Key Dates

Related Announcements

RFA-OD-21-007 - INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Exploratory/Developmental Research Grant Award (R21 Clinical Trial Not Allowed)

RFA-OD-22-007 - INvestigation of Co-occuring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Clinical Trial Readiness (R21 Clinical Trial Not Allowed)

PA-20-194 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-196 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

PA-21-219 - Joint NINDS/NIMH Exploratory Neuroscience Research Grant (R21 Clinical Trial Optional)

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

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 support for exploratory/developmental grant (R21) applications that are focused on community-based participatory research (CBPR) in DS to address health disparities and that meet programmatic objectives for the INCLUDE Project.

Individuals with DS experience greater health disparities than the general population. These disparities in the DS community stem from disparities in healthcare services including receiving preventive services and access to quality care. Although the lifespan of individuals with DS has increased dramatically in the last few decades, the racial disparities in life expectancy are glaring. The median age of survival for Blacks and other racial groups falls way behind that of individuals with DS who are White although the prevalence of DS among all racial groups is about the same. Hence, it is important to understand the social determinants of heath (race, ethnicity, gender, age, geography, and socioeconomic status) that lead to such disparities in the DS population. The Healthy People 2030 initiative [United States Department of Health and Human Services, 2030; https://health.gov/healthypeople] has also added “Social Determinants of Health” as a new objective to reduce health disparities and increase efforts to improve the health and well-being for all.

To fully engage and understand the various factors (social, environmental, economic) contributing to health disparities in those with DS, we encourage collaboration and partnership among DS community members (those with DS, family members, self-advocates, and advocates) as well as various key stakeholders (scientists, clinicians, policy makers, educators) to propose projects that address these issues.

The goal of this Notice is to encourage CBPR where researchers fully engage with the community members to understand culturally appropriate issues, to evaluate barriers (systemic and structural), to determine appropriate research methods, to engage the community in the data collection and analysis process, to plan effective interventions, to share knowledge and skills, to implement interventions with input from community members, to strengthen community partnerships, and to educate and return research findings to the community with the ultimate goal of reducing health disparities. CBPR is defined as scientific inquiry conducted in communities and in partnership with researchers. 

The purpose of this Notice of Special Interest (NOSI) is to support exploratory and developmental research project grant (R21) applications that propose to develop and strengthen partnerships between minority health and health disparity communities and researchers to plan the implementation of effective health interventions that will improve community health and reduce health disparities and improve health outcomes. For the purposes of this Notice, the definitions of minority health and health disparity communities are described in the NIH Minority Health and Health Disparities Strategic Plan (https://www.nimhd.nih.gov/about/strategic-plan/nih-strategic-plan-definitions-and-parameters.html#:~:text=NIH%20defines%20health%20disparity%20populations,or%20more%20of%20these%20descriptions).

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 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/.

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. However, there are stark differences in life expectancy by race among those with Down syndrome. It is important to examine the determinants of health disparities in under-represented groups that will increase understanding of effective health interventions to improve community health and health outcomes.  

Hence, increasing representation of individuals from understudied populations, including those affected by health disparities, in study cohorts is critical for the success of the INCLUDE project, because it will increase the generalizability of DS research and ultimately reduce health disparities among diverse DS populations.

Research Objectives

The purpose of this Notice of Special Interest (NOSI) is to support exploratory/developmental grant (R21) applications that are focused on community-based participatory research (CBPR) in DS to address health disparities 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:

• 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 INCLUDE website has a list of contacts for each participating NIH Institute and Center.

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, 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 those applications that generate clinical data, it is expected that the data sharing plan will include the INCLUDE Data Coordinating Center (DCC).

Scope  

Applications responsive to this Notice will support bi-directional collaborative research on health disparities by engaging community participants in all steps of the research process. Proposals must engage community members from one or more populations of interest: infants, children, adolescents and adults with DS.  

Applications proposing areas of interest include, but are not limited to: 

• Proposals that engage in community needs assessment and plan a pilot intervention methodology with substantial input from the community. 

• Research studies promoting research participation of individuals from racially, ethnically, geographically, and economically understudied populations with DS and their families. 

• Intervention research studies using CBPR principles to reduce and eventually eliminate health disparities in the DS community with emphasis on individuals from racial, ethnic, geographic and economically understudied populations . 

• Research studies that engage CBPR methods to elucidate barriers (social, economic and physical environment) that affect health outcomes and quality of life. 

• Studies that engage the community to promote preventive behaviors (e.g., health screenings, immunizations, adhering to recommended American Academy of Pediatrics healthcare guidelines, equitable access to transition to adolescent/adulthood services)    

• Establishment of a community coalition, partnership development and Community Advisory Board that includes community members, researchers, and other stakeholders with relevant expertise, to inform the intervention development plan and process including dissemination of relevant study findings. 

• Research study that tests a CBPR DS-specific conceptual model using CBPR methods to improve participation of community members with the goal of affecting health equity outcomes through communications strategies such as those outlined here, https://www.cdc.gov/healthcommunication/Health_Equity.html 

• Research studies that examine determinants of Health-Related Quality of Life (HRQOL) trajectories in under-represented groups using CBPR methods 

To maximize comparisons across datasets or studies, and facilitate data integration and collaboration, applications submitted in response to this NOSI are strongly encouraged to incorporate the following standards and resources (where applicable): 

• Projects that propose to recruit subjects with DS are encouraged to promote enrollment of research subjects in the DS patient registry supported by NIH, DS-Connect®. 

• Applicants are encouraged to ensure that data collected by the study 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). 

• Recruitment Plan to Enhance Diversity. The applicant must provide a Recruitment Plan (when applicable) to Enhance Diversity. The application should include outreach strategies and activities designed to recruit potential participants who are from diverse backgrounds, including participants from underrepresented racial and ethnic groups. Describe the specific efforts to be undertaken by the participating investigators to coordinate with efforts to recruit individuals from underrepresented groups. Participating investigators and trainees on the application are expected to be actively involved in recruitment efforts. Please name the file “Recruitment_Plan.pdf”. If this attachment is not included, the application will be considered incomplete and will not be reviewed. 

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 be withdrawn from consideration for this 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 October 16, 2022 and subsequent receipt dates through March 17, 2025.

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

Applications in response to this NOSI must be submitted using the following target funding opportunity or its subsequent reissued equivalent:

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 this NOSI, NINDS will only accept applications submitted in response to PA-21-219.
• For funding consideration, applicants must include "NOT-OD-22-142" (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.
• Resource Sharing Plan: NIH intends to maximize the availability of resources and data generated by INCLUDE-supported projects, while abiding with informed consent language and protecting the identity of participants. It is expected that data generated with support from this NOSI will be shared with the wider scientific community in a timely manner in coordination with the INCLUDE Data Coordinating Center (DCC). Applications generating data should describe the anticipated timelines, formats, and approach to submitting data to the INCLUDE DCC. For software tools, applicants should describe the anticipated timeline, formats, and methods of sharing code, how it will be documented (e.g., public GitHub links), and whether an open-source model will be used.

Applicants planning to submit applications in response to this NOSI are strongly encouraged to contact the Scientific/Research 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.

Although NCI; NEI; NHLBI; NIA; NIAMS; NICHD; NIDCD; 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 INCLUDE website has a list of contacts for each participating NIH Institute and Center.

Scientific/Research Contact(s)

Sujata Bardhan, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Telephone: 301-435-0471
Email: [email protected]

Nathaniel Stinson Jr., Ph.D., M.D., M.P.H.

National Institute of Minority Health and Health Disparities
Telephone: 301-594-8704
Email: [email protected]

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: [email protected]