Background

The INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project was developed in response to Fiscal Year 2018 and 2019 Omnibus Appropriations Reports, which encouraged the NIH to expand its current efforts on Down syndrome (DS) and common co-occurring conditions also seen in the general population while increasing the pipeline of DS investigators. Information about projects that were funded in 2018 and 2019, as well as the INCLUDE Project Research Plan, is available on the INCLUDE Project website.

Individuals with Down syndrome (DS) face significant and changing health challenges but have often been excluded from participation in research that could improve their health outcomes and quality of life. This population is understudied even though DS is the most common genetic cause of intellectual and developmental disabilities (IDD) and, in the past 25 years, the average lifespan has doubled from 30 to 60 years. In addition to intellectual disability, DS is associated with an increased prevalence of autism and epilepsy. About 75% of individuals with DS experience cognitive decline in a syndrome that resembles Alzheimer’s disease, but with onset a decade or two earlier than typical Alzheimer’s disease. Individuals with DS 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 DS infrequently develop solid tumors such as breast or prostate cancer. Despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, people with DS rarely develop atherosclerosis or have myocardial infarctions. Understanding this unique combination of risk and resiliencies will inform medical advances for individuals with DS and for individuals who do not have DS but who share these co-occurring conditions.

Research Objectives

This Notice of Special Interest (NOSI) announces the availability of competitive revision (formerly known as competitive supplement) applications from grantees with active Research Project Grants (R01) who wish to either expand the scope of their grant project focused on DS or to expand the scope of a non-DS grant to incorporate DS-related research. 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).

A list of Funding Priorities by Institute and Center is available on the INCLUDE website. Applications in response to this NOSI should be aligned with the overall 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: Cohort Study to connect existing resources and expand to inclusion of individuals with Down syndrome
• Component 3: Inclusive clinical trials research for co-occurring conditions in individuals with Down syndrome

Projects that propose to recruit subjects with Down syndrome are encouraged to promote enrollment of research subjects in the Down syndrome patient registry supported by NIH, DS-Connect . For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use biorepositories designated by INCLUDE staff that meet requirements for broad sharing. An NIH resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing.

For further information on INCLUDE priorities, resource sharing expectations, and participating NIH Institutes and Centers, see Frequently Asked Questions.

Application and Submission Information

This Notice applies to due dates on or after March 5, 2020 and subsequent receipt dates through September 7, 2022.

Applications for this initiative must be submitted using one of the following funding opportunity announcements (FOAs) or their reissued equivalents. Although not all NIH components indicated above are listed as Participating Organizations in all the FOAs listed below, applications for this initiative will be accepted by the participating Institutes and Centers at NIH.

• PA-19-055 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
• PA-19-056 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-19-091 NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-OD-20-023 in the Agency Routing Identifier field (box 4b) of the SF424 R&R form. Applications without this information in box 4b will not be considered for this initiative.
• Revision applications must be submitted by the same project director/principal investigator (PD/PI), or Contact PD/PI for multi-PI grants, as listed on the current award.
• Select the Revision option in Box 8 of the SF424 R&R form to indicate TYPE OF APPLICATION, and option A Increase Award .
• Use the Project Summary/Abstract field to provide a succinct and accurate description of the work proposed for the revision. Do not use the abstract of the parent grant.
• Applicants must use the same budget format (i.e. R&R Budget Form or PHS 398 Modular Budget Form) as the current award.
• Use the Introduction to Application field of the PHS 398 Research Plan form to attach a one-page Introduction that describes the nature of the revision and how it will influence the specific aims, research design, and methods of the current grant.
• The body of the application should contain sufficient information from the original grant application to allow evaluation of the proposed revision in relation to the goals of the original application.
• Any budgetary changes for the remainder of the project period of the current grant should be discussed in the Budget Justification.
• Revisions may not extend beyond the term of the current award period. Grants in their final year of the project period at the time of application receipt are not eligible under this Notice.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.

Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

A list of contacts for each participating NIH Institute and Center is available on the INCLUDE website.