HIV and Hepatitis B Co-Infection: Advancing HBV Functional Cure through Clinical Research (R21)

HIV and Hepatitis B Co-Infection: Advancing HBV Functional Cure through Clinical Research (R21) is sponsored by NIH/NIAID. This opportunity supports mission-aligned projects and measurable outcomes.

Expired PA-17-278: HIV and Hepatitis B Co-Infection: Advancing HBV Functional Cure through Clinical Research (R21) 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 Allergy and Infectious Diseases ( NIAID ) National Cancer Institute ( NCI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) Funding Opportunity Title HIV and Hepatitis B Co-Infection: Advancing HBV Functional Cure through Clinical Research (R21) R21 Exploratory/Developmental Research Grant December 20, 2018 - Notice of Change in Expiration Date of PA-17-279.

See Notice NOT-AI-19-019 . December 17, 2018 - Notice of Change in Expiration Date of PA-17-278. See Notice NOT-AI-19-018 .

November 26, 2018 - NIH & AHRQ Announce Upcoming Updates to Application Instructions and Review Criteria for Research Grant Applications. See Notice NOT-OD-18-228 . - Updates to Active Funding Opportunity Announcements to Prepare for Policy Changes Impacting Due Dates On or After January 25, 2018.

May 10, 2017 - New NIH "FORMS-E" Grant Application Forms and Instructions Coming for Due Dates On or After January 25, 2018. See NOT-OD-17-062 . Reminder: FORMS-E Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2018.

Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PA-17-279 , R01 Research Project Grant Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) 93. 855, 93.

856; 93. 399, 93. 395, 93.

394; 93.

273 Funding Opportunity Purpose The purpose of this Funding Opportunity Announcement (FOA) is to fill scientific gaps needed to (a) inform HBV functional cure strategies by furthering our understanding of unique challenges impacting HBV and HIV co-infected hosts and (b) advance the discovery and development of novel HBV interventions that are safe and achieve a functional cure in HIV and HBV co-infected individuals Open Date (Earliest Submission Date) Letter of Intent Due Date(s) AIDS datess apply, by 5:00 PM local time of applicant organization.

All types of 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) dates apply, by 5:00 PM local time of applicant organization.

All types of 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 New Date January 8, 2019 per issuance of NOT-AI-19-018 .

(Original Expiration Date: May 8, 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 Worldwide, 2 billion people have been infected with hepatitis B virus (HBV) and 240 million people have become chronically infected; 1-2 million people in the U.S. are chronically infected.

Despite the existence of an effective HBV vaccine, there continues to be challenges to universal access and timely vaccination. Chronic HBV is a leading cause of liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Current treatment for HBV results in HBV viral suppression but rarely achieves sustained loss of HBsAg; therefore, sustaining HBV viral suppression may require lifetime treatment.

The risk for the development of HBV drug resistance and drug toxicities is a major limitation of long-term HBV antiviral treatment. The chronicity of HBV infection is mainly due to the persistence of viral covalent closed circular DNA (cccDNA) and to inadequate host immune Worldwide it is estimated 2.

6 million people living with HIV are co-infected with HBV and as high as 25-36% HIV+ individuals have co-infection with HBV in high endemic areas. HIV and HBV have the similar modes of transmission, putting these populations at risk for co-infection.

HIV infection increases rates of the progression to chronic cirrhosis, end-stage liver disease, and HCC resulting in higher liver related mortality and morbidity in HIV/HBV The success of preventive vaccines and ability of some individuals to clear HBV demonstrates the host ability to clear and control HBV infection.

Novel HBV therapeutic interventions currently in development are likely to provide the backbone for new HBV cure strategies for HIV/HBV co-infected individuals. Strategies for HBV functional cure will likely require a combination of HBV antiviral drugs and immune-mediated approaches. However, HIV infection poses additional challenges for individuals co-infected with HBV.

HIV may reduce the host’s ability to mount an effective, sustained immune response as well as increase risks for adverse events and drug-drug interactions with HBV In summary, this FOA seeks to fill scientific gaps needed to (a) inform HBV functional cure strategies by furthering our understanding of unique challenges impacting HBV and HIV co-infected hosts and (b) advance the discovery and development of novel HBV interventions that are safe and achieve a functional cure in HIV and HBV co-infected individuals.

Areas of Research Interest This FOA invites applications proposing clinical research to identify and better understand the unique challenges to achieve a functional cure in HIV/HBV+ co-infected hosts as well as advance the discovery and development of novel strategies to achieve HBV functional cure for HIV/HBV+ co-infected adult and pediatric populations, including children, adolescents and HIV exposed uninfected children.

Although clinical trials and establishment of new cohorts will not be supported by this FOA, the leveraging of ongoing NIH- or non-NIH supported clinical trials and cohorts to collect samples and data to address areas of research interests is encouraged. Applicants are encouraged to contact the Scientific/Research Contacts listed in Section VII of this FOA to discuss areas of interest for particular institutes.

Examples of research that would fit within the scope of this FOA include, but are not limited to, those listed below: Institute of Allergy and Infectious Diseases (NIAID) Study the effect of HIV infection on the host ability to establish and sustain immune control of HBV infection to inform HIV/HBV functional cure Identify factors critical to inducing an effective immune response to clear and maintain immunologic control of HBV in HIV+ individuals.

Elucidate the mechanisms responsible for and identify factors predictive of HBV reactivation in HIV+ individuals. Enhance the understanding how to prevent HBV relapse & immune reconstitution inflammatory syndrome in HIV+ individuals. Identify interventional targets, biomarkers, diagnostics & endpoints to inform effective HBV cure strategies in HIV+ individuals.

Evaluate the benefits and harm of initiating HBV interventions during different phases of chronic HBV infection (for example, antivirals with dual HIV and HBV activity initiated during the immune-tolerant phase). Study the impact of chronic HIV & HBV co-infection on immune tolerance, immune activation, inflammation, and HBV viral persistence. Assess the impact of HIV exposure on the course of HBV infection in children and adolescents.

Elucidating the role of HIV in the development of hepatocellular carcinoma (HCC) in persons co-infected with HIV plus HBV. Identification of the role of other factors, such as drug effects, in the development of HCC in patients co-infected with HIV plus HBV. Identification of factors that are predictive of the subsequent development of HCC in persons co-infected with HIV plus HBV.

Examination of the genetic and epigenetic signatures of persons co-infected with HBV- associated HCC using global molecular profiling tools to identify biomarkers for the early detection of HCC. Institute of Alcohol Abuse and Alcoholism (NIAAA) To study the effectiveness of the latest medications for treating HBV in HIV/HBV co-infection subjects with alcohol use disorders.

To study the mechanisms by which alcohol affects the mortality and morbidity of co-infected patients including, but not limited to, host antiviral (HIV, or HBV) or vaccine generated immune response and progression of To study the role of alcohol use disorders on emerging patterns of frailty within the co-infection populations.

To develop and test the reliability and validity of alcohol-related biomarkers for monitoring the adverse health effects of the levels of alcohol use and associated disorders in co-infected subjects. Clinical trials (all phases), although the use of existing samples and data from biorepositories is encouraged. Establishment of new cohorts.

Studies of hepatitis other than HBV. Studies of HBV in the absence of HIV infection (except for children exposed to but not infected with HIV). In vitro and animal model studies [see PA-17-280 (R01) or PA-17-281 (R21) for preclinical research proposals].

Note: This FOA uses the R21 mechanism. 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; however, they may be included if available.

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 The OER Glossary and the SF424 (R&R) Application Guide provide details on these application Clinical Trials Not Allowed for due dates on or after January 25, 2018: Only accepting applications that do not propose clinical trials 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. The combined budget for direct costs for the two-year project period may not exceed $275,000. No more than $200,000 may be requested in any single year.

The total project period may not exceed 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) 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 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) (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 Form only available in FORMS-D application packages for use 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 Form only available in FORMS-E application packages for use 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 Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: 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 Foreign (non-U.S.) institutions must follow policies 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 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 . 7. Other Submission Requirements 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 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 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 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 Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes 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 whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy