Basic research examining how Electronic Nicotine Delivery Systems (ENDS) aerosols affect normal and disease states relevant to human cells, tissues and organs

Basic research examining how Electronic Nicotine Delivery Systems (ENDS) aerosols affect normal and disease states relevant to human cells, tissues and organs is sponsored by National Institutes of Health (NIH). This funding opportunity supports basic research focused on understanding the cellular, tissue, and organ-level effects of Electronic Nicotine Delivery Systems (ENDS) aerosols in both normal and diseased states.

Expired PAR-17-475: Electronic Nicotine Delivery Systems (ENDS): Basic Mechanisms of Health Effects (R21 - Clinical Trial Not Allowed) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations Division of Program Coordination, Planning and Strategic Initiatives, Office of Disease Prevention ( ODP ) National Cancer Institute ( NCI ) National Institute of Dental and Craniofacial Research ( NIDCR ) National Institute on Drug Abuse ( NIDA ) National Institute of Environmental Health Sciences ( NIEHS ) Funding Opportunity Title Electronic Nicotine Delivery Systems (ENDS): Basic Mechanisms of Health Effects (R21 - Clinical Trial Not Allowed) R21 Exploratory/Developmental Research Grant June 29, 2018 - This PAR has been reissued as PAR-18-846 .

Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PAR-17-476 , R01 Research Project Grant Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) 93. 113; 93.

121; 93. 279; 93.

396 Funding Opportunity Purpose The purpose of this funding opportunity announcement is to support basic research examining how Electronic Nicotine Delivery Systems (ENDS) aerosols affect normal and disease states relevant to human cells, Open Date (Earliest Submission Date) Letter of Intent Due Date(s) November 27, 2017; June 27, 2018; October 24, 2018; June 27, 2019; October 24, 2019; June 27, 2020, 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) May 2018; January 2019; May 2019; January 2020; May 2020; New Date June 29, 2018 per issuance of PAR-18-846 .

(Original Expiration Date: June 28, 2020 ) 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 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 has increased rapidly. In 2013-2014, 5.

5% of the adult population were current users, representing over 13 million people. In addition, past month use of ENDS among adolescents exceeded combustible cigarettes in 2015, 2016, and 2017. 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 those with 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 are referred to as ENDS. There is limited information on the safety of the devices and the aerosols they generate, how changes in the devices or aerosols affect nicotine delivery, or how the modulation of these aspects affect biological systems and behavior.

ENDS aerosols have begun to be characterized for individual constituents, but further data is needed regarding how the constituents are generated and what risks may be associated with the extent of exposure to individual users. For example, while many of the flavorants used in the e-liquids are approved for use in foods, there is incomplete information on their effects when inhaled.

These gaps in our understanding around ENDS indicate the need for further investigation at the molecular, cellular, physiological and behavioral levels to increase our understanding of the potential risks and Scope and Research Objectives This funding announcement encourages research evaluating the biological mechanisms whereby ENDS aerosols affect the normal and disease states relevant to human cells, tissues or organs.

Studies of interest include understanding the characteristics of ENDS aerosols and how they are generated. Also of interest is how ENDS-specific constituents alter molecular, cellular and physiological pathways important in maintaining normal homeostatic functions or progression to disease states.

Studies should make use of human cells or specimens, and where appropriate, can utilize cell or animal models that are relevant to humans and well justified. Applications should focus on constituents or aerosols unique to ENDS products; studies examining ENDS components that have been well-studied in other tobacco products or other health contexts are not high priority unless there is a unique aspect to ENDS exposure.

Consideration should be given to the development of biomarkers that reflect exposure to ENDS aerosol and could provide information on the risks or benefits of exposure. Research areas of interest for participating NIH 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. The National Cancer Institute encourages submission of applications designed to fill gaps in the knowledge base regarding mechanisms of toxicity and carcinogenicity of ENDS.

Examples of specific topics of interest to NCI include but are not limited to: Effects of ENDS aerosols on carcinogenesis and tumor progression; Effects of ENDS exposure on the response or resistance to targeted, radiation, or chemo therapies; Consequences of ENDS aerosol exposure in relevant animal models Cellular and molecular mechanisms of carcinogenicity by exposure Identification and validation of specific molecular markers of ENDS exposure or toxicity.

Institute of Dental and Craniofacial Research (NIDCR) The NIDCR is interested in all applications that are encouraged to speak with a NIDCR program official to discuss the relevance of proposed research topic(s). Applications that propose to prove causal pathways between ENDS (specifically e-cigarettes) and dental, oral, and/or craniofacial diseases and conditions are of higher priority.

Those applications that demonstrate correlations are of lower priority. NIDCR supports research that examines the basic mechanisms of effects in pre-clinical investigations.

For additional information on the NIDCR mission and NIDCR is interested in investigations that include but are Determination of the synergistic biological effects of e-cigarette aerosol mixtures on cells, tissues and organs of the oral cavity using appropriate in vitro and in vivo model systems, Analysis of genotoxicity/DNA damage, cellular metabolism, mutagenicity, and/or transformation potential, effects on cell proliferation and cell death, of e-cigarette aerosol mixtures using appropriate in vitro and/or in vivo model systems with an emphasis on oral and periodontal High throughput analysis (e.g. genomic, epigenomic and proteomic analyses) to understand the biological and physiological effects of e-cigarette aerosols on cells, tissues and organs of the oral cavity, Examination and comparison of the effects on oral and/or periodontal epithelial cells in chronic users of e-cigarettes, smokers of combustible cigarettes and non-smokers, Analysis of effects of e-cigarettes on factors responsible for the maintenance of oral homeostasis such as cytokine production and downstream signaling pathways, immune cell function, and oral microbiome, and Assessment of effects of e-cigarettes on salivary gland function, saliva flow; and on dental/periodontal health using appropriate in vivo model Institute on Drug Abuse (NIDA) NIDA is interested in supporting pre-clinical and clinical research that examines the basic mechanisms of effects by ENDS as they relate to addiction.

Investigations that explore the interaction between genetics or epigenetics and ENDS are of interest. The Institute also encourages research on the effects of ENDS flavoring via in vitro or in vivo investigations. Further, NIDA is interested in investigations that explore neuronal mechanisms, such as function of neurons, astrocytes, microglia or brain circuitry, associated with the use of ENDS and exposure to the aerosol constituents.

How sex differences might impact the effects of ENDS are also of interest. Potential applicants are advised to speak with a NIDA program official 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: Behavioral or cognitive processes (e.g., learning, memory, emotion), and their neurobiological mechanisms, as variables contributing to ENDS initiation, escalation, maintenance, abstinence, or relapse; Characterization of transition points and stages in the development of an SUD to ENDS, including the use of biomarkers or other neurobiological signatures that predict transition to more compulsive patterns of intake; Effects of genetics/epigenetics on ENDS use and addiction; Assessments of transcriptomic-, proteomic-, or metabolomic profiles either in vitro or in vivo associated with ENDS exposure, including Institute on Environmental Health Sciences (NIEHS) NIEHS is most interested in supporting research that examines basic mechanisms of effects related to substances used in ENDS.

NIEHS seeks to support studies that examine potential relationships between ENDS flavorings and exposure to toxicants. The Institute is also interested in studies that examine the relationship between secondary and tertiary ENDS vapor exposures and genetic and physiological outcomes.

NIEHS invites applications that include but are not limited to: Identifying relationships between individual flavored/non-flavored constituents and specific measures of toxicity, Identifying the flavored /non-flavored constituents of second hand and tertiary e-cigarette vapors linked to known toxic effects, Evaluating health effects associated with toxic second hand/tertiary e-cigarette vapors, Evaluating the air quality in homes where e-cigarettes are used, Identifying or discover pediatric adverse health issues associated with toxic second hand/tertiary e-cigarette vapor exposures, Identifying cardio-pulmonary dysfunction(s) associated with toxic second hand/tertiary e-cigarette vapor exposures, Analyzing of epigenetic reprogramming as a consequence of toxic second hand/tertiary e-cigarette vapor exposures, and Analyzing of gene expression profile associated with toxic second hand/tertiary e-cigarette vapor exposures.

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 Only accepting applications that do not propose clinical 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.

Direct costs are limited to $275,000 over a two-year project period, with no more than $200,000 in direct costs allowed in any The scope of the proposed project should determine the project period. The maximum project period is 2 years. Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: o Hispanic-serving Institutions o Historically Black Colleges and Universities (HBCUs) o Tribally Controlled Colleges and Universities (TCCUs) o Alaska Native and Native Hawaiian Serving Institutions o Asian American Native American Pacific Islander Serving Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Institutions) are Non-domestic (non-U.S.) components of U.S. Organizations are not eligible Foreign components, as defined in the NIH Grants Policy Statement , are not allowed.

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted.

Registration can take 6 weeks or more, so applicants should begin the registration process as soon as Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a 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. Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

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

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

PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3.

Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time.

This means that the NIH will A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101 ). Section IV. Application and Submission Information Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA.

See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2. Content and Form of Application Submission It is critical that applicants follow the Research (R) Instructions (R&R) Application Guide , including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise.

Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant All page limitations described in the SF424 Application Page Limits must be followed.

Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide 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.

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) PHS Inclusion Enrollment Report Use only for applications with due dates on or before January 24, 2018.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 PHS Human Subjects and Clinical Trials Information Use only for applications with due dates on or after January 25, 2018.

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

on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide 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 Electronically . If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must 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 Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy . Section V.

Application Review Information 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 For this particular announcement, note the following: The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research.

An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding.

Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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 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?

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Inclusion of Women, Minorities, When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed.

For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals.

Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section .

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project.

If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan ; (2) Sharing Model Organisms ; and (3) Genomic Data Sharing Plan (GDS) .

Authentication of Key Biological and/or Chemical Resources: For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources. Budget and Period of Support Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed