New Approaches for Measuring Brain Changes Across Longer Timespans (R21 Clinical Trial Optional)
Funding Agency:
- National Institutes of Health
Applications proposing the following will be considered non-responsive and will not be reviewed:
- Studies without in vivo measurements
- Studies without two timepoints
- Studies using invertebrate animal models
- Projects that do not include a scientific component to demonstrate how the methodology expands brain measurement capacity across the lifespan
- Applications that do not include annual milestones
Applications that fail to include a PEDP will be considered incomplete and will be withdrawn.
Institute-specific Areas of Interest
Applicants are encouraged to discuss applications with the I/C contact listed in Section VII. Agency Contacts.
National Institute on Aging (NIA):
NIA is interested in the development of novel approaches and/or innovative expansion of existing approaches to measure brain changes across longer timespans that more closely recapitulate the aging brain and diseases of brain aging. While applications should be primarily focused on development of the approach, the circuits and brain regions of interest should be relevant to either those declining during brain aging or those resilient to the effects of brain aging. NIA is interested in all examples of approaches listed under the Research Objectives that would promote understanding of the aging brain and diseases of brain aging, particularly Alzheimer’s disease. The scientific question should include at least one advanced age timepoint to establish a trajectory for the brain measures assessed. Although applications can include disease-relevant perturbations for model validation and testing assay utility, the focus should be on developing or improving the technology around the approach.
Resources for Applicants: NIA is committed to ensuring that clinical research studies have diverse and inclusive representation, particularly of those communities historically underrepresented in research. NIA’s National Strategy for Recruitment and Participation in Alzheimer’s and Related Dementias Clinical Research provides an emphasis on the urgent need for more diverse research volunteers and encourages examining diversity across multiple factors such as age, race, ethnicity, sex, education, socioeconomic status, geographic location, comorbidities, and cognitive status. To diversify and increase participation in AD/ADRD clinical trials, NIA developed a public facing tool, OutreachPro. OutreachPro is an online recruitment materials generator that enables grantees to develop customizable and culturally appropriate materials in multiple languages to raise awareness of, and interest in, AD/ADRD clinical trials. Grantees and research teams are encouraged but not required to use this free online resource to enhance their recruitment and retention plans and related activities for their NIA-funded clinical studies.
CROMS: NIA utilizes a central resource to NIA staff and extramural investigators to facilitate/support the conduct and management of clinical research. NIA Clinical Research Operations & Management System (CROMS) is a comprehensive data management system to support the business functions, management, and oversight responsibilities of NIA grants that support the conduct of clinical research with human subjects. NIA investigators of grants, contracts, and cooperative agreements that are active as of July 1, 2021 and support human subjects research as defined by the DHS HHS OHRP regulations at 45 CFR 46 will be required to interact with and use existing and future components of CROMS as required by NIA throughout the lifecycle of the grant and as described in NOT-AG-23-017. Data to be submitted to NIA CROMS includes those elements reported in the standard NIH requirement annual progress report (GPS 4.1.15.7). Details regarding the standard operating procedures for CROMS can be found on the NIA CROMS website.
When applicable, all NIA grantees must ensure:
- The study’s Informed Consent Document (ICD) lists “The National Institutes of Health (NIH) and its authorized representatives” as one of the organizations that may look at or receive copies of information in participants’ study records. According to DHS HHS OHRP 45 CFR 46 46.116, all ICDs must contain “A statement describing the extent, if any, to which confidentiality of records identifying the participant will be maintained.” If using the NIA informed consent template please see Section 6: Statement of Confidentiality.
- An assigned NIH ClinicalTrials.gov identifier (NCT number) is reported in its respective CROMS study record within three months after assignment, and the reporting of final enrollment data to CROMS is consistent with final enrollment data reported in ClinicalTrials.gov.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD seeks the development of novel approaches that link early developmental brain changes with later cognitive, affective, and social outcomes, both for health and disease states, within the framework of the NICHD Strategic Plan. Mechanistic studies that cross multiple spatial and temporal levels are encouraged.
National Cancer Institute (NCI):
NCI supports cancer health disparity research focused on basic, hypothesis-driven studies that explicitly address the unequal burden of cancer among racial/ethnic minorities or other underserved populations across the cancer continuum (prevention, early detection, diagnosis, treatment, and survivorship). Research projects are encouraged to investigate the interplay of race/ethnicity and/or other social determinants with cancer biology to mechanistically explain an unequal burden of cancer among populations. As such, proposed studies are encouraged to use biospecimens, patient-derived models, and/or data sets derived from different racial/ethnic and/or underserved groups. Studies investigating age and/or gender disparities, in the absence of race/ethnicity variables, are not solicited. Research projects using a comparative research design between at least two populations are encouraged, in which one or more is underserved.
Plan for Enhancing Diverse Perspectives (PEDP)
The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.
To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.
This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation. Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.
The PEDP will be submitted as Other Project Information as an attachment (see Section IV). Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP Guidance materials.
Direct costs are limited to $275,000 over the two-year project period. No more than $200,000 in direct costs are allowed in any single year.
Direct costs are limited to $275,000 over the two-year project period. No more than $200,000 in direct costs are allowed in any single year.
February 16, 2025; June 16, 2025; October 16, 2025
Elizabeth Newman, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-480-7937
Email: elizabeth.newman@nih.gov
Laura Stoner Machlin
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Phone: 301-827-6575
E-mail: laura.machlin@nih.gov
Anil Wali, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6183
Email: walia@mail.nih.gov