The Office of Research on Women's Health (ORWH) announces the availability of administrative supplements to support research highlighting the impact of sex and gender influences in human health and illness. Sex and gender are important considerations in many areas of research, including basic biological, psychological, social, and behavioral studies. With continuous interaction between sex and gender, human health is determined by both biology and expression of gender. The most robust experimental designs include consideration of both sex and gender; therefore, applications proposing to investigate the influence of both sex and gender factors are highly encouraged. The proposed research must address at least one objective from the five strategic goals of the 2019-2023 Trans-NIH Strategic Plan for Women's Health Research "Advancing Science for the Health of Women".

Background

Women and men are characterized by both sex and gender, as highlighted in the Institute of Medicine (IOM) report, "Exploring the Biological Contributions to Human Health: Does Sex Matter?" (IOM Report, 2001). For this initiative, ORWH will use IOM definitions to describe sex and gender-based studies:

• Sex-based studies: Sex is the classification of living things, generally as male or female according to their reproductive organs and functions assigned by chromosomal complement.
• Gender-based studies: Gender refers to a person's self-representation as male or female, or how that person is responded to by social institutions based on the individual's gender presentation. Gender is rooted in biology and shaped by environment and experience.

Consideration of these variables and comparisons of males and females may be critical to the accurate interpretation, validation, and generalization of research findings. Sex and gender may also determine how health and disease processes differ among women, or between women and men, and inform the development and testing of preventive and therapeutic interventions in both sexes. Sex-based comparisons in research may also ensure that findings are applicable to both women and men.

Specific Areas of Research Interest

A broad range of research may be appropriate for this initiative. Areas of interest include the study of both male and female subjects, and the comparison of their outcomes in the following general areas:

• Preclinical research projects aimed at increasing mechanistic understanding of sex differences
• Comparative studies of male and female cells (including stem cells), tissues, organs or physiological systems
• Systems biology (e.g., "omics") approaches and outcomes
• Bioengineering and imaging studies of structural and/or functional differences; medical device development and implementation, including body armor, assistive exoskeletons, and organs or tissues on chips
• In vivo methods and techniques to identify fetal sex prior to visualization of gonads
• Computational models of disease progression, transmission, prevention, treatment, and relapse
• Prenatal, perinatal, and postnatal development, both normal and abnormal
• Assessment of differences in phenotypic characterization and risk factors for mental disorders; neurobehavioral mechanisms of psychopathology; trajectories of risk and resilience.
• Neurobiological mechanisms relating to alcohol and other addictive drugs
• Sensitivity and specificity of biomarkers (e.g. screening, predisposition/risk assessment, diagnostic, prognostic, predictive, therapeutic)
• Therapeutic interventions for treatment or prevention; development of drugs/identification of targets; Pharmacokinetic/Pharmacodynamic (PK/PD) profiles. Examples Pain; Depression; Prescription drug abuse, addictive drugs; Atherothrombosis including coronary, cerebrovascular, and peripheral artery diseases; Heart failure; Asthma; Myelodysplasia/myeloproliferative disorders; Insomnia- and sleep-related fatigue, depression, stress, and suicide; Sleep-disordered breathing.

ORWH is specifically interested in supporting studies related to the influence of gender on human health. Topics of interest include, but are not limited to:

• The influence of gender on disease incidence, prevention, treatment, and relapse
• Gender roles influencing caretaking responsibilities, and effects on health, resilience, and disease
• Research considering the roles of sex and gender together on the outcome of human health
• Population study examining the role of gender in different cultural, social, and ethnic populations

Eligibility

Only PDs/PIs of an active DP1, DP2, DP4, DP5, K08, K23, K76, P01, P20, P30, P40, P41, P50, P51, P60, PM1, R01, R03, R21, R21/R33, R24, R35, R37, R41, R41/R42, R42, R43, R43/R44, R44, RM1, U01, U10, U19, U42, U44, U54, U56, UG1, UG3/UH3, UH2, UH2/UH3, UH3, UM1, or UM2 award from NIH are eligible to apply. The PDs/PIs are encouraged to apply electronically.

PDs/PIs of above-mentioned activity codes must also fulfill all the following mandatory requirements, otherwise their applications will be deemed non-responsive to this NOSI.

• The parent peer-reviewed NIH funded grant must have at least 16 months of active grant support remaining from the due date as specified in this NOSI. No-cost-extension is not eligible.
• Only one Sex/Gender Admin. Supp. award is permitted to a peer-reviewed NIH funded grant in one grant cycle.
• At least one objective from the five strategic goals of the 2019-2023 Trans-NIH Strategic Plan for Women's Health Research "Advancing Science for the Health of Women" is proposed and identified in the application.
• At least one of the three Sex/Gender-based Study Types is proposed:
  • Pre-Clinical Research includes Cell line, Primary culture from animals, Animal model, Xenograft, non-human primates
  • Clinical Research includes Human subjects, Human Biospecimens, Primary culture from human subjects
  • Both Pre-Clinical and Clinical Research includes above mentioned examples of both study types, and Patients derived xenografts
• At least one of the three Sex/Gender-based Research Approaches is proposed:
  • Add the Opposite Sex/Gender: The addition of animal or human subjects, tissues or cells of the sex opposite to those used in the parent grant to allow sex/gender-based comparisons. Applicants should discuss measures to ensure comparability of new data to data already collected under the parent grant.
  • Increase Sample Size: The addition of more animal or human subjects, tissues or cells to a sample which already includes both males and females to increase the power of a study to analyze for a sex/gender difference. Applicants should discuss methods used to ensure control of potential cohort differences related to the new data compared to data already collected.
  • Analyze Existing Data: Comparative analyses of existing samples/datasets/databases and/or data-mining to investigate the role of sex/gender. Applicants should explain how the proposed experiments or analyses will complement, without expanding the scope of the funded grant.

Foreign Institutions:

• Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
• Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
• Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Budget

• ORWH intends to commit up to $1 million per year to award up to 10 applications.
• Application budget is limited to one year only.
• Application budget cannot exceed a maximum direct cost of $100,000. In addition to the direct cost, applicable F&A (indirect) cost can also be requested.
• Supplements may provide support above the dollar limits of the funding opportunity announcement of the parent grant award.
• Earliest start date July/August 2020 and July/August 2021

Scientific Review Process

The NIH program staff will conduct administrative reviews of submitted applications and will support the most meritorious applications submitted for consideration, pending availability of funds.

Application and Submission Information

• The process for streamlined submissions using the eRA Commons cannot be used for this initiative.
• Applications for this initiative must be submitted using the following opportunity: PA-18-591 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
• Continuous Submission is not permitted. In other words, no late applications will be accepted.
• All instructions in the SF424 (R&R) Application Guide and PA-18-591 must be followed, with the following additions:
  • Application Due Date(s) - January 31, 2020 and January 25, 2021, by 5:00 PM local time of applicant organization
  • For funding consideration, applicants must include NOT-OD-20-049 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.
  • The Research Strategy section of the application is limited to parent application pages.
• It is strongly recommended that the applicant contact their respective program officers at the Institute supporting the parent award to confirm ahead of time that the supplement falls within scope of the parent award.
• Following submission, applicants are strongly encouraged to notify the program contact at the IC supporting the parent award that a request has been submitted in response to this FOA in order to facilitate efficient processing of the request.