?
• Is the Data Hub Core leveraging existing resources to support its mission?
• Does the application provide a clear plan including milestones for the complex work-flow that will be required, including realistic timelines?
• Do the development plans for the Data Hub include obtaining input from potential end users and usability testing?
• Are all appropriate end users considered?
• Has the applicant demonstrated an understanding of avenues for interfacing with other databases, such as international repositories?
• Does the applicant have a plan to ensure that data, consented for different purposes, is used appropriately?
• Will the Portal be flexible and adaptable to the changing needs of the scientific community in a timely manner?
• Will the Data Hub and associated tools and features conform to FAIR principles?
• Does the design of the Portal and associated infrastructure leverage existing resources where appropriate?
• Are resources available within the scientific environment to support electronic information handling, data systems, website development, and data security?

Scored Review Criteria – Data Management Core (DMC)

Reviewers will evaluate the following items while determining the scientific and technical merit, and in providing an Impact Score, but will not give separate scores for these items. For example, a DMC that by its nature is not innovative may be essential to advance a field.

For the Data Management Core, the reviewers will evaluate the following:

• Does the Data Management Core Lead have appropriate experience for overseeing the proposed activities of the Core?
• Are the other Core personnel appropriate? Is the investigative team experienced in dealing with different data modalities and Down syndrome data?
• Is the Data Management Core leveraging existing resources to support its mission?
• Does the application provide a clear plan including milestones for the work-flow that will be required, including realistic timelines, for facilitating deposition of Down syndrome genomic, phenotypic and other -omics data into relevant repositories as part of the INCLUDE DCC and facilitating access to these data through the Portal?
• Does the applicant propose a framework for implementing standards and ontologies and performing phenotype harmonization that builds upon existing efforts?
• Does the application provide a clear plan to support a centralized or networked Biorepository resource? Is the overall strategy for coordinating multiple biorepositories feasible and effective?

2. Review and Selection Process

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 policies and practices, 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 will receive a written critique.

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

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 NOFO. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants &aamp; Funding website, see Award Process.

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

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support.

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

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 (HHS) grant administration regulations at 2 CFR Part 200, 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 recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Accept close coordination, cooperation, and participation of the NIH staff in the aspects of scientific and technical management of the project as described below.
• Ensure that all center goals are met.
• Ensure effective interaction and coordination with project/cohort PIs and the NIH staff.
• Adhere to the NIH policies regarding intellectual property, data release and other applicable resource sharing policies that might be established during the funded period as appropriate.
• Accept and implement any procedures and guidelines developed and approved for the INCLUDE Project.
• Accept and participate in the cooperative nature of the INCLUDE Project, including:
• Attend the Steering Committee meetings, including regular conference calls, and organizing and attending the annual face-to-face INCLUDE Component 2 investigators meetings;
• Organize an annual meeting of External Program Consultants;
• Coordinate and collaborate within the INCLUDE Project as described above;
• Where opportunities are identified, participate in collaborations with other NIH research efforts, such as NIH-convened INCLUDE activities.
• Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.

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

NIH staff will have the role of Project Scientist(s) through technical assistance, advice, and coordination. However, the role of the Project Scientist(s) will be to facilitate but not to direct the activities.

Project Scientists' responsibilities are defined as follows:

• Participate (with other Steering Committee members) in the group process of setting project priorities and making decisions on joint activities and standard practices of the INCLUDE Project. The Project Scientist(s) will assist and facilitate the group process but not direct it.
• Negotiate goals and timelines with the recipients, as necessary.
• Serve as liaisons between the recipients and External Program Consultants, NIH, and the larger scientific community in helping the INCLUDE Project to achieve its goals.
• Coordinate the efforts of the INCLUDE Project with others engaged in similar and related activities.
• 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 INCLUDE NIH Steering Committee and director of NIH.
• Lend relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the recipient institutions who are to serve as the External Program Consultants.
• Serve on subcommittee(s) of the INCLUDE Component 2 Working Group, as appropriate.
• Assist in promoting the availability of the data generated by the INCLUDE Project to the scientific community at large.
• Where warranted, co-author publications about the goals of this NOFO, and of results of studies funded under this NOFO.

Additionally, an agency Program Official or Institute Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

A Steering Committee will be the main governing body of the INCLUDE DCC. The Steering Committee will be composed of the overall and core PDs/PIs of the INCLUDE DCC and NIH program staff. The Steering Committee Chair will not be an NIH staff member. Each full member will have one vote except NIH Project Scientist(s), who will have one collective vote. Other government staff may attend the Steering Committee meetings if their expertise is required for specific discussions. Major scientific and administrative decisions will be determined by majority vote of the Steering Committee.

The Steering Committee will:

• Establish the milestones under this NOFO.
• Develop uniform procedures and policies necessary to meet the Program goals.
• Provide information to the External Program Consultants, which will be appointed by the NIH. The External Program Consultants will evaluate the progress of the INCLUDE Project’s Component 2 efforts, specifically regarding the DCC coordination of activities, and the Project’s recipients, and provide advice to the NIH and Steering Committee about scientific direction.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. 

Data Management and Access Practices Under the Genomic Data Sharing Policy:

Expectations for Developer Use Statement and Overview of NIH Developer Data Access Committee

The Lead Developer(s) (e.g., the Principal Investigator (PI) who is listed as the Project Director (PD) or PI on the funding application), those that they directly supervise, and NHLBI agree that to gain access to data in the NIH Institute, Center, or Office (ICO) controlled-access data repository, the INCLUDE Data Hub, the Lead Developer will submit a request containing a Developer Use Statement (DUS) to the NIH Developer Data Access Committee (NIH Developer DAC) for review. Expectations for the DUS can be found in the NIH Guide Notice, NOT-OD-24-157.

If a project has multiple Lead Developers, (e.g., for multicomponent awards), each Lead Developer must submit a DUS.

Once the NIH Developer DAC has approved, repositories may provide access. Access may be granted for two years. At the end of the approval period, the Lead Developer is expected to submit a progress report through either a close-out or renewal request.

To continue access, a renewal request should be submitted to the NIH Developer DAC that contains at least the following:

• Brief description how access contributed to developer work.
• Affirmation that the Lead Developer and those they directly supervise adhered to the developer terms of access and any NIH program or ICO specific requirements for NIH controlled access.
• Report any data misuse (e.g., violation of the terms of access, the Developer Code of Conduct, and any NIH program or ICO specific requirements for NIH controlled access), breach, or security incident.
• Describe why additional access is needed.

Once the NIH Developer DAC has reviewed and approved, the repository can provide access. Access may be granted for two years.

When access is no longer needed, a close-out should be submitted to the NIH Developer DAC that contains at least the following:

• Brief description on how access contributed to developer work.
• Affirmation that the Lead Developer and those they directly supervise adhered to the developer terms of access and any NIH program or ICO specific requirements for NIH controlled access.
• Report of data misuse (e.g., violation of the terms of access and any additional NIH program or ICO-specific requirements for NIH controlled-access), breach, or security incident.

Terms of Access

The Lead Developer’s institution agrees that if access is approved, the Lead Developer and those that they directly supervise shall become Approved Developers. An Approved Developer is a Lead Developer who has submitted a DUS to the NIH Developer DAC for review and is approved to access data for the purposes described in the approved DUS and agrees to adhere to terms of access described in the Terms and Conditions of Award. Those directly under the supervision of the Lead Developer who are conducting the work described in the approved DUS, are also Approved Developers and must abide by the terms laid out in the terms of access. If the Approved Developers plan to conduct research (e.g., methods research), they must submit a Data Access Request (DAR) for research to a relevant NIH DAC for review and approval.

New uses of these data outside those described in the DUS will require revisions to the DUS and resubmission to the NIH Developer DAC for review.

If a Lead Developer is managing a repository (e.g., performing activities such as repository maintenance and infrastructure development), they agree that they have reviewed and understand the principles for responsible use and data management of controlled-access data as defined in the NIH Security Best Practices for Controlled-Access Data Repositories.

If a Lead Developer is not managing a repository (e.g., not performing activities such as repository maintenance or infrastructure development), they agree that they have reviewed and understand the principles for responsible use and data management of controlled-access data as defined in the NIH Security Best Practices for Users of Controlled-Access Data.

The Lead Developer’s institution and Lead Developer further acknowledge that they are responsible for ensuring that all uses of the data are consistent with applicable law including applicable local, state, Tribal, and federal laws and regulations, as well as relevant institutional policies.

Public Posting of Approved Developer Use

Information about developer activities may be publicly posted. The information may include the name of the Lead Developer’s institution, intended developer activities, in both a scientific and lay format, and de-identified information about inadvertent data releases, breaches of data security, or other violations.

Non-identification

The Approved Developers agree to make no attempt to identify or contact individual participants or groups from whom data were collected or generate information that could allow participants’ identities to be re-identified.

Certificate of Confidentiality

Certificates of Confidentiality (Certificate) protect the privacy of research participants by prohibiting disclosure of protected information for non-research purposes to anyone not connected with the research except in specific situations. Data that are stored in and shared through the NIH controlled-access data repositories are protected by a Certificate. Therefore, Approved Developers, whether or not funded by NIH, who are approved to access a copy of information protected by a Certificate, are also subject to the requirements of the Certificate of Confidentiality and subsection 301(d) of the Public Health Service Act.  

Under Section 301(d) of the Public Health Service Act and the NIH Policy for Issuing Certificates of Confidentiality, recipients of a Certificate of Confidentiality shall not:

• Disclose or provide, in any Federal, State, or local civil, criminal, administrative, legislative, or other proceeding, the name of such individual or any such information, document, or biospecimen that contains identifiable, sensitive information about the individual and that was created or compiled for purposes of the research, unless such disclosure or use is made with the consent of the individual whom the information, document, or biospecimen pertains; or
• Disclose or provide to any other person not connected with the research the name of such an individual or any information, document, or biospecimen that contains identifiable, sensitive information about such an individual and that was created or compiled for purposes of the research.

Disclosure is permitted only when:

• Required by Federal, State, or local laws (e.g., as required by the Federal Food, Drug, and Cosmetic Act, or state laws requiring the reporting of communicable diseases to State and local health departments), excluding instances of disclosure in any Federal, State, or local civil, criminal, administrative, legislative, or other proceeding;
• Necessary for the medical treatment of the individual to whom the information, document, or biospecimen pertains and made with the consent of such individual;
• Made with the consent of the individual to whom the information, document, or biospecimen pertains; or
• Made for the purposes of other scientific research that is in compliance with applicable Federal regulations governing the protection of human subjects in research.

For more information see: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-109.html.

Non-Transferability

The Approved Developers agree not to distribute controlled-access data and any data derivates (e.g., imputed datasets and single nucleotide polymorphisms) to any entity or individual not identified in the approved request without appropriate written approvals from the NIH. The Approved Developer’s institution and Approved Developers agree that controlled-access data accessed through the approved DUS and any data derivatives of controlled-access data, in whole or in part, may not be sold to any individual at any point in time for any purpose.

Data Security Training

The Approved Developers agree to have reviewed IT Administrator or Developer role-based training on the NIH Security Awareness Course(https://irtsectraining.nih.gov/publicUser.aspx).

Data Security and Unauthorized Data Release

If a Lead Developer is managing a repository, the Approved Developers acknowledge NIH’s expectation that they have reviewed and agree to manage the requested controlled-access data and any data derivatives (e.g., imputed datasets and single nucleotide polymorphisms) of controlled-access data according to NIH’s expectations set forth in the NIH Security Best Practices for Controlled-Access Data Repositories.

If a Lead Developer is not managing a repository, the Approved Developers acknowledge NIH’s expectation that they have reviewed and agree to manage the requested controlled-access data and any data derivatives (e.g., imputed datasets and single nucleotide polymorphisms) of controlled-access data according to the NIH Security Best Practices for Users of Controlled-Access Data.

The Approved Developers agree to notify the NIH Developer DAC of any unauthorized data access or sharing, breaches of data security, or inadvertent data releases that may compromise data confidentiality within 24 hours of when the incident is identified. As permitted by law, notifications should include any known information regarding the incident and a general description of the activities or process in place to define and remediate the situation fully. Within 3 business days of the NIH Developer DAC notification, the Lead Developer’s institution agrees to submit to the NIH Developer DAC(s) a detailed written report including the date and nature of the event, actions taken or to be taken to remediate the issue(s), and plans or processes developed to prevent further problems, including specific information on timelines anticipated for action. The Lead Developer’s institution agrees to provide any additional documentation requested by the NIH Developer DAC on the incident, including verifying that the remediation plans have been implemented. Repeated violations or unresponsiveness to NIH requests may result in further compliance measures.

All notifications and written reports of DMIs should be sent to the NIH Developer DAC (DeveloperAccessDAC@od.nih.gov) with a copy to the GDS mailbox (GDS@nih.gov).

NIH, or another entity designated by NIH, as permitted by law, may also investigate any data security incident or policy violation. The Approved Developers agree to support such investigations and provide any requested information as consistent with applicable law including applicable local, state, Tribal, and federal laws and regulations. In addition, the Lead Developer’s institution and the Lead Developer agree to work with the NIH to assure that plans and procedures that are developed to address identified problems are mutually acceptable and consistent with applicable law.

Term of Access Violations (e.g., Data Management Incident (DMI))

The Lead Developer acknowledges that the NIH may immediately revoke or suspend access to all controlled-access data at any time if Approved Developers are found to no longer be in compliance with these terms, any additional program or NIH ICO-specific requirements for NIH controlled-access data repositories, or with other policies and procedures of the NIH. Past violations may be taken into consideration for future requests from the Lead Developer to access the data. The Lead Developer agrees to notify the NIH of any actual or suspected violations of these terms, or any additional program or NIH ICO-specific requirements for NIH controlled-access data repositories within 24 hours of when the incident is identified. Repeated violations or unresponsiveness to NIH requests may result in further compliance measures.

All notifications and written reports of DMIs should be sent to the NIH Developer DAC (DeveloperAccessDAC@od.nih.gov) with a copy to the GDS mailbox (GDS@nih.gov).

NIH, or another entity designated by NIH, as permitted by law, may also investigate any DMI. The Lead Developer agrees to collaborate with such investigations and provide information as consistent with applicable law including applicable local, state, Tribal, and federal laws and regulations. In addition, the Lead Developer agrees to work with the NIH to assure that plans and procedures that are developed to address identified problems are mutually acceptable and consistent with applicable laws and policies. The Lead Developer also acknowledges that NIH may revoke access for any reason without cause.

Developer Use Reporting

The Lead Developer who is seeking Renewal or Close-out of a project agrees to complete the appropriate forms and provide an update, report any violations of the terms of access described, and the implemented remediation.

Non-endorsement, Indemnification

Approved Developers acknowledge that although all reasonable efforts have been taken to ensure the accuracy and reliability of controlled-access data, NIH and all contributors to these data disclaim all warranties as to performance or fitness of the data for any particular purpose. No indemnification for any loss, claim, damage, or liability is intended or provided by any party under this agreement. Each party shall be liable for any loss, claim, damage, or liability that said party incurs as a result of its activities under this agreement, except that NIH, as an agency of the United States, may be liable only to the extent provided under the Federal Tort Claims Act, 28 USC 2671 et seq.

Lower Tier Agreements

If the Lead Developer seeks to work with a partner not directly funded by the federal government that will need access to NIH controlled-access data (and is not a third-party IT system or Cloud Service Provider) NIH will only provide the developer partner access to controlled-access data if:

• Both the Lead Developer and developer partner enter into a contract containing the terms of developer access in the Terms and Conditions of the Award.
• The Lead Developer identifies the developer partner institution and developer partner program manager in their DUS and submits it to the NIH Developer DAC and is approved. For ongoing developer work, the Lead Developer can revise and resubmit the DUS.
• The developer partner submits a DUS to the NIH Developer DAC for review that contains information about the developer partner program manager and IT Director and, if approved, the developer partner and their Institutional Signing Official co-sign the Developer Data Use Agreement and any additional NIH program or ICO-specific requirements.

Termination and Data Destruction

Upon close-out, the Approved Developer agrees to destroy all copies, versions, and data derivatives (e.g., imputed datasets and single nucleotide polymorphisms) of the data retrieved from NIH controlled-access data repositories, on both local servers and hardware, and if cloud computing was used, delete the data and cloud images from cloud computing provider storage, virtual and physical machines, databases, and random-access archives.

Developer Code of Conduct

The Developer Code of Conduct sets forth expectations for the responsible management and use of controlled-access data in NIH controlled-access data repositories. Approved Developers agree to:

1. Use data for the sole purposes of developing, testing, and implementing the environment and building the infrastructure during both development and production phases of deployment (these functions include software development to enable researchers to access and analyze data);
2. The Approved Developers agree to make no attempt to identify or contact, either directly or indirectly, individual participants or their families.;
3. Maintain the confidentiality of the data and not distribute data or derivative data (e.g., imputed datasets and single nucleotide polymorphisms) to any entity or individual without appropriate written approvals from the NIH;
4. Implement administrative and technical safeguards to prevent unauthorized access to the data and adhere to the NIH Security Best Practices for Controlled-Access Data Repositories, or if applicable, NIH Security Best Practices for Users of Controlled-Access Data;
5. Ensure that only authenticated and authorized users can gain access to data files, as appropriate;
6. Report any actual or suspected inadvertent data access or release, breach of data security, or other DMIs in accordance with the terms described herein to the NIH Developer DAC (DeveloperAccessDAC@od.nih.gov) with a copy to the GDS mailbox (GDS@nih.gov) within 24 hours of when the incident is identified;
7. Allow information about its use of controlled-access data to be publicly posted. The information may include the name of the Lead Developer’s institution, intended developer activities, in both a scientific and lay format, and de-identified information about inadvertent data releases, breaches of data security, or other violations;
8. Acknowledge that no ownership rights of the datasets (including derived or derivative data) are granted to developers or their affiliates.
9. Lead Developers who want to perform research must submit a Data Access Request (DAR) to a relevant NIH DAC for review and approval.

• When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

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

Finding Help Online: https://www.era.nih.gov/need-help  (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Huiqing Li, PhD.
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0554
Email: huiqing.li@nih.gov   
 

Melissa Parisi, MD, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6880
Email: parisima@mail.nih.gov

Huiqing Li, PhD.
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0554
Email: huiqing.li@nih.gov   

 Peer Review Contact(s)

Natalia Komissarova, Ph.D.
Center for Scientific Review
Telephone: 301-435-1206
Email: komissar@mail.nih.gov

Center for Scientific Review (CSR)

Email: NOFOReviewContact@csr.nih.gov

Fatima Kamara
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-4916
Email: fatima.kamara@nih.gov 

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: margaret.young@nih.gov

Fatima Kamara
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-4916
Email: fatima.kamara@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.

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 2 CFR Part 200.