Palliative Care in Home and Community Settings (R01 Clinical Trial Optional)

Palliative Care in Home and Community Settings (R01 Clinical Trial Optional) is sponsored by National Institutes of Health (NIH). This funding opportunity encourages research to identify needs and best practices for integrating palliative care into home and community settings.

Expired PAR-19-321: Palliative Care in Home and Community Settings (R01 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 National Institute of Nursing Research ( NINR ) Funding Opportunity Title Palliative Care in Home and Community Settings (R01 Clinical Trial Optional) R01 Research Project Grant NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022 October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available.

See Notice NOT-OD-22-018 . September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022.

August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170 April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109 May 19, 2020 - Notice of Special Interest (NOSI): Development and Preliminary Testing of Health-related Behavioral Interventions.

See Notice NOT-OD-20-106 . 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 .

Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PAR-19-320 , R21 Exploratory/Developmental Grant Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The purpose of this funding opportunity is to stimulate research aimed at determining needs and best practices for the integration of palliative care into home and community settings.

Home and community in this FOA refer to the place where an individual resides or lives. Home- and community-based palliative care programs ensure those with serious, advanced illness who do not require hospitalization but are not appropriate for hospice have access to high quality end-of-life and palliative care.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) The first standard due date for this FOA is October 5, 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 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) The first AIDS due date for this FOA is January 7, 2020. All applications are due, 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 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.

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 The purpose of this funding opportunity is to stimulate research aimed at determining needs and best practices for the integration of palliative care into home and community settings.

Home and community in this FOA refer to the place where an individual resides and lives. Approximately 90 million people in the U.S. are living with serious illness and would benefit from end-of-life and palliative care. Numerous studies have asserted that most individuals with serious illness prefer to stay in their home and community and most Americans wish to die at home.

However, while hospice services and hospital-based palliative care services have seen increased usage, there remains a significant gap in broader access to and receipt of end-of-life and palliative care for individuals with serious, advanced illness who do not require hospitalization and who are not eligible for hospice services. These individuals have varied serious advanced health conditions or diseases.

Individuals also have unique preferences, and values that require tailored approaches to meet their health and social needs.

The need for home- and community-based end-of-life and palliative care has increased with the growing recognition of palliative care as an integral part Home- and community-based end-of-life and palliative care offers a unique opportunity to conduct research that addresses integrating health needs with social services and support.

These can include issues such as assistance with caregiver needs, access to health care services and transportation, housing instability, financial resources and addressing social and environmental factors affecting end-of-life and palliative care. These issues occur simultaneously with the need for core palliative care services like advanced symptom management and communication of goals and preferences for care.

With palliative care increasingly moving into home and community settings, there is an urgent need to further develop the evidence to support these emerging practices and to ensure that these models provide high quality end-of-life and palliative care that is responsive to the needs of individuals, families, and communities.

Evidence is needed for appropriate screening and assessment tools to determine who would benefit from earlier referrals to home and community palliative and end-of-life care programs. Evidence is also needed to understand the needs of those receiving home- and community-based palliative care, including diverse populations, rural, remote and/or urban areas, and to demonstrate which interventions and approaches are most effective.

Further, there is a need for development and testing of models that support personalized care plans that address individual goals, preferences and family needs. There is also a need to develop and test technology that can improve quality of end-of-life and palliative care in the home and community. Understanding key elements of successful home- and community-based end-of-life and palliative care programs is critical.

At the same time individual- and family-centered outcomes benefit from integration with information on health care utilization and costs. To ensure quality palliative care, research is needed to examine the factors that affect successful adaption and implementation in diverse local and settings. To achieve quality end-of-life and palliative care for all where they choose to receive care, these gaps must be addressed.

Proposed studies should include a focus on individual- and/or family-centered outcomes. Family is broadly defined as the spouse, care partner, parent, son, daughter, extended family member, friend or volunteer. Studies may be focused on care across all stages of the lifespan and advanced diseases and conditions (e.g., cardiopulmonary, renal, hepatic, multiple chronic conditions, neurologic disorders, dementias, and cancers).

Applications should consider approaches that may be implemented in rural/remote areas, as well as urban areas, and that are sensitive to ethnicities and cultures. Studies may address identifying and providing high-quality, high-value end-of-life and palliative care in home and community settings.

The integration of social services and supports with health management (e.g., pain or advanced symptom management) aspects of palliative care and those that address family caregiver needs (e.g. social supports, respite care, etc.) are also of interest.

Studies should be focused on home or community settings, which may include (but are not limited to): ambulatory and extended care centers, outpatient clinics, medical homes, home care, assisted living facility, or nursing homes. Studies may include descriptive methods that provide information for intervention and model development and small, multisite clinical trials.

Small dissemination and implementation studies including cost-effectiveness evaluations to address scalability and replicability are encouraged. All applications should be designed to address the challenges of providing end-of-life and palliative care and conduct of research in home- and community-based settings. Applications should include evidence of support and/or participation of local or community resources or organizations.

Describe gaps, barriers and essential elements of comprehensive palliative care in home and community settings. Test and evaluate palliative care models and interventions that are theoretically-based and designed with the goal of translation and implementation in home and community settings.

Develop or adapt, test and evaluate screening or assessment tools, or predictive modeling protocols, to determine who would benefit from home and community palliative care programs. Identify the processes for implementation of such tools in home and community settings.

Describe the needs of family caregivers of those individuals with serious, advanced illness who do not require hospitalization and who are not eligible for hospice services and their preferences for palliative and Integrate local and community resources and ethnocultural preferences related to provision of palliative care in home and community settings.

This includes research that adapts individual- and family-centered outcome measures to home- and community-based palliative care. Develop, test and evaluate methods for personalized care plans that address goals and preferences, family needs, and local resources in providing quality palliative care.

Adapt or develop, test and evaluate assessments for family caregiver quality of life and well-being including symptoms such as fatigue, depression, anxiety, impaired cognition, pain, etc. for use in the home and community settings. Develop, test and evaluate interventions to address family caregiver Adapt or develop technology to improve the access to or quality of palliative care in the home and community.

Studies that incorporate technology with interpersonal care, that includes clinicians, health care navigators or other providers in the delivery of palliative care, are of interest.

In addition to a focus on individual- and family-centered outcomes in home and community settings, analysis of data regarding social integration of services, health services utilization and cost effectiveness may Adapt or develop, test and evaluate methods and measures to accurately assess and track palliative care delivery and outcomes in home and Translate effective home- and community-based palliative care programs across geographic and regional areas, with attention to the factors that require tailoring for broad dissemination and implementation.

Because of the complex, multi-factorial nature of this issue, multi-disciplinary teams are highly encouraged. Investigators are encouraged to consider using existing palliative care research networks, such as the Palliative Care Research Cooperative Group to carry out small, multi-site trials when appropriate.

To fully explore the topic of palliative and end-of-life care in home and community settings, a wide variety of research methodologies may be appropriate including qualitative, mixed methods, quasi-experimental, pragmatic techniques and innovative methods including visualization techniques.

Inclusion of community-, individual- and family-representatives in the design of the study and in the development of interventions is strongly recommended. Inclusion of under-studied populations including NIH-designated health disparity, socioeconomically disadvantaged, rural and/or remote, and sexual and gender minority populations with advanced, serious illness is encouraged. 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 these application types.

Only those application types listed here are allowed 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.

Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period. The maximum project period is 5 years.

Grants Policy Statement will apply to the applications submitted and awards made from 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 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 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) 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 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. 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 ). Section IV. Application and Submission Information 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 Research (R) Instructions (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 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 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: 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.

Only limited Appendix materials are allowed.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) 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 using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide must onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide 3. Unique Entity Identifier and System for Award Management (SAM) See Part 1. Section III.

1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Part I. Overview Information contains information about Key Dates and times.

Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies).

Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration. NIH and Grants. gov systems check the application against many of the application instructions upon submission.

Errors must be corrected and a changed/corrected application must be submitted to Grants. gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applications that miss the due date and time are subjected to the NIH Policy on Late Application are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission. Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide. 5.

Intergovernmental Review This initiative is not subject to intergovernmental 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 .

Requirements and Information Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted. Applicants must complete all required registrations before the application due date.

Section III. Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission Apply Application Guide .

If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII .

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package . Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide. See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Requests of $500,000 or more for direct costs in any year Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy .

Any instructions provided here are in addition to the instructions in the Section V.

Application Review Information Only the review criteria described below will be considered Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review addition, for applications involving clinical trials: A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs.

Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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

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

In addition, for applications involving Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms?

For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy?

For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training?

If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Does the investigator have sufficient expertise in methods and palliative care, through their experience or in partnership with a network such as the Palliative Care Research Cooperative Group, to conduct the proposed study? Does the research team have experience and expertise in provision of palliative care and conducting research in home- and community-based settings?

addition, for applications involving clinical trials With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics?

For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center? 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?

addition, for applications involving clinical trials Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice? Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?

Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented?

If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? design address challenges in providing palliative care and conducting research in home and community settings?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy addition, for applications involving clinical trials Does the application adequately address the Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested?

Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently?

Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available?

Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed?

Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity? Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)?

Does the application propose to use existing