The Office of the Director of the National Institutes of Health (NIH) announces the opportunity for investigators with relevant active NIH-supported grants from the participating Institutes listed above to submit administrative supplement applications for funded projects to meet new NIH Down syndrome research objectives related to the NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project. This Notice is soliciting administrative supplements for the following mechanisms ONLY: R03, R21, R24, P01, P30, P40, P50, P51, U01, U10, U19, U24, U42, U54, UG1, UG3, UL1, U2C, K12, and T32.

Background

The 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 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 NIH support for the professional development of early career scientists aiming to establish a career in DS-related research. By providing these scientists with training, resources, and mentorship, the NIH intends to foster a pipeline of investigators in DS and other intellectual disabilities who will lead future research to improve the understanding of the biology of DS and support development of new treatments for health conditions experienced by those with DS. 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).

Supplement applications will be eligible for funding if they address one or more of the following components related to the INCLUDE Project research objectives:

• 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

Applications will be considered eligible for funding if they:

• Are within the scope of the active parent award
• Are focused on DS
• Propose to address one of the three components listed above
• Are likely to stimulate additional activity leading to progress on DS
• 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.

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.

Before submitting a supplement request, applicants are strongly encouraged to contact their program officer or the program contact at the Institute or Center (IC) supporting the parent award with any questions and to discuss whether the proposed supplement is within the scope of the parent award, focused on the goals of the INCLUDE Project and consistent with IC priorities.

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. The earliest anticipated start date is August 2020, August 2021, and August 2022.

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 project officer 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-18-591 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-18-591 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) March 23, 2020, March 23, 2021, March 23, 2022 by 5:00 PM local time of applicant organization.
• Applications must include NOT-OD-20-024 in the Agency Routing Identifier field (Box 4b) of the SF424 R&R form. Applications without the identifier (NOT-OD-20-024) in Box 4b will not be considered for this initiative.
• The process for Streamlined Submissions using the eRA Commons cannot be used for PA-18-591.
• Use the form package for the existing NIH Grants and/or Cooperative Agreements.
• Applicants are strongly encouraged to notify the program contact at the Institute supporting the parent award that a request has been submitted in response to NOT-OD-20-024 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.

• Application budgets 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 project officer and IC Contact prior to submission.

• The application Abstract section should describe the proposed supplement, and the Research Strategy section should include a summary or abstract of the funded parent award or project. The Research Strategy should state the relevance to the parent award and the INCLUDE project, and articulate the component(s) and any IC-specific priorities that the supplement is addressing.

Page Limits: NIH will consider supplements with a Research Strategy of no more than 6 pages, in addition to the abstract. As part of the application investigators should submit an abstract of the proposed research that shows the relevance to DS. Place the abstract in the Project Summary/Abstract section of the SF424 (R&R) Form. The work may include pilot projects or resource development.

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