It is critical that applicants follow the Research (R) 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

Diabetes is a common chronic disease that imposes considerable demands on the individual as well as the U.S. healthcare system. People with diabetes have a higher rate of cardiovascular disease than those without diabetes and are at increased risk for kidney failure, lower limb amputation, and blindness. Obesity is a significant risk factor for type 2 diabetes and the prevalence of obesity in children and adults in the United States has dramatically increased in the past four decades. Overweight, obesity, and/or excessive weight gain during pregnancy are also contributing to rising rates of gestational diabetes mellitus (GDM) which in turn increases risk of future type 2 diabetes in the mother and child. Both type 1 and type 2 diabetes in youth are on the rise. Aging is also a risk factor for type 2 diabetes, and one in four nursing home patients have diabetes. Although diabetes occurs in all populations in the U.S., many minority racial and ethnic groups and individuals with low education and income are at higher risk for diabetes and its complications. Diabetes currently affects an estimated 29.1 million people in the United States. Another 86 million Americans aged 20 years or older are estimated to have prediabetes. The CDC estimates that one in three American children born in 2000 will develop diabetes at some point in their lives. The estimated current annual cost of diabetes in the U.S. is $245 billion dollars per year, with $176 billion in direct medical costs and the remainder related to reduced productivity.

Large clinical trials clearly demonstrate that glycemic control and cardiovascular risk factor modification can reduce the risk of complications in both type 1 and type 2 diabetes. Although there have been considerable improvements in diabetes treatment options and in risk-factor control over the past three decades, research demonstrates that many individuals with diabetes (youth and adults) do not meet the recommended goals for diabetes care. Of particular concern, youth with type 2 diabetes frequently have poor glycemic control and also have high rates of co-morbidities (e.g., hypertension, microalbuminuria, and dyslipidemia) early in the course of their disease, putting them at high risk for developing cardiovascular complications in the prime of their lives. In addition, emerging adults with type 1 or type 2 diabetes may be particularly vulnerable to poor control of diabetes and CVD risk factors as they transition from pediatric to adult care systems. Women diagnosed with GDM represent another important vulnerable group, as responsibilities for the newborn may interfere with their obtaining appropriate post-partum screening and care to prevent the development of type 2 diabetes. There is a need to test innovative and practical approaches to close gaps in care, including system, policy, clinic, provider(s), and patient-level interventions to improve care and outcomes for patients with diabetes.

It is also well established that behavioral lifestyle interventions, with modest (5-7%) weight loss, can prevent or delay development of type 2 diabetes in individuals at high risk for the disorder and, in individuals who already have type 2 diabetes, can decrease sleep apnea, reduce the need for diabetes medications, help maintain physical mobility, and improve quality of life. Although intensive lifestyle interventions, delivered by trained interventionists with highly motivated participants, lead to clinically meaningful weight loss, there is a need to develop and test approaches to weight loss and/or weight management that are implementable and sustainable in primary care settings and applicable to diverse populations. Governmental and non-governmental organizations have proposed prevention and intervention strategies to be carried out in such settings for adults (e.g., the Centers for Medicare & Medicaid Services) and children (e.g., the American Academy of Pediatrics); however, these strategies have not been widely tested for feasibility and effectiveness in routine clinical care.

This FOA seeks research to test the effectiveness of implementable and potentially scalable and sustainable strategies for healthcare delivery to prevent type 2 diabetes in at-risk individuals, improve care for individuals with type 1 and type 2 diabetes, and reduce associated long-term complications, or to test the effectiveness of obesity prevention and treatment strategies that can be implemented in healthcare settings where individuals receive their routine medical care. Studies focused on improving the engagement, recruitment, and retention of low income and/or diverse populations at disproportionate risk of diabetes, obesity, and diabetes related complications are also encouraged.

This funding announcement encourages applications to test pragmatic research designs. Pragmatic research evaluates the effectiveness of interventions or therapeutic approaches in research designed to maximize applicability of the trial’s results to healthcare settings where individuals receive their routine medical care. As such, the research should make use of staff, resources, and facilities in healthcare setting/s where routine care is provided (e.g., in- and out-patient settings, pharmacy services, nursing facilities, etc.). Proposed interventions should not primarily rely on research staff for implementation and should be well integrated into the healthcare system. The healthcare setting should not simply be used as a venue for recruitment. This approach supports the practicality of the intervention and, if effective, will have greater potential to be adopted by similar healthcare providers and systems. Obesity prevention and treatment strategies likely to be effective in primary care settings may require some differing approaches and resources from those useful in diabetes care (e.g., more linkages with trained interventionists or programs outside of the clinical practice). However, the goal of testing pragmatic approaches that are well integrated into routine care is similar for studies focused on diabetes and/or obesity prevention and treatment.

Applications may include approaches focused on the patient, provider, healthcare team, and/or healthcare system. Studies that focus on providers may target physicians as well as non-physician healthcare professionals or staff within the healthcare system being studied or, for obesity prevention and treatment, may include linkages with providers or programs outside of the clinical settings. Areas of research focus should have the potential to generalize to other settings and types of payment and clinical practice situations. Research focused on older populations can include testing approaches within nursing facilities as the setting for routine healthcare delivery. Trials that include community resources to augment healthcare should be designed so that the community resources are sustainable and well-integrated into healthcare delivery. Applications involving community resources should not create that resource but rather utilize existing community resources that are broadly available in communities. Referral to community programs or to providers outside of the clinical setting by the healthcare system or staff is not, by itself, an adequate linkage. For applications that include referral to or partnership with community programs, there should also be some evidence that the community program or policy is directly linked to healthcare delivery through regular communication about patient progress and outcomes. Applications should study factors that will assist with determination of sustainability, acceptability, and feasibility for wide-spread implementation.

Research for this FOA should determine if the approach tested achieves a clinically meaningful and objective (not self-reported) diabetes or obesity-related primary endpoint (e.g., HbA1c, weight/BMI change, diabetes risk factor control, hospitalizations, ER visits, or healthcare utilization.) Healthcare cost can be one of multiple measured endpoints or outcomes but cannot be the sole or primary endpoint that is measured. Self-reported outcomes are not acceptable as primary endpoints. Self-reported outcomes are encouraged as secondary outcomes or as mediators. Improved processes of care, changes in patient or provider behavior, patient-reported outcomes, or adoption of new models of care are also examples of important measures that, if used, should be included as mediators of the primary diabetes or obesity related endpoints.

Examples of prevention or treatment approaches to be tested include, but are not limited to:

• Studies of new and innovative models of healthcare delivery such as shared medical appointment/group visits, team care approaches, care coordination, approaches to integrate behavioral health into routine care, pharmacy/pharmacist based initiatives, incorporation of lay health workers into care processes, approaches to enhance shared decision making, or use of eHealth, mHealth, or health information technology;
• Studies to improve diabetes risk factor control or manage comorbid conditions that lead to poorer diabetes management or increased risk for complications. For example, detection and prevention or treatment of diabetes in women with a history of gestational diabetes, improving glucose and CVD risk factor management in youth and young adults with diabetes, smoking cessation to reduce risk for complications in high risk patients, or treating depression or diabetes distress in patients with poorly controlled diabetes;
• Studies of incentives to improve obesity or diabetes prevention or treatment. Examples include physician incentives to follow clinical care guidelines, provide weight loss therapy/intervention, and achieve target clinical outcomes in their enrolled patient panels; and/or patient incentives to adhere to prescribed medications or follow prevention and treatment recommendations;
• Studies to enhance uptake and delivery of diabetes self-management education and support (DSME/S). DSME/S approaches that are tested should be evidence-based and designed to assist people with diabetes to acquire the knowledge and behavioral or psychosocial skills needed to improve diabetes and related risk-factor control;
• Studies of approaches to improve patient adherence to medical recommendations in order to promote weight loss or improve glycemic control. Such studies could focus on medication regimen, self-care activities such as blood glucose monitoring, or efforts to achieve weight loss or weight gain prevention. Interventions could target patients (including family or caregivers), healthcare providers (including, but not limited to, the physician), aspects of the healthcare system such as patient or provider portals, pharmacy resources, or lay health workers;
• Redesign of workflow in physicians offices to improve screening, initial counseling, and follow-up of patients with diabetes or at risk for diabetes to enhance adherence to guidelines, promote weight loss, or improve glycemic control;
• Studies to test the effectiveness of implementing recommended strategies (e.g., Prevention Plus ) for obesity prevention or treatment in children and adolescents within primary care settings;
• Studies to test strategies for integrating non-primary care provider delivered weight management (e.g., lifestyle interventions delivered remotely by coaches or low-cost commercial weight loss programs) with primary healthcare delivery, including bi-directional communication of relevant information to improve patient outcomes;
• Studies to improve management of diabetes in older adults (e.g., mitigating hyper- and hypoglycemia for older adults in nursing facilities, facilitating diabetes management for older adults with cognitive impairment, streamlining diabetes care in older adults with multi-morbidities);
• Studies to mitigate diabetes and obesity disparities (e.g., improving the diagnosis, prevention, and management of diabetes in low-income and/or diverse populations at disproportionate risk of diabetes, obesity, and diabetes related complications; pragmatic trials that also use strategies to improve engagement, recruitment, and retention of populations at disproportionate risk of diabetes and obesity);
• Studies to assess or address social and behavioral factors in electronic health records or systems and link health determinants to primary healthcare delivery of obesity or diabetes prevention and treatment programs and recommendations.

The purpose of this FOA is to improve the care and health outcomes of individuals with diabetes or at risk for diabetes and/or at risk for overweight or obesity by improving healthcare delivery.

Interventions testing new or unapproved drugs, or interventions designed with a placebo comparison are not appropriate for this FOA.

Only clinical trials designed with one or two distinct clinical research centers are appropriate under this announcement. For the purpose of this FOA, a clinical research center may encompass one or more physical locations where the clinical trial is being conducted -- i.e., where study participants are recruited and/or are intervened upon and/or have outcomes assessed under a single protocol as long as all locations are under the overall direction of a single investigator. Multi-center clinical trials (not appropriate for this announcement) are defined as those that include three or more clinical research centers where recruitment, intervention delivery and participant assessment occur under the direction of investigators from three or more separate research centers, each responsible for the overall conduct of their center's performance. A data coordinating center is not considered a clinical research center. Applications for clinical trials requiring three or more centers should be submitted to NIDDK multi-center clinical study implementation planning cooperative agreement (U34) and NIDDK multi-center clinical study cooperative agreement (U01) FOAs per NOT-DK-14-025 (http://grants.nih.gov/grants/guide/notice-files/NOT-DK-14-025.html) or other FOAs that allow multi-center studies.

The focus of this FOA is on research in humans. Animal studies are not consistent with the intent of this FOA.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

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

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

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

All PD(s)/PI(s) must have an eRA Commons account. 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:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) 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.

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.

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

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

While most research requires some infrastructure support and staffing, grant expenditures for these functions should be minimized to the extent possible.

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:

The research strategy must include a discussion of how integration into the existing clinical setting will be accomplished (i.e., making use of existing staff, resources, and facilities), as well as the potential scalability, acceptability and sustainability beyond the research funding period. This discussion should include, where applicable, issues related to cost; potential for reimbursement; personnel; relevant partnerships with key decision-makers, and staff; and other necessary resources for implementation and maintenance. In addition, research that evaluates effectiveness using existing healthcare staff or resources to deliver an intervention or make system changes is encouraged. If grant funding will be used to support intervention staff, the applicant must make a strong justification that if the study achieves its aims, these personnel and their associated costs have the potential to be sustained in the healthcare setting beyond the research funding period. For obesity prevention and treatment studies, investigators may include linkage to interventionists or programs outside of the healthcare setting, if such linkage is likely to be feasible and sustainable in routine clinical care settings (e.g., 3rd party reimbursement for dietitians or lifestyle coaches or linkage to low-cost community-based or commercial weight management programs), although referral to such programs alone is not appropriate for this announcement.

Some research funding can also go toward enhancement activities such as adapting or enhancing electronic resources or training personnel but, again, the sustainability of these investments beyond the research period should be justified. A full cost effectiveness analysis is not required but research funded implementation costs should be measured and considered in the study analyses.

The primary study endpoint must be a clinically meaningful and objective diabetes or obesity-related outcome (e.g., HbA1c, weight/BMI change, diabetes risk factor control, hospitalizations, ER visits, or healthcare utilization.) Healthcare cost can be one of multiple measured endpoints or outcomes but cannot be the sole or primary endpoint that is measured). Applicants should describe the power calculations related to detecting change in their primary endpoint. If using more than one primary endpoint, applicants should describe the analytic adjustments in their analyses to accommodate for multiple primary end points. Self-reported outcomes are not acceptable as primary endpoints. Self-reported outcomes and patient-centered outcomes are encouraged as secondary outcomes or as mediators.

Applicants should describe how the intervention may generalize to other healthcare settings; and how the research questions and design will meaningfully inform healthcare practice or policy.

Applicants are encouraged, where possible, to use electronic medical records or registries to ascertain study outcomes.

Letters of Support: Studies should include a letter(s) of support from the healthcare setting or system in which the research will be conducted and should address the level of integration of the proposed project into routine practices, how existing resources will be leveraged, and the potential for sustainability once the research is concluded.

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.

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 involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a delayed onset study record.

Study Record: PHS Human Subjects and Clinical Trials Information: All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: All instructions in the SF424 (R&R) Application Guide must be followed.

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. 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. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

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 and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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. For assistance with application submission, contact the Application Submission Contacts in Section VII.

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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

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).

For this particular announcement, note the following: A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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? Is there a strong scientific premise for the project? 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?

Specific to this PAR:

Will the research question and design meaningfully inform healthcare practice or policy? Does the intervention generalize to other healthcare settings?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is the trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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 design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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?

Does the application adequately address the following, if applicable:

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed? Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate? If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial? If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Sustainability

Is the proposed intervention well integrated into the routine practices of the healthcare setting or system (i.e., making use of existing staff, resources, and facilities)? Has the investigator demonstrated appropriate partnerships with the key decision makers and staff in the healthcare setting to justify that the proposed research is feasible? Have the researchers justified the sustainability and dissemination potential of the approach beyond the research period, including appropriate partnerships and consideration of cost and resources such as personnel and infrastructure? If so, was the plan for sustainability compelling--i.e., if successful, would these research findings be likely to improve patient outcomes in routine care settings? Is there a sufficient evaluation of the implementation costs and implementation process to meaningfully inform scalability and sustainability? This evaluation should include, where applicable, issues related to cost, reimbursement, personnel, and other resources.

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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 criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

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

For Renewals, the committee will consider the progress made in the last funding period.

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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 Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIDDK, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . 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:

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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.

Additionally, ICs may specify any special reporting requirements for the proposed clinical trial to be included under IC-specific terms and conditions in the NoA. For example: If the proposed clinical trial has elevated risks, ICs may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials by law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nig.gov/ClinicalTrials_fdaaa/.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Andrew A. Bremer, M.D., Ph.D. (for gestational diabetes research)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-402-7886
Email: Andrew.bremer@nih.gov

Robert Kuczmarski, Dr.P.H. (for adult obesity research)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-8354
Email: KuczmarskiR@EXTRA.NIDDK.nih.gov

Christine Lee, M.D. (for geriatric medical diabetes research)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8806
Email: christine.lee2@nih.gov

Henry B. Burch, M.D. (for health behaviors and policy effects diabetes research)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-0827
Email: henry.burch@nih.gov

Barbara Linder, M.D., Ph.D. (for pediatric diabetes research)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-0021
Email: bl99n@nih.gov

Stavroula Osganian, M.D., Sc.D., M.P.H. (for pediatric obesity medical research)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-6939
Email: voula.osganian@nih.gov

Pamela L. Thornton, Ph.D. (for behavioral and health disparities diabetes research)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-480-6476
Email: thorntonpl@niddk.nih.gov

Michele L. Barnard, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8898
Email: mb316j@nih.gov

Todd Le
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7794
Email: toddle@mail.nih.gov

Thuthuy Nguyen
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8825
Email: tn122r@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.