October 3, 2022
PA-20-272- Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional) or its subsequent reissued equivalent
PAR-21-336: Limited Competition: Mentored Research Career Development Program Award in Clinical and Translational Science Awards (CTSA) Program (K12 Clinical Trial Optional)
PAR-18-940: Clinical and Translational Science Award (U54 Clinical Trial Optional)
PAR-18-464: Clinical and Translational Science Award (U54 Clinical Trial Optional)
Office of The Director, National Institutes of Health (OD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Center for Advancing Translational Sciences (NCATS)
This Notice of Special Interest (NOSI) announces NIH support for the professional development of trainees aiming to establish a career in Down syndrome (DS)-related research through an administrative supplement to an active NCATS Institutional Career Development Award (KL2 or K12). This NOSI will support additional scholar slots to those KL2/K12 grants currently approved under the CTSA Program. By providing these scientists with career development research experiences, 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.
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. 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.
Several trans-NIH research initiatives were 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/. The INCLUDE Project has three components:
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 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).
All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan that follows the NIH Data Management and Sharing Policy. The Data Management and Sharing Plan will be considered by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program. It is expected that the results of INCLUDE-funded research will be shared with the wider scientific community in a timely manner.
For further information on INCLUDE priorities, resource sharing expectations, and participating NIH Institutes and Centers, see Frequently Asked Questions.
Applicants must have an active NCATS-funded institutional career development (KL2/K12) award.
Application and Submission Information
Applications in response to this NOSI for this initiative 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.
Instructions for Electronic Application Submission through Grants.gov: Use the “Apply” button(s) in Part I of the PA-20-272 program announcement to access the application forms package posted at Grants.gov.
Prepare applications using the SF424 (R&R) forms associated with the chosen package. Please note that some forms marked optional in the application package are required for submission of applications for this announcement. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate required and optional forms, with the following additional guidance:
Program Plan:(may not exceed 12 pages)
Letters of Support: Attach appropriate letters from all individuals confirming their roles in the proposed supplement program. Include a signed letter, on institutional letterhead, that describes the applicant institution’s commitment to the planned proposed research project. The letter should provide assurance that the candidate scholar will be able to devote a minimum of 9 person-months (75 percent of full-time professional effort) to the supplement project. The letter should confirm that the scholar will be supported by the KL2/K12 if the supplement is funded. The letter should also identify the laboratories, centers, and other specialized institutional facilities that will be made available to the scholar for the research project.
Project/Performance Site Location form: Include the primary site where the proposed supplement activities will be performed. If a portion of the proposed supplement activities will be performed at any other site(s), identify the locations in the fields provided.
Senior/Key Person form:
Budget forms: Using the R&R budget form,onlyinclude funds requested for the additional supplement activities.
R&R Other Project Information form, Facilities and Other Resources attachment: Describe how the scientific environment in which the career development activities will be done contributes to the probability of the scholar's success (e.g., institutional support, physical resources, and intellectual rapport). For CTSA Program hub Training Resources, describe the training resources that are available to the scholar.
PHS Human Subjects and Clinical Trials Information form: Complete this section if the scholar will design and conduct their own independent human subjects research. Approval by the human subjects Institutional Review Board (IRB) at the grantee institution is required prior to award. Adherence to the NIH policy for including women and minorities in clinical studies must also be ensured, if additional human subjects involvement is planned for the supplement component.
Jamie Mihoko Doyle, Ph.D.
National Center for Advancing Translational Sciences (NCATS)