National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Chronic Kidney Disease Biomarkers Consortium (CKD BioCon) (U01)
U01 Research Project – Cooperative Agreements
Reissue of RFA-DK-08-015
The purpose of this Funding Opportunity Announcement (FOA) is to establish the second phase of the Chronic Kidney Disease Biomarkers Consortium (CKD BioCon) through a cooperative agreement. The CKD BioCon was established as a cooperative agreement in September 2009 as a result of RFA-DK-08-015 [Chronic Kidney Disease Biomarker Discovery and Validation Consortium (U01)] to discover, develop, validate and qualify biomarkers based on existing stored or reposited biosamples from well-characterized CKD patients with longitudinal follow-up. The current CKD BioCon consists of six Participating Centers (PCs) and is actively engaged in multiple research protocols. The next phase of the CKD BioCon will continue a multicenter consortium to identify new biomarkers or rigorously validate already identified biomarkers for chronic kidney diseases, consisting of successful applicants to this FOA. Application for the second phase of the CKD BioCon will be open to members of the original consortium as well as new investigative teams.
June 11, 2014
November 2, 2014
November 2, 2014
December 2, 2014, 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.
December 3, 2014
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
This FOA invites submission of U01 cooperative agreement applications for Participating Centers (PCs) for the CKD BioCon to work in a multicenter research consortium to identify new biomarkers or rigorously validate already identified biomarkers for chronic kidney diseases (CKD).
The CKD BioCon was established as a Cooperative Agreement in September 2009 (RFA-DK-08-015, Chronic Kidney Disease Biomarker Discovery and Validation Consortium [U01]) to discover, develop, validate and qualify biomarkers for CKD. The first phase of the CKD BioCon included six Participating Centers (PCs) and a Coordinating Center, and will expire in 2015. A number of studies of biomarker discovery and evaluation were conducted during the first project period (see http://www.ckdbiomarkersconsortium.org/BioCon_protocols_20140423.pdf
for a list and brief description of studies completed or in progress). Many of the studies used existing stored or reposited biosamples from well-characterized CKD patients assessed prospectively.
Under a separate FOA (RFA-DK-13-506) an independent Data Coordinating Center (DCC) for the CKD BioCon will be established for the second phase project period of the CKD BioCon. The DCC will provide support for and coordination of consortial administrative and multicenter research activities, including tracking of shipping and maintenance of identity of samples, advanced statistical support to the PCs, coordination of the development and monitoring progress of Pilot and Feasibility projects, and coordination of Steering Committee meetings and meetings of the External Expert Panel.
The purpose of this FOA is to establish the second phase of a multicenter research consortium to identify new biomarkers or rigorously validate already identified biomarkers for CKD. Current measures to detect kidney function and damage are inadequate. New biomarkers are needed to reduce the burden of CKD and kidney failure, allow earlier identification of disease, provide surrogate markers to enable smaller sample sizes in clinical trials, and predict responses to therapeutic interventions. Although serum creatinine concentration and proteinuria or albuminurias have been widely used as markers for detecting and staging CKD, they are not optimal biomarkers. The goal of this FOA is to identify and validate new biomarkers which reflect kidney injury, repair, and progression or regression of damage, including in response to specific therapeutic interventions. Identification of new biomarkers will stimulate bench to bedside translation by providing measures of the biological effects of potential new treatments.
The ideal biomarker can be measured in a minimally invasive way, reliably and reproducibly repeatedly over time. Biomarkers of utility should identify early stages of disease, are indicative of disease prognosis or correlate well with disease progression or response to therapy, and should be strongly associated with clinically meaningful endpoints. Of interest would be studies designed to identify novel biomarkers of CKD initiation, tissue injury, disease progression, response to specific therapies, or to test the validity of candidate biomarkers or to develop new technologies to monitor candidate biomarkers in patient tissue samples or in groups of well-characterized patients. Biomarkers which predict the development of complications of CKD, including the initiation, progression and outcomes of cardiovascular disease would have clinical utility.
Studies of potential biomarkers in animal models of disease, biomarkers to predict glomerular filtration rate or use of imaging studies as potential biomarkers are not responsive to this announcement.
Successful applicants will participate as members of a consortium that shares biological samples and performs collaborative studies to identify and validate biomarkers for CKD.
Currently the CKD BioCon assesses biosamples from participants in the African American Study of Kidney Disease and Hypertension (AASK), the Atherosclerosis Risk in Communities (ARIC) study, the Chronic Renal Insufficiency Cohort (CRIC), the Modification of Diet in Renal Disease (MDRD) study, as well as from smaller cohorts including patients with lupus nephritis, diabetic nephropathy and from tertiary care clinics. Current studies within the CKD BioCon investigate acute kidney injury biomarkers in CKD patients, assess the utility of urinary complement fragments to predict outcomes in CKD, evaluate biomarker changes in early lupus nephritis and diabetic nephropathy, and evaluate the utility of blood biomarkers of glomerular filtration rate and renal tubular function, as well as mineral metabolism to predict kidney and, cardiovascular disease outcomes and death in CKD patients. In addition, proteomic and metabolomic discovery studies are in progress. For a more complete description of these studies see http://www.ckdbiomarkersconsortium.org/BioCon_protocols_20140423.pdf.
A biomarker has been defined as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or responses to therapeutic interventions. Biomarkers may be used as diagnostic tools to identify patients with disease or abnormal conditions, for staging or monitoring disease, as indicators of prognosis, to identify patients who are likely to respond to or not benefit from a therapy, and to predict and/or monitor clinical response to an intervention. A biomarker may also serve as an intermediary endpoint in clinical trials.
Validation has been described as the process of linking a biomarker to a clinical endpoint. While a universal approach to validation of biomarkers has not yet been established, recent efforts have focused on developing quantitative approaches to biomarker qualification/surrogate validation based on the context of the biomarker use and the level of evidence achieved. The process of validation is complex, but includes assay characterization, and establishing the clinical utility and superiority of a biomarker to standard tests. Subsequent qualification involves interaction with regulatory agencies to determine fit-for-purpose uses of the biomarker.
Efforts to reduce the burden of CKD have been hampered by a lack of unique, reliable, quantifiable, easily measured biomarkers that correlate well with disease initiation and progression, as well as with responses to specific therapies. These shortcomings make the design and conduct of clinical trials of patients with CKD challenging and lengthy. Identification and validation of one or more robust biomarkers which could enable stratification of patients or serve as surrogate endpoints in clinical trials may substantially reduce the time and cost necessary to evaluate promising therapies by reducing the sample size and/or duration of follow-up required. Biomarkers of acute kidney injury which have shown utility in CKD patients may also be proposed for validation.
Candidate biomarkers may be identified through discovery-oriented searches using technologies such as gene expression, proteomic or metabolomic approaches in tissues, cells, or body fluids. Biological samples and data from well-characterized study participants in clinical trials and epidemiological studies are available for discovery and validation efforts [see for example resources available from the NIDDK (http://www3.niddk.nih.gov/researchprograms/repositories/FAQ.shtml) and the National Heart Lung Blood Institute (https://biolincc.nhlbi.nih.gov/home ) repositories].
The major goals of this FOA are to:
Applicants should propose biomarker discovery studies, or biomarker validation studies, or a combination of discovery/validation studies. The study samples considered for evaluation in the consortium will be from well-defined cohorts of CKD and appropriate non-CKD participants with well-characterized clinical features and longitudinal follow-up over a substantial period of time. The final biomarker must be assayable in an easily obtainable body fluid, using a quantifiable and reproducible technique that is feasible for a clinical setting. Applicants should consider the effects of multiple storage conditions and characteristics of the particular proposed analyses, including batch effects, on the determined analyte values in their proposed studies. The clinical significance and utility of tissue biomarkers must be adequately justified. Measurement of final biomarkers must be reliable and reproducible. Studies of the utility of biomarkers for acute kidney injury in CKD patients will be considered responsive to this solicitation if their relevance to CKD is strongly justified.
Appropriate topics for discovery might include:
Appropriate topics for validation might include:
It is anticipated that the expertise necessary to conduct validation studies of biomarkers includes experience in assay development and quality control, epidemiology, biostatistics and public health sciences, and knowledge of the regulatory aspects of biomarker development.
Successful applicants will participate in a consortium including the selected PCs, the DCC and the NIDDK that shares ideas, methods, study protocols, samples, data, and conducts collaborative studies to discover and validate individual biomarkers investigated at particular sites in this Cooperative Agreement. The sites will collaboratively work towards qualification of proposed biomarkers, with the appropriate Federal agencies.
CKD BioCon findings will be disseminated through presentations at scientific meetings and manuscripts in scholarly, peer-reviewed journals. The CKD BioCon Publications Committee will approve manuscripts and presentations. The CKD BioCon has also developed mechanisms through which investigators outside of the study group may collaborate with the study investigators to test novel hypotheses, using Pilot and Feasibility Studies and Ancillary Studies.
The PCs will be expected to implement their proposed protocols after approval by an External Expert Panel. The PCs will collect data in accordance with study procedures established by the Steering Committee and the DCC and submit all samples and data to the DCC and central laboratories and central reading centers, as appropriate and required by the protocol.
Investigators at the PCs will conduct analyses in conjunction with the DCC. All study data analyzed for publication will be provided to the NIDDK Repository so that it can be shared according to policies already established by the DCC, the CKD BioCon and the NIDDK.
The first meeting of the second phase of the CKD BioCon will take place July 14 and 15, 2015 in Bethesda, Maryland. All applicants will indicate willingness and ability to attend the meeting in the application.
The primary governing body of the study will continue to be the Steering Committee, comprised of the Program Directors/Principal Investigators of the DCC and each PC, and the NIDDK Project Scientist.
The Steering Committee will continue to develop policies and procedures for the CKD BioCon, and ensure that these policies are properly implemented. These may include approval of pilot and feasibility and ancillary studies, publication and presentation of study findings, monitoring study progress, determining completeness and quality of data collection, and other performance measures.
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.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
NIDDK intends to commit up to $2 million to fund up to six awards in Fiscal Year 2015.
Application budgets for PCs should match the amount of work proposed, but may not exceed $450,000 per year in total costs.
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.
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
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 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.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:
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:
The letter of intent, preferably electronically, should be sent to:
Dr. Francisco Calvo
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: (301) 594-8897
Fax: (301) 480-3505
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
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.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
The applicant for a validation study should demonstrate expertise in principles of epidemiology and biostatistics, patient recruitment and follow-up.
All instructions in the SF424 (R&R) Application Guide must be followed. It is expected that Program Director(s)/Principal Investigator(s) will contribute a minimum of 1.2 person months effort to provide adequate oversight of each PC. Applicants should budget for appropriate personnel to attend three meetings of the Consortium in the Bethesda Maryland area during the first year of the award, and to attend two Consortium meetings each subsequent year.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy: The Participating Center applications should provide the rationale and design of the study, the proposed cohorts and samples to be evaluated, and the assay characteristics of each proposed biomarker. A well-designed application should provide study hypotheses, statistical approaches, relevant power analyses, as well as back-up plans if initial hypotheses are not confirmed and if samples are unavailable or inadequate.
The application should propose a reasonable set of biomarkers and studies that are likely to lead to clinically useful advances.
An application planning to use samples in repositories, or not in their possession, should provide documentation regarding collaborations, sample availability, quality and characteristics, and sharing and access procedures and intellectual property rights, and plans adequate for the study goals.
An applicant who proposes to validate biomarkers of acute kidney injury for CKD should adequately justify their potential importance for CKD.
The applicant should =provide relevant power analyses, as well as back-up plans if initial hypotheses are not confirmed and if samples are unavailable or inadequate.
The applicant should demonstrate understanding of the components of the biomarker development process, including discovery, qualification, verification, assay characterization and optimization, relevant statistical analyses and clinical validation.
The applicant should consider the effects of multiple storage conditions and characteristics of the particular proposed analyses, including batch effects, on the determined analyte values in the proposed studies.
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.
When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
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.
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 and responsiveness by NIDDK, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.
In order to expedite review, applicants are requested to notify the NIDDK Referral Office by email at firstname.lastname@example.org 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-13-030.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? 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? Has the applicant proposed a reasonable set of biomarkers and studies that are likely to lead to clinically useful advances?
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? Has the applicant for a validation study demonstrated expertise in principles of epidemiology and biostatistics, patient recruitment and follow-up?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are 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?
For an applicant planning to use samples in repositories, or not in their possession, have collaboration, sample availability, quality and characteristics, and sharing and access procedures and intellectual property rights, as appropriate, been described, and are the plans adequate for the study goals?
For the applicant who proposes to validate biomarkers of acute kidney injury for CKD, has the applicant adequately justified their potential importance for CKD?
Has the applicant provided relevant power analyses, as well as back-up plans if initial hypotheses are not confirmed and if samples are unavailable or inadequate?
Has the applicant demonstrated understanding of the components of the biomarker development process, including discovery, qualification, verification, assay characterization and optimization, statistical analysis and clinical validation?
Has the applicant considered the effects of multiple storage conditions and characteristics of the particular proposed analyses, including batch effects, on the determined analyte values in their proposed studies?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
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 Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Children
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.
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.
For Renewals, the committee will consider the progress made in the last funding period.
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
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 the NIDDK, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases (NDDK) Advisory Council. The following will be considered in making funding decisions:
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
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 Program Directors/Principal Investigators (for studies involving multiple protocols) may designate a Protocol Chairperson (if the Program Director/Principal Investigator does not assume this role) for each protocol to be carried out by the study group. The Protocol Chairperson shall function as the scientific coordinator for the protocol and shall assume responsibility for obtaining approval to implement the protocol from the Steering Committee and for developing and monitoring the protocol. Significant modifications to approved protocols must be approved by the Steering Committee and the External Expert Panel.
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 DCC and 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 (https://grants.nih.gov/grants/policy/data_sharing/ and,
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 grant are applicable clinical trials subject to FDAAA, the sponsor or his/her designee will perform the mandatory study registration and reporting of study results to ClinicalTrials.gov. For more information about this law and requirements for sponsors and/or investigators, visit the PRS and U.S. Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov/fdaaa.html. In addition, grantees should be aware that clinical trials not covered by FDAAA may still require registration in an approved registry in order to be published, according to the guidelines issued by the International Committee of Medical Journal Editors (http://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 program director(s)/principal investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the program director/principal investigator(s) 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 an External Expert Panel (EEP) as appropriate; the NIDDK Program Official or their designee will serve as the Executive Secretary and/or NIDDK program representative on the EEP.
Areas of Joint Responsibility
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 Program Director(s)/Principal Investigator(s) (including those of data coordinating /statistical centers, if any) and co-investigators as deemed necessary, and the NIDDK Project Scientist. The final structure of the Steering Committee and voting procedures will be established at the first meeting. The NIDDK Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee.
A Chairperson of the Steering Committee, other than the NIDDK Project Scientist, will be selected by the NIDDK. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings, representing the study group to the External Expert Panel established by the NIDDK (see item D2 below) and by interacting closely with the awardees during protocol development and implementation.
2. External Study Oversight.
An independent Data and Safety Monitoring Board will be established by the NIDDK for Phase III clinical trials or other high risk studies as appropriate. An External Expert Panel (EEP) 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.
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.
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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.
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