Mechanisms of Disparities in Chronic Liver Diseases and Cancer (R01- Clinical Trial Not Allowed)

Mechanisms of Disparities in Chronic Liver Diseases and Cancer (R01- Clinical Trial Not Allowed) is sponsored by National Institutes of Health (NIH). This initiative supports multidisciplinary research to understand the underlying etiologic factors and the mechanisms that result in disparities in chronic liver diseases and cancer in the U. S.

Expired PAR-17-151: Mechanisms of Disparities in Chronic Liver Diseases and Cancer (R01) 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 Minority Health and Health National Cancer Institute ( NCI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) Funding Opportunity Title Mechanisms of Disparities in Chronic Liver Diseases and Cancer (R01) R01 Research Project Grant January 14, 2020 - This PAR has been reissued as PAR-20-088 .

November 26, 2018 - NIH & AHRQ Announce Upcoming Updates to Application Instructions and Review Criteria for Research Grant Applications. See Notice NOT-OD-18-228 . Reminder: FORMS-E Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2018.

- 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 .

Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PAR-17-150 R21 Exploratory/Developmental Research Grant Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) 93. 307, 93.

399, 93. 393, 93.

273 Funding Opportunity Purpose The purpose of the initiative is to support multidisciplinary research to understand the underlying etiologic factors and the mechanisms that result in disparities in chronic liver diseases and Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to the application due date May 22, 2017, April 4, 2018, April 4, 2019, by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement 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) August 2017, July 2018, July 2019 January 2018, October 2018, October 2019 March 2018 , December 2018, December 2019 It is critical that applicants follow the Research (R) Instructions (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review. Part 1. Overview Information Part 2.

Full Text of the Announcement I. Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section IV. Application and Submission Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information Full Text of Announcement Section I.

Funding Opportunity Description The purpose of this Funding Opportunity Announcement (FOA) is to support multidisciplinary research to understand the underlying social, cultural, clinical, environmental or biological factors responsible for the increase in chronic liver diseases and cancer and the mechanisms that explain the documented liver cancer disparities in the US.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the most relevant within the United States for the purpose of this FOA. Hepatocellular carcinoma (HCC) is one of the fastest rising causes of cancer-related deaths in the United States, with disparities observed in cancer incidence and survival among racial/ethnic minority populations.

HCC has been shown to disproportionately affect disadvantaged populations, with higher rates and worse survival among racial/ethnic minorities and individuals of low socioeconomic status (SES) than their counterparts. Liver cancer rates are the highest among Asians, particularly among Laotians, Vietnamese and Cambodians. From 2003 to 2011, Latinos had the greatest increase in liver cancer incidence (+35.

8%), whereas Asians experienced a 5. 5% decrease. Surveillance, Epidemiology, and End Results (SEER) data indicate that liver cancer incidence rates have continued to increase and in 2013 the rates are highest especially among American Indians/Alaska Natives and Latinos compared to Whites.

Recent reports indicate that South Texas Latinos have the highest rates of HCC incidence in the country with rates 3 to 4 times higher than Non-Hispanic Whites. In addition, men are about three times as likely to develop liver cancers and more than twice as likely as women to die from these cancers. Better understanding of the causes and the underlying mechanisms for disparities in chronic liver diseases and cancer is needed.

The established risk factors for liver diseases and cancer include chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, heavy and chronic alcohol consumption, genetic predisposition, cirrhosis of any cause, and tobacco smoking. Diabetes is also associated with an increased risk of HCC and antecedent obesity likely contributes.

Also, co-infection with HIV in individuals with chronic infections with either HBV or HCV lead to worse clinical outcomes. The prevalence of these risk factors varies among various racial and Nonalcoholic fatty liver disease (NAFLD), and its subtype nonalcoholic steatohepatitis (NASH) are the major causes of chronic liver disease that may progress to cirrhosis and then HCC.

The disease burden of fatty liver mirrors the rapid recent rise in the incidence of diabetes, and obesity, especially among Latinos. Since fatty liver/NASH is a complex disease state and a precursor to liver cancer, there may be an interplay of multiple factors between genetic, behavioral, and environmental factors that drives the observed racial/ethnic differences.

The increased risk of central obesity and subsequent diabetes in some racial/ethnic minority populations confers additional risk for the development of advanced fibrosis and cirrhosis on those who consume excess alcohol.

The high incidence of alcohol use together with the prevalence of at risk alleles for the development of fatty liver disease may increase the susceptibility of development of advanced liver disease and progression to HCC. Liver cirrhosis is one of the common risk factors for liver cancer; prevalence and mortality from cirrhosis are higher in Latinos and in American Indian populations compared to the general population.

Expanded efforts are therefore needed to understand the interplay of the various genetic, social and environmental causes of liver cancer disparities and to develop strategies to reduce the impact of lifestyle choices in the incidence of cancer in racial/ethnic minority Two families of fungal toxins, aflatoxins and fumonisins, which may contaminate corn, soybean and other crops, are also implicated as a causal factor in HCC.

Racial/ethnic minority populations may have elevated exposures to these toxins due to dietary practices, growing their own crops, and high representation in agricultural and food processing jobs.

The timely detection and appropriate treatment of liver diseases and cancer are also of concern due to lack of access to health care for health disparity populations, resulting in late diagnosis, inadequate or limited access to treatment and poor survival rates.

Concerted efforts are needed to promote comprehensive research on understanding the complex causes of chronic liver diseases and HCC disparities and how their clinical care may affect outcomes.

The overarching objectives of this initiative are to understand the etiologic factors and the underlying mechanisms responsible for chronic liver diseases and documented cancer disparities among racial/ethnic minority and socioeconomically disadvantaged populations in the US.

For the purpose of this initiative the focus is on the causes for increase in both the incidence and mortality rates of chronic liver disease and cancer among the health disparities populations.

Many potential individual, contextual and structural factors influence health disparities; therefore, this FOA invites applications that include multidisciplinary research to understand the influence of multiple factors that cause liver disease/cancer health disparities and the mechanisms through which they operate.

Since the causes of health disparities are complex, applicants are encouraged to focus on the interplay of multiple factors between genetic, behavioral, environmental and structural factors that drives the observed racial/ethnic differences in health outcome.

Studies for this initiative may include multi-disciplinary epidemiological, behavioral, or health services projects that leverage understanding of the biological factors that influence chronic liver disease and HCC. In addition, projects can involve primary and/or secondary data collection and analysis.

Because the goal of this initiative is to better understand documented racial/ethnic and SES disparities in chronic liver diseases and cancer, studies whose sole purpose is to assess incidence of liver disease/cancer in specific populations or subpopulations are not targeted for support under this FOA.

Projects should include a focus on one or more NIH-designated health disparity populations in the United States, which include Blacks/African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders, socioeconomically disadvantaged populations, sexual and gender minorities and underserved rural populations.

For health disparity populations with a significant proportion of immigrants, comparison of health factors between the U.S. and country of origin, length of stay may be considered when appropriate.

Projects are strongly encouraged to involve collaborations, where appropriate, among relevant stakeholders in U.S. health disparity population groups, such as researchers, community organizations, clinicians, health systems, public health organizations, consumer advocacy groups, and faith-based organizations.

As appropriate for the research questions posed, inclusion of key community members in the conceptualization, planning and implementation of the research is encouraged (but not required) to generate better-informed hypotheses and enhance the translation of the research results into practice.

Areas of Research Interest Areas of research interest include but are not limited to the following: Interactions of infectious agents with other risk factors (such as hepatitis B, hepatitis C, HIV, with obesity, diabetes, aflatoxin exposure, alcohol use, smoking) among various racial/ethnic minority populations and the mechanisms through which they act to result in poor health outcomes for chronic liver diseases and liver cancer.

Determine the influence of country of origin, length of stay, cultural beliefs, dietary practices, alcohol use, and other social factors that may play a role in disparities in chronic liver diseases and cancer. Examine biological, environmental/occupational exposures and social factors that may explain larger or smaller gender differences in different racial/ethnic minority populations.

Risk/protective factors for liver cancer health outcomes in various health disparity populations in different regions of US. The role of metabolic abnormalities associated with obesity, pre-diabetes and/or diabetes and influence of other risk factors in the progression of fatty liver, NASH, cirrhosis and liver cancer in health disparity populations.

Integrative studies to examine the interplay of multiple factors including social factors with microbiome, epigenomics, and proteomics to identify risk patterns for liver cancer.

Role of acculturation factors with increased incidence rates among second generation immigrants (US-born) and first generation immigrants (foreign born) from various racial/ ethnic sub-populations in chronic liver diseases and Understanding the health care barriers for early detection of chronic liver diseases and hepatocellular carcinoma (HCC) in high-risk individuals from health disparity populations.

Barriers and facilitators to uptake of screening for HepB/HepC status in individuals and follow up for treatment in at-risk health disparity Genetic risk factors associated with liver cancer among various health disparity populations and the mechanisms through which they act to result in poor health outcome. The role of healthcare access and quality in explaining disparities in liver cancer mortality.

Role of limited English proficiency and health literacy and barriers to utilization of care among medically underserved and high-risk populations Patient, clinician, and system/policy-level factors that predict receipt of curative treatments with available outcomes among liver cancer patients from health disparity populations.

Determine strategies to understand how excess alcohol use in at risk populations, especially those with central obesity, pre-diabetes, and/or diabetes in combination with the presence of one or more risk alleles associated with NAFLD increases the prevalence and poor outcome of chronic liver 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 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. Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period.

The maximum project period is 5 years Grants Policy Statement will apply to the applications submitted and awards made 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 U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Institutions) are Non-domestic (non-U.S.) components of U.S. Organizations are not eligible Foreign components, as defined in the NIH Grants Policy Statement , are allowed.

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

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

After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application. System for Award Management (SAM) (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 Grants. gov 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 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: 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: Strategy: Describe how the project will contribute to the understanding of etiologic factors and mechanisms that explain documented chronic liver disease/cancer disparities or how that influences minority health.

Describe how the project uses a multidisciplinary approach, including descriptions of the discipline and expertise of the research team, to understand the complex factors that underlie disparities in chronic liver disease and liver cancer. If there are foreign component(s), describe how the proposed activities at foreign sites will improve minority health and/or help to reduce or eliminate health disparities in the United States.

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: Also, All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. not use the Appendix to circumvent page limits.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. 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 (R&R) Application Guide.

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 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 4. Submission Dates and Times Part I.

Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next 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 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 Requests of $500,000 or more for direct costs in any year Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy .

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 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?

In addition, specific to the FOA, to what extent can the project contribute to the understanding of the etiology and/or mechanisms that influence disparities in liver disease and or liver cancer? 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?

In addition, specific to the FOA, are the breadth and inclusiveness (e.g. disciplines and expertise) of the research team such as for social science, or public health or molecular biology expertise, appropriate to the scope of the proposed research?

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?

In addition, specific to the FOA, to what extent does the project integrate relevant disciplines in a meaningful and appropriate way to study disparities in chronic liver diseases and or liver 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?

If there are foreign component(s), has the applicant stated how the proposed activities at foreign sites will improve minority health and/or help to reduce or eliminate health disparities 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