Purpose:

The purpose of this Funding Opportunity Announcement (FOA) is to seek research applications that develop and pilot test approaches to improve diabetes and obesity prevention and/or treatment in healthcare settings where individuals receive their medical care. Research applications should be developed to pilot test practical and sustainable strategies to improve processes of care and health outcomes for individuals with or at risk of diabetes and/or obesity. The research should also focus on approaches with the potential to be broadly disseminated outside the specific setting where it is being tested. The goal of the research is to use data from the R34, if the pilot study shows promising results, to support a full-scale trial focused on improving medical care and informing healthcare policy for the prevention or management of diabetes and/or obesity.

This FOA seeks applications for pragmatic pilot and feasibility studies that leverage existing staff and resources in healthcare settings. Applications that rely on grant support for interventionists do not meet the intent of this FOA and may be appropriate for one of the NIDDK FOAs for R21s (https://www.niddk.nih.gov/research-funding/current-opportunities), or other appropriate FOAs.

Background:

Diabetes impact

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 microvascular complications that may lead to 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 prevalence and healthcare economics

Diabetes currently affects an estimated 30.3 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 total estimated cost of diagnosed diabetes in 2017 was $327 billion, including $237 billion in direct medical costs and $90 billion in reduced productivity.

Diabetes treatment improves outcomes but many patients are not at goal

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 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 postpartum screening and care to prevent the development of type 2 diabetes.

Lifestyle modifications prevents or delays diabetes but it is underutilized

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 diverse healthcare 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 clinical care.

Goals for this FOA

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. This FOA seeks research to develop and pilot test 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 pilot test obesity prevention and treatment strategies that can be implemented in healthcare settings where individuals receive their medical care. It is expected that data from pilot and feasibility studies that show promising results will be used to support a full-scale trial focused on improving routine healthcare practice and informing healthcare policy for the prevention or management of diabetes and obesity.

Application focus

This funding announcement seeks applications to pilot 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 medical care. Therefore, proposed interventions must be well-integrated into the existing healthcare delivery structure and/or processes and utilize the staff, resources, and facilities in healthcare setting/s where medical care is provided. Proposed interventions should not rely on research staff for implementation. In addition, the healthcare setting should not simply be used as a venue for recruitment. This supports the practicality of the intervention, and if effective, approaches tested under usual conditions will have greater potential to be adopted by similar healthcare providers and systems.

Obesity prevention and treatment strategies likely to be effective in healthcare 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 medical 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. Pilot studies that focus on providers may target physician as well as non-physician healthcare professionals or staff within the healthcare setting 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. Applications should also study factors that will assist with determination of sustainability, acceptability, and feasibility for wide-spread implementation.

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 be some evidence that the community program or policy is directly linked to healthcare delivery through regular communication about patient progress and outcomes.

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

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

Multicenter trials (defined below) are not appropriate for this FOA.

Acceptable study endpoints

Research for this FOA should evaluate the feasibility of the proposed intervention and the preliminary impact of the intervention on a clinically meaningful and objective diabetes and/or obesity-related primary endpoint (e.g., HbA1c, weight/BMI change, hospitalizations, or ER visits). While blood pressure and lipid control are of major importance to prevention of diabetes complications, studies directed primarily at blood pressure and/or lipid control are outside the mission of NIDDK.
Studies addressing comprehensive management of diabetes including glucose, blood pressure and lipid control are encouraged. A co-primary endpoint that addresses glycemic control and another clinically meaningful endpoint (e.g.,
blood pressure and/or lipids) is responsive. Self-reported outcomes are not acceptable primary endpoints for the R34 or future R18 applications. However, Patient Reported Outcomes (PROs) such as quality of life or diabetes distress are
acceptable as a co-primary endpoint together with an objective clinical diabetes or obesity outcome (e.g., HbA1c, weight/BMI). A PRO is defined as the status of a patient’s health condition/s that is reported directly from the patient without amendment or interpretation of the patient’s response by anyone else ( https://www.fda.gov/downloads/drugs/guidances/ucm193282.pdf ). Under this FOA, PROs do not encompass any measure self-reported by a participant but must reflect this narrow definition. A PRO must also be assessed using a valid and reliable patient reported outcome measure.Other self-reported outcomes (e.g., knowledge, diet, physical activity, adherence) are not acceptable as primary or co-primary endpoints but may be secondary endpoints.

Improved processes of care, changes in patient or provider behavior, or acceptability from the perspective of intervention providers, or adoption of new models of care are also examples of important measures that, if used, should be included as secondary endpoints. Appropriate measures of feasibility may include, but are not limited to, measures to assess acceptability from the perspective of intervention providers and/or patients, an assessment of outreach strategies, recruitment and retention rates, visit attendance rates, and adherence to intervention protocol.

Examples of prevention or treatment approaches

Treatment approaches to be tested and populations of special interest 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; workflow modifications to improve screening, initial counseling, and follow-up of patients; care coordination; approaches to integrate behavioral health into medical 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 assess interventions that integrate technology such as remote clinical services (telehealth, telemedicine) to enhance adherence and/or reduce barriers to healthcare access or care in order to improve clinical outcomes;
• Studies to test whether interventions to promote implementation of recommended guidelines or strategies will improve clinical outcomes (e.g., American Diabetes Association Standards of Care in Diabetes or Prevention Plus or U.S. Preventive Services Task Force recommendations for obesity prevention or treatment in children and adolescents);
• Studies addressing the effects of detection and prevention or treatment of diabetes in women with a history of gestational diabetes;
• Studies addressing depression or diabetes distress to improve glycemic control in patients with poorly controlled diabetes;
• Studies of approaches to improve patient adherence to medical recommendations to promote weight loss or improve glycemic control. Such studies could focus on adherence to medication regimen to self-care activities such as blood glucose monitoring, or to strategies designed 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 provider portals, pharmacy resources, or lay health workers;
• 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 glycemic control or a more comprehensive measure that includes blood glucose as well as other cardiovascular risk factors in populations at risk for poor control including youth and young adults with diabetes;
• 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;
• Studies to test interventions that integrate determinants of health in health care settings (e.g., utilizing predictive algorithms involving patient characteristics/demographics to tailor interventions; leveraging determinants of health data from the electronic health record) to improve on clinical outcomes for prevention or treatment of obesity/diabetes.

Proposed interventions that are designed to address clinical outcomes for lower literacy patients, those with low-access to healthcare services, and diverse populations disproportionately affected by diabetes, prediabetes, and obesity are highly encouraged. Interventions that target populations vulnerable to poor glycemic control, such as adolescents, those transitioning to adult care, and young adults are encouraged. Interventions that test care strategies for older adults with diabetes who struggle with multiple chronic conditions and polypharmacy are also encouraged. Pragmatic trials focused on vulnerable populations should address their engagement, recruitment and retention.

Definition of a multicenter trial (not appropriate for this FOA)

Only pilot and feasibility studies designed with one or two distinct clinical research centers are appropriate under this announcement. For the purpose of this FOA, a clinical center may encompass one or more physical locations where the pilot trial is being conducted -- i.e., where study participants are recruited and/or intervened upon and/or have outcomes assessed under a single protocol as long as all locations are under the overall direction of the principal investigator(s).

Multi-center pilot and feasibility trials (not appropriate for this announcement) are defined as those that include three or more clinical research centers where the study is conducted 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.

Applicants are reminded of the NIH policy on the use of a single Institutional Review Board for multi-site research (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-076.html), as well as the NIH policy on the registration and reporting of the results of clinical trials (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-149.html).

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

• 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