Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Office of Dietary Supplements (ODS)
Funding Opportunity Title	NIDDK Multi-Center Clinical Study Implementation Planning Cooperative Agreements (U34)
Activity Code	U34 Clinical Planning Grant Cooperative Agreement
Announcement Type	Reissue of PAR-10-197
Related Notices	December 11, 2014 - This PAR has been reissued as PAR-15-068. June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.
Funding Opportunity Announcement (FOA) Number	PAR-13-268
Companion Funding Opportunity	PAR-11-157 U01 Research Project Cooperative Agreements
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.847
Funding Opportunity Purpose	NIDDK supports investigator-initiated, multi-center (three or more sites) clinical studies exclusively through a two-part process that includes an implementation planning cooperative agreement (U34). The U34 is designed to: (1) permit early peer review of the rationale for the proposed clinical study; (2) permit assessment of the design and protocol of the proposed study; (3) provide support for the development of documents needed for the conduct of the study, including a manual of operations; and (4) support the development of other essential elements required for the conduct of a clinical study. Completion of the required products of a U34 is a prerequisite for submission of a multi-center clinical study cooperative agreement (U01) application, which will support the actual conduct of the study. Consultation with NIDDK staff is strongly encouraged prior to the submission of the U34 application.

Posted Date	July 9, 2013
Open Date (Earliest Submission Date)	March 15, 2014
Letter of Intent Due Date(s)	30 days before the application due date
Application Due Date(s)	April 15, 2014; New Date: December 12, 2014. This PAR has been reissued as PAR-15-068. February 19, 2015; June 17, 2015; April 18, 2016; February 14, 2017, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June/July 2014; March/April 2015; October/November 2015; June/July 2016; March/April 2017
Advisory Council Review	October 2014; June 2015; January 2016; October 2016; June 2017
Earliest Start Date	December 2014; July 2015; Aril 2016; December 2016; July 2017
Expiration Date	New Date: December 12, 2014 - This PAR has been reissued as PAR-15-068. February 15, 2017
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Most large, multi-center clinical studies supported by NIDDK are conducted by research networks awarded as cooperative agreements under NIDDK Requests for Applications (RFAs). The networks are composed of coordinating centers, statistical units, data centers, central laboratories, clinical centers, and other specialized resources. Additionally, the networks are provided with assistance from NIDDK staff. This combination of collaborating organizations and specialists ensures that all elements of the planning and design of clinical study can be addressed and fully documented before a decision is made to implement a study.

NIDDK has determined that all investigator-initiated, multi-center clinical studies it supports should be developed with the same rigor in planning, design, and documentation. Once a clinical study is designed and subjected to peer review, extensive administrative planning (e.g., protocol finalization, manual of operations development) is required before subject recruitment can occur. Investigators considering submission of an investigator-initiated research grant application for a multi-center clinical study will generally not have the resources to complete this rigorous planning and documentation process without support from NIDDK. NIDDK believes that a two-part cooperative agreement process that separates administrative implementation from subject recruitment and study conduct will remedy these issues. The U34 will provide up to two years of support and will give the investigators the time and funds necessary to complete detailed clinical study planning to meet NIDDK standards and regulatory requirements.

As announced in Notice NOT-DK-13-013 NIDDK will support investigator-initiated, multi-center clinical studies exclusively through a two part cooperative agreement process: 1) an implementation planning U34, followed by 2) a multi-center cooperative agreement (U01). This FOA, NIDDK Multi-center Clinical Study Implementation Planning Cooperative Agreements (U34) , addresses the U34 application; a companion PAR-11-157 "NIDDK Multi-center Clinical Study Cooperative Agreements (U01) addresses the second part of the application process. NIDDK will accept, peer review, and consider for funding applications for investigator-initiated, multi-center clinical studies from U34 awardees only, unless an exemption from this requirement is obtained from NIDDK. An applicant who can demonstrate that all the work required for a submission of a multi-center clinical study cooperative agreement has been completed, may request an exemption from the prerequisite of holding an U34 award prior to submitting the U01 cooperative agreement.

This policy applies to all clinical studies, interventional trials as well as observational studies, conducted at three or more centers. NIDDK will not accept applications for multi-center clinical studies that are submitted as R01s, with the exception of ancillary studies to existing cooperative agreements, which can be submitted as R01s to PAR-12-265 "Ancillary Studies to Major Ongoing Clinical Research Studies to Advance Areas of Scientific Interest within the Mission of the NIDDK (R01)", or applications submitted in response to other or future NIDDK FOAs that allow multi-center applications. This policy does not apply to pilot studies. Investigators who are interested in obtaining support for pilot studies may use the R21 activity code, through the appropriate program announcements.

Scope

The U34 planning cooperative agreement process is designed to:

• Permit early peer review of the rationale for the proposed clinical study
• Permit assessment of the design and protocol of the proposed study
• Provide support for finalization of a complete study protocol and development of associated documents and other essential elements of a clinical study.

The U34 is not designed for the collection of preliminary data, for the conduct of pilot and feasibility studies to support the rationale for a clinical study, or for designing the study. The U34 application must include the proposed study design and a full protocol. The applicant should also provide a full cost estimate for the clinical trial to be conducted under a subsequent U01 award.

These cooperative agreements are intended to support all administrative study group activities that are required in order to begin recruitment of subjects. The activities required in the U34 will depend on the type of study (e.g., epidemiologic study, drug trial, behavior intervention). Activities supported by the U34 include, but are not limited to:

• Finalize the study protocol
• Develop consent form(s) and, if applicable, assent form(s)
• Develop an investigators brochure or equivalent
• Develop a manual of operations including details, validation, and quality control for any non-standard clinical or laboratory/mechanistic testing which will be performed
• Develop the data monitoring and management plan
• Develop a plan for the acquisition and administration of study agent(s) or device(s)
• Obtain required Office of Human Research Protections assurances if not already in place
• Develop a complete set of suitable documents for submission to the appropriate regulatory authorities
• Develop a safety oversight plan. During the U34 phase, NIDDK will appoint a Data and Safety Monitoring Board (DSMB) for clinical trials or an Observational Study Monitoring Board (OSMB) for epidemiological studies.
• Finalize a detailed budget for conduct and completion of the clinical trial including funding for preparation of a final study report
• Identify clinical study site(s) and service cores
• Develop training materials and training/certification plans for study staff
• Initiate the IRB approval process
• Satisfy all regulatory elements of the Food and Drug Administration if an IND/IDE is needed for implementation of the research plan
• Negotiate agreements with industry, as needed, to provide drugs, devices, or other resources

Consultation with NIDDK staff at least 6 weeks prior to the application due date is strongly encouraged for submission of the NIDDK Clinical Study Implementation Planning U34 application, including new and resubmission applications. If requested, NIDDK staff will consider whether the proposed clinical study meets the goals and mission of the Institute, whether it addresses one or more high priority research areas and meets programmatic needs including balance across research areas, whether it is appropriate to conduct as an investigator-initiated clinical study, and whether appropriate funds might be available for the subsequent, full clinical study (U01). NIDDK staff will not evaluate the technical and scientific merit of the proposed trial; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA. During the consultation phase, if the proposed trial does not meet NIDDK’s programmatic needs or is not appropriate as an investigator-initiated clinical trial, applicants will be strongly encouraged to consider other Funding Opportunities. NIDDK reserves the right to provide support for clinical studies through other available mechanisms supported by NIDDK. If NIDDK ascertains that substantial additional preliminary data or planning may be necessary, the applicant will be encouraged to consider applying for funding under the appropriate Pilot and Feasibility Clinical Research Grant (R21) FOA or through other available mechanisms.

The overall goal of the U34 funding period is to complete all administrative tasks required before recruitment of subjects can begin. In the event of an award, the NIDDK and the PD/PI will agree on a list of milestones to be completed during the U34 project period. The product of an awarded and successful U34 will be an application to conduct the clinical study. It is expected that receipt of a U34 will lead to the timely submission of a U01 application for support of the full-scale study, incorporating the elements developed under the planning cooperative agreement. If the planning phase is not successful, a decision may be made not to proceed to an application for the full study. NIDDK will determine whether the U34 has been successful and it should accept a U01 application for the full study. During the U34 phase, NIDDK will appoint an expert panel to review the study design and make recommendations to NIDDK concerning the proposed study, including the study design. The decision to accept the U01 application will be based on the following factors: attainment of pre-specified milestones, the expert panel recommendations, scientific landscape, study cost, opportunity cost, and availability of funds. Award of a U34 does not guarantee submission or funding of a U01 application.

The materials developed in the U34 phase will allow the applicant to initiate study staff training followed by study subject recruitment. In order not to delay the initiation of the clinical study that will be conducted under the U01, the peer review and award of the U01 will be completed within four months of the receipt of the application, when possible.

Further information regarding the U34 process, including a set of frequently asked questions (FAQs), can be found at http://www2.niddk.nih.gov/Research/ClinicalResearch/mcstudies.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New Resubmission The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Award Budget	Budgets for direct costs of up to $225,000 per year are allowed. The funds requested are expected to vary based on the number of clinical sites involved in the study and the complexity of the study.
Award Project Period	The scope of the proposed project should determine the project period. The maximum project period is 2 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.

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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.

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.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Francisco Calvo, Ph.D.
Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Two Democracy Plaza, Room 752
Bethesda, MD 20892-5452
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: [email protected]

All page limitations described in the SF424 Application Guide and must be followed, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages.

The forms package associated with this FOA includes all applicable components, required 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.

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

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

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

Other Attachments: Provide the cost estimate for the full trial that will be conducted through the subsequent U01 as a single PDF file with the name U01 cost estimate.pdf.

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

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: This section should delineate the aims for both the U34 planning period and for the full study. The primary and major secondary endpoints should be specified.

Research Strategy: This section should address both the planning period and the full study.

The investigator should describe how the planning period will be used and what activities will be conducted. Enough information should be provided to allow reviewers to evaluate how the clinical study documents will be developed. Clear milestones should be provided. The application should describe the research team members participating in the planning process, their roles in the development of the plan, and their experience in related studies.

The rationale for the proposed study should be clearly described, documenting the significance and need to perform the study, including potential risks and benefits. Describe the potential impact of the study on health care, policy or practice. Sufficient background information must be provided so the reviewers can assess the appropriateness of the design, selection of experimental and comparator arms, and appropriateness of the study population.

The study must be clearly described, including overall design, primary objective, inclusion and exclusion criteria, proposed study population, proposed study agent(s), sample size, study endpoints, and duration of recruitment and follow-up. There must be enough detail so that reviewers can assess the scientific importance and validity of the design, as well as feasibility. The application must describe the availability of the requisite patient population and plans for recruitment and retention. Plans for addressing issue and challenges regarding adherence to the proposed intervention should be included. The statistical methods to be used and power calculations should be described.

The application should also describe how the study will be organized and managed. This should include information on the leadership of the study, the proposed clinical sites and the ability of the PD/PI to bring together the necessary study network. Describe the mechanism for identification and selection of additional collaborators, if applicable.

Protection of Human Subjects: Even though there are no human subjects involved in the U34 period, the application should include a human subjects section regarding the proposed clinical trial (U01) and a planned enrollment table.

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.

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 modifications:

The following items should be submitted as part of the Appendix: complete study protocol.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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

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

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

In order to expedite review, applicants are requested to notify the NIDDK Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

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? Does the background support the rationale for the study? Are the study objective(s) and hypothesis (es) adequately defined? Are the significance and need to perform a future clinical study adequately justified? Would the results of the proposed study be likely to affect health care policy or practice in the specific area of research? If mechanistic studies are proposed, are they appropriate and will they provide important scientific information?

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/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Are the expertise and ability of the investigator and the clinical study team sufficient to organize and manage complex projects? Are the investigator and the clinical study team appropriately trained with suitable potential to develop and execute the proposed study? Is the work proposed appropriate to the experience level of the investigator and the research team? Are appropriate resources and/or other key personnel identified? Is there clear evidence of scientific and administrative leadership?

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? Will the study concepts and design, methods, and analyses, including preliminary statistical analyses, successfully accomplish the aim(s) of the proposed clinical study? Are the activities proposed for the planning period adequate? Will the activities proposed be sufficient to allow for timely and successful study implementation? Will the proposed planning activities address all major barriers to the future clinical study? Are the administrative plans for the management of the research project appropriate, including plans for resolving conflicts?

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? Are there adequate plans for the development of an effective organizational structure for carrying out the proposed study? Is the study population required for the proposed study available?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

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

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. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council (NDDKAC). The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

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

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

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

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

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

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

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

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

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

7. Establishing procedures, where applicable, for all participating institutions in coordinated awards to comply with FDA regulations for studies involving investigational agents or devices and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects, and the NIH policy requirements for the inclusion of women, minorities and children.

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

9. Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NIDDK support; or special access to study results, primary data/summary information, or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party is permitted only after concurrence by NIDDK.

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

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

12. The NIDDK has established Central Biosample, Genetic, and Data Repositories for the

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

http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm#goals, and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).

13. The Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law requires mandatory registration and results reporting for certain clinical trials of drugs, biologics, and devices. If trials conducted under this cooperative agreement are applicable clinical trials subject to FDAAA, the sponsor or his/her designee will perform the mandatory study registration and reporting of study results to ClinicalTrials.gov. For more information about this law and requirements for sponsors and/or investigators, visit the PRS and U.S. Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov/fdaaa.html . In addition, grantees should be aware that clinical trials not covered by FDAAA may still require registration in an approved registry in order to be published, according to the guidelines issued by the International Committee of Medical Journal Editors (http://www.icmje.org/publishing_10register.html).

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

An NIDDK Project Scientist with substantial involvement will:

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

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

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

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

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

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

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

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

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

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

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

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

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

5. Appoint a Data and Safety Monitoring Board (DSMB) as appropriate; the NIDDK Program Official or their designee will serve as the Executive Secretary and/or NIDDK program representative on the DSMB.

Joint Responsibilities

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

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

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. An Observational Study Monitoring Board (OSMB) will be established for observational/epidemiologic studies. These Boards will review study progress, safety data and interim results, as appropriate, 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.

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY 301-451-5936
Email: [email protected]

Marva Moxey-Mims, M.D.
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: (301) 594-7717
Email: [email protected]

Mary Horlick, M.D.
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: (301) 594-4726
Email: [email protected]

Barbara Linder, M.D., Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: (301) 594-0021
Email: [email protected]

Cindy Davis, Ph.D.
Office of Dietary Supplements (ODS)
Rockville, MD 20892-7517
Telephone: (301) 496-0168
Email: [email protected]

Francisco Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: (301) 594-8897
Email: [email protected]

Diana O'Donovan
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: (301) 594-8868
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.