Alcoholic Hepatitis Clinical and Translational Network Clinical Pilot Trials (U01)

Alcoholic Hepatitis Clinical and Translational Network Clinical Pilot Trials (U01) is sponsored by National Institute on Alcohol Abuse and Alcoholism (NIAAA). This program supports investigator-initiated single-center feasibility and pilot studies aimed at optimizing critical elements for full-scale clinical trials in patients with Alcoholic Hepatitis (AH).

Expired RFA-AA-18-005: Alcoholic Hepatitis Clinical and Translational Network Clinical Pilot Trials (U01) 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 on Alcohol Abuse and Alcoholism ( NIAAA ) Funding Opportunity Title Hepatitis Clinical and Translational Network Clinical Pilot Trials (U01) Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity RFA-AA-18-002 , U01 Research Project Cooperative Agreements RFA-AA-18-003 , U01 Research Project Cooperative Agreements RFA-AA-18-004 , U24 Resource-Related Research Projects Cooperative Agreements RFA-AA-18-006 , UH2 / UH3 Phase Innovation Awards Cooperative Agreement Only one application per institution is allowed, as defined in Section III.

3. Additional Information on Eligibility. Section III.

3. Additional Information on Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The National Institute on Alcohol Abuse and Alcoholism (NIAAA) seeks to continue support of the previously funded program on Translational Research in Alcoholic Hepatitis to accelerate the discovery and validation of new diagnostic and treatment options for patients with Alcoholic Hepatitis (AH).

This initiative, via a set of five FOAs, aims to enhance and consolidate the existing program into AH Clinical and Translational Network , hereafter termed AH Network . This consolidated program will consist of 1) Clinical component, 2) Data Coordinating Center, 3) Translational component, and 4) Basic and pre-clinical component.

Through this FOA, applications are sought to conduct investigator-initiated single-center feasibility and pilot studies aimed to optimize critical elements for full-scale clinical trial in patients with AH under the U01 Research Project Cooperative Agreements funding mechanism. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) October 23, 2017), by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date. 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.

No late applications will be accepted in response to this AIDS Application Due Date(s) 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 Alcoholic hepatitis (AH) is a clinical syndrome of acute liver failure prevalent in people with decades of heavy alcohol use, for which there are no effective treatments.

Research in developing new interventions for AH has been challenging, given its high mortality rate, heterogeneity in clinical presentation, complexity of interacting pathophysiologic mechanisms, the difficulties of recruiting and retaining patients with alcohol use disorders, and the lack of animal models In response to the urgent public health significance of AH, in 2012 the NIAAA launched the Translational Research in Alcoholic Hepatitis program, which established four individually operating consortia each consisting of a set of integrated projects ranging from basic research to clinical studies.

The original AH program made a number of exciting discoveries and made steady progress towards its scientific and programmatic goals including establishing a consensus statement on disease definition and common To further accelerate AH intervention development, the NIAAA seeks to consolidate and integrate the existing AH program into the Clinical and Translational Network.

This consolidation is aimed to increase the efficiency and effectiveness of the program by streamlining processes for designing, initiating and conducting clinical trials, reducing administrative redundancy, facilitating complementary interactions across the Network and making optimal use of scientific innovations.

The consolidated AH Network consists of the following component : consists of up to 9 collaborative U01 clinical centers conducting common multi-center clinical phase 2b trials and observational studies in patients with AH; some of these centers will also conduct the U01 Clinical Pilot Trials of intervention-development related Coordinating Center : serves as the Network data management center and biorepository, provides biostatistical and logistical support, coordinates various trans-Network activities as well as standardizes approaches, procedures and data formats to minimize resources/effort Translational component : consists of up to 10 U01 studies aimed on improving various aspects of AH diagnosis and and pre-clinical component : consists of to-be-determined number of basic and pre-clinical studies aimed to discover novel mechanisms of AH pathogenesis and/or tools for clinical development.

These four components will be individually awarded through the respective FOAs indicated below: Clinical component under RFA AA 18-002 (collaborative U01) (up to 9 awards) and RFA AA 18-005 (U01) (this FOA) (up to 9 awards); Data Coordinating Center under RFA AA 18-004 (U24) (up to 2 awards); Translational component under RFA AA 18-003 (U01) (up to 10 Basic/Pre-clinical component under RFA AA 18-006 (UH2/UH3).

Through this FOA, app lications are sought to conduct investigator-initiated single-center feasibility and pilot studies to optimize critical elements for full-scale clinical trials including agent(s), dosing, enrollment and adherence, data collection and appropriate outcome and follow-up.

The overall objectives of these studies are to generate sufficient data for 1) informing go/no-go decisions about further testing of the candidate interventions and 2) optimization of the design of the late-stage clinical trials for obtaining meaningful results.

To meet these objectives, projects should address the core clinical trial design issues, including the feasibility, tolerability, acceptability, safety, and preliminary indications of effectiveness of therapeutic interventions.

The pilot studies are expected to involve a small number of patients and will not achieve statistical significance, but may lead to new clinical trial design to increase the success rates of drug efficacy studies. Despite their outcomes, the pilot studies will provide information of high utility to the field by informing decisions about whether further testing is warranted and by filling gaps in scientific knowledge.

Both novel investigational drugs and rescued or repurposed drugs are appropriate for this Some examples of research topics appropriate for this FOA include, but are not limited to: Evaluating and optimizing the dose, formulation, safety, tolerability of an intervention in the target population; Assessing pharmacokinetics of the studied agents and establishing relationships between the dose, schedule, exposure and effect; Evaluating the feasibility of recruitment, retention, assessments, and reporting of adverse events; Identifying inclusion and exclusion criteria to be applied in phase 2b and above clinical trials; Developing and refining data collection procedures; Determining the best methods for identifying, stratifying, and recruiting study subjects; Obtaining sufficient evidence of short-term improvement in patients to justify an efficacy trial; Evaluating strategies for recruitment and retention to overcome logistical barriers and disparities in clinical trial participation among racial/ethnic minorities, socioeconomic and other diverse populations.

This FOA may support activities related to the conduct of the pilot studies, including, but not limited to: Regulatory activities to support the implementation of the trial; Training of study personnel related to the conduct of the trial; Enrollment and recruitment of study participants; Data collection, management, and quality control for the trial; Laboratory work and data analysis; Study management and oversight; Other related post-enrollment activities; Preparation of the final study report.

requirements of this FOA: Because the pilot studies are expected to involve a small number of patients and have a shorter duration, applicants must propose two pilot trial designs to be conducted sequentially over the funding period. Applicants must provide a clear scientific premise and compelling rationale for pursuing the proposed pilot studies and development of the intervention.

Pilot projects must be distinct from a cross-Network common clinical trial. All applications are required to use the Network master agreements and to share data and biospecimens with other collaborating sites within the AH Network.

Prior arrangement needs to be made and specified in the submitted application so that pilots will be coordinated with the ongoing clinical trial and observational studies, and statistical and data management support will be provided by Data Coordinating Center unit (DCC). A letter of support from one or more of the NIAAA approved collaborating sites is required.

Given the complexity of the research projects, it is expected that each award will support multidisciplinary teams composed of scientists with diverse expertise.

The PD/PIs are strongly encouraged to include Early Stage investigators in the proposed research projects to provide them with exposure to and experience in clinical research methods and NIAAA will consider clinical research grant applications that focus on already established patient cohorts within the NIAAA-supported Alcoholic Hepatitis Translational and Clinical Network in California, Indiana, Kentucky, Massachusetts, Minnesota, Ohio, Pennsylvania, Texas and Virginia.

NIAAA does not intend to expand the cohort It should be noted that related translational projects, such as those examining whether the intervention engages the target/mechanism or identifying biomarkers, are supported separately by the U01 translational component mechanism (RFA AA 18-003). VIII. Other Information for award authorities and regulations.

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

2 for additional information about the substantial involvement for Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards {NIAAA} intends to commit ${675,000 dollars} in FY {2018} to fund {up to 9} awards. Budgets must reflect the actual needs of the proposed The maximum project period may not exceed 5 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: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted.

Registration can take 6 weeks or more, so applicants should begin the registration process as soon as Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number.

After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application. System for Award Management (SAM) (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 Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed 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 Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: Abraham P. Bautista, Ph. D.

National Institute on Alcohol Abuse and Alcoholism 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 must be followed with additional requirements: SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide Facilities & Other Resources The description of the resources and environment should address how the study utilizes existing infrastructure or utilizes other available resources to increase the efficiency of participant recruitment and SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed.

with additional requirements: The PD(s)/PI(s) should document expertise needed to successfully design and conduct the proposed studies and prior experience with studies in AH including clinical trials under an FDA IND or other types of clinical research studies. The experience of all key personnel must be All instructions in the SF424 (R&R) Application Guide must be followed.

with additional requirements: The budget should be largely planned on a fee-for-service basis with detailed per-patient costs and may include clinical trial costs such as study-related procedures/materials. The budget will not include costs which are already covered by the U01 clinical trials and observational studies award.

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: Significance : Applicants must provide a clear and compelling rationale for pursuing the proposed pilot studies and development of the intervention, as well as for other critical aspects of the trial design.

The clinical significance of the future clinical trial must be clearly stated. It is particularly important that there be discussion of how the results of the proposed research (positive or negative) will guide decisions about whether a subsequent study is feasible or justified, and/or provide evidence that additional studies must be completed before proceeding to a full-scale trial.

Studies and Rationale for Development : The major findings of the preclinical and/or clinical studies that led to the proposed research should be described. Characteristics of any preliminary research results provided in support of the proposed project, whether conducted by the applicant or others, should be described in the application so that peer reviewers may evaluate the strength of the supporting evidence.

The applicant should also discuss the limitations of those data. Design : Applicants must propose two pilot trial designs to be conducted sequentially over the funding period.

A summary of the proposed protocol for each pilot study of the application should be presented in the Research Strategy and must include data to justify the selection of the study intervention; a description of the target population, description of all assessments and outcomes addressing the primary and secondary research questions; statistical methods such as sample size justification, study outcome measures and final analyses, methods of bias control and methods for handling missing data.

All applications must include clearly-specified, well-defined milestones, go/no go decision points, and timelines for assessing progress.

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 When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 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 and responsiveness by components of participating organizations , NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIAAA Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application. 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 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?

Despite their outcomes, will the proposed pilot studies provide information of high utility to the field by informing decisions about whether further testing is warranted and by filling gaps in scientific knowledge? Will the proposed studies adequately inform an effective design of a randomized clinical trial to treat AH?

Is there an adequate description on the significance of biological variables, such as, sex for studies on human 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? If established, have they demonstrated a prior experience with studies in AH including clinical trials under an FDA IND or other types of clinical research studies?

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 there innovative approaches to the scientific question(s), research design, or implementation? Are appropriate biomarkers and alternative outcomes proposed in the design of the study?

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? Does the application propose two pilot trial designs to be conducted sequentially over the funding period?

Does the application address the core clinical trial design issues, including the feasibility, tolerability, acceptability, safety, and preliminary indications of effectiveness of therapeutic interventions in AH? Are there adequate pre-clinical or clinical data to justify the scientific questions proposed?

Do the proposed recruitment plans include a viable approach to recruitment of participants and anticipated rates of progression for the proposed pilot studies? Are there backup plans in case the primary recruitment plan fails?

Does the application include Data Management and Quality Control; Data and Safety Monitoring Plan; statistical methods such as sample size justification, study outcome measures and final analyses, methods of bias control and methods for handling missing data?

Does the application provide plans how pilot projects will be coordinated with the ongoing clinical trials and observational studies, and statistical and data management support will be provided by Data Coordinating Center unit (DCC)? Does the application include plans to share data and biospecimens with other collaborating sites within the AH Network?

Does the application include clearly-specified, well-defined milestones, go/no go decision points, and timelines for assessing progress?

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