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.
I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
This FOA invites collaborative U01 cooperative agreement applications to establish a multi-center, multi-disciplinary group of investigators to be known as the Urinary Stone Disease Research Network (USDRN). The clinical center applications submitted under this FOA are linked to RFA-DK-15-005, which will support the USDRN Scientific Data Research Center.
Urinary Stone Disease (USD) is an important healthcare problem affecting about 1 out of 11 Americans, causing pain and suffering for the patient and a financial burden for the Nation. The prevalence of USD in the US has nearly doubled in the last 15 years, and is increasing in both adults and children. According to the Urological Diseases in America (UDA) project funded by the NIDDK, the annual cost of USD is estimated at $10 billion making it the most expensive non-malignant urologic condition in the U.S. A recent study estimates that the impact of obesity, diabetes and population rates will increase costs of USD to $1.24 billion/year by 2030. An acute symptomatic episode of USD is generally extremely painful and frequently results in Emergency Department (ED) care. ED visit rates for USD have doubled between 1992 and 2009. Computed tomography use for evaluation of USD in ED has tripled during the same time period and use of drugs has also increased. Cross sectional analyses show that about 10% of ED visits for USD are for repeat encounters. The intangible costs to the affected individual and the family, such as pain, diminished quality of life (QoL), time-off from work or school, and professional risks caused by a renal colic are enormous.
The treatment of USD has advanced over the last 30 years. New endourologic approaches allowed most stones to be treated endoscopically without the need for a skin incision. Technical advances have improved surgical USD treatment strategies. Improved optic lens systems and fiberoptic light sources have enabled better visualization. Increased instrument flexibility and miniaturization along with effective energy sources for stone disintegration led to the development of percutaneous nephrolithotomy and ureteroscopic lithotripsy. Extracorporeal shock wave lithotripsy (SWL) was developed for stone fragmentation without invasive instrumentation of the body. Although SWL and endourologic approaches are commonly used for the treatment of an USD episode, there is a major trend towards more frequent use of ureteroscopy (URS). Medical management has also advanced to a certain extent; however the prevalence of USD continues to increase both in adults and children. Despite these advances the limited state of knowledge for USD is reflected in several clinical management guidelines that have been published by the American Urological Association (AUA), and European Association of Urology (EAU) using systematic reviews and data extraction. Only 1 of 27 and 3 of 17 recommendations were based on Level 1 evidence.
USD is often recurrent. Data from the National Health and Nutrition Examination Survey (NHANES) show that 35% of participants had experienced 2 or more distinct episodes of urinary stones. Other epidemiologic data show that recurrence rates of first time stone formers at 2, 5, 10, and 15 years were 11%, 20%, 31%, and 39%, respectively. Thus prevention of USD recurrence could substantially reduce its public health burden.
Ureteral stenting is a common prophylactic procedure after URS to mitigate peri-operative complications. Stenting the ureter is also performed in conjunction with SWL, and after complicated percutaneous nephrolithotomy (PCNL). Ureteral stenting is also used for therapeutic purposes such as obstructive pyelonephritis, bilateral obstructing stones or an obstructing stone in a solitary kidney. However; ureteral stents cause considerable patient discomfort such as pain, dysuria, urinary frequency, incontinence and hematuria.
The goals outlined in this FOA were developed in part, from the NIDDK sponsored workshop "Urinary Stone Disease: Research Challenges and Opportunities" held on April 1-2, 2015.
This FOA will establish a network of investigators to design and conduct clinical research studies in adults and children with USD. The network is expected to include a wide range of expertise including but not limited to adult and pediatric urologists, adult and pediatric nephrologists, pediatricians, ED physicians, clinical trialists, nutritionists, behavioral scientists and radiologists. All studies proposed in the applications will be a starting point for discussions regarding the research undertaken by the network. USDRN investigators will devise studies that will be reviewed by a Protocol Review Committee (PRC) and approved by the NIDDK, then will recruit stone forming patients for the collaborative studies. The final study protocol will be designed by the Clinical Center and Scientific Data Research Center Program Directors/Principal Investigators and approved by the Steering Committee. Network study results are expected to provide evidence for management approaches to USD.
USD has different causes, and there have been many studies to understand the mechanisms of stone formation and prevention of new episodes of USD. In contrast, there is scant information about recurrent episodes of USD. Available evidence suggests a high (about 35%) and unchanging rate of recurrence. Most urinary stones are primarily composed of calcium. There is a need to identify the underlying causes and to improve methods to prevent calcium USD recurrences. Increasing fluid intake and urinary volume, and medical therapies with potassium citrate and/or thiazide or thiazide analog diuretics are the recommended measures for recurrent calcium stone prevention based on moderate quality of evidence.
Although increasing fluid intake is generally recommended for stone-forming patients, a Cochrane review found no studies of increased fluid intake for the primary prevention of USD, and only one study for secondary prevention (to reduce recurrence). A more recent systematic review and meta-analysis including observational studies demonstrated that increased fluid intake significantly reduced incident and recurrent stones. Adherence and safety data were limited. Thus there is a need for a definitive randomized clinical trial (RCT) to evaluate the impact of increased fluid intake on urinary stone recurrence. However, increasing fluid intake and maintaining a daily urine volume of at least 2.5 liters is very challenging in children and adults. There are no reliable recommendations on fluid intake in children. Reluctance to drink increased amounts of water, urinary symptoms due to higher urine volumes, environmental circumstances for bathroom breaks, potential hyponatremia causing altered mental status, confusion, and even seizures, and difficulties in behavior change are some of the impediments for uninterrupted and sustained high fluid intake. The use of wearable devices, smartphone applications and incentives to encourage fluid intake, methods to monitor urine volume, pH and specific gravity are some of the new methods that can be used to facilitate fluid intake. A RCT with sufficient power is needed to determine how to maintain high fluid intake, and then show whether increasing and maintaining urinary volume decreases the urinary stone recurrences in adults and children. Investigators are encouraged to think broadly on incorporating mobile health technology, behavioral economics and/or other innovative strategies to maintain long-term fluid intake. Applicants are also encouraged to propose innovative trial methodologies such as adaptive and pragmatic trial designs, and use of surrogates for stone recurrence.
Ureteral stents are commonly used for therapeutic or prophylactic purposes. Their use is frequently based on clinical judgment of the surgeon to improve stone passage and/or prevent complications rather than evidence. Despite their clinically utility, ureteral stents can cause significant patient pain and discomfort. Years of research by academia and industry to reduce patient discomfort by different stent designs, developing drug-coated stents, and using different stent materials, have not completely eliminated stent related symptoms. Some of the pain and stent related symptoms can be controlled or reduced by medications. Studies are needed to provide evidence for appropriate stent use of ureteral stents during common procedures for stones (SWL, URS, and PCNL), identify patients who will likely experience stent related pain and symptoms, and to mitigate those symptoms. These questions may be answered by establishing new patient cohorts, randomized clinical trials, pragmatic clinical trials or by using other novel clinical study methodologies. Applicants may propose integrated approaches such as an observational study for event rate and risk identification, and a RCT to reduce ureteral stent use and/or mitigate stent pain and symptoms.
The long-term goal of USDRN is to inform clinical practice by a) providing evidence on the effects of fluid intake on urinary stone recurrence, b) understanding and reducing pain and suffering from the use of ureteral stents in USD patients, and c) to create data and biological specimen resources for USDRN investigators and other future researchers.
The USDRN will consist of one Scientific Data Research Center (SDRC) and 3 to 5 Clinical Centers (CC). The SDRC and CC investigators will work collaboratively for the planning, execution and analysis of USDRN studies.
The USDRN Steering Committee (SC) will be composed of the SDRC and CC Program Directors/Principal Investigators (PDs/PIs), other key investigators and the NIDDK Project Scientist. The SC will meet regularly in-person and by telephone conferences as a full committee and in working groups to develop and implement study protocols. The SC will review progress of individual studies, assess and evaluate results, interpret findings, and develop manuscripts for peer reviewed publications. NIDDK will select chair(s) of the SC (Steering Committee Chair [SCC]) either from the PDs/PIs of the CC's or outside the study group. An Executive Committee (EC) will be comprised of the SCC(s), the SDRC PDs/PIs, and the NIDDK Project Scientist. Additional USDRN investigators, NIDDK Program Officers and support personnel will be a part of the EC as needed. The Executive Committee will make operational decisions for the USDRN between SC meetings by means of weekly telephone conference calls. The NIDDK Project Scientist will assist the SC in the development of USDRN study protocols; will monitor the progress of projects and functioning of all network activities; will assist investigators in the analysis and interpretation of USDRN data; will aid in preparation of manuscripts for publication.
The NIDDK will appoint a Data Safety and Monitoring Board (DSMB) to serve as Protocol Review Committee (PRC) and External Experts Panel (EEP) as needed to provide input on the design of studies prior to their implementation, monitor the research efforts and the progress of the studies, and advise the NIDDK and USDRN investigators. CC and SDRC applicants must not suggest potential participants for this committee in their applications.
The first in-person USDRN Steering Committee Meeting will be a 2 day meeting held on 2 consecutive days within 2 months after the inception of the network in Washington, DC metro area. Specific dates will be determined once the USDRN sites are awarded. Subsequent 1-2 day in-person SC meetings will be conducted every 3 months or as needed thereafter.
A Funding Opportunity Announcement information delivery conference call is scheduled for October 14, 2015, between 11:00 a.m. and 12:00 p.m. Eastern Standard Time to describe and explain the objectives, expected structure and functioning of USDRN. Additional conference calls may also be held. Participation in this conference call is not required for application submission.
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.
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 eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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 only supports linked applications. Multiple PDs/PIs are allowed on any single application. Because the FOA already supports a team approach between groups of experts across sites and collaborating applications, the designation of multiple PDs/PIs on a single application may be less likely to apply. PD(s)/PI(s) from each linked application should not be designated as multiple PDs/PIs on each application of a collaborative set
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:
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, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent, preferably electronically, should be sent to:
Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities, NIDDK
6707 Democracy Boulevard, Room 752, MSC 5452
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following modifications:
Descriptive Title of Applicant's Project: To allow NIH to identify a group of applications as a related set of collaborative applications, the titles for each application in the set must have the following format: a "1/N" indicator + Identical Title (e.g., "1/3", where the 1/3 means this is site 1 of 3 sites in
the set. The other sites will be labeled 2/3, etc.) A set of applications is defined as all applications submitted in response to this FOA as well as the companion FOA (RFA-DK-15-005). Titles of all collaborative applications must be identical except as follows: Applications submitted in response to this FOA must include "Research Project" at the end of the title; the application submitted in response to RFA-DK-15-005 should include "Scientific Data Research Center" at the end of the title. The numbering order of the collaborative applications in the consortium is at the discretion of the applicants. Titles may not exceed 200 characters in length, including the tag, e.g., 1/3, at the beginning of the title.
Cover Letter Attachment: The Cover Letter is one pdf file only. The following collaborative information is required in the Cover Letter: a listing of all the applications that are a part of the set of collaborative applications being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., "1/3"), and 3) the Applicant Institution. Each site should submit an identical listing.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed. Applicants should document expertise needed to successfully design and conduct the proposed studies and prior experience with studies of USD including clinical trials and other types of clinical research studies. Applicants are also expected to be able to provide enough effort per year for the entire budget period.
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:
The application from each site must contain a Research Strategy that clearly describes those aspects of the project that are common to all sites of the collaboration. All variations in the Research Strategy between sites, no matter how minor, should be highlighted in a subsection of the Research Strategy with the heading "Elements Unique to This Site." In this subsection, PDs/PIs should describe, for example, how the research site has a unique role in the collaboration, such as data coordination, statistical analyses, (etc).
The common Research Strategy section should include:
In this section, there should be sufficient description of the items listed above to permit thorough evaluation of the proposed study. Technical details contained in the clinical trial synopsis, statistical analysis plan, and data and safety monitoring plan can be referenced from within the Research Strategy section, in order to avoid duplicating text.
To ensure that the USDRN achieves its goals, the Clinical Centers (CC) are required to include expertise needed to successfully design and conduct the proposed studies and prior experience with studies of USD including clinical trials and other types of clinical research studies. As all USDRN studies will require a collaborative effort and will be conducted at all CCs, each CC must present prior experience with, and future plans for, recruiting study participants with incident and recurrent stone formers. The record of achievement of recruitment goals in prior urinary stone studies, annual USD patients seen, number of procedures performed for USD, Emergency Department stone visits and other evidence of successful recruitment should be presented as relevant to the proposed studies. It is expected that each CC is capable of recruiting 200-300 USD study participants per year. The number of participants with USD to be recruited along with realistic strategies, including back-up plans, for recruitment of adults and children must be described. It is recognized that there may not be adequate numbers of both adult and children with USD at each CC; this should be discussed in the application with explanation of the value of the applicant institution`s role in the network despite low numbers of either adults or children with USD.
For the RCT applications to study increased fluid intake, key elements of the trial, such as power calculations, sample sizes for adequately powered subgroups of adults and children, interventions, and primary and secondary outcomes should be provided. For the proposed ureteral stent study(s), clinical study design type such as observational cohort study, case-control study, randomized controlled trial or pragmatic clinical trial may be proposed. Key elements of the proposed study(s), such as population to be studied, specific aims, hypotheses to be tested, sample size estimates and power calculations should be provided. It is anticipated that proposed clinical studies will provide definitive answers to research questions proposed and inform clinical practice.
It is strongly recommended that Clinical Centers centralize recruitment efforts and studies directly assessing study participants at a single geographical location (e.g., the same institution or institutions within the same city). If an application for a Clinical Center proposes collaborations involving recruitment for clinical studies at multiple sites the need must be strongly justified and a description of the sub-site's ability to recruit and participate in all assessments must be included.
An application for a Clinical Center must:
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
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.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. 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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
In order to expedite review, applicants are requested to notify the NIDDK Referral Office by email at email@example.com 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? Are studies designed to address important questions of clinical relevance? Will the proposed RCT provide new evidence for secondary USD prevention (reduce recurrences)? Will the proposed study(s) reduce ureteral stent use or mitigate pain and stent-related symptoms?
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? Have the investigators agreed to work collaboratively within USDRN to design and carry out united protocols? Is appropriate clinical research and USD expertise represented at the CC and their collaborating institutions (if any)? How do the key investigators address productivity and cooperation within a broad, multi-site research effort? Does the application provide evidence that each of the Clinical Center key investigators will be able to provide enough effort per year for the entire budget period? Do the investigators have a stone clinic and treat USD patients?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Does the applicant provide evidence of a cohesive innovative approach to USD? Does the application address the USDRN research goals through novel, multi-disciplinary approaches? Have innovative behavioral and mobile health technologies been considered? Are novel study designs proposed for ureteral stent-related pain and symptom research?
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? Do applicants present robust rationale or supporting preliminary data relevant to the study(s) proposed? Does the applicant have a demonstrated ability to recruit, retain, and evaluate stone patients (especially recurrent stone formers)? Does the applicant provide the number of study participants that they can realistically recruit? Are key elements of proposed RCT (e.g. power calculations, sample sizes for adequately powered subgroups of adults and children, interventions, and primary and secondary outcomes) provided? Are key elements of the study(s) (study design, population to be studied, specific aims, hypotheses to be tested, sample size estimates and power calculations) for the proposed ureteral stent research provided? Is sufficient expertise in place to address requirements of the USDRN, including the coordination of biosample collection, storage, quality control and distribution (e.g. serum, DNA, stone, tissue, feces and urine)? Does the research plan describe the roles, responsibilities of the key investigators with a leadership plan? Does the research plan explain and accept the collaboration across the USDRN; including planning, implementation and analysis of all types of research efforts? Do applicants describe the integration, and communication across the USDRN and ultimately provision of relevant materials to the NIDDK Data and Biorepositories as appropriate?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.
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.
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.
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:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council (NDDKAC). The following will be considered in making funding decisions:
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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies. The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
1. Developing the research design and study protocol, including definition of objectives and approaches, sample size and power calculations, and establishing procedures for participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and publication of results.
2. Establishing a Steering Committee to implement, coordinate and manage the project(s). Awardee(s) will name investigators to serve as members on a Steering Committee and other subcommittees, as appropriate, meeting periodically. Awardees will be required to accept and implement the common protocol(s) and procedures approved by the Steering Committee.
3. Designating Protocol Chairs. The Program Directors/Principal Investigators (for studies involving multiple protocols) shall designate a single Protocol Chairperson (if the Program Director/Principal Investigator does not assume this role) for each protocol to be carried out by the study group. The Protocol Chairperson shall function as the scientific coordinator for the protocol and shall assume responsibility for obtaining approval to implement the protocol from the Steering Committee and for developing and monitoring the protocol. Significant modifications to approved protocols must be approved by the Steering Committee.
4. Implementing collection of data specified by the study protocol. For a multi-center study, each awardee/site is required to ensure that data will be submitted expeditiously to the Data Coordinating Center. Additionally, individual investigators/sites must demonstrate the ability to implement the strategy specifically designed for their individual study population.
5. Establishing procedures for data quality and completeness. Awardees are responsible for ensuring accurate and timely assessment of the progress of each study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis; (2) for clinical trials, as simple as appropriate in order to facilitate cooperation/referral of study participants by physicians to avoid unnecessary expense; and (3) sufficiently staffed across the participating institutions. For research involving multiple sites, a plan for analysis of pooled data will be developed by the Steering Committee.
6. Submitting interim progress reports, when requested, to the NIDDK Program Official including as a minimum, summary data on protocol performance. For coordinated multiple awards or a multi-site single award, the NIDDK Program Official may require additional information from individual awardees/sites. Such reports are in addition to the required annual noncompeting continuation progress report.
7. 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 (https://grants.nih.gov/grants/policy/data_sharing/ and https://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm), as well as the NIDDK policy for data sharing in multi-center and large single-center clinical studies http://www.niddk.nih.gov/research-funding/process/human-subjects-research/Documents/PublicversionNIDDKdatasharingpolicy2013July2013.pdf.
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 https://clinicaltrials.gov/ct2/manage-recs/fdaaa. In addition, grantees should be aware that clinical trials not covered by FDAAA may still require registration in an approved registry in order to be published, according to the guidelines issued by the International Committee of Medical Journal Editors (http://icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html).
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
An NIDDK Project Scientist with substantial involvement will:
1. Serve as the contact point for all facets of the scientific interaction with the awardee (s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the awardee on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Project Coordinator, who will provide direct technical assistance to the awardees to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.
2. For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or Project Coordinator will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.
3. Serve as a resource to study investigators with respect to other ongoing NIDDK activities that may be relevant to the study to facilitate compatibility with the NIDDK missions and avoid unnecessary duplication of effort.
4. Have substantial involvement assisting in the design and coordination of research activities for awardees as elaborated below:
a. Assisting by providing advice in the management and technical performance of the investigations, coordinating required regulatory clearances for investigational agents used in the study, which are held by NIDDK. The NIDDK may reserve the right to cross file or independently file an Investigational New Drug Application or an Investigational Device Exemption form with the FDA.
b. The NDDK Project Scientist or Project Coordinator may coordinate activities among awardees by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results.
c. Reviewing procedures for assessing data quality and study performance monitoring.
d. The NIDDK Project Scientist or Project Coordinator may be co-authors on study publications. In general, to warrant co-authorship, NIDDK staff must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.
The NIDDK Program Official identified in the Notice of Award will:
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 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 Project Coordinator will serve as the Executive Secretary and/or NIDDK program representative on the DSMB.
Areas of Joint Responsibility include:
In addition to the interactions defined above, NIDDK Project Scientist and Awardees shall share responsibility for the following activities:
1. Steering Committee.
A Steering Committee organized by the study investigator(s) will be the main governing body of the study.
The Steering Committee has primary responsibility to design research activities, establish priorities, develop common protocols and manuals, questionnaires and other data recording forms, establish and maintain quality control among awardees, review progress, monitor patient accrual, coordinate and standardize data management, and cooperate on the publication of results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIDDK Program Official, and will provide periodic supplementary reports upon request.
The Steering Committee will be composed of all 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 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.
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.
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.
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Ziya Kirkali, M.D.
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)
Jason D. Hoffert, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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 Part 75.
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