Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)
 

Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Funding Opportunity Title

Advancing Clinical Research in Primary Glomerular Diseases (UM1)

Activity Code

UM1 Multi-Component Research Project Cooperative Agreements

Announcement Type

New

Related Notices
  • September 20, 2012 - Notice of Change in Eligibility of Foreign Institutions for NIDDK RFA-DK-12-014. See Notice NOT-DK-12-021.
Funding Opportunity Announcement (FOA) Number

RFA-DK-12-014

Companion Funding Opportunity

None

Number of Applications

Only one application per institution is allowed as defined in Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.847

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to support translational and clinical research that promotes therapeutic development for primary glomerular diseases.  The emphasis of this FOA is specifically on chronic forms of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), immunoglobulin A nephropathy (IGAN), and idiopathic membranous nephropathy (IMN).

Key Dates
Posted Date

September 7, 2012

Letter of Intent Due Date

January 27, 2013

Application Due Date(s)

February 27, 2013

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

June/July 2013

Advisory Council Review

October  2013

Earliest Start Date(s)

December  2013

Expiration Date

February 28, 2013

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of 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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

A. BACKGROUND:  The disease focus of this solicitation is primary glomerular disease resulting specifically from minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), immunoglobulin A nephropathy (IGAN), and idiopathic membranous nephropathy (IMN).  These chronic disorders often produce symptoms of edema and signs of nephrotic range proteinuria and/or hematuria in both adults and children.  Progressive loss of kidney function occurs over many years, and these diseases are responsible for approximately 10% of incident end stage renal disease (ESRD) patients per year. 

There have been recent knowledge advances in the mechanistic aspects of these diseases that provide hope for new methods of diagnosis and treatment.  Genetic mutations within the Podicin and Nephrin genes result in some forms of childhood nephrotic syndrome of MCD or FSGS, and adult FSGS in people of African descent is now linked to the APOL1 gene.   A hyposialylated Angiopoietin-like 4 protein has been shown to result in MCD with severe proteinuria, which is treatable in rodent models.  Increased levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with FSGS; inhibition of suPAR may be a therapy for this disease.  Recent studies have identified antibodies to the M-type phospholipase A2 receptor (PLA2R) as the cause of a large percentage of IMN in humans.  Other studies have demonstrated a multi-hit mechanism for IGAN involving the increase in an aberrant IgA1 antibody followed by antibody formation to the o-glycan portion of the IgA, formation of circulating immune complexes with subsequent deposition in the mesangium and glomerular injury.  These mechanisms provide potential targets and biomarkers for these diseases.

Major challenges to development of clinical therapies for these diseases are their relative rarity in comparison with the more common diabetic nephropathy and the slow progression that is often measured in decades rather than months to years.   This translates into significant difficulties in participant recruitment for sufficient numbers for the study of mechanisms, identification of disease targets and biomarkers, and diagnostic development in translational and clinical studies.  Subsequent trials of specific new therapies are difficult for the same reasons.  In addition, the hard endpoints of mortality and ESRD are not appropriate in these diseases for trials of only a few years duration.  Alternative outcomes (e.g., biomarkers or patient reported outcomes) are typically required to be validated and acceptable to the FDA prior to the launch of a phase III trial.

B.  OVERALL GOALS: The NIDDK seeks to form a collaboration of academia, industry (e.g., pharmaceutical companies), government (e.g., FDA, NIH), and advocacy groups in order to establish and follow a longitudinal, observational cohort of patients using a common protocol.  The overall goals of this consortium include:

1.  Importance of the scientific question(s) that will form the basis of the longitudinal cohort data collection

2.  Development of a common protocol (with specific elements for each disease, if necessary)

3.  Recruitment of participants for a natural history cohort study

4.  Longitudinal collection of phenotypic, genetic, biochemical, and tissue data

5.  Analysis of these data including Systems biology approaches to the dataset

6.  Applications for subsequent ancillary studies to identify disease targets, develop biomarker-therapy combinations, and establish and validate Patient Reported Outcomes (PROs) and surrogate outcomes for disease progression and remission

The common protocol will be developed in the first two months after award, after which recruitment will take place over the next 3 years or until the number is sufficient for the study goals.   NIDDK estimates that approximately 2400 participants or 600 per disease entity will be required for the future requirements in this research area, as well as 2400 controls.  Follow-up of these patients is anticipated to be ongoing until significant progression (e.g., doubling of creatinine) or ESRD or death occurs.   In the present economic environment, no one agency or entity will be able to fully fund all the research that is required to address these diseases, and therefore the NIDDK is open to collaborations set up as public-private partnerships (http://ppp.od.nih.gov).  Proposed collaborations must include close interaction with the FDA on biomarker and surrogate outcome development.  Collaborations with industry on pre-competitive items are encouraged.  Partnerships with advocacy groups may accelerate and strengthen patient recruitment. 

C.  IMPORTANT ELEMENTS OF APPLICATIONS ARE:

1.  Discussion of scientific questions that need to be addressed within the longitudinal cohort.

2.  Diseases to be studied are restricted to chronic forms of MCD, FSGS, IGAN, and IMN.  Chronicity is defined by a disease progression of months to years versus acute kidney injury with progression of days to weeks.  All sites should recruit for all diseases, and NIDDK recognizes that sites may have to subcontract to other sites to attain their goals.  Diagnosis will be established by renal biopsy either prior to or on entry into the cohort.  Diagnosis with diabetes, diabetic nephropathy or another renal disease will preclude participants from the study.

3.  Definition of inclusion and exclusion criteria as well as a separate control cohort of normal participants without apparent kidney disease.  Recruitment should include adult and/or pediatric participants.  Efficient use of electronic health records or other on-line databases (e.g., advocacy groups) for recruitment and follow-up is encouraged.

4.  Definition of the number of participants with each disease entity to be recruited along with realistic strategies, including back-up plans, for recruitment of adults and children.  It is recognized that there may not be adequate numbers of pediatric patients with all four diseases, particularly IGAN and IMN; this should be discussed in the application with explanation of the value of their longitudinal follow-up despite low numbers.  Existing cohorts can be used, but the steering committees of existing cohorts would have to agree to all aspects of a common protocol designed by the steering committee of this collaboration.   

5.  Proposed protocol for collection of longitudinal data, including timing of visits and specimen  collection, phenotypic data (including symptoms to facilitate development of patient reported outcomes, [PRO]), genomic data, biochemical data, and tissues.  These data should support future R01-funded ancillary studies (to be funded separately with PAR-12-NNN), which likely include the following among many research topics:

a. Establish, validate, and qualify alternative outcomes for disease flare or relapse in conjunction with the FDA.  These might include PROs as well as physician- or other medical practitioner- reported outcomes.  These should include short-term goals, i.e., testing of known biomarkers as well as long-term goals of potential alternative outcomes.

b. Identify biomarkers (diagnostic, prognostic, progression) from pathophysiologic, molecular, and genetic studies of patients and of controls or from the application of Systems biology to the combined data sets that will be collected. 

c. Develop biomarker - therapy combinations that halt or retard disease progression and test these in Phase 0 Studies (FDA qualification).

d. Develop technological solutions for real-time measurements in a.-c.: new techniques to improve the efficiency of data collection (e.g, use of smart phones to report ongoing symptoms (PROs) or vital signs or devices for measuring proteinuria and transmitting to a study site)

e. Facilitate Phase I pilot studies of potential therapies

6.  The successful applicants will meet at NIH on September 11-12, 2013 to draw up the common protocol.

It is envisioned that the Consortium will be composed of four Participating Clinical Centers (PCCs) which will recruit study participants and conduct studies, collecting data which will be submitted electronically to a single Data Coordinating Center (DCC). 

D.  SUCCESSFUL DCC APPLICATIONS WILL HAVE ADDRESSED ALL OF THE FOLLOWING: 

1. How the DCC will coordinate data collection, perform analyses and prepare study reports for the PCCs or other entities performing ancillary studies, in addition to preparing the final protocol(s) for review and approval.

2. The DCC will be responsible for the conduct of Steering Committee meetings and conference calls.  3. It is envisioned that a DCC will require at a minimum a senior Biostatistician, a Master’s level Biostatistician/Epidemiologist and a Database Manager and other key staff. 

4. It is envisioned that ancillary studies performed by the consortium or other entities will include multi-center studies. All data collected by PCCs in single and multi-center studies will be sent to the DCC for quality control and analysis. 

5.  All data collection and analyses (i.e., questionnaires, biochemical measurements, pathological specimens, clinical data) will adhere to the standards of the Clinical Data Interchange Standards Consortium (CDISC) in order to facilitate biomarker, surrogate outcome, and therapy development in accordance with the FDA guidelines. 

6. The DCC should include a description of the operating plan for the study (with characteristics as described in C.4 above) to illustrate how it will operate.  

E. SUCCESSFUL PCC APPLICATIONS WILL HAVE ADDRESSED ALL OF THE FOLLOWING:

1.  Discussion of one or more scientific questions that the PCC will emphasize in its cohort follow-up.

2.  The trial population with specific inclusion and exclusion criteria, data collection, proposed endpoints, and proposed manner of patient longitudinal follow-up in accordance with C."Important Items 1-6" above.  If a PCC applicant is made up of solely pediatric researchers, the entity should provide evidence of how they will carry out this longitudinal follow-up after the participant ages out of an acceptable range at the pediatric institution.

3. The target population should be carefully defined with respect to such variables as: disease entity including pathological (biopsy-proven) diagnosis, duration of disease, renal function, age, co-morbidities (e.g., hypertension, autoimmune and other diseases), gender, race, generalizability for ancillary studies, and other factors deemed important.  

4. Plans for selection and recruitment of study subjects, and backup plans, as appropriate.  Details of collaborations with advocacy groups or other longitudinal cohorts or other subcontracted sites should be given.

5. Plans for data collection of potential renal and non-renal biomarkers and alternative outcomes, if appropriate for the scientific question(s) from E.1.  This might include applications for known as well as potential future biomarkers.  Alternative outcomes should be acceptable to the FDA or should be qualified within future ancillary studies.  All proposed measurements should be justified by the proposed scientific question(s).

6. Statistical considerations, including power calculations for possible studies as outlined in C.5.

7. Demonstration of ability to work with industry or advocacy partners, who will submit letters of support or collaboration stipulating agreement to  a) provide drug(s)/biologic(s)/device(s)/assay to be used in future ancillary studies, b)  the use of provided  interventions in combination studies within the consortial structure,  c) allowing access to recruited participants to all consortial members, and d) working collaboratively with the PCC and other members of the consortium on conference calls and during Steering Committee meetings, and in the dissemination of research findings through presentations at scientific meetings and in publication in the scientific literature.

7.  Applicants for PCCs should demonstrate the importance of the proposed data collection for ancillary studies.  Applicants should demonstrate their experience in and ability to recruit a diverse and appropriate population for the longitudinal studies.  

F.  COMMON STUDY ISSUES FOR DCC AND PCC:

1.  Ability to establish Consortium Agreements (or policies/procedures) that address: (1) data sharing amongst members for data generated not only by the consortium but also data received by a PCC from industry or other collaborators; and (2) procedures for protecting any confidential information, including without limitation, data generated from the consortium or from industry partners or other external collaborators.  These procedures will address appropriate administrative, physical and technical safeguards that protect confidential information and prevent its inadvertent disclosure.  Each industry collaboration will be governed by an appropriate Research Collaboration Agreement with terms that ensure collaboration is conducted in accordance with the terms of the Cooperative Agreement and all applicable NIH policies and procedures.   Each industry/PCC agreement will address ownership of intellectual property discovered from multi-party data generated by the consortium, and the Consortium will develop intellectual property policies and procedures with terms that ensure collaboration and dissemination of research findings are conducted in accordance with the terms of the Cooperative Agreement and all applicable NIH policies and procedures.  Consortium policies will require continued submission of data centrally to the DCC and consortium policies/procedures will address protection of medical and genetic records of individuals. 

2. Awardees will meet to finalize the consortial study protocol(s).  Both PCC and DCC applicants should be prepared to participate in conference calls immediately after funding, and should reserve September 11 and 12, 2013 for the first Steering Committee meeting in Bethesda, Maryland.  Applicants should indicate their availabilities on these dates in their applications.

A Steering Committee will serve as the governing board for the Consortium; its actions and decisions will be determined by majority vote.  Membership on the Steering Committee will include a Steering Committee Chair (chosen by the NIDDK), the Participating Clinical Centers (PCC) and Data Coordinating Center (DCC)PD(s)/PI(s), and a NIDDK Project Scientist. 

The responsibilities of the Steering Committee include: Development of the common protocol that will address points E.1-7 above; Providing input on and approval of all studies developed by the Consortium members prior to or after study implementation; Review and approval of all data analyses, public presentations and publications of research conducted within the consortium; Development of policies and procedures for submission and approval of ancillary research applications using Consortium resources.

NIDDK will appoint an External Expert Group (EEG) who will have oversight over the conduct of the study and provide advice and guidance to the investigators and to the NIDDK during the study.  The steering committee will meet with the EEG at least once per year.

A pre-submission, informational phone conference will be held at 3 pm (EDT), October 11, 2012.  Contact Dr. Flessner for call-in details, flessnermf@niddk.nih.gov.

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

New

The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIDDK intends to commit approximately 3 million dollars in FY 2013 to fund the Consortium in response to this FOA. NIDDK anticipates four PCC awards and one DCC award.

Award Budget

An applicant may request approximately $350,000 direct costs in the first year for the Clinical Centers and approximately $500,000 direct costs for the Data Coordinating Center.  Applicants should specify that they propose to be a PCC or the DCC.

Future year amounts will depend on annual appropriations.

Award Project Period

The total project period for an application submitted in response to this funding opportunity may not exceed five years.    

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.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

 Foreign Institutions  

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.

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Section IV. Application and Submission Information

1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS398 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:

The letter of intent should be sent to:

Dr. Francisco Calvo
Chief, Review Branch
National Institute of Diabetes, Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Boulevard, Room 752
Bethesda, MD  20892-5452
Bethesda, MD  20817 (express/courier service)
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: calvof@niddk.nih.gov

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Dr. Francisco Calvo
Chief, Review Branch
National Institute of Diabetes, Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Boulevard, Room 752
Bethesda, MD  20892-5452
Bethesda, MD  20817 (express/courier service)
Telephone:  (301) 594-8897
FAX:  (301) 480-3505
Email: calvof@niddk.nih.gov

Page Limitations

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed. note:

Research Plan

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS398 Application Guide, with the following modification:.

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.

Foreign Institutions

Not Applicable

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in theNIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

6. Other Submission Requirements and Information

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

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

Pre-Submission Teleconference

A pre-submission, informational phone conference will be held at 3 pm (EDT), October 11, 2012.  Contact Dr. Flessner for call-in details, flessnermf@niddk.nih.gov.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1. Criteria

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.

Overall Impact - Overall

Reviewers will provide an overall impact/priority 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 - Overall

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? 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?Do the applicants discuss significant scientific questions for one or all of the glomerular diseases and propose potential solutions to these questions?

Investigator(s)

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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Do they have experience in collaborative efforts?  Have they been successful in recruiting a large number of participants to a study? 

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? Are there important and timely discussions of scientific challenges and potential solutions for these diseases? Is there evidence of innovative strategies for recruitment and retention of the longitudinal cohort?  Are appropriate biomarkers and alternative outcomes proposed in the design of the study?  Are potentially new biomarkers and/or alternative outcomes discussed in the application?  If these surrogate markers or outcomes have not been validated, does the application contain plans to demonstrate their qualification to the FDA?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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? 

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Do they propose backup plans for recruitment?  If a DCC application,  do data collection and analyses (i.e., questionnaires, biochemical measurements, pathological specimens, clinical data) adhere to the standards of the Clinical Data Interchange Standards Consortium (CDISC) in order to facilitate biomarker, surrogate outcome, and therapy development in accordance with the FDA guidelines?

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? 

Additional Review Criteria - Overall

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/priority score, but will not give separate scores for these items.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

Additional Review Considerations - Overall

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/priority 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) Genome Wide Association Studies (GWAS).

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 NIDDK, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Appeals of initial peer review will not be accepted for applications submitted response to this FOA.

Applications will be assigned  to the appropriate NIH Institute or Center and 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. . The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

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 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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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 (UM1), 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:

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:

In addition, a separate NIDDK Program Official identified in the Notice of Grant Award will be responsible for the normal stewardship and monitoring of the award including review and approval of all progress reports and all budgetary decisions.  Additional responsibilities include: 

Areas of Joint Responsibility include:

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

1. 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 PD(s)/PI(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. 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 (see item D2 below) and by interacting closely with the awardees during protocol development and implementation.

2. External Study Oversight

An independent Data and Safety Monitoring Board will be established by the NIDDK for Phase III clinical trials or other high risk studies as appropriate. The Data and Safety Monitoring Board will review interim results periodically and provide guidance to the NIDDK.

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.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) 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. 

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Dr. Michael F. Flessner
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health
Telephone: (301) 594-7717
FAX (301) 480-3510
Email: flessnermf@niddk.nih.gov

Peer Review Contact(s)

Dr. Francisco Calvo
Chief, Review Branch
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)
Telephone:  (301) 594-8897
FAX:  (301) 480-3505
Email: calvof@niddk.nih.gov

Financial/Grants Management Contact(s)

Ms. Carolyn Kofa
Grants Management Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)
Telephone:  (301) 435-6198
FAX:  (301) 594-9523
Email: kofac@niddk.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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 Parts 74 and 92.


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