Key Dates

Related Announcements

PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-184 - NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PAR-21-038 - Stephen I. Katz Early Stage Investigator Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PAR-21-039 - Stephen I. Katz Early Stage Investigator Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

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 Neurological Disorders and Stroke (NINDS)

National Institute on Minority Health and Health Disparities (NIMHD)

National Cancer Institute (NCI)

Purpose

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 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 support research project grant (R01) applications that are focused on Down syndrome and that meet programmatic objectives for the INCLUDE Project. Sharing of resources and effective communication of outputs of appropriate interest to 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 NIH INCLUDE Project Research Plan, which consists of three components:#160;

• 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 

Program Directors/Principal Investigators (PD/PIs) planning to submit applications in response to this NOSI are strongly encouraged to contact the scientific contacts of this NOSI prior to submission to be advised on appropriateness of the intended resource and research plans for this program, competitiveness of a potential application, and alignment with program priorities of the INCLUDE initiative. The Frequently Asked Questions page of the INCLUDE website has a list of contacts for each participating NIH Institute and Center under "General".  

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 biospecimens collected from human genetic or non-genetic studies, recipients 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 those applications that generate clinical data, it is expected that the data sharing plan will include the INCLUDE Data Coordinating Center (DCC). 

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).  

• 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®.  

Application and Submission Information

Applicants must select the IC and associated FOA to use for submission of an application in response to this NOSI. The selection must align with the IC requirements listed in order to be considered responsive to that FOA. Non-responsive applications will not be considered for the NOSI initiative. In addition, applicants using NIH Parent Announcements (listed below) will be assigned to those ICs on this NOSI that have indicated those FOAs are acceptable and based on usual application-IC assignment practices.

This notice applies to due dates on or after July 5, 2022 and subsequent receipt dates through May 1, 2025.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

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-22-123” (without quotation marks) 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.

Applicants planning to submit an application in response to this NOSI are strongly encouraged to contact and discuss their proposed research/aims with an NIH Program Officer listed on this NOSI well in advance of the grant receipt date.

Although NCI, NHLBI, NIAMS, NIDCD, or NIDCR is not listed as a Participating Organization in all the FOAs listed above, applications for this initiative will be accepted.

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

Inquiries

The Frequently Asked Questions page of the INCLUDE website has a list of contacts for each participating NIH Institute and Center under "General".

Scientific/Research Contact(s)

Charlene Schramm, PhD
National Heart, Lung, and Blood Institute
Telephone: 301-402-3739
Email: schrammc@nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Kelly Fritz
NICHD, GMB
Telephone:301-827-5429
Email: kelly.fritz@nih.gov