Addressing Social Determinants of Health to Eliminate Oral Health Disparities

Addressing Social Determinants of Health to Eliminate Oral Health Disparities is sponsored by National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH). This initiative seeks to identify and address the social determinants of health that affect oral health and also contribute to oral health disparities in vulnerable and underserved groups.

Expired RFA-DE-22-002: Addressing Social Determinants of Health to Eliminate Oral Health Disparities (UG3/UH3 Clinical Trials 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 ) Components of Participating Organizations National Institute of Dental and Craniofacial Research ( NIDCR ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Division of Program Coordination, Planning and Strategic Initiatives, Office of Disease Prevention ( ODP ) Office of Behavioral and Social Sciences Research ( OBSSR ) Office of Research on Women's Health ( ORWH ) Funding Opportunity Title Addressing Social Determinants of Health to Eliminate Oral Health Disparities (UG3/UH3 Clinical Trials Optional) UG3 / UH3 Exploratory/Developmental Phased Award Cooperative Agreement July 08, 2021 - Notice of Corrected Application Forms and Extended Receipt date for RFA-DE-22-002 Addressing Social Determinants of Health to Eliminate Oral Health Disparities (UG3/UH3 Clinical Trials Optional).

See Notice NOT-DE-21-008 . Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility .

Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this Funding Opportunity Announcement (FOA) is to support research on how to effectively identify and optimally address upstream social determinants of health that can often present as a barrier to optimal oral health, impede the effectiveness of interventions, and contribute to oral health disparities in vulnerable and underserved groups.

To achieve this goal, this FOA will encourage multi-disciplinary collaborations, mechanistic research, multi-level research, and/or the use of systems science research approaches.

Applications in response to this FOA must propose research that involves improving oral health outcomes through addressing or better understanding one or more upstream social determinants of health that operate beyond the individual-level of influence (as indicated in the National Institute on Minority Health and Health Disparities Research or Social-Ecological Model frameworks).

Study designs appropriate for this FOA would be clinical trials, observational cohort studies, or studies conducting multi-level systems science analyses. Awards made under this FOA will initially support a planning phase (UG3) for up to one year, with possible transition to an implementation phase of up to five years (UH3) for a total of up to six years of funding.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) Renewal / Resubmission / Revision (as allowed) All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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. Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide ,except where instructed to do otherwise (in this FOA or in a Notice from 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 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 Part 2.

Full Text of Announcement Section I.

Funding Opportunity Description Despite remarkable improvements in the oral health status of the general population in the United States over time, health disparities continue to persist in certain groups, such as racial/ethnic minorities, individuals of lower socioeconomic status, rural and urban dwellers, sexual and gender minorities, and individuals at the intersection of these and other vulnerable and underserved populations who experience a higher prevalence of most oral diseases across the lifespan than their counterparts.

Interventions that have attempted to improve oral health outcomes and reduce oral health disparities by focusing solely on modifying individual health behaviors, have proven to be largely unsuccessful.

The National Institute on Minority Health and Health Disparities (NIMHD) has developed a research framework to model factors or determinants that can occur at multiple levels beyond the individual, to influence health outcomes in populations. Similarly, the Social-Ecological Model displays levels of influences beyond the individual-level (e.g. relationship/interpersonal, community, societal) where determinants can operate.

The factors or determinants occurring at levels beyond that of the individual, are often referred to as "upstream factors" or "social determinants of health." The term social determinants of health (SDOH) has been defined by the Centers for Disease Control and Prevention as, "the conditions in the places where people live, learn, work, and play that affect a wide range of health and quality-of-life risks and outcomes."

HealthyPeople has organized SDOH into the following domains: 1) economic stability, 2) education access and quality, 3) healthcare access and quality, 4) neighborhood and built environment, and 5) social and community context.

Examples of these determinants include: socioeconomic conditions (e.g. employment and poverty status), access to healthy foods, housing quality, transportation options, access to healthcare, neighborhood characteristics (e.g. public safety and neighborhood infrastructure), and societal norms and attitudes (e.g. discrimination, racism, and policies).

The important role that SDOH can play in influencing health outcomes, particularly in vulnerable and underserved populations, has received much attention in recent years.

A report by the National Academies of Sciences, Engineering, and Medicine provided recommendations to not only better incorporate SDOH into clinical healthcare practice, but to also advance research on better understanding SDOH and how to optimally intervene on them at the population-level. As it relates to oral health research, the concept of multi-level research, which recognizes influences beyond the individual level is not new.

However, there has been limited research on understanding the specific mechanisms and pathways through which SODH influence oral health outcomes, the complex interplay between different SDOH, and how comprehensive oral health interventions can incorporate addressing SDOH to improve oral health outcomes and reduce disparities.

Given the complexities around understanding the specific pathways through which SDOH influence health, emerging research methodologies, such as those utilizing data science or system science approaches, have the potential to help elucidate complex interrelationships between SDOH and oral health, and inform interventions.

Although no simulation models can replace real world settings or scenarios, many are becoming beneficial for decision making, such as national or local planning, and can have a profound impact on health policies relevant to minority health and health disparities.

Data science methodologies and the use of simulation modeling and systems science (SMSS) analyses may help to guide oral health disparities research in identifying causal processes and which SDOH will be most amenable to change, policy, and population-level interventions, and in suggesting where leverage may be best applied to improve oral health.

To advance knowledge on the understanding of SDOH impact on oral health and how to optimally intervene on SDOH as part of comprehensive oral health promotion, this FOA will encourage multi-disciplinary collaborations, mechanistic research, multi-level clinical research, and/or the use of data science or SMSS research approaches.

Applications submitted to this FOA should have a central focus on addressing knowledge gaps related to SDOH and their role in influencing oral health outcomes. Because SDOH conditions and factors often operate in a negative manner in underserved communities, it is expected that research proposed in applications will have an overarching focus on reducing oral health disparities and inequities.

Further, given that SDOH impact various sectors, collaborations between researchers from different scientific domains and research expertise are strongly encouraged.

This may include, but would not be limited to, collaborations among those with research expertise in oral health, health disparities, public health, community-based participatory research, data or systems sciences, health economics, and non-health fields/sectors related to SDOH.

All proposed research must incorporate or evaluate one or more SDOH that typically operate beyond the individual-level as depicted in in the National Institute on Minority Health and Health Disparities Research Framework: https://www. nimhd. nih.

gov/about/overview/research-framework/nimhd-framework. html . Only research proposing to examine SDOH that operate beyond the individual level of influence, in the context of their impact on oral health outcomes or oral health status will be considered for this FOA.

Preference will be given to those projects proposing to examine SDOH which have not been previously explored in the context of oral health research. Examples of SDOH can be found in the HealthyPeople topic area on SDOH: https://www. healthypeople.

gov/2020/topics-objectives/topic/social-determinants-of-health . While SDOH are vast, it is expected that some of these determinants may be more amenable to oral health-related research questions than others. Therefore, applicants should carefully consider their research aims in determining which SDOH they propose to examine.

Proposed research must also focus on SDOH in the context of their impact on oral health outcomes (e.g. dental caries, periodontal disease, or oral cavity and oropharyngeal cancer) or oral health behaviors. Study designs appropriate for this FOA include clinical trials, observational cohort studies, or studies conducting SMSS analyses, depending on the specific research question.

Any proposed clinical research should demonstrate community engagement and partnerships that are essential for successful implementation of the research. Any SMSS projects should have compelling justification as to the adequacy of the data source(s) being used to address the research question(s). Data sources used for analyses must have adequate data on SDOH and clinical data to appropriately ascertain oral health outcomes.

Additionally, data quality of data sources must also be addressed, including: the presence of relevant variables, completeness, bias, validity, feasibility of obtaining data, data harmonization and interoperability, and methods that will be used to account for data quality weaknesses.

Specific areas of research interest may include, but are not limited to: Elucidating mechanisms and causal pathways between SDOH and oral health outcomes across multiple socioecological levels. Conducting multi-level interventions that incorporate addressing SDOH as part of the overall intervention to improve oral health outcomes.

Conducting interventions that address SDOH related to structural racism in settings where oral health care is delivered across multiple domains (e.g. provider-patient interactions, service delivery, access to care, etc.) to improve oral health outcomes and reduce disparities.

Leveraging strategies or conducting interventions that integrate oral health into primary care, non-health sectors, or community-based settings to address SDOH and improve oral health outcomes. Demonstrating the use of non-traditional healthcare practitioners (e.g. social workers or case managers) to promote oral health and address SDOH barriers.

Demonstrating the use of technology, including electronic health records, mobile health technologies, smart devices, or sensors to address SDOH barriers and improve oral health, without exacerbating health disparities.

Utilizing SMSS approaches to identify modifiable SDOH barriers across various sectors (e.g., food access, transportation, healthcare) and provide evidence-based simulation or prediction of the impact of effective interventions delivered in real-world settings to address these barriers to improve oral health outcomes.

Utilizing SMSS approaches involving big data or other appropriate data sources to elucidate etiology and complex interrelationships between different SDOH, and causal pathways by which they lead to oral health disparities and provide targets for population-based interventions.

The UG3 award will provide one year of support for planning activities, such as finalizing the protocol and preparing other documents or required data sources to implement the full study.

Additional planning activities are allowable, such as evaluating the number of participants at a site who would fulfill eligibility criteria, data collection or intervention delivery for the purpose of user acceptance testing, establishing acceptability and feasibility of the study procedures, and/or study intervention delivery/fidelity monitoring. The UG3 phase cannot be used to test for intervention efficacy.

Examples of activities supported during the UG3 phase include, but are not limited to, developing the following: A final clinical protocol, prepared using the standard NIDCR observational or interventional protocol template (see NIDCR Toolkit for Clinical Researchers ), that is ready for submission to the central IRB; Successful preparation of the manual of procedures, quality management plan, and data management plan, as applicable; Finalization of all documents necessary to implement the full study (e.g., case report forms, etc.); Consent form(s) and, if applicable, assent form(s); A final statistical analysis plan; A plan to administer study intervention, train interventionalists, and monitor intervention delivery, for clinical trials; A recruitment/enrollment and retention plan for the clinical study; and Obtainment, quality review, assurance of data harmonization and interoperability, and preparation of all data sources for proposed SMSS or data science-focused studies.

Implementation Phase (UH3) The UH3 award will provide up to five years of support to conduct the full study in accordance with activities planned in the UG3 phase, and is contingent upon successful completion of the UG3 milestones. NIDCR expects studies supported during the UH3 phase to be hypothesis driven and have defined milestones.

UH3 activities may include the following operational activities, expressed as UH3 milestones: Completion of data management system(s) Completion of regulatory approvals Registration of clinical trial in ClinicalTrials.

gov (for clinical trials) Enrollment of the first subject for studies with prospective enrollment Enrollment and randomization, if applicable, of 25%, 50%, 75% and 100% of the projected study population for studies with prospective enrollment Completion of data collection for studies with prospective enrollment Completion of primary outcome data analyses Reporting of results in ClinicalTrials.

gov (for clinical trials) All projects must be driven by well-defined milestones for the UG3 planning phase and annual milestones for the UH3 implementation phase. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity.

At the completion of the UG3 planning phase, the applicant will be required to submit a detailed transition application, which will undergo an administrative review to determine whether the study will be awarded funding for the UH3 implementation phase. Continued funding during the UH3 phase will be dependent upon meeting annual UH3 milestones, and it is expected that the study will be completed within the UH3 grant period.

Prospective applicants should note that initial funding of the UG3/UH3 cooperative agreement does not guarantee support of the UH3 implementation phase. Transition to the UH3 phase is dependent on having successfully met the UG3 planning milestones, NIDCR program priorities, and availability of funds.

The quality of the study-related documents and plans are given key consideration when the NIDCR considers the transition to the UH3 phase. Awardees are required to comply with the NIDCR Clinical Terms of Award for any planning phase activities that involve human subjects and all subsequent UH3 implementation phase studies.

It is recommended that applicants use the NIDCR Toolkit for Clinical Researchers for development of the clinical study documents. Implementation of the Clinical Terms of Award ensures that the conduct of the clinical study meets widely-accepted standards for ethical and rigorous research. The clinical study must meet all applicable NIH, and Office of Human Research Protections (OHRP) policy requirements.

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

Award Information Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.

2 for additional information about the substantial involvement for this FOA. Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Optional: Accepting applications that either propose or do not propose clinical trial(s). Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards NIDCR intends to commit $3 million in FY 2022 to fund 3-4 awards, contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Application budgets are limited to less than $300,000 in direct costs for the UG3 phase; Application budgets are not limited for the UH3 phase, but need to reflect the actual needs of the proposed project. The total project period may not exceed one year for the UG3 phase and five years for the UH3 phase.

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

Eligibility Information 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 (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 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 Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

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

Eligible Individuals (Program Director/Principal Investigator) 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. 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 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 ) Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this 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 instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide 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. 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: All page limitations described in the SF424 Application Guide and the Table of 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 application to this FOA. All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. Other Attachments. Applications responding to this FOA must include one additional attachment: The filename "Milestone Plan" should be used to name this attachment.

A milestone is defined as: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. The Milestone Plan must describe objective, measurable milestones with separate milestones for the UG3 and UH3 phases. The milestone plan must include clearly stated milestones that will be reached at the end of the UG3 phase and annual milestones that will be completed during the UH3 phase.

The milestone plan should address anticipated challenges to meeting milestones and propose potential mitigation or corrective action strategies.

Milestones to be completed during the UG3 phase, should include, as applicable: Finalization of the clinical protocol, prepared using the standard NIDCR observational or interventional protocol template (see NIDCR Toolkit for Clinical Researchers ), that is ready for submission to the central IRB; Successful preparation of the manual of procedures, quality management plan, and data management plan, as applicable; Finalization of all documents necessary to implement the full study (e.g., case report forms, etc.); Finalization of consent form(s) and, if applicable, assent form(s); Finalization of the statistical analysis plan; A plan to administer study intervention, train interventionalists, and monitor intervention delivery, for clinical trials; Finalization of the recruitment/enrollment and retention plan for studies with prospective enrollment; and Obtainment, quality review, assurance of data harmonization and interoperability, and preparation of all data sources for proposed SMSS or data science-focused studies.

Milestones to be completed during the UH3 phase should include, at a minimum: Completion of data management system(s) Completion of regulatory approvals Registration of clinical trial in ClinicalTrials.

gov (for clinical trials) Enrollment of the first subject for studies with prospective enrollment Enrollment and randomization, if applicable, of 25%, 50%, 75% and 100% of the projected study population for studies with prospective enrollment Completion of data collection for studies with prospective enrollment Completion of primary outcome data analyses Reporting of results in ClinicalTrials.

gov (for clinical trials) The filename "Data Management Plan" should be used to name this attachment. The purpose of the Data Management Plan is to establish validated systems and controls to ensure the integrity of the clinical research data being collected for the proposed study. Describe the methods and systems for data verification and data validation.

Describe the frequency of data verification, data query process, and any planned mitigation strategies in the event of data system noncompliance. Describe methods and systems to ensure data confidentiality and subject privacy. SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. For the initial UG3/UH3 application, a complete detailed budget is required for both the UG3 phase and the UH3 phase. The applicant should estimate the costs for the UH3 phase based on the scope of work described in the application for the UH3 phase.

Budget justifications must be included. All instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: For this announcement, note the following: Only research proposing to examine social determinants of health (SDOH) that operate beyond the individual level of influence (as depicted in the National Institute on Minority Health and Health Disparities, https://www. nimhd. nih.

gov/about/overview/research-framework/nimhd-framework. html ), in the context of their impact on oral health outcomes or oral health status will be considered for this FOA.

Applicants should address the following elements in the research strategy section of the Research Plan: Provide justification for the application’s focus on one or more specific SDOH that are hypothesized to act as a barrier to maintaining optimal oral health in the population/community of interest. Provide information adequate to determine the significance and timeliness of, as well as the need to perform the study.

This may include preliminary data, clinical and/or preclinical studies, or information in the literature.

Provide a compelling argument of how the proposed study will inform community, organizational, or public health practice paradigms or inform health policy as it relates to SDOH and improving oral health Describe the expertise of the study team and the team’s ability to plan and implement the planned study and perform appropriate analyses of data collected.

The Approach section should have a clear demarcation of the UG3 and UH3 portions of the application. Describe the study development activities planned for the UG3 phase. Define milestones for determining progress in the UG3 phase, and demonstrating readiness to progress to the UH3 phase.

For the UH3 phase, if the proposed study is a SMSS project : Provide compelling justification as to the adequacy of the data source(s) being used to address the research question(s).

Address the data quality of data sources, including: the presence of relevant variables, completeness, bias, validity, feasibility of obtaining data, data harmonization and interoperability, and methods that will be used to account for data quality weaknesses.

For the UH3 phase, if the proposed study design is not a clinical trial (this may include observational clinical studies or SMSS studies) : Address the feasibility of recruiting participants who are eligible for the proposed research (if applicable). Provide a concise snapshot of the planned clinical study. It is expected to: Clearly state the study objectives.

Describe and provide rationale for the study design, including study groups. Specify the primary and important secondary outcome measures that align with each objective and provide justification for selection of the study outcomes. Describe how the primary and important secondary outcome variables will be collected and the criteria for measuring the outcomes.

Describe the study population, including the sample size, pertinent demographic information, required health status or disease condition, and geographic location. Explain why the study population is an appropriate group to address the study objectives. Do not duplicate information described in Section 2 (Study Population Characteristics) of the Study Record: PHS Human Subjects and Clinical Trials Information form.

Provide a statistical analysis plan, including power calculations, data analysis approaches, and plans for handling missing data Discuss potential biases or challenges in the proposed study and how they will be minimized and/or addressed. For the UH3 phase, if the proposed study design is a clinical trial : Address the feasibility of recruiting participants who are eligible for the proposed research.

Provide an overview of the proposed study design that must justify the selected trial elements provided in the Protocol Synopsis, including: Rationale for the selected trial design/interventional model (e.g., single-group, parallel, cross-over, factorial) and allocation method. Rationale for selection of the intervention to be tested and a description of how and at what frequency the intervention will be administered.

For behavioral interventions, demonstration that an intervention engages the mechanism of action target(s) it intends to, and that target engagement can be measured. Justification for selection of the primary and secondary outcome measures and