Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

The 2020 NHGRI Strategic Vision notes that genomics has become increasingly woven into the fabric of biomedical research, medical practice, and society and points to the continued importance of focusing on ethical, legal, and social implications (ELSI) research. As biomedical investigators are applying genomic knowledge and tools to study an expanding range of diseases and traits in a wide array of settings, novel ELSI questions continue to emerge.

Innovations in gene editing, gene therapy, polygenic risk scores, and genomic testing across various life stages continue. However, the use of new genomic technologies and information is not always preceded by confirmation of their validity, reliability or utility across populations. Sufficient evidence may be lacking to determine whether new innovations are transferrable across health care settings or valid in populations whose genomic data were not used in their discovery. Professional norms, systemic practices, and societal forces may affect the uptake of genomic medicine across communities. Furthermore, significant distribution and re-distribution of financial and genomic healthcare resources may be needed to achieve genomic equity in the United States and abroad.

Globally, genomic data are being generated, shared and commercialized in an array of settings from academic medical centers to the pharmaceutical industry to law enforcement. Fueled by advances in informatics and sequencing technologies, genomic data is increasingly merged with data from personal mobile health devices, electronic health records, direct-to-consumer tests, social media accounts, assays of environmental exposures, and geocoding systems. The size and scope of research datasets continue to grow, at the same time that broad data sharing has become standard scientific practice. In response, models of data ownership and data stewardship are under scrutiny and in flux. Assessing how governance strategies and technology can be used to ensure that genomic data are ethically sourced and responsibly shared remain considerable challenges.

Translating genomic research and data into fair and appropriate benefits for society presents another set of challenges. The relative dearth of genomic data collected from populations who remain understudied in biomedical research and underserved in the healthcare system threatens the just and equitable distribution of benefits from genomic innovation. Potential inequity may be exacerbated by the application of artificial intelligence and machine learning approaches to genomic data analysis. These methods will not produce accurate results if the data upon which they are trained lack broad representation. Efforts to help ensure that the human genome reference sequence and population-based genomic datasets better represent existing human genomic diversity and genetic ancestry are underway. However, evaluating and addressing the availability and quality of genomic information across different groups is an ongoing challenge.

Genomic information can have profound implications for how people understand themselves as individuals, and in relationship or contrast to others. History is replete with examples where the value and predictive nature of genomic information was overstated, misappropriated and weaponized to the detriment of targeted communities and to society more broadly. Such examples are often thought of as part of the field’s troubled and distant past. However, intentional and unintentional misinterpretations and misuses of genomic research that disparage groups of people have resurfaced. Extreme examples are typified by people reimagining current genomic findings as justification for racist beliefs and actions. Other problematic examples include research suggesting that complex phenotypes such as hypertension, diabetes, and depression can be meaningfully explained by genomic factors without accounting for the effects of social determinants of health. The rise of oversimplified attributions of individual and group differences to genetic causes threatens the integrity of genomic science and research.

Overall, ongoing advancement and change in the conduct of genomic research and the translation of genomic science may require key stakeholders to revisit, revise and reiterate the norms and responsibilities that guide the field. New ELSI questions continue to arise about genomics while other questions endure, resurface, or are transformed. Yet, at the forefront of genomics remains an incredible array of opportunities to improve the health and wellbeing of people across all social and genetic backgrounds.

The purpose of this NOFO is to solicit applications for research projects that identify, examine, and address the ELSI of advances in genomics for individuals, families, communities, groups, institutions, and society.

To address the broad scope and reach of genomics and corresponding ELSI issues, applications are invited from investigators representing a wide range of academic disciplines, including, but not limited to, bioethics, the humanities (e.g., history, religion, philosophy, literature), behavioral and social sciences (e.g., psychology, sociology, anthropology, political science, economics, communication science), law, genetic and genomic science, genetic counseling, clinical medicine, health services and implementation science research, health disparities and inequities research, health communication, public health, and data science.

Applications are encouraged from multidisciplinary investigator teams who represent a broad range of disciplines, lived experiences and perspectives.

Applications may propose studies using either single or mixed methods. Approaches may include, but are not limited to, conceptual, legal, and normative analyses, and empirical qualitative and quantitative methods. Applied research conducted to address real-world ELSI issues facing genomics or to facilitate the uptake of ELSI findings may also be proposed.

NIH encourages applicants to consider the use of variables provided in the PhenX Toolkit which provides recommended standard measures for use in biomedical research. These measures have been selected by domain experts using a consensus process. The Toolkit provides protocols for collecting data, and tools to help investigators incorporate protocols into their studies. Using protocols from the PhenX Toolkit facilitates cross-study analysis, potentially increasing the scientific impact of individual studies. Of note, the Social Determinants of Health (SDOH) Collections may be important for some ELSI projects to consider. In addition to protocols for core SDOH measures, the collection includes measures at individual and structural levels.

Population Descriptors

For the purpose of this NOFO, population descriptors are defined as variables used to describe or distinguish people from each other based on perceived or actual differences. Population descriptors may be used for example, to describe who is participating in a study, what groups are being compared, or to whom particular study findings may apply.

Descriptors measuring the complex concepts of race, ethnicity, genealogical ancestry and genetic ancestry are commonly employed in biomedical, health services, genomic and ELSI research. In the United States, there are real and measurable impacts of one’s racial, ethnic or ancestral identity on health, wellness, and life experiences. It may be valid and valuable to use population descriptors in a given analytical context. However, in some cases socially constructed population descriptors like race and ethnicity are used as proxies for human genetic variation in genetic and genomic research, which can lead to conflation between social and biological groups and can cause harm (NASEM Report Using Population Descriptors in Genetics and Genomics Research).

Similarly, sex, gender, gender identity and sexual orientation are complex, related constructs that are conceptually distinct (NASEM Consensus Report, Measuring Sex, Gender Identity, and Sexual Orientation). They are commonly studied aspects of human identity that impact health, access to health care services, and experiences with discrimination; however, they are often mismeasured and misrepresented in research. Investigators using sex- and gender-related population descriptors in their analyses must understand the distinctions between different measures and choose accordingly.

Overall, the scientific questions to be addressed should guide whether and which population descriptors are used in a given study. Investigators should use established theory, frameworks, or scientific evidence to inform their use of population descriptors. Investigators must consider which population descriptors measure the phenomena of interest, and whether other validated variables (e.g., social determinants of health) may be more directly associated with those phenomena. The communities or groups involved in a study may have important insights about the most relevant descriptors to use. Investigators can consider collecting data on multiple descriptors of a concept, while also collecting only necessary data in pursuit of well-defined research goals.

To enhance the rigor and replication of proposed research, applications to this notice should be transparent in the Research Plan about the use of population descriptors. Applications should also be transparent about the use of race, ethnicity or ancestry as proxies for other contributing factors, and acknowledge the challenges and limitations of doing so.

Community and Stakeholder Involvement

There are a variety of communities and stakeholders whose knowledge, perspectives and experiences can inform and improve the field of genomics. Community or stakeholder involvement in any and all phases of a research project is encouraged where appropriate, but not required. For the purposes of this NOFO, the term community refers to "a group or groups of people affiliated by geographic proximity, special interest, or similar situations" (Centers for Disease Control and Prevention, 2011). The term stakeholders refers to individuals, organizations or communities that have a direct interest in the process and outcomes of a project, research or policy endeavor (Deverka et al. 2012). Community and stakeholder involvement may include a range of methods or approaches that vary in level and intensity including, but not limited to, establishment of advisory boards or panels, stakeholder-driven research, community-oriented research, or community-based participatory research.

National Human Genome Research Institute

The NHGRI is interested in research that addresses:

• Genomics and Sociocultural Structures and Values: These projects may explore and elucidate the personal, social and cultural factors that shape the generation, interpretation, understanding and use of genetic and genomic information and associated technologies.
• Genomics at the Institutional and System Level: These projects may explore the interplay and influences between genetics and genomics and organizations, institutions, governments, systems or other organized stakeholders.
• Genomic Research Design and Implementation: These projects may investigate the ethical, legal, social and policy issues that arise in connection with the design and conduct of genetic and genomic research.
• Genomic Healthcare: These projects may examine issues that arise as genetic and genomic research are integrated into clinical medicine and healthcare in a variety of settings.

Research which focuses on the acceptability and accessibility of genetics or genomics to all communities is highly encouraged, particularly communities that have been understudied , underserved and/or marginalized (treated as insignificant or peripheral) by research institutions or healthcare systems . These communities could include, but are not limited to the health disparity populations defined by the NIH. .

Further detail on topics of interest is included on the NHGRI ELSI Research Domains website at: https://www.genome.gov/Funded-Programs-Projects/ELSI-Research-Program/domains. The examples provided here and online serve as a general guide to areas of importance and should not be viewed as a comprehensive list of research topics. Applicants are encouraged to propose topics and issues that are ripe for research, especially given rapid advances in genomic science and continued growth in the interpretation and use of genomic information.

Research projects may develop tools and findings that can be applied across many diseases and conditions. Projects focused on a single disease or disorder may be of lower priority for NHGRI unless generalizability or transferability of findings and resources is clearly demonstrated and described.

National Cancer Institute

The NCI is interested in research that focuses on the ethical, legal, and/or social implications of genetics and genomics in cancer-related research, care, and public health contexts; with additional emphasis on incorporating populations understudied in cancer research and addressing cancer disparities. In particular, the NCI is interested in the following:

• Studies on the ethical, regulatory, and policy challenges in cancer research involving genetic and genomic information (e.g., clinical oncology trials, population-based studies, observational studies, etc.); this includes innovative approaches to these challenges
• Studies on models of participant and community engagement or participatory research methods in cancer genomics research.
• Studies on the ethical, legal, and/or social implications of the use of genomic technologies and addressing cancer disparities; this includes studies on the challenges of improving genomic-based targeted therapies for a range of populations .
• Studies assessing the perspectives of populations from multiple racial, ethnic, and socioeconomic backgrounds, as well as children, older adults, and people with disabilities regarding the integration of genetics/genomics into cancer-related settings (including perspectives on genomic-based targeted therapies).
• Studies examining the uptake and outcomes of personalized genomic testing across populations.
• Studies on the ethical, legal, and/or social implications of the collection, storage, and future research uses of biological samples and of associated data obtained from cancer-related settings (e.g., participant preferences, informed consent, governance, privacy and security, and data sharing); this includes innovative approaches to these issues; additionally, multi-level studies examining patient, caregiver, provider, organizational, and health system perspectives on these issues.
• Studies on the ethical and social issues related to equitable patient access to precision oncology biomarker testing, as influenced by challenges such as tissue collection; provider, patient, and organizational knowledge and perception; reimbursement; and clinical trial access.
• Studies evaluating the ethical, legal, and/or social implications of communication strategies and tools used to share or disseminate genetic and genomic information with individuals, families, and communities/populations; this includes studies examining and aiming to improve the communication processes and disclosure of information about cancer genetics and genomics in a variety of contexts (clinical encounters, telemedicine, family communication, direct-to-consumer advertising).
• Studies evaluating the emerging ethical, legal, and/or social implications of having individuals genetic and genomic information made available digitally or online (through social media, electronic medical records, telemedicine, and participation in research on the Internet)
• Studies on the anticipated and actual psycho-social and behavioral impact of genetic and genomic information on affected individuals, their families, and populations; including studies on the adoption of risk-reduction health behaviors (diet, physical activity, obesity/weight loss) after receiving genetic/genomic testing results.
• Studies on understanding and improving well-being among individuals at elevated genetic risk for cancer.
• Studies on how context affects use of genomic technologies and related patient outcomes of cancer care delivery (examples of context include community setting vs. academic setting, availability of relevant clinical expertise, extent of clinical team collaboration, patterns and channels of communication, and use of various IT systems).

The ultimate goal of this research will be to understand how people make sense of and act upon genetic and genomic information related to cancer; to inform the ethical conduct of cancer research involving genetic and genomic information and data; and overall to improve outcomes related to cancer.

National Eye Institute

The National Eye Institute (NEI) is interested in supporting projects that address ethical, legal and social issues arising from genomic research relevant to our mission of eliminating vision loss and improving quality of life through vision research, especially those that are relevant to NEI’s Strategic Plan (i.e., to understand the eye and visual system, prevent and treat vision diseases, and expand opportunities for people who are blind or require vision rehabilitation).

National Institute of Allergy and Infectious Diseases

NIAID is NOT interested in supporting clinical trials under this announcement but would consider non-IND trials, e.g., social/behavioral-relevant trials.

NIAID is interested in supporting projects that focus on ethical, legal, and social implications of genomic research that derive from domestic or international research on HIV/AIDS, other infectious diseases including those transmitted by vectors; immunologic and allergic diseases, or organ transplantation; and other ELSI issues arising from genomics that are relevant to NIAID's scientific mission. Applications should consider the following:

• Supporting the integration of bioethics work with genomic research in immunology, allergies, infectious diseases, transplantation, and other topics within NIAID’s mission.
• Enhanced engagement of key populations in genomic research on HIV and other infectious disease prevention, treatment, cure; HIV-related comorbidities and co-infections including those transmitted via sexual contact; to improve dissemination and communication of results and mitigate barriers to research participation.
• Representation of key populations in genomic research on immune-mediated diseases and transplantation for disease prevention, treatment, and/or cure; improving dissemination, communication of results, and mitigating barriers.
• Research on genome editing for correcting heritable traits and genetic disorders that impact diseases relevant to NIAID’s mission (e.g., inborn errors of immunity, primary immunodeficiencies).
• Investigate perceptions, beliefs, and attitudes towards genomic research among diverse stakeholders including researchers, clinicians, patients, community members, IRB/Ethics committee members, and regulators; analyze ethical implications of these views in planning and conducting NIAID research.
• Research to avoid or mitigate negative consequences of genetic findings on human phenotypes or identity, as well as genetic findings that reveal directionality of disease transmission of pathogens.
• Research to improve the implementation of Artificial Intelligence (AI) and Machine Learning methods to minimize bias in algorithms, coding, and analyses of genomic data.

Eunice Kennedy Shriver National Institute of Child Health and Human Development

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is interested in supporting ELSI research on topics relevant to NICHD's populations of interest, including children; adolescents; pregnant and/or lactating individuals; and persons with intellectual, developmental, and/or physical disabilities across the lifespan.? NICHD is particularly interested in research that relates to the Institute’s high-priority research areas: see https://www.nichd.nih.gov/grants-contracts/research-areas/priorities for current research priorities, and https://www.nichd.nih.gov/about/org/strategicplan regarding research themes for the Institute.?Please note that applications assigned to NICHD that address the mission and priorities of other Institutes that are not participating in this NOFO will not be prioritized for funding by NICHD.

Specific topics of interest to the NICHD include, but are not limited to, ELSI research on the following, subdivided by the NHGRI ELSI research areas:

Genomics and sociocultural structures and values

• The influence of ableism in genomic research on intellectual, developmental, and/or physical disabilities, and the societal implications of developing genomic therapies that aim to treat or cure disabilities.
• The societal impact of the development or use of cognition-altering genetic therapies for intellectual or developmental disabilities.
• Changes in national or regional policies and societal trends that impact the willingness to participate in genetic research and/or undergo genetic testing.

Genomics at the institutional and system level

• Equitable distribution of downstream benefits of genomic research with marginalized communities, such as benefit-sharing or equitable access to gene therapies.
• Genomic sequencing and newborn screening:
  • Real and perceived benefits and harms of genomic sequencing of newborns.
  • Impact of newborn sequencing on families/caregivers, healthcare providers, and state public health newborn screening programs.
  • Lifelong implications of being sequenced as a newborn, such as the inability to have an open future, genetic privacy, and insurance or job discrimination.
  • Use of residual newborn screening dried blood spots for purposes beyond public health, like medical research, forensic investigations, or initiation of cascade screening of biological relatives.
  • Facilitators and barriers for implementing population-wide newborn sequencing, such as whether parental/caregiver consent is needed.
• Considerations around population-wide genomic sequencing, such as ethical and societal concerns, like population-wide acceptance of genomic sequencing; legal, regulatory, and policy needs, like gaps in genetic anti-discrimination legislation or unintended secondary uses of these data; and public health resource constraints, like costs and personnel.
• Impact of germline gene editing technologies on the consent and autonomy of future generations.
• Use of genomic technology to identify genetic causes of disease and disability that currently lack effective treatments or other evidence of clinical utility, thereby ending the diagnostic odyssey but perhaps providing personal utility to patients/families.

Genomic research design and implementation

• Attitudes toward use and modification of patient-derived or genetically modified organoids to study NICHD populations of special interest (e.g., children, IDDs) and/or NICHD research priorities.
• Returning secondary findings to participants in genomic research, such as carrier status, environmental exposures, or pharmacogenomics; assent considerations when returning genetic risks for adult-onset conditions to infants, children, and adolescents; and cascade screening and the impact on family members, especially from prenatal, newborn, or pediatric sequencing.
• Informed consent and/or assent considerations toward genomic research, especially among vulnerable populations (e.g., pregnant women, fetuses and newborns, children and adolescents, individuals with intellectual and developmental disabilities, youth affected by or at high risk of HIV and/or other infectious diseases).
• Research on human genetic determinants of HIV and/or infectious disease transmission, acquisition, and associated co-morbidities among vulnerable populations of mothers, infants, children, adolescents, and young adults, in the US or in international settings.
• Returning genetic research results about HIV and/or other infectious diseases to participants from vulnerable populations and/or resource-limited settings, especially among marginalized groups of youth.
• How differential access to clinical genetic testing impacts the equitable application of genotype-driven recruitment approaches.

Genomic healthcare

• Use of genomic and other omics technologies for screening and/or diagnostic purposes and the implications of these results on patients, families, and caregivers; this includes carrier status, preimplantation selection of embryos, and prenatal and/or newborn risk assessment.
• Considerations for the use of genomic technologies to diagnose and treat benign gynecologic disorders and fertility-related disorders.
• Use of polygenic risk scores in preimplantation embryo screening.
• Clinical and personal utility of the "portable genome" across the lifespan.
• Facilitators and barriers to accessing clinical genetic testing, such as biases around which types of tests are offered and to whom; access to follow-up specialty care; coverage and reimbursement considerations; initiation of cascade testing; and trust in healthcare providers and researchers, especially around the handling and protection of genomic data.

National Institute on Deafness and Other Communication Disorders

The NIDCD is interested in addressing ethical, legal and social issues, related to normal and disordered process, that evolve from genomic research in our mission areas of hearing, balance, taste, smell, voice, speech, and language.

National Institute on Drug Abuse

The National Institute on Drug Abuse (NIDA) is interested in research that focuses on the ethical, legal, social, and policy issues related to genetic, epigenetic, and genomic research on addiction and addictive substances, especially those that align with NIDA’s Strategic Plan (https://nida.nih.gov/about-nida/noras-blog/2022/09/nida-releases-its-2022-2026-strategic-plan).

NIDA encourages applicants to consider developing novel collaborations between the ELSI and Addiction research communities. ELSI research topics of particular interest to NIDA include, but are not limited to, the following:

• What policies should/should not be adopted to protect individuals legally, e.g. If one is genetically predisposed to addiction, knows about this prediction, and decides to use addictive substances? What factors are important for these policies?
• Does genetics predict risk for problem use of opioids better than what is currently achieved? Will such a test improve clinical outcomes?
• What specificity and selectivity are needed to predict a substance use disorder (SUD) in a clinical setting? What are the consequences of misclassification?
• What is the best experimental design to validate risk prediction for substance use disorder (SUD)?
• If we validate genetics and other biomarkers to risk for OUD how do we use it clinically for acute pain and/or chronic pain?
• What are the potential misuses by clinicians of genetic test and other biomarkers of problem misuse of different drugs with addictive potential?
• Does current genetic data and or methods reinforce bias against any ethnic group?
• Will a device that predicts a substance use disorder (SUD) be accepted by patients?
• What impact does genetic liability for substance use disorders (SUDs) have on the stigma associated with substance use disorders?
• How would genetic tests for addiction impact treatment decisions?
• What implications does it have for insurance?
• Will genetic and other biomarker tests for substance use disorders (SUDs) be cost effective?

National Institute of Environmental Health Sciences

The NIEHS is interested in addressing social, ethical, and legal concerns in research related to gene-environment (G x E) interactions, genetic susceptibility to environmental exposures, and ELSI issues related to research involving children, aged populations, tribal communities, and other vulnerable populations impacted by specific environmental exposures. NIEHS is interested in environmental justice and health disparities issues associated with the identification of vulnerable populations in G x E studies and the incorporation of social determinants of health into the G x E research framework. The potential evolving ELSI issues associated with developing improved health risk assessments that leverage emerging findings from combined epigenomics, exposomics, and genomics research is particularly welcome. Identifying, developing, and testing strategies for responsibly reporting back health results from research on G x E interactions to study participants is relevant. Exploring best practices to identify and share actionable environmental exposures (e.g., giving participants and communities access to resources to mitigate environmental exposures) and exploring how people and communities respond and modify their behavior with report-back is also of interest.

NIEHS is additionally interested in research on potential stigmas, discriminations, and privacy concerns associated with either identification of subpopulations at disease/disorder risk due to genetic susceptibility of environmental exposures or potential identification of individuals living in geographic areas linked to high exposures of environmental pollutants. Exploration of best practices to protect the privacy and use of G x E research data at the community level is of particular interest as well. ELSI issues surrounding community engagement approaches and best practices to establish sustainable infrastructures to conduct community-based/community-led research in G x E is also needed.

National Institute of Mental Health

The NIMH is interested in research to address a range of ethical, legal and social issues for individuals and communities relevant to its core mission, and the subjects and disorders which it serves as a primary lead at the NIH.

Areas of emphasis include but are not limited to:

• Implementation of psychiatric genomic medicine that takes into account cultural practices and values to promote inclusion and equity in mental health outcomes
  • Studies on outreach and community engagement in neuropsychiatric genetics research study design and execution, especially the inclusion of diverse cultural values and perspectives from populations currently underrepresented in the scientific community and/or the research subject population whose populations may be the focus of increased recruitment efforts for neuropsychiatric research.
  • Advance understanding on how to avoid or mitigate against stigmatization, group harms, and unintended negative social implications/exacerbations of structural inequalities when conducting research addressing the genomic underpinnings of cognitive and behavioral traits across the spectrum of human phenotypic variation (e.g. intelligence, sexual orientation, gender identity, socio-economic activities) when examined in the context of their contribution to risk and resilience in mental health outcomes.
  • Research related to implications of investigating genetic risk for mental health disorders in communities that experience sustained systemic community stressors that may influence risk for poor mental health outcomes, such as the experience of marginalization, discrimination, and/or racism.
  • Investigations into how to appropriately contextualize genetic information with environmental, cultural, intervention combinations and response, mental and physical health comorbidities, and societal (e.g. systemic racism) factors when assessing diagnosis, disorder trajectory, treatment recommendations, and drug-drug interactions in diverse patients.
  • Research related to the implementation of Artificial Intelligence that integrates genetic information with environmental and other health information in the diagnosis and/or stratification of clinical populations for treatment. The goal should be developing efficient computational strategies to reduce model bias, improve data coverage, equity, fairness towards under served racial and ethnic minorities (e.g., through Generative Adversarial Networks & Digital-Twin technology).
• Research on the use of genetic screening and genetic testing for neuropsychiatric disorders in medical practice, especially among vulnerable and/or underserved populations, including the implications for:
  • Ethical and cultural issues surrounding informed consent, data sharing, and privacy for data collected in a health care setting (i.e. EHR or health-care system biobanks).
  • Return of results and communication of primary findings and secondary findings in a health care setting (e.g. how would the communication of the absence/presence of genetic findings influence patient behavior or encourage/discourage individuals from seeking treatment).
  • The ethical issues related to early intervention therapies (e.g. somatic gene editing, drugs, behavioral) for neuropsychiatric developmental conditions identified by genomic technologies, especially in 1) disorders with late childhood, adolescent or adult onset; or 2) early childhood onset disorders that present with a broad spectrum of severity in outcomes. These studies should consider differences in cultural practices and values across different communities.
  • Use of genomics in Precision Medicine, both for clinical and personal decision making, including indications favoring specific interventions (e.g. genetic testing that suggests favoring biological rather than psychosocial interventions; pharmacogenomic testing favoring higher-risk treatments as potentially more effective than those with lower risk; absence/presence of genetic finding discouraging providers from considering all available treatment options).
  • Effects on the legal and regulatory landscape and existing structural inequalities. (e.g. avoiding discrimination in employment, housing, military service, etc. based on genetic risk of mental disorder and/or use of preventive interventions or services).
• Studies on ethical, legal, and social implications raised by the collection, storage, and future research uses of biological samples and genetic data collected for neuropsychiatric research (e.g. participant preferences, informed consent, governance, privacy and security, and data sharing)
  • Risk assessment is needed for how changes in the science of a neuropsychiatric disease would impact the research subject community (i.e. those living with the disorder and their families who have contributed data or samples to prior research) with respect to informed consent. An example is the increased understanding of the genetic interrelatedness of neuropsychiatric disorders, pleiotropy and locus heterogeneity as it applies to consent for use in related disorder research. Assessment is needed to determine how such a change can most easily be appreciated by the study population and research subject community at large, and how these changes impact subjects understanding of informed consent and the ability to share data and samples.
  • Investigations relating to ethical and cultural issues raised by collections of data and samples from vulnerable and underserved populations in US, including Tribal communities, and populations in different cultural contexts in LMICs, whose populations may be the focus of increased recruitment efforts for neuropsychiatric research.

NIMH encourages projects that will partner with/embed within existing large-scale psychiatric genetics research efforts and others global research network to facilitate answering questions relevant to the execution of that research and implementation of the findings. Such networks include, but are not limited to, PsychENCODE, PsycheMERGE, Psychiatric Genomics Consortium, the Autism Sequencing Consortium, the Convergent Neuroscience Research Network, the Genes 2 Mental Health Network, and the Global Mental Health Genetics Network, Collaborative Hubs for International Research in Mental Health and Collaborative Hubs to Reduce the Burden of Suicide among American Indian and Alaska Native Youth. NIMH also strongly encourages groups to leverage existing ELSI resources developed by NHGRI under prior ELSI funding calls.

NIMH will only award non-trials or mechanistic clinical trials under this announcement. Groups wishing to Address the Safety, Efficacy, and Effectiveness of Preventive, Therapeutic, and Services Interventions should apply through the NIMH Clinical Trial Pipeline.

National Institute on Minority Health and Health Disparities

Racial and ethnic minority populations are understudied in genomic research, particularly those who do not identify as White.Historical misuse of race and ethnicity data as population descriptors in genomics research has resulted in miscommunication of complex relationships between social identity, ancestry, socioeconomic status and health, perpetuating misguided ideas and mistrust. NIMHD is interested in supporting research that promotes scientifically and socially meaningful uses of genomic research and genomic health care for racial/ethnic minority populations. NIMHD is also interested in supporting research that will advance creation of guidelines and adoption of consensus practices for the use of social determinants of health and ancestry data in study design, interpretation of results, publications, and medical care for genomic studies.

Projects should focus on the ethical, legal, and social implications of research participation and/or health care for racial/ethnic minority and persons of less privileged socioeconomic status (SES) and at the intersection of race/ethnicity and lower SES for sexual and gender minorities and underserved rural residents. Research may use available secondary data, health system data and/or collection of primary data.

National Institute of Neurological Disorders and Stroke

The NINDS is interested in research that addresses ethical, legal, and social issues for individuals and communities that emerge from human genome research in the domain of NINDS’s core mission and the topics and disorders for which NINDS serves as a primary lead at the NIH. Please visit: https://www.ninds.nih.gov/About-NINDS. Areas of interest specific to NINDS include but are not limited to the ethical, legal, and social implications of: aspects of neurogenetic research with human participants, such as differing stakeholder views on return of research results to participants or patient consent-related issues (including, but not limited to, waivers of informed consent or exceptions from informed consent), or therapeutic misconception, including for rare genetic diseases; neurogenetic research with human nervous system tissue; development and/or application of gene therapy and gene editing technologies for neurogenetic disorders; issues collecting and sharing human neurogenetic data, such as de-identification, privacy, and re-use practices; predictive/diagnostic neurogenetic research related to nervous system disorders; management and understanding of uncertain individual neurogenetic research results and secondary findings; and issues pertaining to neurogenetic research with children, patients with rare diseases, and other vulnerable populations who may have a limited ability to consent for themselves.

NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes the NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm) and provides additional guidance to the scientific community (https://www.ninds.nih.gov/Funding/grant_policy).

While this funding opportunity also accepts clinical trials, only applications proposing mechanistic clinical trials or studies (studying pathophysiology or mechanism of action of an intervention, but not safety or efficacy) or basic experimental studies with humans (BESH) will be supported by NINDS.

Applications for clinical trials studying efficacy or safety will not be supported, and may be better suited for PAR-22-142, PAR-21-237, or other relevant clinical trials funding opportunities supported by NINDS. In addition, applications addressing ethical issues associated with and resulting from research on emerging technologies and advancements supported by the BRAIN Initiative will not be supported and may be better suited for RFA-MH-21-205.

Office of Research on Women's Health

The Office of Research on Women’s Health (ORWH) is part of the NIH Office of the Director and works in partnership with the NIH Institutes, Centers, and Offices (ICOs) to ensure that women's health research is part of the NIH scientific framework and supported throughout the biomedical enterprise. ORWH uses a multidimensional framework to represent the intersection of factors that underlie patterns of disease and determinants of health outcomes in populations.

For this NOFO, ORWH is interested in supporting research that addresses health equity in genomic research that will eliminate health inequities among women, including those who are understudied, underrepresented, and underreported (U3). The evolving conceptualization of factors relevant to the understanding and promotion of minority health and to the understanding and reduction of health disparities is illustrated in the NIMHD Minority Health and Health Disparities Research Framework. Applying such a framework to genomic research will help to advance the community engagement, access to genomic technology, acceptability of genomic approaches, and interventions to the public needed to advance the equitable use of genomics to improve health in US populations.

There is also a crucial need to address sex and/or gender influences in genomic research relevant to women's health, and, where appropriate, include both sexes to better understand the influence of sex as a biological variable (SABV) on health and disease. Integrating the purposeful accounting for SABV in biomedical research, from the most basic to the clinical and applied efforts, will fill gaps in our knowledge, and will inform more effective and personalized approaches for women and men. For additional guidance, please review the 2019-2023 Trans-NIH Strategic Plan for the Health of Women.

Related Notices of Funding Opportunity

For small projects that are primarily exploratory in nature or designed to generate pilot data in preparation for a larger study, applicants should consider PAR-23-294, the ELSI Exploratory/ Developmental Research (R21) NOFO, which provides a total of up to $275,000 in direct costs over three years. For very small projects, such as those involving single investigators, focused conceptual or analytical studies, or secondary data analyses, applicants may wish to consider PAR-23-295, the ELSI Small Research Grant (R03) NOFO, which provides a total of up to $50,000 in direct costs a year for two years. Note that not all Institutes and Offices participating in this R01 NOFO participate in the R21 and R03 NOFOs.

Data sharing

Recipients must comply with the NIH Data Management and Sharing Policy (NOT-OD-21-013) and NIH Genomic Data Sharing Policy (NOT-OD-14-124). NHGRI supports broad appropriate data sharing with timely data release through widely accessible data repositories. Please follow the NIH guidance on writing a Data Management and Sharing (DMS) Plan. Applications directed to NHGRI should ensure the Plan is in alignment with NHGRI’s data sharing expectations, which are summarized at genome.gov/data-sharing.

Plan for Enhancing Diverse Perspectives (PEDP)

• This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in NOT-MH-21-310, 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 material. The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

Applicants are strongly encouraged to contact NIH Scientific/Research Staff at the relevant participating ICO(s) listed at the end of this NOFO, prior to developing an application to discuss whether their application is responsive.

See Section VIII. Other Information for award authorities and regulations.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Other Attachment:

Plan for Enhancing Diverse Perspectives (PEDP)

In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity

• The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate.
• Where possible, applicant(s) should align their description with these required elements within the research strategy section
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured
• The PEDP may be no more than 1 page in length and should include a timeline and milestones for relevant components that will be considered as part of the review

Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups historically under represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see

https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

Budgets should include any funds required to support sharing of scientific data under this NOFO. NIH provides guidance on allowable costs for data management and sharing here. For projects generating genomic data derived from research participants, investigators should also consider costs associated with complying with the NIH and NHGRI GDS Policy expectations (e.g., obtaining samples with explicit informed consent for future research use and broad data sharing, implementing processes to seek new consent from study participants, etc.).

Applications that include community members or stakeholders as research team members or advisors should describe their research roles in the budget justification and describe budgetary support to enable their successful involvement in the project.

PEDP implementation costs

• Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm ).

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: Research projects that will use population descriptors in the analyses should name and define those variables, provide a rationale for their use and note any associated limitations. Variables whose use should be explained include population descriptors related to race, ethnicity, genealogical ancestry, genetic ancestry, sex, gender, and sexual orientation. The rationale should be supported by established theory, frameworks, or scientific evidence. The Research Strategy should describe how planned use of the selected variables relates to the proposed research question(s), and describe any assumptions or limitations associated with their use.

Applicants who propose to address or analyze race, ethnicity, genealogical ancestry or genetic ancestry are strongly encouraged to review the 2023 National Academies of Sciences, Engineering, and Medicine (NASEM) report, Using Population Descriptors in Genetics and Genomics Research: A New Framework for an Evolving Field and Recommendations for Transforming the Use of Population Descriptors in Human Genetic and Genomics Research. Those proposing to address or analyze concepts related to sex and gender are strongly encouraged to review the 2022 NASEM report Measuring Sex, Gender Identity, and Sexual Orientation.

Applicants are not required to include in their scientific analyses any variable that is required for NIH inclusion enrollment reporting. Do not explain in the Research Plan any variables that are collected solely for the purpose of NIH inclusion enrollment reporting that will not be used in data analysis.

NIH encourages applicants to consider the use of variables provided in the PhenX Toolkit which provides recommended standard measures for use in biomedical research. These measures have been selected by domain experts using a consensus process. The Toolkit provides protocols for collecting data, and tools to help investigators incorporate protocols into their studies. Using protocols from the PhenX Toolkit facilitates cross-study analysis, potentially increasing the scientific impact of individual studies. Of note, the Social Determinants of Health (SDOH) Collections may be important for some ELSI projects to consider. In addition to protocols for core SDOH measures, the collection includes measures at individual and structural levels.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

All applications, regardless of the amount of direct costs requested for any one year, must develop a Resource Sharing Plan consistent with the goals of the proposal.

The Resource Sharing plan should summarize whether and how research findings and products (e.g., publications, meeting reports, software, websites, research tools) will be made available to relevant communities and stakeholders. Applicants should include a proposed timeline for implementing the Resource Sharing Plan, name the platform(s) or mechanism(s) that will be used to make research findings and products publicly accessible, and indicate who will be responsible for implementation. Applicants sharing software are encouraged to use software licenses that allow for unrestricted redistribution and modification of the software. Additionally, NHGRI encourages investigators to consider disseminating research findings and products via publicly accessible platforms such as the Center for ELSI Resources and Analysis.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Please follow the NIH guidance on writing a Data Management and Sharing (DMS) Plan here, and ensure the Plan is in alignment with the NHGRI’s data sharing expectations explained below. Additional information can be found at genome.gov/data-sharing.

Per NOT-HG-21-022, NHGRI expects applications awarded under this NOFO to share comprehensive metadata and phenotypic, clinical, and environmental exposure data associated with the study; use standardized data collection protocols and survey instruments for capturing data, as appropriate; and use standardized notation for metadata (e.g. controlled vocabularies or ontologies) to enable the harmonization of datasets for secondary research analyses.

To ensure that maximal scientific benefit is derived from this significant public investment, this funding opportunity aims to advance and accelerate research by supporting rapid sharing of the resulting data with the broad scientific community. All resulting scientific data should be submitted to an established repository as described in the Data Management and Sharing Policy guidance and NHGRI’s guidance on where to submit scientific data.

Where human biological samples will be studied, they are expected to have been obtained using a documented informed consent process that allows for future research use and broad data sharing (NOT-HG-20-011). If new human biospecimens will be collected, or if clinical application is included in the application, the consent process should be described at a high level in the Research Plan and detailed in the Human Subjects Section.

NHGRI strongly encourages studies that propose to derive genomic data from human specimens and cell lines to obtain participant consent either for general research use through controlled access or for unrestricted access. Similarly, consent language should avoid both restrictions on the types of users who may access the data and restrictions that add additional requirements to the access request process. NHGRI acknowledges that this will not always be possible or appropriate. In addition, individual participants who do not consent to future research use or broad sharing of their data (i.e., submission of their data to a publicly accessible data repository) may still participate in the primary study if consistent with study design. Additional guidance on informed consent can be found in the NHGRI Informed Consent Resource.

Applicants are encouraged to get feedback from the communities in which the research will be performed regarding plans for how individual level data resulting from the research projects will be shared with the scientific community for research purposes. Feedback and recommendations for data access, protection of participant and patient privacy and confidentiality, and management of health information should be integrated into the project’s Data Management and Sharing Plan. Note that any project receiving NIH funding that collects or uses identifiable, sensitive information is automatically issued a Certificate of Confidentiality (CoC).

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applications must include annual milestones. Applications that fail to include annual milestones will be considered incomplete and will be withdrawn. Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

Awardees will provide updates at least annually on implementation of the PEDP.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Dave Kaufman
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-4997
Email:[email protected]

Nicole Lockhart
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-4997
Email: [email protected]

Rene Sterling
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-1275
Email: [email protected]

Rosemary McKaig, Ph.D., M.P.H.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3214
Email: [email protected]

Bracie Watson
NIDCD - NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
Phone: 301.402.3458
E-mail: [email protected]

Charlisse Caga-Anan
National Cancer Institute (NCI)
Telephone: (240) 276-6738
Email: [email protected]

Rajeev K Agarwal, Ph.D.
ORWH - Office of Research on Women's Health
Phone: 301-451-7058
E-mail: [email protected]

Elena K Gorodetsky, M.D., Ph.D.
ORWH - Office of Research on Women's Health
Phone: (301) 402-1770
E-mail: [email protected]

Amy Tsou, MD, MSc
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Phone: 240.987.2815

Mollie Minear, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Email: [email protected]

Miri Gitik, Ph.D.
National Institute of Mental Health (NIMH)
Phone:301-827-3523
E-mail: [email protected]

Nancy Lynne Jones, PhD
NIMHD - NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES
Phone: 301-594-8945
E-mail: [email protected]

Kimberly A McAllister, PhD
NIEHS - NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
Phone: 984-287-3287
E-mail: [email protected]

Cheri Wiggs
NEI - NATIONAL EYE INSTITUTE
Phone: (301) 402-0276
E-mail: [email protected]

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

Deanna Ingersoll
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-78658
Email: [email protected]

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: [email protected]

Samantha Tempchin
National Institute on Deafness and Other Communication Disorders (NIDCD)
Telephone: 301-435-1404
Email: [email protected]

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected]

Pamela G Fleming
NIDA - NATIONAL INSTITUTE ON DRUG ABUSE
Phone: 301-480-1159
E-mail: [email protected]

Priscilla Grant JD
NIMHD - NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES
Phone: 301-594-8412
E-mail: [email protected]

Clark Phillips
NIEHS - NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
Phone: 984-287-4037
Email: [email protected]

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: [email protected]

Karen Robinson Smith
NEI - NATIONAL EYE INSTITUTE
Phone: 301-435-8178
E-mail: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.