Key Dates

Related Announcements

NOT-AI-23-047 - Notice of Participation of the NIAID in NOT-OD-22-137, Notice of Special Interest (NOSI): Availability of Administrative Supplements for the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project

PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

PA-21-071 - Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)

NOT-OD-21-076 - Notice of Change to NOT-OD-20-024: Availability of Administrative Supplements for the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project

Issued by

Office of The Director, National Institutes of Health (OD)

National Eye Institute (NEI)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute on Aging (NIA)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

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

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute of General Medical Sciences (NIGMS)

National Institute of Neurological Disorders and Stroke (NINDS)

National Institute on Minority Health and Health Disparities (NIMHD)

Fogarty International Center (FIC)

National Center for Advancing Translational Sciences (NCATS)

National Cancer Institute (NCI)

National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

The NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project seeks to improve health and quality-of-life for individuals with Down syndrome (DS). This Notice of Special Interest (NOSI) announces NIH's continued support for administrative supplement applications for actively funded projects to meet NIH Down syndrome research objectives related to the NIH INCLUDE Project as listed below.

Background

Down syndrome 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 (DS). 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 FOA is one of several trans-NIH research initiatives created in response to Fiscal Year 2018, 2019, 2020, 2021, and 2022 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 pipeline of Down syndrome investigators. 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/.

Research Objectives

The purpose of this Notice of Special Interest (NOSI) is to administrative supplement applications that are focused on Down syndrome and that meet programmatic objectives for the INCLUDE Project. Sharing of resources and effective communication of outputs to the broader communities are a high priority of the?INCLUDE Project. Applicants responding to this NOSI are strongly encouraged to describe plans for rapid sharing of data and results as well as innovative data analytics approaches (see Goal 3,?NIH Strategic Plan For Data Science).

Applications in response to this NOSI should be aligned with the overall NIH INCLUDE Project?Research Plan, which consists of 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

Applications will be considered eligible for funding if they:

• Are within the scope of the active parent award
• Are focused on Down syndrome
• Propose to address one of the three components listed above
• Are likely to stimulate additional activity leading to progress on Down syndrome
• Address a priority for the IC that issued the parent award (see below for more information)

Supplements to existing clinical trials are allowed. The proposed research must be within the scope of the parent clinical trial and the parent clinical trial award must have two or more budget years remaining in the current project period. The addition of a new clinical trial that was not a part of the parent award is not allowed. Supplement requests addressing INCLUDE Components 2 or 3 should encourage participants with DS or their caregivers to register in DS-Connect : The Down Syndrome Registry. For those applications that generate clinical data, it is expected that the data sharing plan will include the INCLUDE Data Coordinating Center (DCC; https://includedcc.org/). Applications generating clinical data should describe the anticipated timelines, formats, and approach to submitting data to the INCLUDE DCC.

The INCLUDE website has a list of Funding Priorities by Institute and Center, as well as list of contacts for each participating NIH Institute and Center.

Award Project Period

To be eligible, the parent award must be active in the current fiscal year (i.e., the parent award received funds in the current fiscal year and is not in an extension period), and the research proposed in the supplement should be requested for one year. The awarding institute may consider a no-cost extension of up to an additional year at the conclusion of the first year.

Budget

Requests must reflect the actual needs of the proposed project. Supplement budget requests that exceed $500,000 in direct costs or 50% of the direct costs of the current year of the parent award (exclusive of Facilities and Administrative costs on sub-contracts) must receive permission from the program officer for the parent award and IC Contact prior to submission.

Eligible Individuals (Program Director/Principal Investigator)

Individual(s) must hold an active grant or cooperative agreement. For supplements to parent awards that include multiple PDs/PIs, the supplement may be requested by any or all of the PDs/PIs (in accordance with the existing leadership plan) and submitted by the awardee institution of the parent award.

Application and Submission Information: Applications in response to this NOSI must be submitted to PA-20-272 Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional) or its subsequent reissued equivalent. All instructions in the SF424 (R&R) Application Guide and PA-20-272 must be followed, with the following additions:

In order to ensure identification, tracking, and appropriate review of their applications, all applicants MUST follow these special instructions:

• Application Due Date(s) Applications will be accepted at any time, but applications should be received by NIH by June 1 for award during that federal fiscal year.
• Applications must include "NOT-OD-22-137" (without quotation marks) in the Agency Routing Identifier field (Box 4b) of the SF424 R&R form. Applications without this information in Box 4b may not be considered for this initiative.
• Applicants are strongly encouraged to notify the program contact at the NIH Institute supporting the parent award that a request has been submitted in response to NOT-OD-22-137 in order to facilitate efficient processing of the request.
• Applicant organizations may submit more than one application to this NOSI. Use unique project titles for each application to ensure our systems treat each application as a distinct submission.
• Use the Abstract section to describe the proposed supplement, its relationship to the parent award, and the relevance of the supplement to the INCLUDE project, any IC-specific INCLUDE priorities, and indicate which component it addresses.

Additional Considerations: To maximize comparisons across datasets or studies, and facilitate data integration and collaboration, researchers funded through this NOSI are strongly encouraged to use the following standards and resources (where applicable):

• Applicants are encouraged to conform to Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
• NIH encourages researchers to explore the use of the HL7 FHIR (Fast Healthcare Interoperability Resources) standard to capture, integrate, and exchange clinical data for research purposes and to enhance capabilities to share research data (NOT-OD-19-122). The FHIR standard may be particularly useful in facilitating the flow of data with EHR-based datasets, tools, and applications.
• NIH encourages clinical research programs and researchers to adopt and use the standardized set of data classes, data elements, and associated vocabulary standards specified in the United States Core Data for Interoperability (USCDI) standards (NOT-OD-20-146), as they are applicable. Use of the USCDI can complement the FHIR standard and enable researchers to leverage structured EHR data for research and enable discovery.
• NIH encourages the use of data standards including common data elements, such as those available through the PhenX Toolkit (www.phenxtoolkit.org) and the NIH CDE repository (cde.nlm.nih.gov), terminologies and ontologies such as Mondo Disease Ontology (mondo.monarchinitiative.org), Human Phenotype Ontology (hpo.jax.org), and common data models such as the Observational Medical Outcomes Partnership (OMOP; ohdsi.org).It is expected that all de-identified human data generated by INCLUDE-funded projects will be submitted to NIH-designated repositories in coordination with the INCLUDE Data Coordinating Center (DCC; https://includedcc.org/).
• Projects that propose to recruit subjects with Down syndrome are encouraged to promote enrollment of research subjects in the Down syndrome registry supported by NIH, DS-Connect .

Page Limits: NIH will consider supplements with a Research Strategy of no more than 6 pages.

Review Process: Each IC will conduct administrative reviews of applications from their IC separately.

Inquiries

Please direct all inquiries to:

Investigators planning to submit an application in response to this NOSI are strongly encouraged to contact and discuss their proposed research/aims with a Program Officer from the appropriate Institute or Center listed on this NOSI well in advance of the grant receipt date to better determine appropriateness and interest of the awarding ICO.

Please direct all inquiries to the contact at the Institute, Center or Office supporting the parent award as indicated on the funding page of the INCLUDE Project website.