Electronic Nicotine Delivery Systems (ENDS): Population, Clinical and Applied Prevention Research (R01 Clinical Trial Optional)

Electronic Nicotine Delivery Systems (ENDS): Population, Clinical and Applied Prevention Research (R01 Clinical Trial Optional) is sponsored by National Institutes of Health (NIH). This funding opportunity supports research on electronic nicotine delivery systems (ENDS) to examine population-based, clinical, and applied prevention of disease, including etiology and epidemiology of use, potential risks, benefits, and impacts on other tobacco use behavior am…

Expired PAR-18-847: Electronic Nicotine Delivery Systems (ENDS): Population, Clinical and Applied Prevention Research (R01 - Clinical Trial Optional) This notice has expired. Check the NIH Guide for active opportunities and notices. Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations Division of Program Coordination, Planning and Strategic Initiatives, Office of Disease Prevention ( ODP ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The NIH Office above may co-fund applications assigned to those Institutes/Centers.

National Cancer Institute ( NCI ) National Institute of Dental and Craniofacial Research ( NIDCR ) National Institute on Drug Abuse ( NIDA ) National Institute on Minority Health and Health Disparities ( NIMHD ) Funding Opportunity Title Electronic Nicotine Delivery Systems (ENDS): Population, Clinical and Applied Prevention Research (R01 - Clinical Trial Optional) R01 Research Project Grant April 23, 2021 - Notice of Intent to Reissue PAR-18-847 Electronic Nicotine Delivery Systems (ENDS): Population, Clinical and Applied Prevention Research (R01- Clinical Trial Optional) and PAR-18-848 (R21 - Clinical Trial Optional) as a Notice of Special Interest (NOSI).

See Notice NOT-OD-21-114 . 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 .

December 04, 2019 - Notice of Additional Receipt Dates for PAR-18-847. See Notice NOT-OD-20-035 . 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 . Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PAR-18-848 , R21 Exploratory/Developmental Grant See Section III. 3.

Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) 93. 121; 93.

279; 93. 307; 93. 399 Funding Opportunity Purpose The purpose of this funding opportunity announcement is to support studies on electronic nicotine delivery systems (ENDS) that examine population-based, clinical and applied prevention of disease, including etiology of use, epidemiology of use, potential risks, benefits and impacts on other tobacco use behavior among different populations.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) New Dates October 24, 2018; June 27, 2019; October 24, 2019; June 27, 2020, October 15, 2020; June 15, 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 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. AIDS Application Due Date(s) New Dates May 2019; January 2020; May 2020; January 2021, May 2021; January 2022 New Date June 16, 2021 per issuance of NOT-OD-20-035 .

(Original Expiration Date: June 28, 2020 ) 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 Electronic Nicotine Delivery Systems (ENDS) are battery powered inhalation devices designed to deliver to the user an aerosol typically containing nicotine. Since their introduction into the U.S. nearly a decade ago, the prevalence of ENDS use has increased rapidly. In 2013-2014, 5.

5% of the adult population were current users, representing over 13 million people. Although recent trends suggest decreasing past month use of ENDS by adolescents, the use of ENDS in this population exceeded that of combustible cigarettes in 2015, 2016 and 2017.

Emerging evidence also suggests that ENDS use and their relationship to other tobacco products may vary by population subgroup; however, limited attention has been given to examining subgroup differences and their etiology. ENDS are a complex class of devices. A broad nomenclature is used to describe them, including e-cigarette, e-hookah, and vape pen.

Their designs vary, from disposables that look like combustible cigarettes, to devices with rechargeable batteries and refillable tanks, and some have a box-shaped format that allow user control over aspects of the liquid aerosolization, such as the voltage supplied to the heating element. For the purposes of this FOA, the entire class of products is referred to as ENDS.

Despite the widespread use of ENDS in the US population, research has yet to establish a clear picture of their effects on public health. There is limited data available on the impact of various patterns of ENDS use and exposure to ENDS aerosol on biological, physiological and behavioral health outcomes.

For example, it has not been established what characteristics of ENDS, or of individual users, affect the choices made regarding the extent of ENDS use, either in place of or as dual use with combustible cigarettes. Also, little information is available on the role ENDS may have in prevention of disease. More specifically, little is known about the relative risk of using these devices compared to other tobacco products.

Many of these questions will be best addressed in clinical studies. These gaps in our understanding around ENDS support the need for a comprehensive investigation of the potential risks and benefits of ENDS use. Program Scope and Research Objectives This funding announcement encourages research to generate data to address gaps in our understanding related to population-based, clinical and applied prevention of disease related to ENDS.

The goal of these studies will be to better understand the impact of ENDS use on the prevention of disease or the risk of disease (including cancer, dental, oral, and/or craniofacial), patterns of use with other tobacco products and how that affects addiction to nicotine, alcohol and other drugs, as well as the effects of second and third hand exposure to the aerosol.

Each of the NIH Institutes participating in this Funding Opportunity Announcement list their priority areas of research, although there may be areas of overlap among the Institutes. Where appropriate, the standardized research e-cigarette ( https://www. drugabuse.

gov/funding/supplemental-information-nida-e-cig ) should be considered for use in addressing specific research questions, or as a comparator for commercially available ENDS. Observational, clinical and interventional human studies are appropriate. National Cancer Institute (NCI) The National Cancer Institute encourages the submission of applications to fill gaps in the science base regarding population and applied research on ENDS.

NCI is interested in studies that explore determinants of risk and protective factors related to the trajectories of ENDS use patterns. Studies are also needed to understand how ENDS use may influence intentions to quit and cessation of tobacco products. Research to determine programmatic and policy approaches to address ENDS use among adolescents, young adults, and other vulnerable populations is also encouraged.

Studies are encouraged that investigate potential contributions to cancer risk from ENDS use or through the interaction of ENDS use with other tobacco product use (dual/poly tobacco use), especially smoked tobacco product use.

Specific topics of interest to NCI include, but are not limited to: Studies of ENDS use among vulnerable populations (e.g., low SES, substance use, mental health, pregnancy, cancer patients and survivors) Studies to identify risk and protective factors for ENDS use, including dual/poly-tobacco product use among youth and young adults (such as, but not limited to, perceptions of risk/benefit, parent influences, peer influences, relationship to other substance use, proximity to tobacco outlets, density of tobacco outlets and other environmental factors) Studies of policies that impact ENDS use, such as smoke-free or ENDS-free laws and tobacco product price policies Studies investigating how ENDS use may influence intention to quit cigarette smoking and cessation of cigarettes and other tobacco products Studies investigating clinical and other health care providers' advice and practice pertaining to ENDS Studies to determine appropriate methods and measures for ENDS use (e.g., characterizing use behavior, dependence) National Institute of Dental and Craniofacial Research (NIDCR) NIDCR is interested in investigations that include but are not limited to: Feasibility and acceptability of ENDS prevention efforts in the dental setting Outcomes of ENDS prevention efforts currently conducted in the dental setting Epidemiology of ENDS and dental/oral/craniofacial diseases and conditions National Institute on Drug Abuse (NIDA) The NIDA is interested in supporting research to inform policy, improve practice, and advance addiction science.

Studies of interest to NIDA include how ENDS affects nicotine addiction, particularly in relation to conventional tobacco, in populations considered at risk for substance abuse. The impact of ENDS on other substances of abuse, especially in vulnerable populations, are encouraged. Investigations that explore the role of genetics or epigenetics on ENDS use and addiction are also of interest.

Potential applicants are advised to speak with a NIDA Scientific/Research contact to discuss the relevance and priority to NIDA of potential research topic(s).

NIDA is interested in studies that include but are not limited to: Harm reduction studies that involve switching from combustible cigarettes to ENDS Relationship between ENDS use and comorbidities (e.g., mental health, HIV/AIDS) Relationship between ENDS use and vulnerable populations (e.g., pregnancy, low SES, youth) Sex differences on reasons for use of ENDS, trajectories of use, and for switching between ENDS and conventional cigarettes ENDS use, including trajectories of use, with other tobacco products and other substances of abuse (e.g., marijuana, alcohol) Relationship between the pharmacology and physiological effects of ENDS liquids and use behaviors How is ENDS use affected by policy changes for tobacco (including ENDS) or other substances (e.g., marijuana) National Institute on Minority Health and Health Disparities (NIMHD) The National Institute on Minority Health and Health Disparities seeks to support population, clinical and applied research projects to understand mechanisms and health determinants that influence the use of Electronic Nicotine Delivery Systems (ENDS) and the potential risks and benefits for minority or health disparity populations.

Successful projects will examine use of ENDS and/or associated health risks through a socioecological framework considering determinants from more than one domain of influence (biological, behavioral, physical/built environment or healthcare system) and/or level of influence (individual, interpersonal, community, and societal) (See NIMHD Research Framework https://nimhd. nih. gov/about/overview/research-framework.

html ). The research must focus on one or more minority or health disparity population (African Americans/Blacks, Hispanics/Latinos, American Indians/Alaska Natives, Asians, Native Hawaiians and Other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minority populations) to be considered for funding by NIMHD.

Research may propose using available secondary data, health system data and/or collection of primary data.

NIMHD is interested in studies that include but are not limited to: Understanding how determinants from multiple domains of influence (biological, behavioral, physical/built environment or healthcare system) and/or levels of influence (individual, interpersonal, community, and societal) effect ENDS use and/or associated health risks of ENDS.

Understanding the role of culture, community, and social factors on the reasons for use of ENDS, trajectories of use, and for switching between ENDS and combustible cigarettes. Understanding the role of protective and resilience factors for the use of ENDS. Understanding how geographic and regional differences in combination with socioeconomic and behavioral risk factors influence use of ENDS.

Understanding the role of ENDS in promoting cessation from combustible tobacco use. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

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 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. 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) Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply Non-domestic (non-U.S.) components of U.S. Organizations are 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) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually.

The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants. gov registration.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed 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. 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. 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: Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. The following modifications also apply: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information When involving NIH-defined human subjects research, clinical research, and/or 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 Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide must be followed .

with the following additional instructions: All instructions in the SF424 (R&R) Application Guide must be followed. PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide must be followed. Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement , and procedures for foreign institutions described throughout 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 Grants. gov 4. Submission Dates and Times Part I.

Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration.

NIH and Grants. gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.

gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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

Intergovernmental Review (E. O. 12372) This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Policy Statement . 7.

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

Section III. Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically .

If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues . 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 (R&R) Application Guide.

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 policy. Section V.

Application Review Information Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019. Only the review criteria described below will be considered in the review process. As part of the NIH mission , all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following: 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 project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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 proposing clinical trials Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms?

For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?

If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition, for applications proposing 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?

In addition, for applications proposing 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 presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

In addition, for applications proposing clinical trials Does the application adequately address the following, if applicable: Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research?

Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently?

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

Is the eligible population