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

Novel Interventions to Reduce Morbidity and Mortality of Hemodialysis Patients – Safety and Other Early Phase Studies (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-DK-12-010

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 initiate and implement a network of participating clinical centers and a data coordinating center to perform pilot and feasibility studies of novel therapies and procedures, including anti-inflammatory therapies, device or procedural interventions, anti-depressive therapies and other psychosocial interventions, and/or combination therapies, in end-stage renal disease (ESRD) patients undergoing chronic maintenance hemodialysis (HD).  Studies will focus on safety; feasibility; identification of dosing, pharmacokinetic, and pharmacodynamic aspects (where appropriate); and identification and preliminary evaluation of potential outcomes.  Applicants are required to propose two studies to be performed sequentially over the funding period. When applicable, clinical site investigators will enlist industry collaboration to achieve the goals of the network. Investigators will also work collaboratively to implement common study protocols developed by the Steering Committee. The ultimate goal of this FOA is to obtain the necessary information to design and implement one or more full-scale randomized controlled clinical trials of therapies or interventions to reduce morbidity and mortality in patients undergoing maintenance hemodialysis.

Key Dates
Posted Date

September 11, 2012

Open Date (Earliest Submission Date)

October 19, 2012

Letter of Intent Due Date

October 19, 2012

Application Due Date(s)

November 21, 2012, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February/March 2013

Advisory Council Review

May 2013

Earliest Start Date(s)

July 1, 2013

Expiration Date

November 22, 2012

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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.

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

More than 400,000 people are currently treated by hemodialysis under the auspices of the US ESRD program.   The mortality in this group of patients is unacceptably high.  Many of the mortality risk factors, such as age, gender, ethnic background, and presence of diabetes are not modifiable.   A majority of the deaths are due to cardiovascular diseases, followed by infectious complications and malnutrition.  Strategies to reduce the mortality of HD patients, including those directed at cardiovascular risk factors, have largely been ineffective. 

Many drug, biologic, device, or procedural interventions have been suggested for reducing the morbidity and mortality of HD patients. However, they have not been assessed by well-designed, definitive randomized controlled trials to determine if they are safe, improve patient comfort and well-being, and enhance long-term outcomes. Some interventions may work directly; some may affect hemodialysis patient risk factors, and therefore may be associated with improved patient outcomes. They include but are not limited to:

The benefits and adverse consequences of single and combination therapies or procedures in ESRD patients undergoing maintenance hemodialysis are unknown, and need to be tested in diverse patient groups before definitive randomized controlled trials can be initiated.

As an example, inflammation has been implicated in the pathogenesis of atherosclerotic cardiovascular disease, as well as malnutrition and depression, and has been shown, using diverse measures, to be linked to increased mortality in HD patients for over a decade. Anti-cytokine therapies have been used successfully to treat patients with inflammatory bowel disease, psoriasis and rheumatoid arthritis, but patient selection is critical to clinical success and the use of such medications must be monitored because of side effects. Therapeutics directed against tumor necrosis factor-a, interleukin-1 (IL-1), the IL-1 receptor, and IL-6 are commercially available and approved by the Food and Drug Administration (FDA) for specific indications. Safety issues with such drugs include infections (recurrence of infections and incident infections, such as mycobacterial and fungal infections, as well as viral hepatitis), demyelinating syndromes, development of autoantibodies and induction of autoimmune disease, and hepatic, hematologic and oncologic complications.  Currently available drugs have different safety and efficacy profiles in different disease states, as well as different pharmacokinetic properties and metabolic clearance pathways. Drug-drug interactions are expected with the use of such drugs as combination therapies. It is possible because of the redundancy and pleiotropy of the inflammatory response that multiple or combined anti-inflammatory interventions will be required, but such strategies may have increased risks of adverse effects.  Adverse consequences of anti-inflammatory therapies in an already immunosuppressed population must be assessed before definitive RCTs can be performed. How frequently and in what doses such drugs should be administered to maintenance hemodialysis patients areunknown, and the length of follow-up observation to determine adverse events is unclear. There is potential for academic/industry and public/private collaboration in a consortial study.

The NIDDK sponsored a workshop, held  in conjunction with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Novel Therapies to Enhance Survival – Inflammation in ESRD on April 21-22, 2010. This meeting addressed inflammation and anti-inflammatory cytokine responses, and therapeutic considerations for ESRD patients.  The workshop considered several interventions, outcome measures, and addressed the sample sizes necessary for effective pilot and feasibility trials of anti-inflammatory therapies. The consensus was that short duration pilot and feasibility studies, addressing intermediary outcomes, pharmacokinetic and pharmacodynamic issues, and adverse events should be undertaken in order for the field to advance.  A report from the meeting may be found at http://www3.niddk.nih.gov/fund/other/conferences-arch.shtml#2010.

Personalized approaches to alterations in the dialysis prescription and technique hold promise, but may be difficult and costly to implement and monitor.  Small studies have identified changes in temperature during hemodialysis, and changes in dialysate sodium and bicarbonate concentration which may be associated with changes in patients’ hemodynamic stability.   Changes in dialysate sodium concentration may alter hemodynamic stability and sodium balance during treatment, but the effect of such interventions on long-term outcomes has not been determined in well-designed, rigorous randomized controlled,  double blinded studies.  Changes in bicarbonate composition may enhance hemodynamic stability, but the effects of such interventions on intermediary and long-term outcomes, such as calcium/phosphate/mineral metabolic and hormonal changes, progression of bone disease, anemia control, and morbidity and mortality have not been evaluated.  Individualizing changes in dialysate acid/base composition and monitoring acid/base and mineral metabolic changes after dialysis may be challenging.  Whether distinct subpopulations of patients might be at risk from such therapeutic changes, or experience improved outcomes is unknown. 

The effects of different  fluid removal strategies or of systematic implementation of  dry weight targets may be determined  over a  single treatment, but studies to show improvement in long-term outcomes associated with such interventions are lacking.  The long-term outcomes of initiating systematic changes in the care of maintenance hemodialysis patients have not been evaluated in rigorous, well-designed randomized controlled trials. 

Inadequate social support and long-standing increased depressive affect have been linked to mortality in observational studies. It is unclear which social support interventions would be feasible in dialysis patients, and which might convey improvements in ESRD HD patient morbidity and mortality.  Although there have been limited studies of treatment of depressed maintenance HD patients with anti-depressant drugs, their long-term effects, and the risks and benefits of pharmacologic therapies  compared to non-drug therapies for depression, such as cognitive behavior therapy or other non-drug interventions have not been assessed in ESRD patients treated with HD.   

Purpose

The purpose of this FOA is to establish a multi-center consortium  to carry out pilot and feasibility studies to obtain information  to inform critical elements of the study design of a subsequent full-scale randomized controlled clinical trial of novel therapies, including procedural or technical changes, psychosocial interventions or  anti-inflammatory treatment(s) for end-stage renal disease patients undergoing maintenance HD. The outcomes for the full-scale trial will include measures of morbidity and mortality. It is anticipated that clinical center applicants will need to collaborate with industry in the case of a proposed drug study. Information to be gained from pilot and feasibility studies of drug interventions supported by this FOA will include data assessing appropriate drug dosing and dosing intervals, defining other aspects of the drug’s pharmacokinetics and pharmacodynamics, safety and adverse events, and possibly early evidence of effectiveness (using surrogate or pharmacologic endpoints or clinical measures).  It is expected that members of the consortium will adhere to the procedures and requirements governing clinical investigations, including the procedures and requirements for submission to, and review by, the FDA of an investigational new drug application.  In addition, it is expected that the consortium members will interact with the FDA to assure the safety and rights of study subjects and to assure the quality of the studies are adequate to permit an evaluation of the therapy’s safety and effectiveness. 

It is envisioned that the Consortium will be composed of two or three Participating Clinical Centers (PCCs) which will recruit study participants and conduct studies, collecting data which will be submitted electronically to a Data Coordinating Center (DCC).  Applications considering home hemodialysis or peritoneal dialysis patients are not responsive to this FOA.

Applications for the DCC should consider:

a.     How the DCC will coordinate data collection, perform analyses and prepare study reports for the PCCs performing studies, in addition to preparing final protocols for review and approval. The DCC will be responsible for the conduct of Steering Committee meetings and conference calls.  It is envisioned that a DCC will require a senior Biostatistician, a Master’s level Biostatistician/Epidemiologist and a Database Manager and other key staff.  It is envisioned that pilot and feasibility studies performed by the consortium will include single center and 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.

b.    The DCC should include a single example of an interventional study (with characteristics as described under PCC below) to illustrate how the DCC will operate.

Applications for PCCs should consider:

1. Two clinical trial interventions (drugs, biologics, devices, or procedures)  that specify the trial population with specific inclusion and exclusion criteria, intervention, outcomes, and proposed manner and length of patient follow-up.  The target population for the pilot studies should be carefully defined with respect to such variables as: residual renal function, age, co-morbidities of diabetes, hypertension, autoimmune and infectious diseases, gender, race, generalizability for a full-scale clinical trial, and other factors deemed important. Drug tolerance, dosing/dose-ranging studies, and studies of dosing intervals should be proposed to explore the toxicity and safety of specific therapeutic interventions.

2. Plans for recruitment of study subjects, and backup plans, as appropriate.

3. Plans for data collection of renal and non-renal outcomes. Surrogate outcomes should be acceptable to the FDA or should be validated within this study.

4. Potential adverse effects associated with the interventions.  Procedures designed to ensure patient safety should be described in detail.

5. Statistical issues, including power calculations.

6. If appropriate, one or more industry partners, who will submit letters of collaboration stipulating agreement to  a) provide drug(s)/biologic(s)/device(s) to be used in the pilot and feasibility studies, b)  the use of provided  interventions in combination studies within the consortial structure,  c) allowing access to HD patient recruitment, and implementation of technical and/or procedural changes,  and/or drug  therapeutic interventions for patients treated in specific dialysis units, 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.

Applicants for PCCs are expected to demonstrate the importance of the preliminary data collection for the implementation of a definitive randomized controlled trial of a potentially important therapy/intervention. How such a proposed intervention might impact the morbidity and mortality of HD patients should be justified in detail. Applicants should demonstrate their ability to recruit a diverse and appropriate population for the pilot and feasibility studies, from a specific group of hemodialysis units. Letters from dialysis providers acknowledging the ability of PCC investigators to recruit HD patients from their units are required.  Applicants should demonstrate experience with regulatory agency procedures involved in bringing new therapies into clinical practice, as appropriate.

DCC and PCC applications are expected to address common study issues such as:

a. Ability to work collaboratively to establish Consortium Agreements that address: (1) procedures for data sharing among consortium members and data sharing with industry partners; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the consortium as well as data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing biological specimens; and (5) procedures for reviewing publications, determining authorship, and industry access to publications.

b. Each industry collaboration will be governed by an appropriate Research Collaboration Agreement agreement (e.g. Clinical Trial Agreement [CTA], Research Collaboration Agreement [RCA], etc) 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. 

c. Awardees will meet to finalize the consortia study protocol(s).  Both PCC and DCC awardees should be prepared to participate in conference calls immediately after funding, and should reserve September 9 and 10, 2013 in Bethesda, Maryland for the first Steering Committee meeting.   Applicants should indicate their availabilities on these dates in their applications.

d. Applicants for PCCs and the DCC should budget for 3 meetings in the Bethesda Maryland area in the first year, and at least two meetings a year in subsequent years. Applicants for the DCC should budget for 2 meetings of a Data Safety and Monitoring Board in the Bethesda Maryland area in the first year, and at least one such meeting a year in subsequent years.  

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 the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) of the Participating Clinical Centers (PCC) and the Data Coordinating Center (DCC), a Steering Committee Chair appointed by the NIDDK, and a NIDDK Project Scientist.  The responsibilities of the Steering Committee include:  Providing input on and approval of all studies developed by the Consortium members prior to study implementation; review and approval of all data analyses, public presentations and publications of research conducted within the consortium;  and development of policies and procedures for submission and approval of research applications using Consortium resources.

A Data Safety Monitoring Board (DSMB) will be appointed by the NIDDK at the beginning of the funding period.  The DSMB will include biostatisticians, pharmacologists, nephrologists, rheumatologists, gastroenterologists, dermatologists, infectious disease physicians, ethicists, and patients on maintenance hemodialysis. The DSMB will review study protocols prior to implementation, and will monitor progress and safety of the studies.    

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

New

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIDDK intends to commit approximately $1.5 million in FY 2013 to fund 3-4 awards to the Consortium.

The aggregate amount shown below must reflect the contribution of all participating ICs/components.  A document or MOU must be attached in SharePoint that specifies the contribution for each IC/component.

Award Budget

Application budgets for PCCs should match the amount of work proposed, and may approximate $200,000 to $300,000 in direct costs per year. Application budgets for DCCs should match the amount of work proposed, and may approximate $200,000 to $450,000 in direct costs per year.   

Award Project Period

The scope of the proposed project should determine the project period.  The maximum project period is 5 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

You may not edit any bullets except those that are unprotected, below. If you wish to remove any text, insert a comment with reasoning.

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 SF 424 (R&R) 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 least 4-6 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 SF 424 (R&R) 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

Only one application per institution is allowed.

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.  

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide, with the following modifications:

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, with the following additional modifications:

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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.

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 the NIH 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 submitted electronically following the instructions described in the SF 424 (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.

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 SF 424(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.

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 Central Contractor Registration (CCR). 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 by the Center for Scientific Review and responsiveness by the NIDDK, NIH.  Applications that are incomplete and/or nonresponsive will not be reviewed.  

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

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

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 are improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Are the studies proposed in the application by the PCC essential for the clinical development of an important intervention which is likely to favorably affect the morbidity and mortality of HD patients? Are the proposed studies likely to be feasible and generalizable?  Will the results of the proposed studies inform the design of a full-scale clinical trial of agent(s)/interventions that will likely substantially reduce morbidity and mortality of maintenance hemodialysis patients? Are appropriate biomarkers and alternative/surrogate outcomes proposed in the design of the study?

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 the PD(s)/PI(s) have experience in conducting clinical research studies, including randomized clinical trials? 

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?   

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? 

Has the applicant for a Participating Clinical Center (PCC) proposed two important, well-designed pilot and feasibility studies focused on identification of appropriate drug doses, pharmacokinetic and pharmacodynamic aspects of therapy and adverse events, as well as identification and preliminary evaluation of potential surrogate outcomes for a pharmacologic intervention study? Are the proposed surrogate end-points and safety considerations scientifically and clinically valid? Are the safety considerations and follow-up plans designed to ensure patient well-being during and after the studies?  Will the applicants for a PCC be able to recruit an appropriate study population? Have the investigators provided letters from dialysis providers acknowledging the ability of PCC investigators to recruit HD patients from the particular dialysis facilities?  Have they provided back up plans for recruitment? Has the applicant for a DCC demonstrated expertise in and understanding of issues involved in meeting planning, coordination and administration of multicenter studies across sites, monitoring progress, handling and presenting data,  and provided a detailed plan on how they will accomplish these tasks?

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

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.

FOA-Specific Criteria:

Has the applicant for a PCC or a Data Coordinating Center (DCC) demonstrated understanding of the principles of pilot and feasibility studies, experience in performing pilot and feasibility studies and indicated willingness to work with regulatory agencies, such as the FDA, as appropriate?

Do the applicants understand the roles of DSMBs and regulatory agencies in participation in the proposed studies? 

Has the applicant for a PCC identified an industry partner and provided a letter of collaboration from the partner indicating willingness to work in the consortial structure of a NIH Cooperative agreement? 

Has the applicant agreed to work collaboratively with other members of the consortium, including agreeing to participate in the September 2013 meeting?

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.

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

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), 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 in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines 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 Institute of Diabetes, 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 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 primary responsibility for:  

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

Areas of Joint Responsibility include:

Dispute Resolution

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR 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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

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. Paul L Kimmel
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health
Telephone: (301) 594-7717
FAX: (301) 480-3510
Email: kimmelp@extra.niddk.nih.gov

Dr. John W. Kusek
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health
Telephone: (301) 594-7735
FAX: (301) 480-3510
Email: kusekj@mail.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. Diana Ly
Grants Management Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)
Telephone:  (301) 594-9249
FAX:  (301) 594-9523
Email: dianaly@mail.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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy
NIH . . . Turning Discovery Into Health

Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.