Key Dates

Related Announcements

NOT-TR-24-014 - Termination of NOSI NOT-OD-22-192 - Administrative Supplements to NCATS CTSA Program KL2/K12 Institutional Career Development Awards as part of the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndrome) Project.

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)

Issued by

Office of The Director, National Institutes of Health (OD)

National Institute of Dental and Craniofacial Research (NIDCR)

National Center for Advancing Translational Sciences (NCATS)

Purpose

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.

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 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:

• 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

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.

Eligibility

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.

All instructions in the SF424 (R&R) Application Guide and PA-20-272 must be followed, with the following additions:

• Application Due Date(s) - July 1, 2023. July 1, 2024, and July 1, 2025 by 5:00 PM local time of the applicant organization.
• For funding consideration, applicants must include “NOT-OD-22-192” (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.
• Only existing awardees of KL2 (award funded previously under PAR-18-940 or PAR-18-464) / K12 (PAR-21-336) active awards are eligible to apply. The supplement must comply with all of the parent FOA requirements of the KL2/K12 programs, respectively.
• To be eligible, the parent award must be active (i.e., not be in an extension period), and the activities proposed for the supplement must be accomplished within the remaining active project period. A grant must have at least two years remaining to request a supplement.
• Award Project Period. Requests must be for a minimum of two years and a maximum of four years of consecutive funding for each scholar, consisting of 12-month appointments (depending on the eligibility of the parent award). The proposed project period of the supplement cannot extend beyond the current project period end date of the active KL2/K12 award.
• Scholar appointment(s) must be able to be fulfilled within the active project period.
• The process for Streamlined Submissions using the eRA Commons cannot be used for PA-20-272.
• 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-22-192 in order to facilitate efficient processing of the request.
• Applicant organizations may submit more than one application to this NOSI. Each application should include only one named candidate for the supplement. Use unique project titles for each application to ensure that each application is treated as a distinct submission
• R&R Budget, PHS 398 Training Budget. Application budgets must reflect the actual needs of the proposed project with the following limitations.
  • For each scholar, the following should be budgeted: Salary support will be provided up to $120,000. In general, 9 person-months (75 percent of the KL2/K12 full-time professional effort) must be devoted to the KL2/K12 program, except for those in surgical specialties, which can have less than 9 person-months (75 percent), but no less than 6 person-months (50 percent), protected time for this program, if sufficiently justified and programmatically approved. Additional support may be requested for research-related activities detailed below.
  • Other Direct Costs: The KL2/K12 supplement budget must include funds to support the scholar's research project and career development activities. No less than $10,000 and up to $30,000 per individual Scholar must be provided for the following types of research-related expenses: (a) research expenses, such as supplies, equipment, and technical personnel; (b) tuition and fees related to required career development courses and activities; (c) travel to scientific meetings or training that the institution determines to be necessary for the individual’s career development experience; and (d) statistical services including personnel and computer time. It is expected that the KL2/K12 Scholar will be working in a funded research environment and that support provided by the KL2/K12 grant will augment existing research support to the scholar.
  • Mentor support may be requested for up to $10,000 per year in associated laboratory or other research-related expenses. Salary support for mentors excluding laboratory- or research-related expenses is not an allowable budget item. Travel support for mentors is not an allowable budget item.
  • The total amount budgeted per scholar must not exceed $180,000 in direct costs per year.

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)

• Background: Include a summary or abstract of the funded parent award project. Provide rationale for the proposed supplement program and its alignment with the main goals of the INCLUDE Project (to accelerate the development of new therapies, while simultaneously bringing promising agents already in development to individuals with DS as quickly as possible).
• Research Program Plan: The proposed plan should align with the missions of the INCLUDE Project and the NCATS CTSA Program. Describe how the proposed project will contribute to the scholar's career goals and path to independence. Present a timeline for career development activities and potential publications and grant applications for future support.
• Career Development Plan: Describe key activities of the candidate scholar during the supplement, included mentored team science activities, didactic coursework (including formal degree programs if appropriate), and other activities. Describe how the proposed career development activities experiences will enhance the candidate's clinical and translational science skills and prepare them for an independent research career.
• Mentoring Faculty: Provide information about the program faculty who will be involved in the supplement activities, including the complementary expertise and experiences, active research and other scholarly activities in which the faculty are engaged, as well as experience mentoring individuals at the proposed career stages. A primary mentor must be named. If any co-mentor is not located at the sponsoring institution, describe the frequency and type of communication that will be used to engage the scholar. A plan that describes how candidate scholar will be evaluated both overall and across multiple mentors (if applicable) must be described.
• Data Management and Sharing Plan: The Data Management and Sharing Plan should describe how an applicant will share their final research data. The specifics of the plan will vary on a case-by-case basis, depending on the type of data to be shared and how the investigator plans to share the data, but should follow the NIH Data Management and Sharing Policy.

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:

• List the PD/PI as the first person (regardless of their role on the supplement activities).
• List Senior/Key Personnel who will be serving as members of the scholar's mentoring team.
• List the scholar proposed to be added through this supplement. Scholars for this supplement support must have an eRA Commons account, and the scholar's Commons Username must be entered in the Credential field.
• Biographical sketch, Senior/Key Personnel: Include a biographical sketch of the KL2/K12 PD/PI(s) and of each of the individuals who will compose the scholar's mentoring team. The personal statement of each individual who will serve on the scholar's mentoring team should include a description of his/her specific role in mentoring the scholar, how the mentoring will occur (e.g., frequency and mode), and how the scholar's progress will be monitored during the supplement award period.
• Biographical sketch, Scholar: The personal statement of the scholar's biographical sketch should include a description of his/her research objectives and career goals, and why their experience and qualifications make them particularly well-suited to receive an INCLUDE / NCATS CTSA Program KL2/K12 supplement award. Relevant factors include previous training and research accomplishments in Clinical and Translational Science research, Down syndrome, and any source(s) of current funding.

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.

Inquiries

Please direct all inquiries to:

Jamie Mihoko Doyle, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-402-0403
Email: [email protected]