National Institutes of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Not applicable
R01 Research Project Grant
NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
The goal of this FOA is to support collaborative research projects conducted by multidisciplinary teams on early liver transplantation (ELT) for alcohol-associated liver disease (ALD) patients. The research objectives of these observational clinical studies concern factors that influence the selection, management, and outcomes of ELT. Recruited into these longitudinal studies would be adult ALD patients being considered for ELT. Patients would be followed for sufficient time to determine long-term outcomes related to ELT.
August 30, 2022
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| September 30, 2022 | Not Applicable | Not Applicable | March 2023 | May 2023 | July 2023 |
All applications are due by 5:00 PM local time of applicant organization.
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.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Research Objectives
A. Background
Over the past 30-40 years liver transplantation (LT) has become the standard of care and the only cure for some of the end stage liver diseases. The waiting list for transplant has expanded, while scarcity of the donor liver supply has remained. Therefore, the waiting time has grown. The number of alcohol-associated liver disease (ALD) patients as liver transplant recipients has increased over the past 15 years, particularly in the past 7 years. Although now ALD has emerged as the most common indication for liver transplantation in the United States, many US centers require 6 months of abstinence pre-LT for ALD. The rationale for this waiting period is based in part on the belief that a significant period of abstinence might allow decompensated disease to stabilize, thereby obviating the need for transplantation. There is also a concern that the public might be less likely to donate organs if they perceive that most of the recipients have a self-inflicted disease. On the other hand, critics argue that this waiting period is not well supported by evidence and is an imperfect predictor of compliance to alcohol abstention post-LT. Most importantly, for severe forms of ALD, such as acute alcoholic hepatitis, this requirement presents an unrealistic barrier alcoholic hepatitis has a high mortality rate in the first 3 to 6 months after diagnosis. Although glucocorticoids have been shown to improve 30-day survival, one out of four patients do not respond to this treatment, with a mortality rate of 75% in non-responders. In fact, no treatments other than LT can significantly improve longer-term outcomes in alcoholic hepatitis patients.
Several retrospective studies in the US found that Early Liver Transplantation (ELT) for severe ALD achieved excellent 1- and 3-year survival rates, and the sustained alcohol use after LT was not as high as predicted. Actually, these studies also found that the likelihood of relapse to drinking in patients who received a transplant for ALD is related to factors other than a specific duration of pre-transplant abstinence. These results support the conclusion that early liver transplantation may offer lifesaving therapy for severe alcohol-associated liver disease.
Over the past few years, the 6-month rule has become a subject of controversy in decisions about listing patients with ALD for transplant. Some transplant centers follow the rule; others use locally determined policies to select patients with severe ALD for early liver transplantation. There are urgent needs to provide evidence for standardizing the criteria for patient selection, and to better understand the post-ELT outcomes, including post-ELT survival and key factors influencing alcohol abstinence or relapse to alcohol use and effective interventions/treatments. Examples of such factors include baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and prediction and prevention methods for co-morbid complications and relapse of alcohol use after ELT.
B. Research Scope
The goal of this FOA is to support collaborative research projects conducted by multidisciplinary teams on early liver transplantation for ALD patients. The research objectives of these observational clinical studies concern factors that influence the selection, management, and outcomes of ELT. Recruited into these longitudinal studies would be adult ALD patients being considered for ELT. Patients would be followed for sufficient time to determine long-term outcomes related to ELT.
These prospective studies may answer the following questions:
1). What are the appropriate selection criteria for ALD patients receiving ELT? The criteria could, for example, include age, patient’s history of severe ALD not responding to medical therapy, no prior liver decompensation episodes, supportive family members, commitment to abstinence, etc., and other criteria used by current transplant sites.
2). What will be the short term (i.e., 1 month and 3 month) and long term (1 year and longer) survival rates for ALD patients with ELT?
3). What is the relapse rate and time to alcohol use after transplantation and the factors that predict relapse, especially over an extended period (1 year and longer)?
4). What supportive and preventive methods are effective for reducing the relapse to alcohol misuse after ELT?
5). What is the incidence of cancer and other medical complications in post-transplant patients?
These study questions are examples only. Applicants should not feel limited to the subjects mentioned above and are encouraged to submit other topics pertinent to the objectives of the FOA. Applicants may also suggest and justify other study designs.
The ability to recruit a sufficient number of patients is important for meeting the required study size and to ensure the quality of study. Participating centers are encouraged to pool outcome data on their current patients that have already undergone ELT to provide preliminary information on the study’s major questions.
All projects must be completed within 7 years (84 months).
Study Organization
Applicants of each collaborative set should apply to this FOA with one or more partner R01s performing liver transplantation (transplantation centers). Accordingly, the collaborating studies share a specific protocol across these providers and are organized as such in order to increase sample size, accelerate recruitment, or increase sample inclusion and representation. For a linked set of collaborative R01s, each R01 application has its own Program Director/Principal Investigator (PD/PI), but one provider will be submitted as a coordinating R01 for data management and/or other centralized administration.The coordinating PI’s application will include an administrative component. This collaborative R01 program provides a mechanism for cross-R01 coordination, quality control, database management, statistical analysis, and reporting. Participating transplantation centers (TCs) of each set of collaborative R01s will be required to conduct the study in a cooperative and interactive manner. The PI of the coordinating R01 will support the following: database of clinical information, serum and tissue sample collections, protocol finalization, sample size calculation, statistical advice, questionnaires, data analysis, support for manuscript preparation, overall study coordination and quality assurance, and coordination of the activities of the Data and Safety Monitoring Board (if needed).
Each collaborative R01 partner is required to submit a Data and Safety Monitoring Plan (DSMP) in the application (https://www.niaaa.nih.gov/research/guidelines-and-resources/data-and-safety-monitoring-guidelines).
Clinical protocols must be approved by a single institutional review board (sIRB).
Per NOT-AA-22-011, NIAAA expects that new grant applications involving applicable human subjects studies include an appropriate plan for submitting grant-related human subjects data to the NIAAA Data Archive.
The ELT Study Investigators are also encouraged to seek out separate funding for special projects and to develop collaboration with laboratory and basic research investigators to draw upon the resources (clinical data, biospecimens) made available by the ELT Study
NIAAA intends to commit up to $3,000,000 in FY 2023 to fund up to 2 collaborative sets, each set with at least two liver transplantation centers.
NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research
The National Institutes of Health (NIH) Policy on the Use of a Single Institutional Review Board of Record for Multi-Site Research establishes the expectation that all sites participating in multi-site studies involving non-exempt human subjects research funded by the National Institutes of Health (NIH) will use a single Institutional Review Board (sIRB) to conduct the ethical review required by the Department of Health and Human Services regulations for the Protection of Human Subjects at 45 CFR Part 46. This policy, which is consistent with 45 CFR Part 46.114, is intended to enhance and streamline the process of IRB review and reduce inefficiencies so that research can proceed as expeditiously as possible without compromising ethical principles and protections for human research participants. (https://grants.nih.gov/grants/guide/notice-files/not-od-16-094.html)
Diversity
.
Every facet of the United States scientific research enterprise from basic laboratory research to clinical and translational research to policy formation requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust.
It is expected that the transplant centers will seek to recruit a diverse group of potential participants, including individuals from underrepresented groups as per NOT OD 20-031 (Notice of NIH's Interest in Diversity) and NOT OD 22-019 (Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities).
Individuals from underrepresented groups are encouraged to serve as key contributors to the biomedical research . In addition, research teams are encouraged to include investigators from various disciplines/departments and specialties.
NIAAA is especially interested in transplant centers which cover patient populations experiencing health disparities and whose current liver transplantations already include a certain number of patients from minority health and NIH-designated populations that experience health disparities..
This FOA requires a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application (see Section IV). Applicants are strongly encouraged to read the FOA instructions carefully and view the available PEDP guidance material. The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.
For further information on PEDP, please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp.
Applications Not Responsive to this FOA
Applications that include the following topics will be considered non-responsive to this FOA, and will be withdrawn.
- HIV/AIDS related studies
- Clinical trials of alcohol-associated liver diseases
- Basic experimental studies involving humans
- Experimental transplantation using animals and development of animal models
- Mechanistic studies on alcohol-associated liver diseases and related pathologies
See Section 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.
R01 (collaborative)
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
NIAAA intends to commit up to $3,000,000 in FY 2023 to fund up to 2 collaborative sets, each set with at least two liver transplantation centers.
Application budgets need to reflect the actual needs of the proposed project but may not exceed $350,000 Direct Costs for each R01, inclusive of sub-contracts. Sub-awards in excess of the $350,000 Direct Costs are not allowed.
7 years
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
1. Eligible Applicants
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Local Governments
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
Federal Government
- Eligible Agencies of the Federal Government
- U.S. Territory or Possession
Other
- 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
- Regional Organizations
- Participating sites of each set of R01 applications must be conducting liver transplantation for alcohol-associated liver disease patients.
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 to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
Applicant Organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
- System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
- eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
Multiple PDs/PIs are allowed on any single application. Because the FOA already supports a team approach between groups of experts across sites and collaborating applications, the designation of multiple PDs/PIs on a single application may be less likely to apply. PD(s)/PI(s) from each linked application should not be designated as multiple PDs/PIs on each application of a collaborative set.
2. Cost Sharing
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
3. Additional Information on Eligibility
Number of Applications
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, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:
- A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
- A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
- An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications)
This FOA only accepts applications that are part of a collaborative set of multiple applications. A set must contain at least 2 applications.
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
2. Content and Form of Application Submission
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
Letter of Intent
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 plan the review.
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 (NIAAA)
Bethesda, MD 20892 (20817-FEDEX)
Telephone: 301-443-9737
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
Descriptive Title of Applicant's Project:To allow NIH to identify a group of applications as a related set of collaborative R01s, the titles for each R01 in the set must have the following format: a 1/N indicator + Identical title (e.g., 1/6-Multisite Comparison of Drug A vs. Drug B for Treatment of Disorder X , where the 1/6 means this is site 1 of 6 sites in the set.The other sites will be labeled 2/6, 3/6, etc.) Titles may not exceed 200 characters in length, including the tag, e.g., 1/6, at the beginning of the title.
Cover Letter Attachment:The Cover Letter is one pdf file only. The following collaborative information is required in the Cover Letter:a listing of all the applications that are a part of the set of collaborative R01s being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., 1/6 ), and 3) the Applicant Institution.Each site should submit an identical listing.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Attachments:
Plan for Enhancing Diverse Perspectives (PEDP)
In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:
- Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
- Description of any planned partnerships that may enhance geographic and regional diversity.
- Plan to enhance recruiting of women and individuals from groups traditionally under-represented in the biomedical, behavioral, and clinical research workforce.
- Proposed monitoring activities to identify and measure PEDP progress benchmarks.
- Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
- Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
- Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
- Publication plan that enumerates planned manuscripts and proposed lead authorship.
- Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.
For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp.
Site Liver Transplantation Experience
In an "Other Attachment" entitled "Site Liver Transplantation Experience", the following list of five questions with corresponding answers (one page only) must be included:
- Does the research team have direct access to patient care? Yes [ ], No [ ]
- Are the participating sites currently doing liver transplantation for alcohol associated liver disease patients? Yes [ ], No [ ]
- Do the participating sites have established protocols of early liver transplantation for alcohol associated liver disease patients? Yes [ ], No [ ].
- How many liver transplantation cases have been done during the past 2 years?
None [ ] , (1-10) [ ], (10-30) [ ], (30-50) [ ], (50-70) [ ], (70-100) [ ], (100 150) [ ], (150-200) [ ], (>200) [ ].
- How many liver transplantation cases in the past 2 years were for alcohol associated liver diseases (please specify the numbers)?
Applications omitting the attachment "Site Liver Transplantation Experience", which is mandatory, or exceeding the page limits will be considered noncompliant with FOA instructions and will be withdrawn without review.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R or Modular Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims:The Specific Aims must include an Overview section that should be identical for all applications that are linked together for the collaborative R01. The Overview should provide an overall rationale for applying as a collaborative study; the role of each site (partner R01); the approach to project management; and elements unique to any of the sites.
Research Strategy:The application from each partner/site or collaborative component R01 must contain a Research Strategy that clearly describes those aspects of the project that are common to all sites of the collaboration. All variations in the Research Strategy between sites, no matter how minor, should be highlighted in a subsection of the Research Strategy with the heading "Elements Unique to This Site." In this subsection, PDs/PIs should describe, for example, how the research site has a unique role in the collaboration, such as data coordination, statistical analyses, (etc.). In addition, each human subjects section should be site specific.
The separate applications from the partner sites will also have unique Budget sections (see Section II. 2. Funds Available and IV. 6. Other Submission Requirements for greater details).
Applications must describe a feasible mechanism for scientific integration of research procedures, overall managerial and administrative responsibilities, and cross-site comparability of training to assure reliability and quality control. Plans for ensuring access to data by all sites, analytic resources, publication and authorship rights, and a means of arbitrating disagreements on publication and other issues should be included in the application.
Without duplicating information in the biosktech(es), describe the following: (1) PD(s)/PI(s)' expertise, experience, and ability to organize, manage and implement the proposed clinical observational study and meet timelines, (2) PD(s)/PI(s)' expertise in study coordination, data management and statistics, and (3) PD(s)/PI(s)' capacity and commitment to enroll subjects.
Any location that provides resources on a fee for service for some portions of this work should list this fact under "Elements Unique to This R01," and provide a full description of the nature, purpose and oversight of this service arrangement. When applicable, PIs are encouraged to pursue fee for service, rather than sub-awards.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
- All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
- Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA.
- Applications that include human subject research are expected to describe basic plans for submitting grant-related human subjects data to the NIAAA-sponsored data repository, as described in NOT-AA-22-011.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Per NOT-AA-22-011, NIAAA expects that new grant applications involving applicable human subjects studies include an appropriate plan for submitting grant-related human subjects data to the NIAAA Data Archive.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission. Each application of a collaborative set must be on-time. Considerations for late applications that are based on the institution or PD/PI apply only to his/her individual application.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile form. 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 unique entity identifier provided on the application is the same identifier 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 NIAAA, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. Each application of a collaborative set must be complete, compliant, and responsive.
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.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
1. Criteria
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Overall Impact
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Scored Review Criteria
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.
Significance
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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?
Specific to this FOA
To what extent do the efforts described in the Plan for Enhancing Diverse Perspectives further the significance of the project?
Investigator(s)
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?
Specific to this FOA
Do the PD(s)/PI(s) have the appropriate expertise, experience, and ability to organize, manage and implement the proposed clinical observational study and meet timelines? Do they have appropriate expertise in study coordination, data management and statistics? Do they have adequate capacity and commitment to enroll subjects?
To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives strengthen and enhance the expertise required for the project?
Innovation
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?
Specific to this FOA
To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives meaningfully contribute to innovation?
Approach
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Specific to this FOA
Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspectives well-developed and feasible?
Environment
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?
Specific to this FOA
Based on answers provided to the questions in the "Site Liver Transplantation Experience" attachment, does the research site have appropriate experience with liver transplantation?
To what extent will features of the environment described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support) contribute to the success of the project?
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.
Collaboration
Does the research plan justify the need for a collaborative multi-site project using this FOA? Are sufficient and feasible mechanisms in place to ensure collaboration across health service providers to achieve scientific integration of research procedures, overall managerial and administrative responsibilities, appropriate quality control and reliability assurance, and planning for data management, analysis and reporting of results? Are there adequate plans for shared decision making among PDs/PIs with regard to personnel, clinical decisions, changes in study protocol, and authorship?
Protections for Human Subjects
For research that involves human subjects but does not involve one of the 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 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 Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
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 individuals of all ages (including children and older adults) 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 in Clinical Research.
Vertebrate Animals
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.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
Not applicable
Renewals
Not Applicable
Revisions
Not applicable
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 Organizations
Not Applicable.
Select Agent Research
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).
Resource Sharing Plans
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.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIAAA, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
- Scientific and technical merit of the proposed project as determined by scientific peer review.
- Availability of funds.
- Relevance of the proposed project to program priorities.
3. Anticipated Announcement and Award Dates
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:
- Federalwide Research Terms and Conditions
- Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
- Acknowledgment of Federal Funding
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
- For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
- HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
- For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
Not Applicable
3. Reporting
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Zhigang (Peter) Gao, MD.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Bethesda MD, 20892-6902
Tel: 301-443-6106
Email: [email protected]
RV Srinivas, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone:3010-451-2067
Email: [email protected]
Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.
and Human Services (HHS)
