Conformance to all requirements (both in the Application Guide and the FOA) 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.

Background

The purpose of this funding opportunity announcement is to advance our understanding of the impact of extreme weather and disaster events in aging human populations. Together with the companion FOA (PAR-19-249) that focuses on underlying mechanisms of aging utilizing animal models, these two FOAs will help to explicate the behavioral, biological, and socioecological processes that occur during extreme weather or disaster events and that affect aging processes and how affected individuals, community organizations and governmental entities can more effectively prepare for and respond to such events. Through the integration of the population studies and the companion mechanistic studies FOA, the ultimate goal is to improve the health and well-being of older adults via increased knowledge about extreme weather and disaster preparedness, response, and recovery.

Clinical and mechanistic studies demonstrate that aging is a major risk factor for chronic disease and degenerative conditions. In addition, the past decade has seen considerable advancement in understanding the biologic hallmarks of aging which includes genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, cellular senescence, stem cell exhaustion, altered intercellular communication, and mitochondrial dysfunction. However, there is little mechanistic understanding of how exposure to extreme environmental changes, e.g. heat and other climate and disaster related exposures, interact with the biology of aging in human populations, either alone or along with other stressors (e.g., the status of social networks, the timing and duration of exposure in relation to the life course, and the type and severity of chemical exposures in disaster events). Although many studies have focused on early-life exposures and the later life health effects (e.g., Developmental Origins of Disease), limited research has addressed the effects of environmental exposures in the setting of later life on how this may affect biological aging. Furthermore, although increasing research has explored the effects of disaster events in specific regions and among specific subpopulations, relatively fewer studies have focused on extreme weather and natural or manmade disaster events in aging populations.

The impetus behind this population-based FOA are four converging factors that have led to heightened interest in research to understand how extreme weather and disaster events impact older adults.

First, health improvements have driven increases in life expectancy. Adults aged 65 and older make up about 13% of the current U.S. population, but by 2040 that number is projected to increase to 20%. For the first time in American history, people aged 65 and older will outnumber people under the age of 18 by 2030.

Second, while the US population is getting older, several types of extreme weather and disaster events have increased in frequency and/or severity. These events appear to have differential effects by age with older individuals being particularly vulnerable during and following these events. Though it is not fully clear why, physical well-being, functional health, cognitive function, residential context (e.g. community-dwelling versus living in a nursing home or assisted living), and social connectedness represent potential pathways to disproportionate effects in older adults.

Third, health inequities among vulnerable populations amplify the effects of natural disasters such as hurricanes, tornadoes, earthquakes, wildfires and manmade disasters. Inequalities may be particularly prevalent among older adults, given that disparities by race, ethnicity, class, and gender may grow across the life course.

Finally, because experiences aggregate across the life course, examining the impacts of current extreme weather and disaster events on older people enables an investigation not only of present conditions but myriad past experiences both separately and together with current events.

Scope of Research

Although all segments of the population will be vulnerable to the environmental, physiological, and psychological stressors associated with extreme weather or disaster events, this FOA focuses on aging processes in elderly adults. However, elderly is a characteristic that is only monolithic in the sense of a common age group. Specific considerations will need to be addressed among different racial and ethnic populations and variable conditions associated with geography, demographics, and culture. Some of these include:

• Seasonal variation which may differentially affect various subpopulations based on variation in biologic sensitivity, socioeconomic factors, and geographic setting. Taken together seasonality may contribute to heightened risk for climate-sensitive health outcomes. For public health planning, it will be critical to identify those populations that are expected to experience the synergistic effects of multiple risk factors for health problems and whose existing health and environmental health disparities make them particularly vulnerable.
• Changes in the frequency, location and/or intensity of climate-related stressors such as temperature variation and extreme weather events. A recent study has shown that extreme heat was associated with a 3% (95% CI: 2%, 4%) increase in all-cause hospital admissions over the subsequent 8 days. In cause-specific analyses, extreme heat was associated with increased hospitalizations for renal conditions (15%; 95% CI: 9%, 21%) and respiratory diseases (4%; 95% CI: 2%, 7%). Other research has shown that a rise in summer mean temperature of 1 F was associated with 1.0% higher death rate. In addition, the location of these extreme weather events is shifting and areas that historically did not record extreme heat or cold are increasingly experiencing extreme weather that stresses infrastructural resources and preparedness activities.
• Geographic location. Relatively higher concentrations of older adults live in coastal zones, large urban areas and in the Sunbelt which are expected to be particularly affected by climate stressors such as heat events, droughts and wildfires and higher concentrations of ground-level ozone and other air pollutants and airborne allergens; as well as by disaster events such as hurricanes, storm surges, floods and the chemical exposures associated with these climatic and manmade disasters, e.g., oil and gas spills. For elders with existing co-morbidities, the increase in environmental and manmade stressors might pose a particular risk for health.
• Socioeconomic status. Elderly adults living in poverty or on limited fixed incomes may lack resources that would be protective to extreme weather events. This includes housing without adequate air conditioning during heat waves and lack of access to social services and medical care during extreme weather events or disasters. In addition, elderly individuals may be functionally, physiologically, or psychologically impaired which combined with lower socioeconomic status could affect their resilience and adaptability to a changing climate and increased disasters.

The release of this FOA and its companion together provide opportunities to take a holistic approach whereby socio-cultural factors as well as biological pathways shared between humans and animal models that are known to be affected by aging, can be used to understand the biological responses. This FOA and the Companion PAR-19-249 are targeted to address the lack of knowledge of the biological and socioecological consequences resulting from these acute exposures at various times during the life course and determine its effects on the aging process and subsequent health outcomes later in life ages.

Terminology

Environmental influences on aging include biological, environmental, epigenetic, and socioecological factors. However, there are a variety of definitions that can be used to describe the environmental influences on aging and related factors. For the purposes of this FOA, we provide definitions relevant to this announcement:

1. Aging populations We conceptualize human aging as a continuous process across the life span. We understand aging populations to include those in midlife and older life stages, while recognizing that the boundaries between life stages are fluid and conditional on context (e.g., cultural, economic, and health status).
2. Biological factors include chemical, molecular, structural, or infectious factors that impact senescence processes at the cellular, tissue, or organismal level.
3. Disasters acute events causing substantial harm. This includes both natural and manmade disaster events such as:

• Different kinds of slow disasters in human populations
  • Neighborhood and household violence
  • Disaster regions where natural and manmade disasters occur on a regular basis such as low-lying coastal regions (e.g., the Gulf of Mexico, barrier islands)
• Manmade disasters (oil spills, chemical spills, terrorism)
• Weather extremes (prolonged or excessively high heat waves, severe unseasonal cold spells)
• Extreme weather-related disasters (hurricanes, storm surge, floods, wildfires)

4. Displacements (resulting from loss of customary living environment) - defined as the loss of social networks, separation from family members, caregivers and pets, or from familiar settings, and disruption of daily living.

?5?.? Dissemination and Implementation - research on how evidence-based practices, interventions, and policies are effectively translated to and used in real-world settings like hospitals, schools, and communities.

6?.? Environmental factors encompass exogenous chemical and metal exposures, climatic conditions, as well as financial, cultural, natural, and built social capitals that impact a person’s health. Specifically, environment includes non-chemical stressors (e.g., social isolation) and chemical stressors (e.g., polycyclic aromatic hydrocarbons, volatile organic compounds, metals, etc.) that can result from extreme environmental changes or disaster events.

7. Epigenetic factors - molecular or chemical factors that affect how cells express genes, without modifying the underlying DNA sequence.

8. Socioecological factors - factors that impact an individual’s behavior by working at various levels of a person’s social interactions (e.g. interpersonal relationships, social networks, community structures, government services).

9. Mixtures is the study of multiple factors that may work synergistically as well as additively to impact the health of an individual. Mixtures may be of the same type of factor (e.g. multiple environmental chemicals released during a flooding event) or may represent different types of factors (e.g. heat stress, exposure to flame retardant aerosols/smoke, and social stresses that may result from evacuating in a wildfire event). This type of study is also referred to as research on combined or cumulative exposures which may include chemical stressors and the potential cumulative effects of chemical and non-chemical stressors

10. Risk communication - refers to language, images, and other symbols that facilitate cognitive-processes, decision-making, and other human processes to understand health-related benefits and deficits

11. Community engaged research - involves community organizations, agencies, health and transportation departments,affected individuals, their families and caregivers, etc.

12. Health disparity - is defined as an adverse difference in a health outcome that affects one of the defined disparity populations

13. Health disparity populations include racial/ethnic minorities, less privileged socio-economic status, underserved rural residents, and/or sexual gender minorities

Research Approaches

Multidisciplinary research projects that can potentially address the multifactorial nature of exposures affecting aging are welcomed and, when appropriate, that address cultural considerations of specific elderly subpopulations. Studies submitted in response to this FOA are therefore encouraged to utilize the appropriate inclusion of various scientific disciplines, methodologies, and theoretical frameworks.

• Multidisciplinary research - may include the participation of mechanistically oriented scientists, epidemiologists, social scientists and communications research experts, among others, to conduct multidisciplinary research on mixtures (i.e., combined and cumulative exposures).
• Social scientific, community-engaged and behavioral interventional research studies of the combined effects of socioeconomic, cultural, and behavioral stressors on aging populations.
• Communications research includes dissemination & implementation studies and development of culturally appropriate risk messages.
• Fundamental research research on the biological pathways and mechanisms of aging.

An additional purpose of this FOA is to encourage community engaged research that involves community organizations, agencies, health and transportation departments, as well as affected individuals, their families and caregivers, to collaboratively address the effects of extreme weather and disaster events on aging populations.

Research Topics

Studies for both this FOA and the companion aging processes FOA are encouraged to focus on one of the following four research themes.

Research topics of interest include, but are not limited to:

Understanding Effects of Combined Exposures

Exploration of the interactions or additive effects of combined chemical and non-chemical stressors

• Consideration of the interplay of social determinants of health with biological health
• Development of methods for analysis of combined exposures that incorporates qualitative and quantitative data or that considers the cumulative effects of multiple environmental exposures (e.g., chemicals and particulates)
• Research that considers the role of infections in elderly populations that contribute to health risks in the context of extreme environmental exposures (e.g., in the aftermath of disasters or as the result of extreme weather (e.g., STDs, community acquired pneumonia))
• The exposure of the older person to changing environmental hazards in their daily environment that raises their risks or exacerbates existing health conditions (e.g, exposure to heightened amounts of air pollutants, flood waters, extreme heat or cold)

Hallmarks of Aging

The impacts of disasters or extreme weather on processes (e.g., sensory and mental decline deficits and cellular and molecular processes) related to health outcomes.

• Circadian rhythm changes over the course of aging.
• Biopsychosocial mechanisms of exposure and aging
• Evaluation of immune function in population-based setting
• Changes in telomere length, and other relevant biological response indicators, in the aftermath of extreme weather events or disasters

Biomarkers of Resilience

Health promotion and resilience in the aftermath of disaster events.

• The pathology related to underlying resilience (e.g., biological markers, like cell counts, glucose tolerance, that can easily be measured)
• Studies that examine the effects of changes in nutrition or access to food that affect response (resilience) during and after natural disasters and extreme weather events
• Identification of the most vulnerable populations during disasters and innovative interventions and solutions that would improve health promoting behaviors
• Comparative studies about preparedness in rural vs urban environments

Health services delivery and supporting infrastructure, e.g. infrastructure readiness and general infrastructure issues that affect access to healthcare, food, clean water, safe and dry housing

• Transportation needs assessment particularly related to access to medical care, food or clean water
• Facilitators and barriers to implementing health care services in vulnerable populations during disaster event
• Food insecurity (in context of diseases such as diabetes)
• The increased risk associated with being older and aging in place at home or at a senior citizen center or hospice, and the potential loss of power, water, medical equipment or building infrastructure that can lead to renal failure, or disruption of clinical care for CVD, cancers, respiratory conditions, or dementias/cognitive decline

Dissemination and Implementation

Studies that develop, implement and evaluate the effectiveness of risk communication or educational resources for specific elderly populations or stakeholders

• Dissemination research to develop communications based on culturally appropriate formats, languages and imagery for specific audiences (ethnic and racial elder populations, caregivers, health professionals, etc.)
• Dissemination research that adapts existing validated educational resources, information on preparedness and health risk communications for specific stakeholders/audiences
• Dissemination research to explore the use of social media and other modalities (media, the arts, school or hospital based internal communication systems) for communicating health risks and the availability of preparedness resources
• Implementation research that evaluates the effectiveness and uptake of risk information
• Implementation research to assess the utility of preparedness resources in the aftermath of extreme weather events or disasters

Additional research topics of interest include but are not limited to:

Studies that focus on functional abilities in aging populations rather than on disease endpoints, (e.g. limited skill sets, day to day function)

• Sensory deficits and their influence on perception, cognition, and behavior during disaster events or in the context of extreme weather conditions
• Screening for early signs and treatment of mental health problems in socioeconomically disadvantaged and underserved populations in disaster prone regions or regions where extreme weather is common (e.g. coastal regions, polar regions, tropical regions)

Policy and economic and systems analysis research towards system changes (in preparedness)

• Research that assesses the effectiveness of policies on preparedness or response activities for aging populations
• Economics analyses to determine the utility and sustainability of preparedness or response initiatives
• Systems analysis research to identify needs for coordination among agencies, public health units, community organizations, health professionals, families and affected individuals in relation to preparedness or response to disasters or extreme weather.

Changes in both therapeutic and side effects of medications due to extreme temperatures, etc.

Applicants are encouraged to contact a Program Officer to discuss their proposed topics to ensure their application is responsive to this announcement and within the purview of one or more of the participating Institutes and Centers. A research focus on individuals solely from childhood or young adulthood is strongly discouraged. In addition, applications will not be considered responsive that propose a natural disaster event, such as a hurricane or flood, as the sole environmental factor of concern; instead applications must identify an environmental exposure (e.g., in soil, air, water or the built environment) that arises from the disaster event and that poses a risk for health.

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)

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)

• Eligible Agencies of the Federal Government

• U.S. Territory or Possession

• 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

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 Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• 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.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration , but 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 DUNS number and 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.

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

3. Additional Information on Eligibility

Number of Applications

The NIH will not accept duplicate or highly overlapping applications under review at the same time. 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 NOT-OD-11-101)

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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Alfonso Latoni, PhD

Telephone: 984-287-3279

Fax: 301-480-3704

Email:alfonso.latoni@nih.gov

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

Joint Meetings: Each PD/PI is expected to budget sufficient funds to attend up to three joint meetings of the Environmental Influences on Aging Population and Aging Processes program. The three meetings are anticipated to occur in Years 1, 3 and 5 in venues to be determined in collaboration with the Principal Investigators and NIEHS.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

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.

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 Policy on Late Application Submission.

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 Component of the SF424(R&R) Application Package. 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 FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number 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.

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.

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.

In addition, for applications involving clinical trials:

If a clinical trial is proposed, the 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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

In addition, for applications involving clinical trials:

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition, for applications involving clinical trials:

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications involving clinical trials:

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project ? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

In addition, for applications involving clinical trials:

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications involving clinical trials:

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Study Timeline

?Specific for applications involving clinical trials:

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

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.

• 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.

• Will receive a written critique.

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

1. Award Notices

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. 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 FOA 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: Grantee 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 awardee 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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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.

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 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

3. Reporting

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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 $25,000. 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 Appendix XII to 45 CFR Part 75, 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 Award Term and Conditions for Recipient Integrity and Performance Matters.

Finding Help Online: http://grants.nih.gov/support/ (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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Lindsey Ann Martin, PhD
National Institute of Environmental Health Sciences (NIEHS)
Phone: (984) 287-4036
Email: Lindsey.Martin@nih.gov

Amelia Karraker, PhD
National Institute on Aging (NIA)
Telephone: 301-496-3131
Email: Amelia.karraker@nih.gov

Nishadi DeAbrew Rajapakse, PhD, MHS
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-496-4338
Email: chandima.rajapakse@nih.gov

Augusto Diana, PhD
National Institute of Nursing Research (NINR)
Telephone: 301-402-6423
Email: dianaa@mail.nih.gov

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

Jenny Greer, M.A.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3332
Email:jenny.greer@nih.gov

Eva Lawson-Lipchin
National Institute on Aging (NIA)
Telephone: 301-435-2020
Email: eva.lawson-lipchin@nih.gov

Priscilla Grant
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8412
Email: pg38h@nih.gov

Ron Wertz
National Institute of Nursing Research (NINR)
Telephone: 301-594-2807
Email:wertzr@mail.nih.gov