Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. 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

This FOA encourages innovative research to improve our understanding of how to increase and maintain health-enhancing physical activity to make meaningful and lasting change, with an emphasis on multi-level interventions that have the potential to be scalable, implementable, and sustained in real-world settings. Interventions to be tested should seek to increase participants progression toward achieving the 2008 Physical Activity Guidelines for Americans as appropriate to the participants health, abilities, and conditions. The intent of this announcement is to address physical activity as it relates to conditions other than obesity or energy balance, such as cardiorespiratory fitness, reduced rates of cancer, bone health, mental health, or substance abuse. The interventions to be tested can include diverse strategies delivered at multiple levels to promote health-enhancing physical activity as a primary outcome. Studies across the lifespan that address a wide range of population groups are sought (e.g., racial and ethnic minorities, children, elderly populations, persons with medical conditions, and persons with disabilities). Investigators are encouraged to refine interventions and make use of innovative partnerships within and across sectors (e.g., partnerships with community organizations, faith-based organizations, businesses, government, and/or healthcare providers). For studies that are ready to implement, test, and evaluate scalable interventions, please see the companion Research Project Grant (R01) PAR-14-315.

Physical activity is an important health behavior that is associated with numerous health conditions and outcomes. Findings delineated in the evidence report for the 2008 Physical Activity Guidelines for Americans as well as numerous other publications, show that moderate-to-vigorous aerobic physical activity in adults is associated with many health benefits. Physical activity is defined as bodily movement that expends energy, but not all the positive health outcomes from physical activity are due to the expenditure of energy per se. For example, aerobic activity increases the contractility and stroke volume of the heart muscle, increases blood flow through the body’s vascular system, improves oxygen uptake in the lungs, and relaxes the peripheral vasculature. These changes improve the body’s cardiorespiratory fitness level and lower blood pressure, which help reduce cardiovascular events like heart attacks and strokes. Aerobic physical activity also increases uptake of blood glucose by the body’s cells through increases in insulin sensitivity, thus helping to control blood sugar levels in people with diabetes or pre-diabetes. Strength training and weight-bearing physical activity improves the contractility of peripheral muscles and preserves muscle mass during aging, improving the ability to function independently during the aging process. In youth, studies have shown that physically active children and youth have higher levels of cardiorespiratory endurance and muscle strength, lower levels of body fat, more favorable cardiovascular and metabolic disease risk profiles, enhanced bone health, reduced symptoms of anxiety and depression, and improved academic performance.

Despite the well-recognized benefits of physical activity, the proportion of people in the United States that engages in a level of physical activity that can promote their health is far less than desired, with only one in five U.S. adults meeting the overall 2008 Physical Activity Guidelines for Americans. Because of the myriad of health conditions that physical activity affects, it is important to assess the level of physical activity in various population groups and to determine what strategies might be useful for increasing the type of physical activity that could benefit those groups.

In December 2012, the NIH Office of Disease Prevention (ODP) held a trans-NIH workshop on research priorities for physical activity and disease prevention. The workshop focused on research to increase and promote health-enhancing physical activity in the U.S. Discussions addressed the NIH s interest in supporting innovative research to improve physical activity interventions in diverse age and racial/ethnic populations; identifying barriers and facilitators to achieving national physical activity guidelines; and prioritizing the NIH physical activity research agenda. Extramural grantees were clear that current physical activity funding mechanisms did not provide 3 things that could be solved by offering a phased innovation grant mechanism: 1) ramp up time to build the necessary collaborations and partnerships with different stakeholders from the different levels of a potential multi-level intervention ; 2) the opportunity to do the feasibility phase of the study followed immediately by the full-scale test without having to submit an R21 and then wait years to get the subsequent R01 award; 3) grantees who were ready for a full-scale R01 said they needed a mechanism to give them time on the back-end of the study to assess maintenance and sustainability. Another of the main messages that emerged from the workshop was to support research that moves beyond individual and single-level interventions to incorporate action at two or more levels, such as families, organizations, and communities in addition to individuals (for more information, see multi-level intervention examples listed below). Multi-level interventions are thought to hold promise in enabling individuals to successfully change and maintain their physical activity-related health behaviors.

The 2008 Physical Activity Guidelines for Americans recommend that healthy adults engage in at least 150 minutes per week of moderate intensity aerobic activity, 75 minutes of vigorous aerobic activity, or an equivalent combination of moderate and vigorous activity, in addition to twice a week muscular strengthening exercises. For youth, the Guidelines recommend an hour a day of moderate to vigorous aerobic activity. Recommendations for persons with various medical conditions are also included in the Guidelines.

The Guidelines recommendations are based on evidence showing that the level of activity is associated with improved health benefits and well-being. Studies also show that gradually increasing activity in persons who are inactive is safer than increasing activity rapidly and dramatically and is more likely to result in long-term adherence. In addition, health benefits may begin with less activity than the level recommended, with more activity leading to greater and additional benefits. So, increasing activity levels across the spectrum from sedentary to meeting the guidelines and even higher has the potential to improve the nation’s health.

Studies have been conducted to test various intervention strategies to help inactive people become more active. In general, behavioral strategies which include approaches like individualized goal setting, self-monitoring, problem solving around barriers to activity change, and positive reinforcement for achieving goals are more effective. Interventions that consider the context in which physical activity may happen (e.g., in families, social groups, worksites) also hold potential. There is also evidence that living in an environment more conducive and supportive of physical activity, such as a more walkable community with interconnected streets and sidewalks, is associated with higher levels of physical activity. However, there has been little research examining interventions that target both individuals and their environments. Despite the paucity of research in this area, promising examples include a multilevel ecological approach to promoting walking in communities and a socio-ecological approach to promoting physical activity and limiting sedentary behavior in adolescents.

This FOA seeks studies that develop multi-level interventions to increase physical activity levels based on well-established theory and existing data. Interventions to be developed should have an expanded focus beyond the individual level, or beyond the environmental level, to include two or more levels, such as individuals, families, social groups, institutional/organizational environments, worksite, healthcare systems, or community environments. Investigators are encouraged to incorporate both personal and environmental interventions that take into account motivational, cognitive and emotional components along with environments that facilitate and sustain change. Investigators may propose other levels, but whatever levels are selected should be well-justified.

Interventions developed for more real-world settings that have the potential to be scalable, packaged for broad use, or informative for policy are encouraged. Packaging for broad use applies to interventions that have developed and tested: toolkits that provide implementation guidance, procedures and strategies, including recruitment tools, intervention design, recruitment of partners; analytical tools; appropriate measures of physical activity for the intervention and diverse population groups and settings; and supporting information so that others can replicate the study and potentially implement the program.

Due to the phased nature of this R21/R33 award, applications should propose to conduct formative assessments and pilot studies in the R21 phase with possible transition to expanded research support in the R33 phase. Such planning activities and feasibility studies can include studies utilizing systems science to develop new intervention models based on analyzing key upstream influences, fractional factorial designs that identify promising intervention components, studies testing adaptive interventions that change during the course of the study, or other innovative and state-of-the art approaches to developmental work. Novel approaches based on clinical experience that are well-justified will also be considered.

Studies in any age group and special population, including populations at high risk for sedentary behavior, are appropriate to this announcement. Sustainability for the purpose of this announcement is defined as one to two years post-intervention. For example, an intervention targeting a population at risk for developing osteoporosis may include bone strengthening exercises, or an intervention targeting children at risk for obesity or diabetes may include increased physical education time during school hours. Populations of interest include, but are not limited to:

- Healthy but sedentary or inactive individuals

- Persons or groups at high risk for a particular disease or condition that can be improved by physical activity

- Persons with an existing disease or condition (e.g., cardiovascular disease, cancer, clinical depression, or diabetes) whose outcomes could be improved by physical activity

- Children and adults of diverse socioeconomic, ethnic, and racial groups with low activity levels

- Persons with physical, developmental, or intellectual disabilities who may need special approaches for activity promotion

- Inactive or sedentary elderly individuals or groups

- Minority and underserved populations at higher risk for conditions associated with inactivity

- Other groups, if justified by the investigator

Comparison of male and female populations or subjects on the desired outcome is highly desired. Of particular interest are research activities which increase the understanding of sex and gender differences and factors in health and disease, to support implementation of the NIH Strategic Plan for Women's Health Research, available at http://orwh.od.nih.gov/research/strategicplan/index.asp.

Settings for the interventions can include healthcare settings, worksites, households, schools, green space, parks and recreation centers, other community organizations and settings, or entire communities. Because this solicitation seeks multi-level interventions that have the potential to be scalable and sustainable, the use of multiple settings for intervention implementation or support may be considered. Illustrative examples of studies testing multi-level interventions with two or more levels can be found in existing systematic reviews.

To date, the available body of research includes numerous studies with methodological issues and systematic reviews from the Cochrane Collaboration and the Community Preventive Services Task Force have resulted in conflicting findings. Investigators should propose the strongest study design that can evaluate the effects of the intervention program with high internal validity, taking into account external validity and generalizability. Investigators should pay close attention to the quality of measurement of physical activity, ensuring that the measures are reliable and sensitive to change at the population level. In general, this would be a randomized controlled trial (RCT) design. Most of studies proposed in response to this announcement will probably need randomization at the group level (Group Randomized Trial, or GRT) to match the level of intervention and to minimize or prevent contamination of the comparison group. In some cases, a randomized design may not be possible or feasible, or would raise ethical concerns that are difficult to address. In such instances, investigators could propose and justify alternative, high-quality study designs. Such designs include, but are not limited to, quasi-experimental designs such as multiple baseline or time series, regression discontinuity, pre-to-post intervention with external comparison, natural experiments, or others.

Given the strong evidence that physical activity is associated with many health benefits, the primary outcome being sought is a measure of physical activity and/or change in physical activity over the duration of the 1-2 year intervention period in the direction of achieving the health-enhancing physical activity goals for the targeted population or patient subgroup, as identified in the 2008 Physical Activity Guidelines for Americans. Therefore, the intervention and any comparison/control group should use appropriate and well-justified physical activity measures to enable proper comparisons that are also feasible in real world settings. Measurement of intervention processes and impacts also are encouraged to enable assessment of intervention fidelity and whether hypothesized mediators were affected. Measurement of secondary outcomes such as social outcomes and possible co-benefits of physical activity participation (e.g., effects on behavioral, cognitive, or psychosocial outcomes; effects on substance abuse, tobacco use, or cardiovascular disease risk factors) or adverse outcomes (e.g., injuries) may also be included. Given the relatively large cost in mounting community interventions, an assessment on resources spent on intervention development and maintenance is desired.

It is anticipated that each award will support multidisciplinary project teams composed of scientists with expertise to enable all the specific aims to be addressed. A range of disciplines is likely to be needed; for example, teams may include public health, clinical, behavioral, and social scientists, statisticians, exercise physiologists, and others.

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

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)

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

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) 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 not 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 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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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.

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

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. 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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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 FOA.

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

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed. Application budgets must include funds for two investigators from each grant to attend one meeting of grantees annually, to be held in the Washington, DC area.

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

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

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

Specific Aims: Applicants must provide a single page of Specific Aims to include both the R21 and R33 phases.

Research Strategy: In preparing the R21/R33 application, investigators should consider that the application will be assigned a single overall impact score. Thus, clarity and completeness of the application with regard to specific goals and the feasibility of each phase and the Milestones are critical. The Research Strategy should include:

• Separate sections that describe both the R21 and R33 phases, as appropriate. It is not necessary to repeat information or details that are described in the R21 section.
• Transition Milestones for the R21 Phase: Transition Milestones should be placed at the end of the R21 Research Strategy section and are included in the page limit.
• The Transition Milestone section must propose milestones for completion of the R21 part of the project, a discussion of the suitability of the proposed milestones for assessing success in the R21 phase, and a discussion of the implications of successful completion of these milestones for the proposed R33 study. Transition Milestones should be well-defined, specific, quantifiable and scientifically justified; they should not be simply a restatement of the R21 specific aims. Milestones may be provided for the R33 phase at the discretion of the applicant.
• Transition Milestones should be sufficiently rigorous scientifically to be valid for assessing progress in the R21 phase
• Any available preliminary data that will support or justify the proposed hypothesis, rationale or development plan. However, preliminary data are not required for an R21/R33 application.

Additional Considerations:

Investigators should justify the population group of interest and the suitability and tailoring of the intervention, physical activity goals, and measures for the target population.

The statistical analysis and power calculations should reflect the design. That is, if group randomization is used (GRT), the hierarchical nature of the data needs to be addressed, and the number of groups, not just individuals, needs to be considered. If individual randomization is used, but participants will interact post-randomization either with each other in small groups or with a common change agent (Individually Randomized Group Treatment design, or IRGT), the hierarchical nature of the data needs to be addressed, and the number of groups or change agents, not just individuals, needs to be considered.

Letters of Support: Applications should include letters of support for critical reagents, resources, or collaborations required to support the research proposed.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

This initiative is not subject to intergovernmental review.

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.

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 Applying Electronically.

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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow our Post Submission Application Materials policy.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The R21/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R21/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the R21 and R33 phases.

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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

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 children, 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?

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.

Study Design

The committee should evaluate whether or not the study design can evaluate the effects of the intervention program with high internal validity, taking into account external validity and generalizability. In general, this would be a randomized controlled trial (RCT) design. If a randomized design is not possible or feasible, or would raise ethical concerns that are difficult to address, reviewers should evaluate whether alternative, high-quality study designs are proposed.)

The committee should also evaluate whether the statistical analysis and power calculations reflect the design appropriately.

Transition Milestones

Given the critical nature of the milestones for the potential R21 to R33 transition, are the proposed Transition Milestones well-defined with quantifiable measures that are appropriate for assessing the success of the R21 phase of the application? Do the Transition Milestones have specific quantifiable criteria that will enable clear decisions about their attainment? Is it clear how the R33 phase of the study will develop and expand once the R21 Transition Milestones are achieved? Given the potential benefits of the proposed research, do the Transition Milestones support the transition and will the overall project advance the intervention, method, or strategy?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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 Children

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 children 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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

Not Applicable

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.

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) Genome Wide Association Studies (GWAS).

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.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR, 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:

• 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 submitted in response to this FOA. 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.

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.

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

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 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.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, 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.

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.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-945-7573
Email: [email protected]

Rachel Ballard, MD, MPH
Office of Disease Prevention (ODP)
Telephone: 301-827-5559
Email: [email protected]

Frank Perna, Ed.D., Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6782
Email: [email protected]

Lanay M. Mudd, Ph.D., FACSM
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-9346
Email: [email protected]

Lyndon Joseph, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email: [email protected]

Beverly A. Ruffin, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-0281
Email: [email protected]

Will Aklin, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-3207
Email: [email protected]

Amy Mistretta, M.P.H
Office of Research on Women's Health (ORWH)
Telephone: 301-402-1770
Email: [email protected]

Weijia Ni, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-594-3292
Email: [email protected]

Carol Perry
National Cancer Institute (NCI)
Telephone: 240-276-6282
Email: [email protected]

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH) (Previously NCCAM)
Telephone: 301-594-3788
Email: [email protected]

Mahasin McCall
National Institute on Aging (NIA)
Telephone: 310-402-7736
Email: [email protected]

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Diana Haikalis
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1373
Email: [email protected]

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 Parts 74 and 92.