Developing Interventions for Health-Enhancing Physical Activity (R21/R33 - Clinical Trial Optional)

Developing Interventions for Health-Enhancing Physical Activity (R21/R33 - Clinical Trial Optional) is sponsored by National Institutes of Health (NIH). This opportunity supports mission-aligned projects and measurable outcomes.

Expired PAR-18-307: Developing Interventions for Health-Enhancing Physical Activity (R21/R33 - Clinical Trial Optional) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations Division of Program Coordination, Planning and Strategic Initiatives, Office of Disease Prevention ( ODP ) National Cancer Institute ( NCI ) National Institute on Aging ( NIA ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Institute on Drug Abuse ( NIDA ) National Center for Complementary and Integrative Health ( NCCIH ) Funding Opportunity Title Developing Interventions for Health-Enhancing Physical Activity (R21/R33 - Clinical Trial Optional) R21 / R33 Phased Innovation Award April 9, 2021 - Notice of Information Reissuance of PAR-18-307.

See Notice NOT-OD-21-085 . November 23, 2020 - Notice Extending Expiration Date and Adding Receipt Date for PAR-18-307. See Notice NOT-OD-21-031 .

May 19, 2020 - Notice of Special Interest (NOSI): Development and Preliminary Testing of Health-related Behavioral Interventions. See Notice NOT-OD-20-106 . April 9, 2020 - Notice of An Additional Cycle of Receipt Dates Added to PAR-18-307.

See Notice NOT-OD-20-093 . March 10, 2020 - Reminder: FORMS-F Grant Application Forms & Instructions Must be Used for Due Dates On or After May 25, 2020- New Grant Application Instructions Now Available. See Notice NOT-OD-20-077 .

Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128 .

November 26, 2018 - NIH & AHRQ Announce Upcoming Updates to Application Instructions and Review Criteria for Research Grant Applications. See Notice NOT-OD-18-228 . August 23, 2018 - Notice of Webinar for PAR-18-30 and PAR-18-32.

See Notice NOT-OD-18-220 . July 10, 2018 - Notice Announcing FAQs Page for PAR-18-307. See Notice NOT-OD-18-208 .

May 23, 2018 - Notice of Change to Correctly Identify the Companion Funding Opportunity for PAR-18-307. See Notice NOT-OD-18-184 . February 21, 2018 - Notice of Change to Instructions for Application Submission for PAR-18-307.

See Notice NOT-OD-18-142 . Reminder: FORMS-E Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2018. Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PAR-18-324 , R01 Research Project Grant Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) 93. 213; 93. 273; 93.

279; 93. 393; 93.

866 Funding Opportunity Purpose The purpose of this Funding Opportunity Announcement (FOA) is to fund highly innovative and promising research aimed at developing multi-level physical activity intervention programs acting on at least two levels of the socioecological model and designed to increase health-enhancing physical activity: 1) in persons or groups that can benefit from such activity; and 2) that could be made scalable and sustainable for broad use across the nation.

This FOA provides support for up to two years (R21 phase) for research planning activities and feasibility studies, followed by a possible transition to expanded research support (R33 phase) for optimizing the intervention and conducting larger-scale feasibility studies. Transition to the R33 depends on the completion of applicant-defined milestones, as well as program priorities and the availability of funds.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) New Date New applications: February 16, 2018; October 16, 2018; June 16, 2019; February 16, 2020; June 16, 2020, October 16, 2020, February 16, 2021, by 5:00 PM local time of New Date Resubmission applications: March 16, 2018; November 16, 2018; July 16, 2019; March 16, 2020; July 16, 2020 , November 16, 2020, March 16, 2021, by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement are due on Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s) New Date May 7, 2018; January 7, 2019; September 7, 2019; May 7, 2020; September 7, 2020, January 7, 2021, May 7, 2021, by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. New Date October 2018; May 2019; January 2020; October 2020; May New Date May 8, 2021 per issuance of NOT-OD-21-031 .

(Original Expiration Date: January 8, 2021) It is critical that applicants follow the Research (R) Instructions (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 I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Full Text of Announcement Section I. Funding Opportunity Description Current evidence indicates that interventions provided simultaneously at several levels across the Socio-Ecological Model are most likely to be successful in achieving increases in physical activity.

The socioecological model of behavior change provides a framework for understanding the interactive effects of factors that determine behaviors, including physical activity. There are five nested levels of the socioecological model: individual, interpersonal, organizational, community, and policy.

The individual level encompasses characteristics of an individual that influence behavior change; the interpersonal level includes formal and informal social networks; the organizational level includes organizations and social institutions; the community level refers to relationships among organizations and the built environment; and the policy level includes local, state, and national laws and policies that can impact individual behavior.

Therefore, this Funding Opportunity Announcement (FOA) encourages innovative research to improve our understanding of how to increase and maintain health-enhancing physical activity using multi-level interventions. Applicants should use the Socio-Ecological Model as a framework and should test multi-level interventions targeting at least two levels of the model.

Interventions to be tested should seek to increase participants' progression toward achieving the physical activity recommendation appropriate to the participants' health, abilities, and conditions.

This FOA also seeks studies that address a wide range of population groups across the lifespan (e.g., racial and ethnic minorities, children, older adults, persons with medical conditions or addictive disorders, and persons with disabilities).

Investigators are encouraged to build on prior research to refine evidence-based physical activity interventions and to make use of innovative partnerships within and across sectors as needed to study the implementation and outcomes of the proposed intervention. This FOA is meant to support developmental work in preparation for a full-scale efficacy study.

The R21 phase will support formative assessments and preliminary feasibility studies of the multi-level intervention or intervention components. If the R21 phase milestones are met, the R33 phase will support expanded feasibility work and optimization of the multi-level intervention in preparation for a fully-powered efficacy study.

For studies that are ready to implement, test, and evaluate scalable multi-level interventions, please see the companion Research Project Grant (R01) PAR-18-324. Physical activity is an important health behavior that is associated with numerous health conditions and outcomes. The Physical Activity Guidelines for Americans show that moderate-vigorous physical activity in adults is associated with many health benefits.

Despite the well-recognized benefits of physical activity and the myriad of health conditions that physical activity affects, 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, in five U.S. adults meeting the overall 2008 Physical Activity Guidelines for A key conclusion from a 2012 trans-NIH workshop on research priorities for physical activity and disease prevention and other subsequent reports is the need for research that moves beyond individual and single-level interventions to incorporate action at a higher level, such as environments, organizations and communities.

Since that time, the Surgeon General released a report " Step it Up: The Surgeon General's Call to Action to Promote Walking and Walkable Communities ," which included a call for evaluating community intervention to promote walking and walkability.

In addition, the Center for Disease Control's Community Preventive Services Task Force has also issued a number of insufficient evidence statements and positive recommendations that highlight future research needs for physical activity programs that target schools, families, workplaces, and built environments.

This FOA seeks applications to develop multi-level interventions that are designed to increase physical activity or reduce sedentary behavior among specific populations, and are based well-established theory and existing data. Given the strong evidence that physical activity and limited sedentary time are associated with many health benefits, the proposed intervention must include physical activity change as a primary outcome.

Applicants are encouraged to use the Socio-Ecological Model as a framework for conceptualizing ways to develop a multilevel intervention (i.e. incorporating intervention targets at the intrapersonal, interpersonal, organizational, community, and/or public policy levels).

For example, an intervention might include pedometer-based challenges at the interpersonal level, as well as the initiation/strengthening of joint-use agreements for community members to use school recreation facilities at the public policy level. A different intervention might focus on methods for enhancing motivation at the intrapersonal level and creating online social support groups for physical activity at the interpersonal level.

Policy or built environmental intervention across worksites at an organizational level may be paired with individually targeted intervention components to promote physical activity. There are many ways for an intervention to qualify as multilevel.

Settings for the interventions can include but are not limited to healthcare settings, worksites, households, schools, green space, parks and recreation centers, other community organizations and settings, or Specific interventions incorporated into their application should be justified by the population group of interest and the suitability and tailoring of the intervention, physical activity goals, and measures for the target population.

Investigators should pay close attention to the quality of measurement of physical activity and/ or factors influencing physical activity at the individual and other levels, ensuring that the measures are reliable and sensitive to change.

Using intervention components with previously developed Investigators are encouraged to address how specific intervention(s) selected at each level will reinforce each other to potentiate a large effect for the overall intervention(s). To clarify how interventions are related, investigators are encouraged to develop a graphic representation of the overall logic model for the proposed study.

To facilitate more complete understanding of the logistics of the intervention(s), investigators are also encouraged to develop a graphic representation of the timeline for the intervention and associated measurements.

Investigators may consider collecting qualitative data (e.g., focus group discussions, semi-structured interviews) to better assess fit and capture adaptation within the context in which the intervention is being tested and implemented.

Investigators should also consider collecting data on intervention processes and outcomes as well as implementation processes Physical activity must be one of the outcome measures for an application to be appropriate for these FOAs.

While R21/R33 applications must address physical activity change, they are not required to have sample sizes sufficient to measure statistically significant changes in physical activity or related health outcomes.

In these developmental or pilot interventions, physical activity should be measured, but with the goal of assessing feasibility and acceptability of the physical activity measurement tool and its administration, such as timing, frequency of measurement, response rate or For all applications, 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 is also encouraged to enable assessment of intervention fidelity and whether hypothesized mediators were affected.

For R21/R33 applications, tests of the effects of the intervention on behavioral mediators and/or intermediate outcomes of physical activity change can be used to enable the identification of components of the intervention that appear most promising to investigate in an efficacy study, provided the study is appropriately powered to analyze these Studies in any age group and special population, including populations at high risk for sedentary behavior, are appropriate for this announcement.

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 (e.g. substance use disorder or nicotine dependence) that can be improved by physical activity Persons with an existing disease or condition (e.g., cardiovascular disease, obesity, cancer, or diabetes or Alzheimer's or related dementias) whose outcomes could be improved by physical activity Where the population of interest is those with obesity or overweight, the intervention should principally aim to improve physical activity and/or reduce sedentary behavior rather than weight loss as the Persons of diverse socioeconomic, ethnic, and racial groups with Persons with physical, developmental, or intellectual disabilities who may need special approaches for activity promotion Inactive or sedentary elderly individuals or groups Alzheimer's and related dementias 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 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.

Due to the phased nature of this R21/R33 award, applications should propose to conduct formative assessments and feasibility studies in the R21 phase with possible transition to expanded research support in the R33 phase in order to optimize the multi-level intervention and/or conduct larger-scale feasibility studies in preparation for a powered efficacy study.

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. Multiple research designs are appropriate for this FOA, and the choice will depend on the stage of development of the research, the research question, and whether randomization is possible.

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.

Interventions that are ready for efficacy testing should apply to the companion Research Project of research projects that may be appropriate for the R21 phase include but are not limited to the following: Qualitative or mixed-methods approaches to determine acceptability and refine intervention components Assessment of adherence to dose, frequency and/or duration of Feasibility study of a single-level intervention with measurement of contextual factors operating at another level of the socioecological model to inform the design of a multi-level intervention in the R33 phase Separate feasibility studies for each level or component of the proposed multi-level intervention Single site feasibility study for the combined multi-level of research projects that may be appropriate for the R33 phase include but are not limited to the following: Larger scale feasibility study of the combined multi-level Multi-site feasibility study of the multi-level intervention to assess fidelity of implementation Assessment of the effect of the multi-level intervention on hypothesized mediators of physical activity change Optimization of the multi-level intervention ODP: The Office of Disease Prevention is interested in co-funding applications for multi-level physical activity interventions that have strong implications for disease prevention, promise for wider uptake, and that showcase innovative and appropriate design, measurement, and analysis NCI: The National Cancer Institute is interested in applications of multi-level physical activity interventions that have implications for outcomes across the cancer continuum and that have the potential for adoption, implementation, and sustainability in real-world research goal of NIA is to develop effective interventions to maintain health, well-being, and function and prevent or reduce the burden of age-related diseases, disorders, and disabilities.

Sub-categories include developing efficacious and cost-effective strategies for promoting and ensuring adherence to healthy and safe behaviors among older adults and developing interventions for treating, preventing, or delaying the onset of age-related NIAAA: The National Institute on Alcohol Abuse and Alcoholism is particularly interested in research activities which increase the understanding of the role physical activity plays in alcohol use behaviors.

More specifically the possible co-benefits of physical activity on alcohol use NIDA: NIDA's strategic priorities are devoted to research that advance science on the causes and consequences of drug use and addiction, and to apply that knowledge to improve more efficacious and effective prevention and treatment interventions that can ultimately reduce the negative is available at https://www. drugabuse.

gov/about-nida/2016-2020-nida-strategic-plan NCCIH: The National Center for Complementary and Integrative Health has a strategic research goal to study complementary health approaches to promote health and wellness across the lifespan in diverse populations.

For this FOA, NCCIH is particularly interested in applications that propose to incorporate a mind-body intervention as part of the multi-level intervention for promoting physical activity. NCCIH will not support research proposing efficacy or effectiveness clinical trials with this mechanism. Investigators are strongly encouraged to discuss their research plans with NCCIH program staff prior to submitting their application.

VIII. Other Information for award authorities and regulations. Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Optional: Accepting applications that either propose or do not propose clinical trial(s) help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

The R21 phase may not exceed $275,000 in direct costs for the 2-year project period, with no more than $200,000 in direct costs in any single year of the R21 phase. The R33 phase may not exceed $750,000 in direct costs for the 3-year project period, with no more than $250,000 in direct costs in any single year of the R33 phase. The scope of the proposed project should determine the project period.

The maximum period of the combined R21 and R33 phases is 5 years, with up to 2 years for the R21 phase and up to 3 years for the R33 phase. Applications with a project period less than 5 years are encouraged 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: o Hispanic-serving Institutions o Historically Black Colleges and Universities (HBCUs) o Tribally Controlled Colleges and Universities (TCCUs) o Alaska Native and Native Hawaiian Serving Institutions o Asian American Native American Pacific Islander Serving Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally 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 Non-domestic (non-U.S.) Entities (Foreign Institutions) are Non-domestic (non-U.S.) components of U.S. Organizations are not eligible Foreign components, as defined in the NIH Grants Policy Statement , are not allowed.

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 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 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. 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.

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 must have an active DUNS number and SAM registration in order to complete the 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.

Eligible Individuals (Program Director/Principal 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 This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3.

Additional Information on Eligibility 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 A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission 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 ). Additional Information on Eligibility Individuals involved in NIH-funded clinical trials must meet the requirements for documented ICH-Good Clinical Practice (GCP) training.

Documented means GCP training that provides a certification/documentation of completion indicating that the training requirement has been successfully Appropriate personnel are those individuals responsible for the design or conduct of the study, including all personnel of participating consortia and performance sites participating in the clinical trial.

The description of GCP training for new key personnel or GCP refresher training for other personnel should be part of the progress report submitted as a prerequisite to award. GCP refresher training should occur every 3 years for Section IV. Application and Submission Information Buttons to access the online ASSIST system or to download application forms 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 It is critical that applicants follow the Research (R) Instructions (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 For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant All page limitations described in the SF424 Application Page Limits must be followed.

Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide 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, to be held in the All instructions in the SF424 (R&R) Application Guide PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Aims : Applicants must provide a single attachment of Specific Aims to include both the R21 and R33 phases.

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 Separate sections that describe both the R21 and R33 phases, as appropriate.

Information or details that are described in the R21 section should not be repeated in the R33 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 may be included. However, preliminary data are not required for an R21/R33 Investigators should describe the strongest study design that 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) or a hybrid trial design. Most studies proposed for this announcement may require 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 GRTs, groups of participants are randomized to study conditions and interventions are delivered to members of those groups, often defined by their workplace, school, primary care provider, or other organization entity. Interactions occur among participants in the same group or cluster both pre- and post-randomization.

The statistical analysis and power calculations should reflect the design and the implications of the study design choice on the methods required for data analysis and sample size estimation. Standard methods are appropriate for RCTs, but adaptations are required for GRTs to reflect the positive intraclass correlation expected in data obtained from participants in the same groups or clusters.

The methods proposed for data analysis and the methods used for sample size calculation should reflect both the extra variation expected in the data and the degrees of freedom available to estimate that extra variation. For more guidance, please visit this resource developed GRTs are often used for pragmatic trials.

R21/R33 applications do not need to be powered to assess differences in physical activity since the goal of this FOA is on developing the multi-level intervention, and not on testing efficacy. If proposing a GRT, applications should be testing the feasibility of 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 interrupted time series, regression discontinuity, pre-to-post intervention with external comparison, natural Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Do not use the Appendix to circumvent page limits.

Follow all instructions for the Appendix as described in the SF424 (R&R) PHS Human Subjects and Clinical Trials Information When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions: If you answered "Yes" to the question "Are Human Subjects Involved?"

on the R&R Other Project Information form, you must include at least one human subjects study record