EXPIRED
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Limited Competition: Continuation of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study (U01)
U01 Research Project Cooperative Agreements
Reissue of RFA-DK-14-502
None
RFA-DK-15-504
None
93.847
The purpose of this Funding Opportunity Announcement (FOA) is to continue the follow-up of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort through a cooperative agreement. TODAY was a multi-center controlled clinical trial examining the efficacy of three approaches to treat recently diagnosed type 2 diabetes in youth aged 10-17 years. TODAY demonstrated that combination therapy with metformin plus rosiglitazone sustained glycemic control longer than either metformin plus an intensive lifestyle program or metformin alone. TODAY study results also suggest that type 2 diabetes is more aggressive when it occurs at a young age. The primary purpose of this FOA is to continue follow-up of the TODAY cohort to define the long-term clinical course of youth-onset type 2 diabetes.
March 17, 2015
June 9, 2015
June 9, 2015
July 9, 2015, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date. No late applications will be accepted for this Funding Opportunity Announcement.
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.
Not Applicable
January 2016
April 2016
July 10, 2015
Not Applicable
Required Application Instructions
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Part 1. Overview Information
Part 2. Full Text of the Announcement
Section
I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission
Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
This FOA invites a renewal U01 cooperative agreement from the existing TODAY awardees to undertake continued research on and follow-up of the TODAY cohort.
Type 2 diabetes has traditionally been viewed as a disease of adults; however, since the 1990s, type 2 diabetes has emerged in the pediatric population, especially among adolescents and in certain minority populations. The development of type 2 diabetes in children and adolescents is presumed to be a consequence of widespread obesity. Data from the SEARCH for Diabetes in Youth Study indicate that the prevalence of type 2 diabetes has increased among U.S. youth over the last decade.
When children develop diabetes, efficacious therapy is needed to maintain euglycemia in order to prevent the development of complications. Diabetes is currently estimated to cost the U.S. health care system approximately $245 billion annually. Much of the cost is related to the micro- and macrovascular complications of diabetes. Since the development of complications is related, in part, to the duration of diabetes, children represent a population at high risk. Unfortunately, other than metformin, the drugs currently approved for use in adults with type 2 diabetes have not been systematically studied in children. Thus, treatment options for those children diagnosed with type 2 diabetes are restricted by the lack of data on the use of such pharmacological agents.
Treatment programs must also consider cultural differences among racial and ethnic groups that may influence acceptance of medical or lifestyle regimens. This is especially important for type 2 diabetes in children, which disproportionally affects minority groups. Finally, interventions designed for adults may not be directly applicable to the pediatric population. The majority of children with type 2 diabetes are in the pre-adolescent or adolescent age range. The adolescent period presents special challenges to health care providers and families when attempting to promote medication adherence in the context of a chronic disease, or behavior and lifestyle changes.
In response to these concerns, NIDDK funded the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study. Between 2004 and 2009, TODAY enrolled 699 children and teens 10-17 years old with type 2 diabetes for less than two years. Participants were randomly assigned to one of three treatment groups: metformin alone; metformin and rosiglitazone; and metformin plus intensive lifestyle change aimed at losing weight and increasing physical activity. All participants were followed for a minimum of two years. TODAY was designed to test the hypothesis that initial aggressive therapy would provide better glycemic control than traditional, step-wise therapy. This could potentially have long-lasting benefits in adolescents who may be thrown into diabetes by pubertal insulin resistance.
The TODAY cohort was predominantly minority (32% African American, 41% Hispanic, 6% American Indian) and of low socioeconomic status (42% with household income <$25,000); the majority of the TODAY participants came from single-parent households. The economic and psychosocial barriers faced by these families make aggressive glucose control a challenge.
The TODAY study's main goal was to determine how well and for how long each treatment approach controls blood glucose levels. The primary outcome was time to treatment failure, defined as a hemoglobin A1c greater than or equal to 8% for 6 months. Secondary outcomes included measures of beta cell function and insulin resistance, body composition, nutrition, physical activity and fitness, microvascular complications, cardiovascular risk factors, side effects, quality of life, and psychological outcomes. The influence of individual and family behaviors on treatment response and the relative cost effectiveness of the treatment arms were also evaluated.
TODAY demonstrated that the combination of metformin plus rosiglitazone reduced glycemic failure by 25% compared with metformin alone. Metformin plus lifestyle was intermediate but not statistically different from either metformin alone or metformin plus rosiglitazone. In addition, the primary result of the TODAY study demonstrated that T2D may have a much more aggressive course in youth, with approximately half of patients unable to maintain glycemic control on metformin monotherapy despite good medication compliance. Race/ethnic differences in medication response were also seen, with 66% of African American youth in TODAY unable to sustain glycemic control with metformin alone. The data on insulin resistance and secretion derived from serial oral glucose tolerance tests in the TODAY study suggest early and rapid deterioration of beta cell function in these youth compared with data published on adult individuals with newly diagnosed T2D. Furthermore, the rates of co-morbidities and risk factors for diabetes-related complications were alarmingly high in the TODAY cohort. At the end of the study, when mean diabetes duration was less than 5 years, 34% of participants had hypertension, 17% had microalbuminuria, 11% required LDL-lowering therapy, and nearly 14% had retinopathy by fundus photography.
These findings are ominous--especially in the context of a rigorous clinical trial with extensive individual attention provided and a population selected for its ability to comply with protocol requirements, and may portend poor outcomes, including early cardiovascular disease. Further follow-up of the TODAY participants will provide valuable information about the development of diabetes complications in this population.
Once the interventional component of the TODAY study ended, rosiglitazone was stopped in all participants because of emerging concerns about drug-related CVD risk in adults, For the past two years, TODAY has followed participants and provided protocol-driven diabetes care using metformin and insulin.
Continued follow-up of the TODAY cohort will enable investigators to address multiple questions related to understanding the course and treatment of type 2 diabetes in youth, including: 1) documenting the clinical course of T2D that occurs at a young age, including the development of vascular complications and risk factors, and co-morbidities; 2) determining the predictors of glycemic control, to better understand which individuals would benefit from early, aggressive treatment; and 3) understanding race/ethnic disparities in achieving/sustaining glycemic control and developing complications.
One award will be made to the Biostatistics Research Center, which will include subcontracts to each of the 15 clinical centers that conducted the TODAY study, and to the central laboratory, reading centers, and scientific cores.
In the next follow-up phase, medical care will not be provided to participants, who will return to their local physicians for care of their diabetes. Participants will be seen annually for assessment of outcomes.
The TODAY study group, consisting of the investigators from the Clinical Centers and the Biostatistical Research Center, collaboratively develops the study design and develops plans for implementing the protocol. The study group jointly analyzes data from the study, and disseminates this information through presentations at scientific meetings and manuscripts in scholarly, peer-reviewed journals. The study group has also developed mechanisms through which investigators outside of the study group may collaborate with the study investigators to test novel hypotheses using the TODAY cohort or TODAY samples and/or data.
1. Clinical Centers (CCs)
The Clinical Centers are responsible for re-consent and retention of existing TODAY participants and for collecting outcomes.
The CCs are expected to implement the protocol. The CCs collect data in accordance with established study procedures and submit all samples and data to the Biostatistics Research Center (BRC) and central laboratory and central reading centers, as appropriate and required by the protocol.
Investigators at the CCs conduct analyses in conjunction with the BRC. The TODAY study group will have exclusive access to data from the TODAY study population for a defined period, according to NIDDK data sharing policies. All study data analyzed for publication of the primary study outcome(s) are expected to be provided to the NIDDK Repository so that it can be shared within six months of the publication date for the primary outcome publication or within two years of the date that the database is locked for analysis, whichever occurs first. All data analyzed for publication of the secondary outcome(s) are expected to be provided to the Repository so that it can be shared within two years of the date that the database for these outcomes is locked for analysis. The TODAY Steering Committee has already established policies under which ancillary studies may be conducted while the study is ongoing.
2. Biostatistics Research Center (BRC)
There is a single BRC. The BRC biostatisticians work with the Clinical Center investigators to develop the scientific design of the study. The BRC investigators have primary responsibility for ensuring that the design of the study, including the primary outcome, is scientifically sound and is supported by appropriate power calculations. The BRC provides biostatistical and analytic expertise and conducts analysis and interpretation of the laboratory and clinical data in conjunction with the investigators at the Clinical Centers. The BRC is responsible for guiding development of the statistical analysis plan for the study as a whole and for each manuscript reporting pre-specified primary and secondary outcomes.
In additional to conducting the research described above, the BRC is responsible for the oversight and coordination of CC activities. The BRC oversees the collection and management of all clinical and laboratory data. The BRC continues to be responsible for ensuring subject confidentiality and safety, and quality control. The BRC conducts training and certification of study staff, and maintains and updates the manual of operations. The BRC continues to oversee implementation of and adherence to the study protocol. The BRC coordinates communication among and with the CCs.
The BRC continues to be responsible for the movement of biologic samples from the CCs to the central laboratory and, subsequently, to the NIDDK Repository, where samples will be stored for future analysis. The BRC similarly continues to ensure the flow of radiographic tests and other collected data to the appropriate central reading center. The BRC also collaborates with the NIDDK Data Repository to prepare all TODAY data for eventual archiving and distribution, according to the timeline described above.
The BRC continues to prepare appropriately detailed reports to the Steering Committee and to the TODAY Observational Study Monitoring Board (OSMB), and to the NIDDK staff at regular intervals. The BRC is responsible for the planning and logistics of meetings of the Steering Committee and its subcommittees, and assists NIDDK with the logistics for OSMB meetings.
3. Steering Committee
The primary governing body of the study continues to be the Steering Committee, comprised of the Program Directors/Principal Investigators of the BRC and each CC, and the NIDDK Project Scientist.
The Steering Committee continues to develop policies and procedures for the TODAY study group, and ensures that these policies are properly implemented. These may include procedures for modification of study design, use of study samples and data, approval of ancillary studies, publication and presentation of study findings, monitoring of study progress, determining completeness and quality of data collection, and other performance measures.
4. Project Scientist
The NIDDK Project Scientist continues to assist the Steering Committee in carrying out the TODAY study. The Project Scientist provides scientific support to awardees' activities, including protocol development, quality control, interim data monitoring, final data analysis, preparation of publications, and overall performance monitoring.
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.
Renewal
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
NIDDK intends to commit $7.3 million in FY 2016 to fund one award.
Application budgets are not limited but need to reflect the actual needs of the proposed project.
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.
This FOA is a limited competition for the continuation of the TODAY study, which was previously funded from RFA-DK-14-502. Only the currently funded Biostatistics Research Center (BRC) is eligible to apply. Only the currently funded Clinical Centers (CC) are eligible to be CCs as subcontracts to the BRC.
Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible
to apply.
Foreign components, as defined in
the NIH Grants Policy Statement, are allowed.
Applicant Organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
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:
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 should be sent to:
Dr. Francisco Calvo
Chief, Review Branch
National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK)
6707 Democracy Blvd., Room 752
Bethesda MD 20892-5452
(for express/courier service: Bethesda, MD 20817
Telephone: 301-594-8897
Fax: 301-480-3505
Email: calvof@mail.nih.gov
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..
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.
Other Attachments: The following items should be included as attachments.
1. Clinical Protocol Synopsis
The file name "Clinical Protocol Synopsis.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.
The clinical protocol synopsis must include the following information:
Applications that lack the Clinical Protocol Synopsis are incomplete and will not be peer reviewed.
2. Statistical Analysis Plan
The filename "Statistical Analysis Plan.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.
The applicant(s) should describe the statistical methods to be used, including the sample size and power calculation, plans for the primary and secondary analyses, and pre-specified interim analyses. The plan is critical to knowing whether applicants have selected the correct cohort size based on the proper power calculations and/or are using the most appropriate methods to analyze the resulting data and make correct conclusions at the end of the study.
Applications that lack the Statistical Analysis Plan are incomplete and will not be peer reviewed.
3. Data and Safety Monitoring Plan (DSMP)
The filename "Data and Safety Monitoring Plan.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.
The DSMP should be commensurate with the risk level of the proposed clinical research and must be included for all clinical trials (see http://grants.nih.gov/grants/guide/notice-files/not98-084.html) and multi-center clinical studies. Information about DSMPs is available on the NIDDK website: http://www.niddk.nih.gov/research-funding/process/human-subjects-research/policies-for-clinical-researchers/data-safety-monitoring-plans/Pages/data-and-safety-monitoring-plans.aspx. All applications or study protocols must include a general description of the monitoring plan, policies, procedures, responsible entities, and approaches to identifying, managing and reporting reportable events (adverse events and unanticipated problems), to the applicable regulatory agencies (e.g., Institutional Review Board (IRB), the Office of Human Research Protections, and the NIDDK-appointed Observational Study Monitoring Board Monitoring Board.
The DSMP must address the following areas:
Applications that lack the DSMP are incomplete and will not be peer reviewed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy: In the work to be supported through this FOA, medical care will not be provided to participants, who will return to their local physicians for care of their diabetes. Participants will be seen annually for assessment of outcomes and may have additional contacts via phone or other communication modalities at established intervals to maintain contact and enhance retention. The Research Strategy should reflect this change and 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 protocol 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.
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. The study protocol may be attached as an appendix.
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. 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.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness 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 calvof@mail.nih.gov 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 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?
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?
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.
Not Applicable
For Renewals, the committee will consider the progress made in the last funding period.
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Not Applicable
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. 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 Principal Investigators (for studies involving multiple protocols) shall designate a single Protocol Chairperson (if the Principal Investigator does not assume this role) for each protocol to be carried out by the study group. The Protocol Chairperson shall function as the scientific coordinator for the protocol and shall assume responsibility for obtaining approval to implement the protocol from the Steering Committee and for developing and monitoring the protocol. Significant modifications to approved protocols must be approved by the Steering Committee.
4. Implementing collection of data specified by the study protocol. For a multi-center study, each awardee/site is required to ensure that data will be submitted expeditiously to the Data Coordinating Center. Additionally, individual investigators/sites must demonstrate the ability to implement the strategy specifically designed for their individual study population.
5. Establishing procedures for data quality and completeness. Awardees are responsible for ensuring accurate and timely assessment of the progress of each study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis; (2) for clinical trials, as simple as appropriate in order to facilitate cooperation/referral of study participants by physicians to avoid unnecessary expense; and (3) sufficiently staffed across the participating institutions. For research involving multiple sites, a plan for analysis of pooled data will be developed by the Steering Committee.
6. Submitting interim progress reports, when requested, to the NIDDK Program Director including as a minimum, summary data on protocol performance. For coordinated multiple awards or a multi-site single award, the NIDDK Program Director may require additional information from individual awardees/sites. Such reports are in addition to the required annual noncompeting continuation progress report.
7. Establishing procedures, where applicable, for all participating institutions in coordinated awards to comply with FDA regulations for studies involving investigational agents or devices and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects, and the NIH policy requirements for the inclusion of women, minorities and children.
8. Reporting of the study findings. Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. The awardee must also be adherent to Study Publication and Presentation Policy. The NIDDK will have access to and may periodically review all data generated under an award. NIDDK staff may co-author publications of findings with awardees consistent with NIH and study policies.
9. Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NIDDK support; or special access to study results, primary data/summary information, or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party is permitted only after concurrence by NIDDK.
10. Study investigators are encouraged to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols and steering committee policies on publications.
11. Maintaining confidentiality of information: The awardee(s) will maintain the confidentiality of the information developed by the investigators (i.e., protocols, data analysis, conclusions, etc.) as well as proprietary information of a company collaborating with the study.
12. The NIDDK has established Central Biosample, Genetic, and Data Repositories for the
archiving and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. The PI or his/her designee is expected to coordinate with the NIDDK Data Repository to prepare the collected data for eventual archiving and distribution, consistent with achieving the goals of the program. In addition, if applicable, the PI or his/her designee is expected to work with the NIDDK Biosample Repository to coordinate procedures for coding, shipping, processing, receipt, and storage of study samples that are to be maintained in the Repository. All samples and data transferred to the Repositories will be under the custodianship of the NIDDK, although the study s Steering Committee will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time. Subsequently samples and data will be available to the wider scientific community in accordance with the NIH policy on Data Sharing (http://grants.nih.gov/grants/policy/data_sharing/ and,
http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm#goals , and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).
13. The Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law requires mandatory registration and results reporting for certain clinical trials of drugs, biologics, and devices. If trials conducted under this 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://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 Analyst, who will provide direct technical assistance to the awardees to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.
2. For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or designee will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.
3. Serve as a resource to study investigators with respect to other ongoing NIDDK activities that may be relevant to the study to facilitate compatibility with the NIDDK missions and avoid unnecessary duplication of effort.
4. Have substantial involvement assisting in the design and coordination of research activities for awardees as elaborated below:
a. Assisting by providing advice in the management and technical performance of the investigations, coordinating required regulatory clearances for investigational agents used in the study, which are held by NIDDK. The NIDDK may reserve the right to cross file or independently file an Investigational New Drug Application or an Investigational Device Exemption form with the FDA.
b. The NDDK Project Scientist or designee may coordinate activities among awardees by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results.
c. Reviewing procedures for assessing data quality and study performance monitoring.
d. The NIDDK Project Scientist or designee may be co-authors on study publications. In general, to warrant co-authorship, NIDDK staff must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.
The NIDDK Program Official identified in the Notice of Award will:
1. Interact with the principal investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the principal investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, data safety and monitoring board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.
2. Review and approve protocols prior to implementation to insure they are within the scope of peer review, for safety considerations, as required by Federal regulations.
3. The NIDDK Program Official will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; (f) low likelihood of showing a benefit of the intervention (futility); and (g) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.
4. Make recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
5. Appoint a Data and Safety Monitoring Board (DSMB) as appropriate; the NIDDK Program Official or their designee will serve as the Executive Secretary and/or NIDDK program representative on the DSMB.
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 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 (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 Observational Study Monitoring Board (OSMB) will be established for observational/epidemiologic studies. These Boards will review study progress, safety data and interim results, as appropriate, and provide guidance to the NIDDK.
Dispute Resolution
Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NIDDK may be brought to dispute resolution. A dispute resolution panel will be composed of three members --one selected by the awardee (or the Steering Committee, with the NIDDK member not voting), a second member selected by NIDDK, and the third member elected by the two prior selected members. These special dispute resolution procedures in no way affect the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CR Part 16.
When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
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Telephone: 301-402-7886
Email: andrew.bremer@nih.gov
Francisco Calvo, Ph.D.
National Institute of Diabetes and Digestive and Kidney
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E-mail: calvof@mail.nih.gov
Todd Le
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7794
Email: toddle@mail.nih.gov
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.