It is critical that applicants follow 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 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

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This FOA invites collaborative U01 cooperative agreement applications to establish a multi-center, multi-disciplinary study group to be known as the APOL1 Long-term Kidney Transplantation Outcomes (APOLLO) Research Network, with a primary focus on the relationship of APOL1 genotypes of kidneys donated by African Americans for transplantation in the United States to kidney recipient outcomes. The successful Clinical Center applications submitted under this FOA will work collaboratively with the APOLLO Scientific Data Research Center invited through RFA-DK-16-024.

The APOLLO Network consortium will design and conduct studies to determine the impact of APOL1 genetic variants as susceptibility factors in US kidney transplant recipients who received kidneys from African American donors. In addition, the consortium will follow the course of African American kidney donors. Primary outcomes are the rate of change of kidney function in recipients, and rates of acute rejection of the kidney transplant, graft failure, and return to maintenance dialysis rates in the recipients. Outcomes in donors, focusing on vital and renal functional status, will be assessed to the greatest extent possible.

African Americans have higher rates of incident end-stage renal disease (ESRD) than European Americans. MYH9 and APOL1 loci on Chromosome 22 have been linked with non-diabetic kidney disease in several recent studies. Two alleles of the APOL1 gene, G1 and G2, are associated with higher risk of focal glomerulosclerosis and hypertension-attributed kidney disease. The G1 and G2 APOL1 kidney risk alleles are common throughout Sub-Saharan Africa and in African-Americans, and are also found in other individuals with African-ancestry admixture, such as Caribbean Latinos. While the risk allele frequency in African Americans for G1 or G2 is approximately 30%, it is much lower in Hispanics with African admixture and extremely low in European Americans. These variants may explain 70% of the excess focal segmental glomerulosclerosis, HIV-associated nephropathy and hypertensive kidney disease in African Americans.

The pathogenesis of kidney disease in those with APOL1 variants is thought to depend on "second hits" such as the presence of additional genetic susceptibility factors, or the result of environmental factors such as viral infections. Although some work has been published, little is known about the interaction of sickle cell disease and trait with APOL1 variants in persons at risk to result in renal disease.

Studies from the NIDDK-supported African American Study of Kidney Disease and Hypertension (AASK) and the Chronic Renal Insufficiency Cohort (CRIC) suggest poorer outcomes in participants with APOL1 variants. The value of genetic screening programs for APOL1 susceptibility variants in African-Americans with or at risk for chronic kidney disease (CKD) and cardiovascular disease (CVD) is uncertain, since there is no known specific intervention for such patients.

Screening for APOL1 susceptibility variants in kidney donors prior to surgery may have an important impact on outcomes for kidney transplant recipients. Several small studies suggest the presence of donor variants is associated with adverse outcomes for the recipients of kidneys with APOL1 susceptibility variants. Donors with two APOL1 variants convey higher risk of allograft failure to recipients. Those who receive kidneys with one APOL1 variant have outcomes similar to that of patients who receive a kidney from a donor without these variants, in small studies. The number of observations published, however, also remains relatively small.

Published studies typically have genotypes only from either kidney donors or transplant recipients, not from pairs, and do not include nationwide data. In three observational studies that assessed the impact of APOL1 positive kidney donors on outcomes after kidney transplantation, the adjusted hazard ratio for graft loss ranged from 0.96 (not significant) to 3.84 (p=0.008) and 2.26 (p=0.001). Follow up was 6-7 years in both of the larger studies, but graft loss occurred disproportionately in the first two to three years.

Screening of African American kidney donors for APOL1 alleles may exclude many potential donors, which may further reduce the availability of transplants in a population already less likely to undergo transplantation. Furthermore, differential kidney allocation might ensue following incorporation of APOL1 data into the Kidney Donor Profile Index.

Currently, transplantation of organs from HIV infected donors to HIV infected recipients is allowed in the US under research protocols.

The consequences of APOL1 status in living donors are also important, as the outcomes of donation in people with one or more variants are unknown, thus having implications for both donors and recipients. However, the number of transplant donors needed to detect statistically significant differences in their outcomes is likely to be considerable. It is unclear whether APOL1 variant status should be assessed routinely in either donors or recipients, highlighting the need for more rigorous studies using information from paired donors and recipients, with evaluations of both genotypes and longitudinal kidney disease and transplant outcomes. In addition, kidney biopsy data to exclude confounding causes of graft failure, such as rejection and infection, would be useful in understanding outcomes. Of note, the pathognomonic biopsy findings of APOL1-mediated kidney disease in a transplant setting are currently undefined.

Forty of the transplant centers within the US perform the majority of kidney transplants in African-American recipients. 40 of the transplant centers within the US perform the majority of harvests of kidneys from African-American donors. In each case, a substantial minority of harvests of kidneys donated by African-Americans and the transplantation of those kidneys are performed in a relatively large number of centers, each with a small patient population. Between 500 and 600 living African-American donors a year are the source of kidneys for US transplant centers. A challenge is devising a research strategy with which information from all deceased and living donor kidneys can be accessed.

At a NIDDK-sponsored workshop held in June 2015, speakers raised a wide spectrum of questions about clinical manifestations, epidemiology, and molecular pathophysiology of APOL1-mediated disease in kidney transplant donors and their recipients. This area of research was considered very high priority by workshop participants.

This FOA will establish Clinical Centers to work collaboratively with a Scientific Data Research Center (SDRC) in an APOL1 Long-term Kidney Transplant Outcomes (APOLLO) Network assembled to design and conduct one or more clinical cohort studies in African-American adult and pediatric kidney transplant donors and recipients. The network is expected to comprise a wide range of expertise, including but not limited to adult and pediatric transplant nephrologists and surgeons, geneticists, and biostatisticians and ethicists.

The APOLLO Network Consortium will design and conduct studies to determine the impact of APOL1 genetic variants as susceptibility factors in all US kidney transplant recipients who received kidneys from African American donors. It will also be important to evaluate donors for potential African ancestry and the presence of APOL1 risk alleles. Primary outcomes are the rate of change of kidney function in recipients, and rates of acute rejection of the kidney transplant, graft failure, and return to maintenance dialysis rates in the recipients. In addition, the consortium will follow the course of African American kidney donors to the greatest extent possible, focusing on vital and renal functional status.

The Clinical Centers will work in a collaborative, harmonious and efficient manner with the United Network for Organ Sharing (UNOS), in order to comprehensively maximize the number of participants and collection of genotypic information and assessment of comprehensive and important clinical outcomes on all African-American kidney donors, and when relevant, other donors with African ancestry, as well as the patients who receive those transplanted kidneys in the US, during the study period, within the purview of the Network.

The primary objective of the APOLLO Network consortium will be to assess outcomes in all the patients in the US who receive a kidney from an African-American donor. Although power will be limited, the APOLLO Network Consortium will also attempt to ascertain meaningful longitudinal clinical outcomes in the African-American, and when relevant, other African ancestry donors in the study, focusing on vital and renal functional status. The Clinical Centers will have the primary responsibility for obtaining genetic and clinical information from all African American, and, as appropriate, other African ancestry donors and the recipients of their kidneys, and following the course of the kidney transplant recipients and the living donors.

The SDRC will have primary responsibility for performing genotyping, coordinating ascertainment of relevant genotypes and linking these to the outcomes of the donors and recipients, from data provided by the Clinical Centers.

It is envisioned that a successful applicant for a Clinical Center will have a large population of African-American living and deceased kidney transplant donors, and a large population of recipients of those kidneys. In addition, a successful applicant will have established relationships with a large number of the smaller centers (perhaps geographically based) that perform relatively small numbers of harvests of kidneys from African-American donors and perform transplantation of these kidneys. In this manner, it is envisioned that the Clinical Centers of the Network will obtain clinical and genetic information from every one of the African-American kidney donors in the US, and from the patients who receive these kidneys.

Studies proposed in the applications will be the starting point for discussions regarding the research to be undertaken by the network. APOLLO investigators will devise studies that will be reviewed by an External Expert Panel (EEP) and approved by the NIDDK, in order to provide the most comprehensive inclusion of African-American kidney donors and the recipients of those kidneys in the US. The final study protocol will be designed by the Clinical Center and Scientific Data Research Center Program Directors/Principal Investigators and approved by the Steering Committee, and then the EEP and the NIDDK. Network study results are expected to provide evidence for management approaches to kidney donation in African-Americans.

The long-term goal of the APOLLO Network Consortium is to inform clinical practice by a) providing data regarding the effects of APOL1 variants on outcomes of the recipients of kidneys from African-American, and, when relevant, other African ancestry donors, b) providing data regarding the effects of APOL1 variants on long-term survival and renal functional outcomes of the donors of the kidneys, and c) establishing a resource of clinical and genetic data, and biological specimens for APOLLO Network and other future researchers through the NIDDK Central Repository.

The APOLLO Network Consortium will consist of up to 15 Clinical Centers (CC) and one Scientific Data Research Center (SDRC). The SDRC and CC investigators will work collaboratively on the design, planning, execution and analysis of APOLLO studies.

The Clinical Centers will be responsible, as a group, for obtaining biological samples, genetic and clinical information from all the African-American kidney donors and the recipients of those kidneys, across the United States, at baseline and longitudinally, and transmission of those data and samples to the SDRC.

The SDRC will be primarily responsible for insuring the scientific integrity, comprehensiveness and robustness of the research design, biostatistics, data quality, implementation, and data analysis of all study protocols. The APOLLO SDRC investigators, including biostatisticians, will work with the Clinical Center investigators to develop the scientific design of the study.

The SDRC will have primary responsibility for ensuring that the relevant genetic information from all US African American donors, and the recipients of their donated kidneys is obtained, stored and available for study both within and eventually outside the APOLLO Network.

The APOLLO Network investigators will have the primary responsibility for ensuring that the design of the studies, including the primary outcome, is scientifically sound, comprehensive (including the vast majority of African-American kidney donors and the recipients of their kidneys) with sufficient statistical power to study the primary outcomes. The SDRC will provide biostatistical and analytic expertise, and conduct analyses and interpretation of the genetic, laboratory and clinical data in conjunction with the investigators at the Clinical Centers. The SDRC and CCs will work closely with UNOS to achieve the goals of the APOLLO.

Administration and Meetings

The APOLLO Steering Committee (SC) will be composed of the SDRC and CC Program Directors/Principal Investigators (PDs/PIs), other key investigators and the NIDDK Project Scientist. The SC will meet regularly in-person in the Bethesda / Washington DC metropolitan area, and by telephone or webinar, as necessary, as a full committee and in working groups to develop and implement study protocols. The SC will review progress of individual studies, assess and evaluate results, interpret findings, and develop manuscripts for peer reviewed publications.

The NIDDK will select a chair of the SC [Steering Committee Chair (SCC)] either from the PDs/PIs of the CC s, or outside the study group. An Executive Committee (EC) will be comprised of the Steering Committee Chair, the SDRC PDs/PIs, and the NIDDK Project Scientist. Additional APOLLO Network investigators, NIDDK Program Officers and other NIH officers, and support personnel may participate in the EC as needed. The Executive Committee will make operational decisions for the APOLLO Network between SC meetings by means of weekly telephone conference calls. The NIDDK Project Scientist will assist the SC in the development of APOLLO Network study protocols, will monitor the progress of projects and functioning of all network activities, will assist investigators in the analysis and interpretation of APOLLO Network data and will participate in all aspects of the research and in preparation and writing of all manuscripts from consortial studies for publication.

The NIDDK will appoint an External Expert Panel (EEP), as needed, to provide input on the design of studies prior to their implementation. The EEP will monitor the research efforts and the progress of the studies, and advise primarily the NIDDK as well as the APOLLO investigators. CC and SDRC applicants should not suggest potential participants for this committee in their applications.

The first in-person APOLLO Network Steering Committee Meeting will be a 2-day meeting held on 2 consecutive days within 1 month of the inception of the network in the Washington, DC metropolitan area. Specific dates will be determined once the APOLLO sites are awarded. Subsequent 1-2 day in-person SC meetings will be conducted every 3 months for the first year and yearly or more often as needed thereafter.

A Funding Opportunity Announcement informational conference call will be scheduled December 14 2016 to describe and explain the objectives, expected structure and functioning of the APOLLO Network. Participation in this conference call is not required for application submission.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving 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)

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)
• 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

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.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• 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.
• eRA Commons - Applicants 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 submit an application.
• Grants.gov Applicants must have an active DUNS number and 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 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 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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 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 NOT-OD-11-101).

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.

It is critical that applicants follow the Research (R) Instructions in the SF424 (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 review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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, preferably electronically, should be sent to:

Michele Barnard, PhD
Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
6707 Democracy Boulevard, Room 752, MSC 5452
Bethesda MD 20892-5452
(for express/courier service: Bethesda MD 20817)
Telephone: 301-594-8898
Fax: 301-480-3505
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 applications, the titles for each application in the set must have the following format: a 1/N indicator + Identical Title (e.g., 1/3 , where the 1/3 means this is site 1 of 3 sites in the set. A set of applications is defined as all applications submitted in response to this FOA as well as the companion FOA (RFA-DK-16-024). Titles of all collaborative applications must be identical except as follows: Applications submitted in response to this FOA must include "Clinical Center" at the end of the title; the application submitted in response to RFA-DK-16-024 should include "Scientific Data Research Center" at the end of the title. The other sites will be labeled 2/3, etc.) Titles may not exceed 200 characters in length, including the tag, e.g., 1/3, 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 applications being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., 1/3 ), 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: The following attachments must be included

1. Clinical Protocol Synopsis

The filename "Clinical Protocol Synopsis.pdf" should be used.

The synopsis is meant to supplement rather than duplicate the information provided in the Research Strategy and should include the following information:

A description of the study population, including subject eligibility and inclusion/exclusion criteria; A discussion of the participants at each center; a table showing the demographics of the population at each site and overall should be included; Approaches to be used for retention, addressing any anticipated changes in the composition of the study population over the course of the study; A description of all primary and secondary outcomes measures; A timeline of study activities.

Applications that lack the Clinical Protocol Synopsis are incomplete and will not be peer reviewed.

2. Statistical Analysis Plan

The filename "Statistical Analysis Plan.pdf" should be used.

The Statistical Analysis Plan is meant to supplement the information provided in the Research Strategy. The applicant(s) should describe the statistical methods to be used, including the sample size and power calculations, plans for the primary and secondary analyses, and any pre-specified interim analyses. The plan is critical to knowing whether applicants have selected the correct cohort size and/or are using the most appropriate methods to analyze the data and make the correct conclusions at the end of the study.

Applications that lack the Statistical Analysis Plan are incomplete and will not be peer reviewed.

All instructions in the SF424 (R&R) Application Guide must be followed.

Key personnel must include transplant nephrologists and surgeons, geneticists, ethicists, biostatisticians, and advisors from UNOS, organ procurement organizations and from the relevant community patient population as personnel for the Clinical Center.

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:

Research Strategy: The application must contain a Research Strategy that clearly describes those aspects of the project pertaining to the Clinical Center, as well as those that are common to all sites of the collaboration. All variations in the Research Strategy between sites 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 obtaining data from smaller transplant centers.

The Research Strategy section for the CC should include:

• A discussion of the significance of the problem being studied, the need for the studies, and the potential impact of the results of the studies, as well as how the studies will test the hypothesis(es) proposed;
• A concise description of the overall strategy, methodology and analyses to be used to accomplish the goals and specific aims of the study;
• A description of and rationale for the proposed study designs;
• A description of the participants to be included, the data to be collected and the protocols to be followed, including a discussion of potential biases or challenges in the protocols and how they will be addressed;
• Statistical methods that are appropriate for the study designs, including sample size and power calculations and the underlying assumptions (and data) used to link these calculations to the endpoints and to the hypothesis(es) being tested;
• A consideration of how the most comprehensive and all-encompassing initial evaluation and follow-up of all US African-American kidney donors and the recipients of these kidneys will be accomplished by the Clinical Center, in collaboration with the other Clinical Centers and the SDRC;
• A consideration of how non-African American donors with African ancestry will be evaluated for APOL1 risk alleles and for study participation;
• A plan for partnering with a large number of kidney transplant centers performing relatively few harvests of kidneys from African-American donors and transplanting them; all Clinical Center applications must present a plan for collaborating with smaller renal transplant centers to achieve the overall APOLLO goals of comprehensive longitudinal evaluation of African American donors.
• Evidence of commitment of specific smaller centers is not required at this point, but is strongly recommended.
• Discussion of how genotype data will be obtained from the African American donors and the recipients of the kidneys, how the data will be collated and analyzed by the Network, and how genetic material and information will be transferred to the SDRC and the NIDDK Central Repository and deposited in dbGaP.
• Discussion of how data on renal functional status and other important baseline and longitudinal clinical outcomes of recipients will be collected by the Clinical Center, and how their relationship to genetic status, including APOL variants and other genetic findings, will be analyzed by the Network, in cooperation with UNOS.
• Discussion of how data on initial and longitudinal renal functional status and other important clinical outcomes of African American kidney donors will be collected and how their relationship to genetic status will be analyzed by the Network, in cooperation with UNOS. Yearly evaluation of serum creatinine concentration and urinary protein excretion should be provided.
• Discussion of how analyses of genetic findings and clinical findings will be analyzed together.
• Demonstration of the ability of the Clinical Center to work seamlessly with UNOS so data on all African-American kidney donors and the recipients of those kidneys can be accessed;
• Demonstration of the ability of the Clinical Center to work seamlessly with the organ procurement organizations so data on all US African-American kidney donors and the recipients of those kidneys can be accessed.
• Discussion of how the center will partner with other transplant groups so data on all US African American kidney donors and the recipients of those kidneys will be included in the studies of the Network.
• Discussion of studies that led to the proposed clinical studies and information or data from preliminary studies that address the need for and the feasibility of the studies; and
• An acknowledgement and discussion of the responsibilities of the Center as part of a multi-center collaborative project.

Clinical Center applicants should describe how they will carry out major scientific responsibilities, including:

• Providing research study design and implementation expertise for all APOLLO Network studies.
• Ensuring the scientific integrity and robustness of the research design, implementation, adherence, and data quality of all study protocols.
• Handling subject confidentiality and safety.
• Conducting training and certification of study staff.
• Monitoring the implementation of the studies including adherence and data quality.
• Obtaining genotypic information, including information on genetic and environmental "2nd hits" of all donors and recipients.
• Working collaboratively with the APOLLO Network SDRC PDs/PIs, UNOS and organ procurement organizations in planning and conducting the various research efforts undertaken by the Network.
• Staffing the CC with transplantation clinicians, including nephrologists and surgeons, geneticists, ethicists and advisors from UNOS and organ procurement organizations, and from the relevant community patient population, in a meaningful way.

An application for a Clinical Center must:

• Propose study designs incorporating innovative strategies, and analytical approaches to accomplish the goals of the FOA, including obtaining comprehensive inclusion of data on outcomes of all kidneys donated by African-Americans in the US.
• Present experience of the team as a whole with a wide range of clinical studies.
• Present a plan for coordination of biosample (e.g. serum, plasma, DNA, tissue, stool and urine, as applicable) collection, storage, quality control and distribution of data and clinical samples.
• Present a plan to work collaboratively with the SDRC investigators and UNOS representatives in the planning, implementation and analysis of all major studies
• Describe the roles, responsibilities and interactions of the CC investigators with the SDRC and provide a leadership plan.

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, with the following modification:

• Clinical Center applications should provide a Data Sharing Plan.
• APOLLO Network investigators are expected to share their findings with the scientific community through scientific presentations and publications, and through sample and data sharing, according to NIDDK policies.
• All APOLLO Network-derived data and biological samples are expected to be provided to the NIDDK Data and Sample Biorepositories in accordance with Institute guidelines, consistent with achieving the goals of the program.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

All instructions in the SF424 (R&R) Application Guide must be followed.

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.

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.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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 field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

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 review system.

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).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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

Do the CC key investigators have documented kidney transplantation expertise? Does the CC have expertise in ensuring scientific integrity and robustness of the proposed clinical research studies? Are personnel from UNOS and organ procurement organizations included in the leadership structure of the CC?

Does the application describe the roles and responsibilities of the key investigators with a leadership plan?

Does the CC have expertise in performance of genetic studies? Does the CC have expertise in design, performance and analysis of kidney transplantation studies? Does the CC have expertise in design, implementation, adherence, and data quality? Is there evidence of experience in analyzing data from observational studies, pragmatic studies and biomarker studies? Do CC key investigators have a track-record of research productivity and cooperation within a broad, multi-site research effort?

Is sufficient expertise in place for the collection, coordination and transfer of biosample collection, storage, quality control and distribution (e.g. serum, plasma, DNA, tissue, stool and urine, as applicable)? Have the investigators demonstrated that they can work collaboratively with UNOS to achieve comprehensive identification and followup of outcomes related to all kidney donations of African-Americans in the US? Have the investigators demonstrated that they can work collaboratively with organ procurement organizations to achieve comprehensive identification and followup of outcomes related to all kidney donations of African-Americans in the US?

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?

Does the CC propose innovative approaches to the scientific question(s), research design, data quality, implementation, or data analysis efforts? Does the CC propose innovative approaches to achieving comprehensive identification and followup of outcomes related to all kidney donations of African-Americans in the US? Has the CC included representatives of the kidney donor and recipient communities, and organ procurement organizations to provide advice on the planning and conduct of the studies? Has the CC proposed innovative ways of interacting and partnering with UNOS and organ procurement organizations to maximally use, in a comprehensive, synergistic fashion, the data collected by that organization, to achieve the goals of the FOA?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Does the CC propose research study designs and analytical approaches to achieve the goals of this FOA? Does the CC propose integrated analyses of the clinical, genetic and treatment data in recipients? Does the CC propose comprehensive plans for collection and analysis of genetic information in the universe of African-American kidney donors and the recipients of those kidneys, including quality control and assurance efforts and assessments? Does the research plan provide relevant materials to the NIDDK Central Repository? Has the CC proposed feasible ways of interacting and partnering with UNOS to maximally use, in a comprehensive, synergistic fashion, the data collected by that organization, to achieve the goals of the FOA?

Have the CC investigators considered pitfalls in attempts to cover the US African American donor population comprehensively, as well as all recipients of those kidneys, including issues related to obtaining informed consent and longitudinal followup, in addition to using data provided by UNOS?

Have the CC investigators presented a plan for efficient evaluation of non-African American donors with African ancestry for study participation?

Has a plan been proposed for collaborating with smaller renal transplant centers to achieve the consortial goal of evaluation of all African American donors and the recipients of these kidneys?

Has the CC proposed ways to engage the large number of transplant centers harvesting smaller numbers of kidneys from African American donors, and performing transplantation of these kidneys, so the goal of including 100% of all kidneys donated by African Americans for transplantation in the US for analyses is achieved by the APOLLO Network?

Has the CC proposed a plan to evaluate all African American donors, as well as non-African American donors with African ancestry-specific APOL1 alleles, longitudinally with measurements of renal function and urinary protein excretion?

Has the CC proposed feasible ways of interacting and partnering with organ procurement organizations and UNOS to maximally use, in a comprehensive, synergistic fashion, the data collected by the organizations, to achieve the goals of the FOA?

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

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

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.

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

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

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

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

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

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.

Not Applicable

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

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

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.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIDDK, 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:

• 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.
• Will receive a written critique.

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 National Diabetes and Digestive and Kidney Diseases Advisory Council (NDDKAC). 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.

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.

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 grantee’s business official.

Awardees 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.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

1. Developing the research design and study protocol, including definition of objectives and approaches, sample size and power calculations, and establishing procedures for participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and publication of results.

2. Establishing a Steering Committee to implement, coordinate and manage the project(s). Awardee(s) will name investigators to serve as members on a Steering Committee and other subcommittees, as appropriate, meeting periodically. Awardees will be required to accept and implement the common protocol(s) and procedures approved by the Steering Committee.

3. Designating Protocol Chairs. The Program Directors/Principal Investigators (for studies involving multiple protocols) shall designate a single Protocol Chairperson (if the Program Director/Principal Investigator does not assume this role) for each protocol to be carried out by the study group. The Protocol Chairperson shall function as the scientific coordinator for the protocol and shall assume responsibility for obtaining approval to implement the protocol from the Steering Committee and for developing and monitoring the protocol. Significant modifications to approved protocols must be approved by the Steering Committee.

4. Implementing collection of data specified by the study protocol. For a multi-center study, each awardee/site is required to ensure that data will be submitted expeditiously to the Data Coordinating Center. Additionally, individual investigators/sites must demonstrate the ability to implement the strategy specifically designed for their individual study population.

5. Establishing procedures for data quality and completeness. Awardees are responsible for ensuring accurate and timely assessment of the progress of each study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis; (2) for clinical trials, as simple as appropriate in order to facilitate cooperation/referral of study participants by physicians to avoid unnecessary expense; and (3) sufficiently staffed across the participating institutions. For research involving multiple sites, a plan for analysis of pooled data will be developed by the Steering Committee.

6. Submitting interim progress reports, when requested or agreed upon by both parties, to the NIDDK Program Official including as a minimum, summary data on protocol performance. For coordinated multiple awards or a multi-site single award, the NIDDK Program Official may require additional information from individual awardees/sites. Such reports are in addition to the required annual noncompeting continuation progress report.

7. Reporting of the study findings. Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. The awardee must also be adherent to Study Publication and Presentation Policy. The NIDDK will have access to and may periodically review all data generated under an award. NIDDK staff may co-author publications of findings with awardees consistent with NIH and study policies.

8. Any involvement of a third party in the study, including access to any study data; study results; using the name of the study; or the name of the NIH or NIDDK, is permitted only after concurrence by the NIDDK Program Official who may consult with others at NIH including the NIDDK Technology Advancement Office.

9. Study investigators are encouraged to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols and steering committee policies on publications.

10. Maintaining confidentiality of information: The awardee(s) will maintain the confidentiality of the information developed by the investigators (i.e., protocols, data analysis, conclusions, etc.) as well as proprietary information of a company collaborating with the study.

11. The NIDDK has established Central Biosample, Genetic, and Data Repositories for the archiving and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. The PI or his/her designee will coordinate with the NIDDK Data Repository to prepare the collected data for eventual archiving and distribution. In addition, if applicable, the PI or his/her designee will work with the NIDDK Biosample Repository to coordinate procedures for coding, shipping, processing, receipt, and storage of study samples that are to be maintained in the Repository. All samples and data transferred to the Repositories will be under the custodianship of the NIDDK, although the study’s Steering Committee will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time. Subsequently samples and data will be available to the wider scientific community in accordance with the NIH policy on Data Sharing (http://grants.nih.gov/grants/policy/data_sharing/ and,

http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm#goals, and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm), as well as the NIDDK policy for data sharing in multi-center and large single-center clinical studies http://www.niddk.nih.gov/research-funding/process/human-subjects-research/Documents/PublicversionNIDDKdatasharingpolicy2013July2013.pdf.

12. The Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law requires mandatory registration and results reporting for certain clinical trials of drugs, biologics, and devices. If trials conducted under this grant are applicable clinical trials subject to FDAAA, the sponsor or his/her designee will perform the mandatory study registration and reporting of study results to ClinicalTrials.gov. For more information about this law and requirements for sponsors and/or investigators, visit the PRS and U.S. Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov/fdaaa.html. In addition, grantees should be aware that clinical trials not covered by FDAAA may still require registration in an approved registry in order to be published, according to the guidelines issued by the International Committee of Medical Journal Editors (http://icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html).

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

An NIDDK Project Scientist with substantial involvement will:

1. Serve as the contact point for all facets of the scientific interaction with the awardee (s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the awardee on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Project Coordinator, who will provide direct technical assistance to the awardees to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.

2. For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or Project Coordinator will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.

3. Serve as a resource to study investigators with respect to other ongoing NIDDK activities that may be relevant to the study to facilitate compatibility with the NIDDK missions and avoid unnecessary duplication of effort.

4. Have substantial involvement assisting in the design and coordination of research activities for awardees as elaborated below:

a. Assisting by providing advice in the management and technical performance of the investigations, coordinating required regulatory clearances for investigational agents used in the study, which are held by NIDDK. The NIDDK may reserve the right to cross file or independently file an Investigational New Drug Application or an Investigational Device Exemption form with the FDA.

b. The NIDDK Project Scientist or Project Coordinator may coordinate activities among awardees by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results.

c. Reviewing procedures for assessing data quality and study performance monitoring.

d. The NIDDK Project Scientist or Project Coordinator may be co-authors on study publications. In general, to warrant co-authorship, NIDDK staff must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.

The NIDDK Program Official identified in the Notice of Award will:

Interact with the Program Director(s)/Principal Investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the Program Director/Principal Investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, data safety and monitoring board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.

Review and approve protocols prior to implementation to insure they are within the scope of peer review, for safety considerations, as required by Federal regulations.

The NIDDK Program Official will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; (f) low likelihood of showing a benefit of the intervention (futility); and (g) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.

Make recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.

Appoint an independent Data and Safety Monitoring Board (DSMB) as appropriate for Phase III clinical trials or other high risk studies, or an Observational Study Monitoring Board (OSMB) for observational/epidemiologic studies; these Boards will review study progress, safety data, and interim results, as appropriate, and provide guidance to the NIDDK. The NIDDK Program Official or their Project Coordinator will serve as the Executive Secretary and/or NIDDK program representative on the DSMB/OSMB.

Areas of Joint Responsibility include:

In addition to the interactions defined above, NIDDK Project Scientist and Awardees shall share responsibility for the following activities:

Steering Committee

A Steering Committee organized by the study investigator(s) will be the main governing body of the study.

The Steering Committee has primary responsibility to design research activities, establish priorities, develop common protocols and manuals, questionnaires and other data recording forms, establish and maintain quality control among awardees, review progress, monitor patient accrual, coordinate and standardize data management, and cooperate on the publication of results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIDDK Program Official, and will provide periodic supplementary reports upon request.

The Steering Committee will be composed of all Program Director(s)/Principal Investigator(s), (including those of data coordinating /statistical centers, if any) and co-investigators as deemed necessary, and the NIDDK Project Scientist. The final structure of the Steering Committee and voting procedures will be established at the first meeting. The NIDDK Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee.

A Chairperson of the Steering Committee, other than the NIDDK Project Scientist, will be selected by the NIDDK, in consultation with the Steering Committee. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings, representing the study group to the External Oversight Committee established by the NIDDK and by interacting closely with the awardees during protocol development and implementation.

Dispute Resolution

Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NIDDK may be brought to dispute resolution. A dispute resolution panel will be composed of three members --one selected by the awardee (or the Steering Committee, with the NIDDK member not voting), a second member selected by NIDDK, and the third member elected by the two prior selected members. These special dispute resolution procedures in no way affect the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CR Part 16.

When multiple years are involved, awardees 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 progress report, 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Paul L Kimmel, MD, MACP
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-1409
Email: [email protected]

Nishadi Rajapakse, PhD, MHS
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-496-4338
Email: [email protected]

Jonah Odim, MD, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3540
Email:[email protected]

Barbara Woynarowska, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-402-7172
Email:[email protected]

Charlette Kenley
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8847
Email: [email protected]

Priscilla Grant
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8412
Email: [email protected]

Donna Sullivan
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2979
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.