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 Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 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 and changing 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 risk 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 Notice of Funding Opportunity (NOFO) is one of several trans-NIH research initiatives created in response to Fiscal Year 2018, 2019, 2020, 2021, 2022, and 2023 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

Purpose

The purpose of this NOFO is to support a Down Syndrome Clinical Cohort Coordinating Center (DS-4C) to provide overall management and oversight for the Down syndrome Cohort Development Program (DS-CDP), including coordination and communication across all subsections and cores of the program, and also facilitating data sharing within the research community through the INCLUDE Data Coordinating Center (DCC). The DS-4C will work in concert with the Down Syndrome Cohort Research Sites (DS-CRS; (RFA-OD-24-003)  ) that will recruit participants with DS across the lifespan, collect biospecimens, and assemble phenotypic data, images, and omics for deep phenotyping. A related NOFO (RFA-OD-24-004)  ) will support a Federated Biobanking Resource (DS-Biorepository) to store and distribute biospecimens collected under the auspices of the DS-CDP.

Scope

This NOFO addresses Component 2 of the INCLUDE Project. Specifically, it is designed to support the Down syndrome Cohort Development Program (DS-CDP). Coordination, aggregation, and harmonization of demographic, clinical, electronic health record (EHR), remote digital health, laboratory, and imaging data from large numbers and a diverse population of people with Down syndrome has the potential to improve our understanding of the general epidemiology of DS, the risk factors leading to DS, and the longitudinal course of DS, and in addition, to help uncover novel targets for mechanism-based therapies. 

A new prospective cohort of people with DS will undergo a comprehensive deep phenotyping and biosample acquisition protocol ("common protocol") at the Cohort Research Sites (DS-CRS). This common protocol will be developed in conjunction with the DS-CRS and DS-Biorepository during the first year of the awards. Collection of demographic, clinical, laboratory, biospecimen, and imaging data from people with DS will be combined with further bioprofiling (e.g., genomics, proteomics, metabolomics) to enable discovery and validation of new biologic targets. The DS-4C is expected to work closely with the INCLUDE DCC to share clinical cohort data through the INCLUDE Data Hub which is a centralized data resource that shares large-scale clinical and multi-omics data and supports collaborative, cloud-based analyses to accelerate scientific discoveries related to Down syndrome and its co-occurring conditions.

Clinical Cohort Coordinating Center Objectives

The primary role of the DS-4C will be to provide overall management and oversight for the DS cohort development program, including coordination and communication across all subsections and cores of the program; most importantly, it will lead the effort to outreach to a broader DS community  .

Clinical Cohort Coordinating Center staff must possess strong scientific qualifications, including, but not limited to, expertise in clinical/health informatics, bioinformatics, -omics, biostatistics, epidemiology, and data science. The DS-4C personnel must have experience in the supervision of complex, multi-center clinical studies, as well as experience in the statistical analysis of high-volume demographic, clinical, laboratory, and imaging data. The activities of the 4C will require effective communication and outreach with the DS and clinical communities to achieve INCLUDE goals; therefore, they must have personnel capable of serving as liaisons and translators among the DS families, clinical researchers, clinicians, and bioinformaticians. DS-4C personnel should also have experience with health IT standards, phenotype ontology, and harmonization, as well as experience in coordinating biospecimen collection and linking them to a biospecimen repository(ies), in coordination with a Federated Biobanking Resource being created by the INCLUDE Project (RFA-OD-24 -00 4).

The DS-4C’s responsibilities will cover four areas:

(1) the Administrative Core will oversee study operations, research skills development, and oversee capitation to the DS-CRS for deep phenotyping and biospecimen collection costs;

(2) the Outreach Core will oversee communication with the broader DS community to increase DEIA for DS cohort recruitment, and support a call center to follow participant outcomes, in conjunction with the DS-CRS;

(3) the Cohort Core will develop and coordinate the implementation of a common protocol by the DS-CRS and oversee their data collection and quality approaches, and coordination of biospecimen and biorepository activities with the DS-Biorepository; 

(4) the Data Management Core will ingest, aggregate, integrate, harmonize, and curate data from the DS-CRS, and work with the INCLUDE DCC to rapidly share these data through the INCLUDE Data Hub to facilitate use by the broad research community.

The Cohort Core of the DS-4C will plan and provide oversight to implement the common protocol, state-of-the art deep phenotyping protocol at DS-CRS selected under a separate RFA.This common protocol, adjusted for co-occurring conditions that impact people with DS across the lifespan, will be developed by awarded sites in collaboration with the Cohort Core of the DS-4C and DS-Biorepository during the first year of the project.  The Cohort Core of the DS-4C will also coordinate and implement EHR data acquisition from each Research Site to collect baseline and longitudinal data on enrolled participants. It will provide oversight for research testing; acquisition of participant-provided home monitoring digital health data; acquisition of biospecimens; integration of various data types to form a rich data resource; and advanced analysis and interpretation of results. The Data Management Core of the DS-4C will be expected to develop procedures for data harmonization and standardization for all data types, in collaboration with the Research Sites and the INCLUDE DCC, as necessary.

In addition to the funds awarded directly to the DS-4C for conducting DS-4C responsibilities, funds to conduct the common protocol will be part of the DS-4C’s grant award and will be distributed by the DS-4C as capitation to the DS-CRS sites in accordance with protocol budgets (see RFA-OD-24-003 ) as determined by NIH and the Steering Committee. The DS-4C will establish core laboratories as determined by the needs of the common protocol with input from NIH and the Steering Committee.

Clinical Cohort Coordinating Center Organization and Governance

The DS-CDP Steering Committee (SC) will provide oversight and direction for the entire program and will consist of Principal Investigators from the DS-4C and from each Research Site, NIH Project Scientists and Program Officials, and academic researchers involved in the project. The SC will meet shortly after funding to begin planning for cohort development and implementation of the common protocol, establish scientific goals, and develop and implement a Steering Committee charter. It is highly recommended that each core propose a strong project management plan to oversee and track its activities, and that an overall project management plan for the coordination of all core activities be provided. 

In particular, DS-4C applications lacking any of the following components (Overall component, Administrative Core, Outreach Core, Cohort Core, and Data Management Core), will be considered nonresponsive and will not be reviewed.

The DS-CRS, described in RFA-OD-24 -003 , will serve as performance sites for cohort recruitment and the common protocol. Research sites are responsible for recruiting participants, assuring good clinical practice, supporting remote monitoring, and participating in a cooperative and interactive manner with one another, the DS-4C, and the NIH. Research Sites will be responsible for the planning and collection of high-quality data, images, and biospecimens for omics analyses and their transfer to the DS-4C and/or appropriate core labs or biorepositories for curation and analysis.

NIH will provide overall support for DS cohort development. The NIH Program Officer and the Office of Grants Management are responsible for the federal stewardship of the award (management, financial and administrative oversight). In addition to regular award oversight, the NIH Project Scientists will be involved substantially with the awardees as partners, consistent with the Cooperative Agreement mechanism.

Independent Program Consultants (PCs), appointed by the NIH and funded through the DS-4C, will review the progress of the program annually and as needed to provide advice to the NIH about scientific direction.

An Observational Safety and Monitoring Board (OSMB), also to be appointed by the NIH and funded through the DS-4C, will monitor patient safety and data integrity and review the performance of each study involving human subjects. The OSMB will also review proposed ancillary studies for issues of participant burden. As a part of its monitoring responsibility, the OSMB will submit recommendations to the NIH regarding the conduct and continuation of each protocol.

Data Sharing

The NIH Policy for Data Management and Sharing (Policy) expects researchers maximize the sharing of scientific data and data be accessible as soon as possible and no later than the time of an associated publication or the end of the award period, whichever comes first. Additionally, rapid data sharing is a critical component of INCLUDE’s goal to accelerate discovery of etiology and biologic pathways underlying co-occurring conditions of Down syndrome. NIH requires all applications submitted in response to this NOFO to include a Data Management and Sharing Plan (Plan) outlining how scientific data and any accompanying metadata will be managed and shared. It is expected that all de-identified human data coordinated and generated by this project will be submitted to the INCLUDE Data Hub (portal.includedcc.org) in coordination with the INCLUDE Data Coordinating Center (DCC). The INCLUDE Data Hub is a centralized data resource that allows access to large-scale clinical and multi-omics datasets specific to Down syndrome and supports collaborative, cloud-based analysis to accelerate scientific discoveries related to Down syndrome and its co-occurring conditions. The Data Management and Sharing Plan will be considered by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program as well as the NIH Policy for Data Management and Sharing.

Notice of NIH's Interest in Diversity 

Every facet of the United States scientific research enterprise—from basic laboratory research to clinical and translational research to policy formation–requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. In spite of tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups that are underrepresented in the biomedical, clinical, behavioral and social sciences. See NOT-OD-20-031 and 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 for details. 

To support the best science, the INCLUDE project encourages inclusivity in research. Examples of structures that promote diverse perspectives include but are not limited to: 

• Transdisciplinary research projects and collaborations among neuroscientists and researchers from fields such as biochemistry, bioengineering, computational biology, molecular biology, health services, pharmacology, computer and data sciences, bioinformatics as well as bioethics. 
• Engagement from different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-colleges). 
• Individual applications and partnerships that enhance geographic and regional heterogeneity. 
• Investigators and teams composed of researchers at different career stages. 
• Participation of individuals from diverse backgrounds, including groups historically underrepresented in the biomedical, behavioral, and clinical research workforce (see NOT-OD-20-031), such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women. 
• Project-based opportunities to enhance the research environment to benefit early- and mid-career investigators. 

For the purposes of this NOFO, diverse refers to diversity of the scientific workforce supporting this resource as well as diversity of participants participating in the Cohort Development Program. 

Plan for Enhancing Diverse Perspectives (PEDP) 

• This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in NOT-MH-21-310, submitted as Other Project Information as an attachment (see Section IV). 
• Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material. The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions. 

Pre-Application Webinar and Frequently Asked Questions

A Pre-Application Webinar for all interested prospective applicants will be hosted by INCLUDE Program staff. Webinar date and other details will be posted on the INCLUDE website: https://www.nih.gov/include-project/. Frequently Asked Questions (FAQs) will also be posted and updated on the INCLUDE website: https://www.nih.gov/include-project/frequently-asked-questions.  

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

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

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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. 

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

The PD/PI is strongly encouraged to devote a minimum of 4.2 person-months to this resource.  For applications with multiple PDs/PIs, a minimum effort of 2.2 person-months is required of the Contact PD/PI and 1.2 person-months of effort per additional PD/PI is required.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

NIH will not accept duplicate or highly overlapping applications under review at the same time per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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 Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Huiqing Li, PhD
Telephone: 301-435-0554
Email: huiqing.li@nih.gov

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

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

Overall Component

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

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

 Plan for Enhancing Diverse Perspectives

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity.
• The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate.
• Where possible, applicant(s) should align their description with these required elements within the research strategy section.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review.

Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups historically under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.

For the purposes of this NOFO, diverse refers to diversity of the scientific workforce supporting this resource as well as diversity of participants participating in the Cohort Development Program.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp. 

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 overall goals of the DS-4C and how its work supports the overall objectives of the DS cohort development effort. 

Research Strategy:

• Provide a general overview including considerations that will lead to successful development and coordination of the proposed DS-4C.
• Describe the overall design and structure of the DS-4C including its management structure, integration of components, and any possible subcontracts. Include an organizational chart of the cores, their associated tasks, and a milestone plan. Identify the types of staff associated with each task and describe their respective roles and responsibilities.
• Describe plans for the coordination and integration of the DS-4C resource into the overall goals of the DS-CDP and INCLUDE Project to achieve a cohesive resource for the research community.
• Describe procedures to coordinate activities of a Steering Committee (SC), an Observational Study Monitoring Board (OSMB), and independent Program Consultants (PCs).
• Describe plans to maximize the impact of the INCLUDE Project by creating an “open science” framework with rapid data curation and sharing.

Letters of Support: An Institutional Letter of Support should be provided stating the institutional support for the proposed center. Applicants are encouraged to reach out to the INCLUDE DCC (https://includedcc.org/) for guidance and a letter of support for their proposal.

Letters of support from any partner organizations that will be supporting outreach activities are encouraged and can be included in the “Overall” section.

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

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component. 

All instructions in the SF424 (R&R) 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.
• It is expected that all de-identified human data coordinated and generated by this project will be submitted to the INCLUDE Data Hub (portal.includedcc.org) in coordination with the INCLUDE Data Coordinating Center (DCC). The INCLUDE Data Hub is a centralized data resource that allows access to large-scale clinical and multi-omics datasets specific to Down syndrome and supports collaborative, cloud-based analysis to accelerate scientific discoveries related to Down syndrome and its co-occurring conditions. 

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Overall)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form (Overall)

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

Administrative Core 

When preparing your application, use Component Type ‘Administrative Core.’

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

SF424 (R&R) Cover (Administrative 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 Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

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

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

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

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

List all performance sites that apply to the specific component.

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

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

• 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 (Administrative Core)

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

The DS-4C Administrative Core budget should reflect support for personnel and infrastructure costs of the core. Budgets should include support for at least 9 person months effort for the administrative coordinator; a minimum of 2.4 calendar months effort for the PD/PI or a minimum of 2.4 person months combined effort for all multi-PDs/PIs; and other investigators and staff as required. Travel costs for a Steering Committee meeting and an investigators’ meeting each year in Bethesda, MD should be included for 4-6 members of the DS-4C, including at least one PD/PI and the coordinator for each Core.  The capitated costs for the per-person enrollment and phenotyping, as well as biospecimen collection and omics generation, will be provided through separate funding streams. These budget estimates should not be included in the budget calculations for the DS-4C application.

PEDP implementation costs: Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

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

PHS 398 Research Plan (Administrative Core)

Specific Aims: Describe how the specific aims for the Administrative Core will be accomplished.    

Research Strategy: Discuss how the activities listed below will be accomplished, staffed, and managed in support of the DS-4C. Describe how the proposed plans will leverage the experience described in the Biographical Sketch(es). 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 administrative activities, including but not limited to:

• Designing, implementing, and integrating program components.
• Monitoring and reporting metrics for patient enrollment, engagement, and retention.
• Supporting a call center that facilitates acquisition of outside records, additional data collection, and longitudinal contact with patients.
• Coordinating with clinical centers for any required agreements related to EHR extraction and acquisition of longitudinal research data and transfer of data to the DS-4C. Any agreements must be consistent with the plan for ultimately sharing all de-identified cohort data with the broad research community through the INCLUDE Data Hub.
• Establishing a consent template for use by all Clinical Centers and sites, including appropriate language to allow broad sharing and future use of study data and biospecimens aligned with the goals of this NOFO.  
• Ensuring consistency and standardization across clinical sites for all aspects of the program.
• Working directly with the INCLUDE DCC to coordinate data storage and access.
• Monitoring program resources and planning publications.
• Coordinating yearly face-to-face meetings for the Steering Committee and investigators.
• Hosting regular Program Consultant (PC) engagements to evaluate the progress of the program and to provide advice to the NIH and the Steering Committee about scientific direction; PCs will be selected by NIH.
• Documenting discussions, decisions and actions discussed during meetings and conference calls, and following up with relevant stakeholders when necessary.
• Compiling formal progress reports, or other reports as directed by the NIH Program Officer and Project Scientists.
• Promoting and facilitating all communications between and among all aspects of the program.
• Establishing processes as needed to support the common phenotyping protocol and biospecimen collection.
• Providing oversight to meet performance metrics for enrollment, retention and data quality, and developing reports for the OSMB.
• Reimbursing DS-CRS with funds for each participant enrolled and phenotyped as agreed to by the common protocol.

Letters of Support: Only letters of support specific to ‘Administrative Core’ should be attached to this section.

Resource Sharing Plan: A resource sharing plan is not required for this component.  Resource sharing Plans should be included under the Overalll component.  Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Administrative 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 SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Outreach Core

When preparing your application, use Component Type ‘Outreach Core’.

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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

Enter Human Embryonic Stem Cells in each relevant component.

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

Specific Aims: Describe how the specific aims for the Outreach Core will be accomplished. 

Research Strategy: Discuss how the activities listed below will be accomplished, staffed, and managed in support of the DS-4C. Describe how the proposed plans will leverage the experience described in the Biographical Sketch(es). Propose and justify any other outreach activities that would be useful to the INCLUDE Project but are not listed explicitly elsewhere in this NOFO.

Describe plans for outreach activities, including but not limited to:

• Describe how to improve community engagement to build good relationships with community organizations and stakeholders to increase trust and interest in study participation. While individual DS-CRS sites will be tasked with local recruitment responsibilities, the DS-4C Outreach Core will be responsible for a national strategy for outreach to the DS population for cohort development efforts.
• Provide effective plans to increase diversity and representation among investigators and study participants.
• Describe plans to share information about the study and its goal to reach a wider audience and increase participation utilizing direct mail, social media and/or other methods.
• Describe plans on collaborating with different partners, such as hospitals, clinics, and advocacy groups to reach out and enroll participants who may not have been aware of the study otherwise.
• Describe plans on how to incentivize participation in the study.

Letters of Support: Only letters of support specific to ‘Outreach Core’ should be attached to this section. 

Resource Sharing Plan:

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

Appendix:

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

PHS Human Subjects and Clinical Trials Information (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 SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Cohort Core

When preparing your application, use Component Type ‘Cohort Core.’

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

SF424 (R&R) Cover (Cohort 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 (Cohort Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Cohort 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) (Cohort 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 (Cohort 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.   

Specific to this NOFO: Describe the previous experience, if any, of the Cohort Core Lead in organizing and managing epidemiological cohort studies and/or clinical trials. 

Budget (Cohort Core)

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

 In this budget section, applicants should include costs of personnel to support the activities of the Core and any costs required to support the development of the final common protocol during year one and costs to implement it (years 2-5). Do not include the actual capitation costs for enrollment and phenotyping of each subject, which will be reimbursed under a separate mechanism.

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 (Cohort Core)

Specific Aims: Briefly describe how the specific goals of the Cohort Core will be addressed.

Research Strategy: Discuss how the activities listed below will be accomplished, staffed, and managed in support of the DS-4C. Describe how the proposed plans will leverage the experience described in the Biographical Sketch(es). Propose and justify any other activities that would be useful but are not listed explicitly elsewhere in this NOFO.

• While a common protocol should not be included within the application, describe a process and timeline to develop and coordinate the implementation of a common protocol that will include clinical, laboratory, physiological, and behavioral assessments in an age-appropriate manner to cover deep phenotyping by the DS-CRS. Describe how the DS-4C will coordinate with the DS-CRS, DS-Biorepository, and NIH Program Staff to develop and finalize the common protocol during year one. 
•  Describe the needed expertise in epidemiology, ontology, clinical data standardization and statistical support. 
• Describe the strategy for collecting a variety of data types from multiple DS-CRS to create the DS cohort, addressing how it will facilitate a broad DS research agenda.
• Describe plans for quality management, including oversight for how the data collection activities and quality control measures by the DS-CRS will be managed by the DS-4C.
• Adopt, and adapt as necessary, existing data standards used by the DS research community, including ontologies, common data models, and common data elements used and/or recommended by the INCLUDE DCC. Propose the creation of resources and tools that will facilitate the collection of data by the DS-CRS using these standards, including tools to facilitate de-identification.
• Develop methods to facilitate the extraction of electronic health records (EHR) data at the DS-CRS using relevant HealthIT standards such as HL7 Fast Healthcare Interoperability Resources (FHIR®). 
• Describe how available study biospecimens will be collected, managed, and analyzed, in conjunction with the DS-Biorepository, which will store the specimens, and the DS-CRS.

Letters of Support: Only letters of support specific to ‘Cohort Core’ should be attached to this section.

Resource Sharing Plan:

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Cohort 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 SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Data Management Core

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

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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.   

Specific to this NOFO: Describe the previous experience, if any, of the Data Management Core Lead in participating in large-scale collaborative programs involving coordination of data generation across multiple projects. 

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: State the specific aims for the Data Management Core and how they will be accomplished.

Research Strategy: Discuss how the activities listed below will be accomplished, staffed, and managed in support of the DS-4C. Describe how the proposed plans will leverage the experience described in the Biographical Sketch(es). Propose and justify any other activities that would be useful but are not listed explicitly elsewhere in this NOFO.

• Propose methods for data management, internal and external data sharing strategies as appropriate and consistent with achieving the goals of the program.
• Develop workflows and standards for data pooling, cleaning, curation, integration and harmonization of all data from the DS-CRS cohorts.
• Provide expertise in ontology, clinical data harmonization, data governance, bioinformatics, statistical support, and systems biology.
• Develop and implement best approaches for data standardization.
• Prepare data submission and ensure data submitted to the INCLUDE Data Hub are fully de-identified.
• Ensure efficient visualization, reporting, and communication of findings.
• Develop strategies to integrate self-reported data, EHR data, research testing data, remote digital health data, imaging data, outcome data, and all kinds of data modalities to form a rich longitudinal data resource. Coordinate linkages across data types and DS-CRS, as appropriate.
• Support implementation of Natural Language Processing technologies for unstructured clinical data.
• Provide expertise to facilitate data analysis by DS-CRS.
• Work with the INCLUDE DCC to transition data into the INCLUDE Data Hub, implement governance compatible with the INCLUDE Data Hub, and make tools/workflows cloud-compatible.
• Describe how the Data Management Core would leverage existing harmonization and tool development efforts led by the INCLUDE DCC and the DS-Biorepository also being competed and established.

Letters of Support: Only letters of support specific to ‘Data Management Core’ should be attached to this section.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment of the Overall component in FORMS-H application forms packages.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (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 SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH 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 the SF424 (R&R) 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.

7. Other Submission Requirements and Information

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

For information on how 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 the SF424 (R&R) Application Guide.

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

Applications must include annual milestones. Applications that fail to include annual milestones will be considered incomplete and will be withdrawn. Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review. 

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 the 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 project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

Significance

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

• To what extent do the efforts described in the Plan for Enhancing Diverse Perspectives further the significance of the project?

Investigator(s)

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

Specific to this NOFO:

• Does the PD(s)/PI(s) have the appropriate experience in managing complex, multi-site projects involving teams of scientists? 
• Do the PD(s)/PI(s) and research team have a strong track-record of generating, integrating and analyzing high-quality data as part of a consortium? 
• Does the research team have a strong expertise across all areas of the data generation pipeline and a clear leadership plan for integrating their experience to meet the specific aims of the DS-4C? 
• To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives strengthen and enhance the expertise required for the 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?

Specific to this NOFO:

• Does the DS-4C propose innovative approaches to data management/standards, data collection, and/or active/passive participant follow-up/surveillance?
• To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives meaningfully contribute to innovation?

Approach

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

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

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

Specific to this NOFO:

• How feasible are the data collection, curation, and integration goals? How rigorous are the applicant's plans for managing study data? How achievable are the study’s timeline and milestones? Does the plan provide ample opportunity for collaboration, integration, and interaction within the DS-4C, with the Research Sites, with the INCLUDE DCC, and the wider DS research community?
• Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspectives well-developed and feasible?

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?

Specific to this NOFO:

• Are the resources, equipment and infrastructure available and in place (or readily obtainable) to achieve the required output from the screening and analysis pipeline? Are the computational resources in place (or readily obtainable) and adequate to support the project? Are safeguards in place to protect personally identifiable information? Will the available facilities and other resources enable the applicant(s) to effectively aggregate data from participants and operate a large consortium efficiently?
• To what extent will features of the environment described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support) contribute to the success of the project?

Additional Review Criteria - Overall

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

Coordination, Cohesion, and Synergy

• Is the leadership plan, including how decisions will be made across the overall Down syndrome Cohort Development Program (DS-CDP), among the DS-4C Cores, Cohort Research Sites (DS-CRS), and Federated Biobanking Resource (DS-Biorepository), appropriate?
• Are the plans for communicating and collaborating with the DS-CDP and NIH staff appropriate and likely to facilitate overall program objectives?
• Are the plans for submitting data, protocols, and making resources available to the INCLUDE Project acceptable?
• Will there be coordination, communication, cohesiveness and synergy among the components of the DS-4C as they relate to achieving the overall objectives?
• Are mechanisms proposed for regular communication and coordination among investigators in the DS-CDP?

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

Not Applicable.

Revisions

Not Applicable.

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

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.

Review Criteria - Administrative Core

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

• Are the staffing, equipment, and other resources that are available to the Administrative Core sufficient and relevant to meeting the goals?
• Are plans for participants outcome ascertainment, including the Call Center, sufficient and likely to facilitate research efforts for longitudinal follow-up?

Review Criteria - Outreach Core

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

• Are the staffing, equipment, and other resources that are available to the Outreach Core sufficient and relevant to meeting its goals?
• How feasible are the national outreach efforts planned by the Outreach Core to promote participant engagement and enrollment in the common protocol? Is there a practical plan for integration with the DS-CRS for local recruitment? 
• Are plans for community engagement, partnership and communication, sufficient and likely to effectively increase the diversity and representation of the cohort, as well as improve the accuracy and validity of the research findings? Are plans tailored to the specific population and goals of the study, and do they consider ethical and cultural considerations?

Review Criteria - Cohort Core

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

• How feasible is the plan to develop and coordinate the implementation of the common protocol among the DS-CRS, DS-4C, DS-Biorepository, and NIH Program Staff?
• How feasible are the data integration goals? How rigorous are the applicant's plans for managing study data? How achievable are the study’s timeline and milestones?
• How will the facilities and other resources available to the applicant(s) enable the effective data aggregation of cohort participants and, if applicable, the efficient operation of a multi-site study? 

Review Criteria - Data Management Core

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

• Are plans for data curation, data harmonization and data integration with the INCLUDE DCC feasible?
• Are any overlap functions identified between the proposal core and the INCLUDE DCC?

2. Review and Selection Process

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

As part of the scientific peer review, all applications will receive a written critique.

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

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.
• Compliance with resource sharing expectations.

3. Anticipated Announcement and Award Dates

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

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

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690)) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

•  For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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

 he 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:

The PD(s)/PI(s) assume(s) responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported by the U54 award in accordance with these terms and conditions of the award. As such, the recipient  PD(s)/PI(s) will be responsible for all aspects of the study and cohort, as well as any modification(s), unless otherwise provided for in these terms or by action of the cohort Steering Committee.  

Specific responsibilities include:  

• Defining objectives and approaches of the research 
• Defining the research plan and goals 
• Project design and common protocol development with the DS-CRS and DS-Biorepository 
• Obtaining all requisite study and protocol approvals 
• Data collection and quality control 
• Data monitoring 
• Oversight of study activities, such as protocol development, data curation and harmonization, manuscript preparation, etc. 
• Overseeing/performing other scientific activities of the research plan 
• Monitoring the completion of the supported activities and taking corrective actions if needed 
• Participating in the activities of the Steering Committee 
• Accepting and implementing the decisions approved by the Steering Committee to the extent consistent with applicable grant regulations 
• Cooperating with NIH programmatic, technical, and administrative staff 
• Administratively managing the U54 award 
• Developing collaborations with and making data accessible to external investigators 
• Ensuring submission of reports to the OSMB, if applicable  
• Participating in an annual INCLUDE Investigators' Meeting and any other meetings as recommended by NIH Program Staff 
• Host at least one meeting annually of the independent Program Consultants (PCs) for the DS-CDP 
• 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.

The recipient  will be required to provide updated descriptive and metadata to the NIH upon request, including cohort characteristics, study protocols, basic counts of study participants, enrollment progress, biospecimen availability, and study variable definitions. Recipient s must also provide analytical data files (illustrative examples include: derived/calculated data variables; finalized questionnaire data; data from procedures, such as echocardiography, ECG, MRI, exercise testing, polysomnography, etc.; participant follow-up data; clinical event outcomes data) to the NIH periodically based upon a mutually agreed schedule and format and at the end of the period of this award, along with documentation necessary for their use. 

Recipient s will be expected to evaluate and document compliance with NCI's Best Practices for Biospecimen Resources for collection, processing, and storage of previously collected biospecimens (http://biospecimens.cancer.gov/bestpractices). Recipient s will be required to explore, with NIH staff, the feasibility of data harmonization and pooling with other cohorts and studies. Recipient s will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies (http://biospecimens.cancer.gov/bestpractices).  

Recipient s agree to the governance of the study through a Steering Committee and to accept and implement decisions approved by the Steering Committee (see "Joint Responsibilities" section below). 

Recipient s are expected to make their data widely available to other investigators per NIH and NIH Data Management and Sharing Policy (https://sharing.nih.gov/data-management-and-sharing-policy). Study investigators are strongly encouraged to publish and disseminate results, tools, resources, and other products of the study, in accordance with the study protocols and governance. It is expected that all methods, analyses, software, and algorithms will be made available in a timely manner to the scientific community (https://sharing.nih.gov/data-management-and-sharing-policy).  

Support or other involvement of industry or any other third party in the study may be advantageous and appropriate. Participation by the third party; involvement of study resources; citing the name of the study or NIH support; or special access to study results, data, findings, or resources requires notification of and concurrence by NIH. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification to and concurrence by NIH.  

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

A designated NIH Project Scientist(s) will have the following responsibilities:  

• 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 and DS-CDP. 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 recipient s and 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 Program Consultants. 
• Ensuring disclosure of conflicts of interest and adherence to NIH policies 
• 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.   

In addition to the Project Scientist, a separate NIH Program Official will be responsible for the normal program stewardship of the cooperative agreement and will be identified in the Notice of Award. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NIH staff other than the Project Scientist. The responsibility for final decision-making may reside with Senior Institute management, separate organizational components, and/or oversight committees. Because it is anticipated that the Program Official will participate in activities that rise to a level of involvement (i.e., additional role as Project Scientist) that results in conflicts of interest (e.g., co-publication), other staff members such as direct line supervisor and/or other Senior NIH Program management staff may serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award. Additional NIH staff members may be designated to have substantial involvement in the study. 

The NIH policy on authorship and manuscript review of NIH-sponsored extramural research protects against conflicts of interest with the Program Officer.  

The NIH reserves the right to withhold funding or curtail the study in the event that any of the following occur: 

• Substantial shortfall in conducting the projects including but not limited to outreach to a diverse community, data curation and data harmonization, participant data reporting or quality control 
• Major breach of the protocol or substantive changes in the agreed-upon protocol, methodologies, and/or tools with which the NIH cannot concur 
• Failure to develop or implement a mutually agreeable deep phenotyping protocol in a timely manner 
• Human participant ethical issues that may dictate a premature end of the award 
• Results that substantially diminish the scientific value of study continuation   

Areas of Joint Responsibility include:

A Steering Committee (SC) will be the main governing body of the INCLUDE DS-CDP and DS-4C. The SC voting membership shall be determined jointly by the DS-4C PDs/PIs and the NIH, but shall minimally consist of the DS-CRS PI(s), the NIH Project Scientist(s), the Data Coordinating Center PI(s) (if applicable), and the DS-Biorepository PI(s) (if applicable). Additional members may be added by majority vote of the SC. Meetings of the SC will ordinarily be held by teleconference, videoconference, or in-person. 

The appointed voting Steering Committee members will be required to attend all Steering Committee meetings and tele/videoconferences, or to appoint a substitute that will be fully briefed on the issues at hand. Additional non-voting members to serve in an advisory capacity may be added to the Steering Committee as needed by a decision of the existing voting committee members. The Steering Committee may also form an Executive Committee (EC) and/or subcommittees as needed. The NIH Project Scientist(s) may serve on the EC and on subcommittees as deemed appropriate. The Chair of the Steering Committee will be selected from the SC voting members.  

The Steering Committee will have primary responsibility for: 

• Overseeing the overall organization of the study's core functions 
• Providing guidance on scientific and infrastructural issues pertinent to the funded cohort study 
• Providing guidance, oversight, and coordination of the activities of the cohort investigators towards cross-cohort data harmonization, if requested by the NIH 
• Contributing to the development of policies and processes pertinent to the cohort infrastructure  

All investigators/staff within the study will be required to accept and implement the policies approved by the Steering Committee to the extent consistent with applicable grant regulations. 

Where applicable, the recipient  will work with the NIH on efforts to harmonize data across NIH cohorts and studies, and explore the feasibility of using common data standards and elements.  

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

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the 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. 

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.

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. 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 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75and 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

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, Ph.D. (Primary point of contact)
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0554
Email: huiqing.li@nih.gov

Sujata Bardhan, MS, PhD 

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 

Telephone: 301-435-0471 

Email: sujata.bardhan@nih.gov

Huiqing Li, PhD
NHLBI - NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Phone: 301-435-0554
E-mail: huiqing.li@nih.gov

Robert C Rivers, Ph.D.
NIDDK - NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
Phone: 301-443-8415
E-mail: riversrc@mail.nih.gov

Jyoti Dayal
NHGRI - NATIONAL HUMAN GENOME RESEARCH INSTITUTE
Phone: 301.480.2307
E-mail: jyotig@nhgri.nih.gov

Marie Mancini, PhD
NIAMS - NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
Phone: 301-594-5032
E-mail: mancinim2@mail.nih.gov

Laurie Ryan, Ph.D.
NATIONAL INSTITUTE ON AGING (NIA)
Division of Neuroscience
Phone: 301.496.9350
E-mail: ryanl@mail.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

Katherine Malinda, Ph.D.
Center for Scientific Review (CSR)
Email: malindakm@mail.nih.gov  

Fatu Kamara
NHLBI - NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Phone: 301-435-7916
E-mail: fatima.kamara@nih.gov

Elizabeth Gutierrez
NIDDK - NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
Phone: 301-594-8844
E-mail: gutierrezel@mail.nih.gov

Erik Edgerton
NIAMS - NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
Phone: 301-594-7760
E-mail: erik.edgerton@nih.gov

Philip E. Smith
NATIONAL INSTITUTE ON AGING (NIA)
Phone: 301-555-1212
E-mail: philip.smith2@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

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 45 CFR Part 75 and 2 CFR Part 200.