Foa_Content_of_RFA-DP-22-001 Amend 1.pdf

Centers for Disease Control and Prevention

NATIONAL CENTER FOR CHRONIC DISEASE PREVENTION AND HEALTH

PROMOTION

Real-world effectiveness of structured lifestyle interventions in preventing type 2 diabetes

RFA-DP-22-001

01/24/2022

Table of Contents 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

Overview Participating Organization(s) Centers for Disease Control and Prevention Components of Participating Organizations Components of Participating Organizations:

National Center for Chronic Disease Prevention and Health Promotion Notice of Funding Opportunity (NOFO) Title Real-world effectiveness of structured lifestyle interventions in preventing type 2 diabetes Activity Code U18

Notice of Funding Opportunity Type New Agency Notice of Funding Opportunity Number

RFA-DP-22-001

Assistance Listings Number(s) 93.068 Category of Funding Activity HL - Health NOFO Purpose The purpose of this Notice of Funding Opportunity Announcement (NOFO) is to create a research network consisting of multiple study sites for assessing (1) system and individual level barriers and facilitators to participation in and completion of structured lifestyle intervention (SLI) programs as implemented by the CDC National Diabetes Prevention Program (NDPP), including the Medicare Diabetes Prevention Program (MDPP) and (2) the long-term effectiveness and cost-effectiveness of NDPP/MDPP.

This NOFO has two (2) components:

Component A-Longitudinal cohort: The purpose of Component A is to establish a study cohort to:

1. identify system and individual level barriers and facilitators to the enrollment and completion of the NDPP/MDPP, and

2. evaluate the long term (≥5 years) effectiveness and cost-effectiveness of the NDPP/MDPP, which includes the effect of the SLI programs on:

(a) reducing type 2 diabetes onset;

(b) improving cardiovascular disease (CVD) risk factors including body mass index (BMI), blood pressure and lipid levels, and smoking status;

(c) improving health-related quality of life;

(d) reducing health care services utilization and costs.

Component B-Coordinating Center: The purpose of component B is to provide the infrastructure for data storage (if needed), harmonizing data collection and data analysis based on a core study protocol; ensure statistical, logistics, and communications support to enhance the efficiency and productivity for component A activities.

Key Dates Publication Date:

To receive notification of any changes to RFA-DP-22-001, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link.

An email address is needed for this service.

Letter of Intent Due Date:

12/27/2021 12/27/2021

Application Due Date:

01/24/2022 01/24/2022

On-time submission requires that electronic applications be error-free and made available to CDC for processing from the NIH eRA system on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov no later than 5:00 PM U.S. Eastern Time.

Applicants will use a system or platform to submit their applications through Grants.gov and eRA Commons to CDC. ASSIST, an institutional system to system (S2S) solution, or Grants.gov Workspace are options. ASSIST is a commonly used platform because it provides a validation of all requirements prior to submission and prevents errors.

For more information on accessing or using ASSIST, you can refer to the ASSIST Online Help Site at: https://era.nih.gov/erahelp/assist. Additional support is available from the NIH eRA Service desk via http://grants.nih.gov/support/index.html.

E-mail: commons@od.nih.gov Phone: 301-402-7469 or (toll-free) 1-866-504-9552.

Hours: Monday - Friday, 7 a.m. to 8 p.m. Eastern Time, excluding Federal holidays.

Note: HHS/CDC grant submission procedures do not provide a grace period beyond the application due date time to correct any error or warning notices of noncompliance with application instructions that are identified by Grants.gov or eRA systems (i.e., error correction window).

Scientific Merit Review:

03/23/2022 Secondary Review:

05/13/2022 Estimated Start Date:

09/01/2022 Expiration Date:

01/25/2022 Required Application Instructions It is critical that applicants follow the instructions in the How to Apply - Application Guide except where instructed to do otherwise in this NOFO. Conformance to all requirements (both in the Application Guide and the NOFO) 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.

Page Limitations: Pages that exceed the page limits described in this NOFO will be removed and not forwarded for peer review, potentially affecting an application's score.

Applications that do not comply with these instructions may be delayed or may not be accepted for review.

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348

Executive Summary The purpose of this Notice of Funding Opportunity Announcement (NOFO) is to create a research network consisting of multiple study sites for assessing (1) system and individual level barriers and facilitators to participation in and completion of structured lifestyle intervention (SLI) programs as implemented by the CDC National Diabetes Prevention Program (NDPP), including the Medicare Diabetes Prevention Program (MDPP), and (2) the long-term effectiveness and cost-effectiveness of NDPP/MDPP.

This NOFO has two (2) components:

Component A: Applicants for component A will establish a study cohort to (1) identify system and individual level barriers and facilitators to the enrollment and completion of the NDPP/MDPP and (2) evaluate the long term (≥5 years) effectiveness and cost-effectiveness of the NDPP/MDPP, which includes the effect of the SLI programs on (a) reducing type 2 diabetes onset; (b) improving cardiovascular disease (CVD) risk factors including body mass index (BMI), blood pressure and lipid levels, and smoking status, (c) improving health-related quality of life; and (d) reducing health care services utilization and costs.

Component B: The Coordinating Center provides the infrastructure for data storage (if needed), harmonizing data collection and data analysis based on a core study protocol; ensure statistical, logistics, and communications support to enhance the efficiency and productivity for component

A activities.

Mechanism of Support. Cooperative Agreement funding mechanism (CDC U-18).

Funds Available and Anticipated Number of Awards. The estimated total funding (direct and indirect) for the entire period of performance is $16,000,000 to support up to 6 awards in two components:

1. Component A: It is anticipated that up to 5 awards will be made for up to $570,000 (direct and indirect) each in FY2022.

2. Component B: It is anticipated that one award will be made for up to $350,000 (direct and indirect) in FY2022.

Awards issued under this NOFO are contingent upon availability of funds and a sufficient number of eligible applications.

Budget and Project Period. The estimated total funding (direct and indirect) for all components for the first budget period, 09/01/2022 to 08/31/2023, is $3,200,000. The estimated total funding (direct and indirect) for the 5-year period of performance, September 1, 2022 to August 31, 2027, is $16,000,000.

Application Research Strategy Length: Page limits for the Research Strategy are clearly specified in Section IV. Application and Submission Information of this announcement.

Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.

Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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.

NOTE: CDC does NOT make awards to individuals directly.

Number of PDs/PIs. Applications may include more than one PD/PI; however, the first PD/PI listed on the application will be the “contact PD/PI” for all correspondence. Any additional PDs/PIs are permitted but would be referred to as Co-PIs.

Number of Applications. If an applicant organization intends to apply to more than one component in this NOFO, the applicant must submit separate applications for each component. To be funded for Component B, applicants are not required to apply for and be funded for Component A. The PI for Component A may be different from the PI for Component B.

Application Type. New (type 1).

Special Date(s). None.

Application Materials. See Section IV.1 for application materials Hearing Impaired. Telecommunications for the hearing impaired are available at:

TTY: 1-888-232-6348.

Section I. Funding Opportunity Description Statutory Authority Awards are made under the authorization of 317(k) (2) of the Public Health Service Act (PHS Act), 42 U.S.C. 247b(k)(2) and 301(a) of the PHS Act, 42 U.S.C. 241(a).

1. Background and Purpose In 2018 an estimated 88 million Americans aged 18 years or older had prediabetes, representing about one third of the US adult population. In 2002, the landmark US Diabetes Prevention Program (DPP) study showed that a structured lifestyle intervention (SLI) was effective in delaying/preventing type 2 diabetes in adults with impaired glucose tolerance (IGT). The SLI was an intensive lifestyle modification program consisting of structured behavioral training sessions aiming at changing diet and physical activity behaviors of individuals who had overweight/obesity and at high risk of type 2 diabetes. The effectiveness of the DPP SLI was similar in all racial/ethnic groups (1-6).

Follow-up data from the US DPP trial and similar trials in China, Finland, and India and computer simulation studies have demonstrated that SLI programs are both effective and cost-effective beyond the active intervention period (7-10). However, the long-term effectiveness and cost-effectiveness of the DPP-like SLI programs as implemented in a real-world setting remain largely unknown because of changes in enrollment criteria and translation strategies of the SLI programs. For example, the study populations in nearly all earlier major type 2 diabetes prevention trials included persons with IGT. In comparison, the SLI programs as implemented in the real-world setting, enrolled persons with prediabetes defined by HbA1c, fasting glucose, or 2-hour glucose levels, or based on type 2 diabetes risk scores with or without blood test values.

Also, the SLI program in the US DPP trial included 16 core sessions in the first six months and additional monthly follow-up sessions after that. The intervention program in the trial was delivered in person (group or one-on-one). In contrast, the SLI programs in the real-world settings vary in delivery methods (e.g., in-person versus virtually or individual versus group coaching) and intervention intensity (e.g., frequency of contacts or intervention duration).

Two recent type 2 diabetes prevention trials tested the effectiveness of the SLI in persons with prediabetes identified by HbA1c or impaired fasting glucose (IFG) criteria, but findings from these trials were mixed (11, 12). The Diabetes Community Lifestyle Improvement Program (D- CLIP) study found a stepwise intervention including lifestyle intervention plus metformin as needed was effective in reducing type 2 diabetes incidence among persons with IGT or IFG plus IGT, but not in persons with isolated IFG (11). The Norfolk Diabetes Prevention lifestyle intervention found that the SLI was effective in reducing type 2 diabetes incidence in persons with IFG and A1c levels of ≥6.0% to <6.5% (12). The study did not include persons with prediabetes with HbA1c values of 5.7% to 5.9%, which account for a significant proportion of the prediabetes population. A systematic review of US studies published between 2003 and 2011, and that translated the DPP trial lifestyle curriculum to real-world settings, found that among the 28 studies included, there was considerable variation in design (four randomized controlled trials, two cluster randomized controlled trials, twenty single group pre-post studies, and two nonrandomized controlled studies), setting (twelve were based in community environments, such as community centers, recreation centers, and faith-based organizations, eleven were conducted in health care facilities, and four studies used online tools), and analytic approach (13). Generally, studies offering more core sessions achieved greater attendance and greater weight loss. In addition, lay educators were as effective in motivating participants to lose weight as qualified professionals, contributing to lower cost of the programs (13). However, these translational trials normally lasted less than 2 years and nearly all studies used body weight reductions as their primary study outcomes. Thus, the long-term effectiveness of the interventions implemented in these trials on type 2 diabetes prevention remains unclear.

In 2010, Congress authorized CDC to establish and manage the NDPP to scale the DPP-like SLI programs nationwide. Eligibility criteria for the NDPP enrollment are broader than those used in the DPP clinical trial, including people with prediabetes, or at high risk for developing type 2 diabetes defined by a score of 5 or higher on the CDC/American Diabetes Association (ADA) Prediabetes Risk Test. A participant entering the DPP must have a high diabetes risk based on either family history, clinical risk factors, history of gestational diabetes mellitus (GDM), or glucose level (HbA1c, fasting or 2-hour after an OGTT glucose levels). The program consists of 16 hourly sessions held at approximately weekly intervals during the first 6 months, followed by a minimum of six sessions held at approximately monthly intervals during months 7–12. The specifics of program delivery can be customized by stakeholders as long as key criteria are met, including the use of a CDC-approved curriculum that focuses on lifestyle change with a moderate physical activity of 150 minutes or more each week, healthy eating, and weight loss of 5–7% over a 1-year period of time. As of July 2021, there were 554,721 people in 1,961 recognized organizations enrolled in the NDPP program.

In March 2016, the HHS Secretary announced that the Diabetes Prevention Program model met the statutory eligibility criteria for expansion into Medicare, based on the results of a model test and the ensuing statement by the CMS Office of the Actuary certifying that expansion of the model would reduce net Medicare spending.

The Medicare Diabetes Prevention Program (MDPP) is a SLI program designed to prevent type 2 diabetes in individuals 65 years and older with prediabetes, as defined by the threshold values of any of the three blood glucose tests (A1c, fasting or 2-hour glucose levels). The MDPP consists of a minimum of 16 intensive “core” sessions of a CDC approved curriculum delivered over six months in a group-based, classroom-style setting and monthly follow-up meetings after the first six months. A payment up to $761 per participant meeting retention goals is reimbursed over a two-year period to MDPP suppliers that achieve the primary goal of at least 5 percent weight loss by participants in 2021.

Using different enrollment criteria and program specification in the implementation of the DPP-like SLI in the NDPP/MDPP is likely to result in different effectiveness and cost-effectiveness than shown in the original clinical trials, translational trials, and computer simulation studies. In addition, participation in and completion of the NDPP curriculum as well as reaching the 5 percent weight loss goal have been lower among eligible individuals, in particular among racial and ethnic minority groups in the NDPP/MDPP (14), who are at higher risk of developing type 2 diabetes than non-Hispanic white people. The low participation and completion rates of the NDPP could change the effectiveness and cost-effectiveness of the SLI program in real-world settings. Identifying the determinants of the lower uptake of the NDPP in all eligible populations especially in minority groups is critical to improving the effectiveness and cost-effectiveness of the NDPP and MDPP and reducing diabetes-related health disparities.

The purpose of this Notice of Funding Opportunity Announcement (NOFO) is to assess system and individual barriers to and facilitators of participation in the SLI programs of the NDPP/MDPP, and to evaluate the long-term effectiveness and cost-effectiveness of the SLI as implemented in the NDPP/MDPP using real-world data. The study population are individuals who are eligible for the NDPP/MDPP, i.e., persons with prediabetes (defined by HBA1c, fasting glucose, or 2-hours glucose levels, or any combinations of the three measures), or high-risk scores of developing type 2 diabetes identified by risk score tools or risk equations. The SLI programs to be evaluated include interventions that are delivered in person, virtually, or a combination of the two in the NDPP/MDPP.

Healthy People 2030 and other National Strategic Priorities This NOFO supports the Diabetes Healthy People 2030 objectives: Reduce the number of diabetes cases diagnosed yearly — D-02; Reduce the proportion of adults who don’t know they have prediabetes — D-06; Reduce the rate of death from any cause in adults with diabetes — D-09 This NOFO supports the CDC Strategic Framework to reduce the number of new diabetes diagnoses from 1.4 million in 2018 to 1.1 million cases per year by 2025. https://www.cdc.gov/about/organization/strategic-framework/index.html

Measurable outcomes of this NOFO will be in alignment with the following performance goal for the National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP): to monitor, prevent, delay, detect and control chronic disease, to achieve health equity by eliminating health disparities and achieving optimal health for all Americans.

Measurable outcomes of this NOFO will be in alignment with the Division of Diabetes Translation mission statement to reduce the preventable burden of diabetes through public health leadership, partnership, research, programs and policies that translate science into practice.

Public Health Impact This NOFO is designed to assess system and individual barriers to and facilitators of participation in the NDPP/MDPP, and to evaluate the long-term effectiveness and cost-effectiveness of the SLI program as implemented in the NDPP/MDPP using real-world data.

Preventing type 2 diabetes through implementing the SLI program nationwide is the main goal of the NDPP/MDPP to reduce the harmful health and economic impact of diabetes for the nation. In 2018, 34.2 million Americans had diabetes.

Findings from this NOFO will provide critical information needed to further improve the NDPP/MDPP. Identifying the system and individual barriers to and facilitators of participation in and completion of the NDPP/MDPP is critical to increasing the participation rate in these programs. Selecting the most appropriate population to intervene in the NDPP/MDPP and implementing the most effective and cost-effective SLI strategies to the target population can improve the program efficacy. Specifically, results from this work could provide answers to the following questions:

1. What are the barriers to and facilitators of enrollment in and completion of the NDPP/MDPP? How do health equity-related characteristics, including socio-economic status, neighborhood environment, language and culture, housing, and transportation access such as public transit, differ between those who enrolled (intervention group) and those who were eligible but did not enroll (control group) and between those who successfully complete the program and those who drop out before program completion?

2. What are the long-term (≥5 years) effectiveness and cost-effectiveness of the SLI used in the NDPP/MDPP for type 2 diabetes prevention among adults with high risk of developing type 2 diabetes in a real-world setting in the US?

3. How do the effectiveness and cost-effectiveness of the SLI differ by eligibility criteria (e.g., blood test vs risk test, IFG, IGT)?

4. How do the effectiveness and cost-effectiveness of NDPP/MDPP differ by program delivery mode (in-person, online/virtual, group, individual)?

5. What is the most effective and cost-effective strategy to implement and expand the SLI program in the NDPP/MDPP?

Relevant Work CDC created the National DPP to address the increasing burden of type 2 diabetes in the United States (National Diabetes Prevention Program | Diabetes | CDC). Through partnerships between public and private organizations, this national program offers evidence-based interventions that help prevent type 2 diabetes in communities across the United States (https://coveragetoolkit.org/). The NDPP lifestyle change program is offered through CDC-recognized organizations, including community-based organizations, hospitals, provider groups, pharmacies, and health plans. These organizations deliver the program in person, online, through distance learning (e.g., remote classroom or telehealth), or a combined approach. Since 2018, the MDPP is offering a SLI program designed to prevent type 2 diabetes in individuals 65 years and older with prediabetes.

About 2,000 recognized organizations and over a half million people enrolled in the NDPP as of July of 2021. From 2012 to 2016, 35.5% of the participants achieved the 5% weight loss goal, 41.8% met the physical activity goal of 150 min per week (14). About half of participants in the NDPP lifestyle change program were retained past 28 weeks. Individuals who were younger or were members of racial/ethnic minority populations and who reported less physical activity or less early weight loss were significantly less likely to be retained in the NDPP (15). Changes in diabetes incidence, CVD risk factors and health care expenditures among the NDPP participants have not been evaluated. Barriers to participate in and to complete the NDPP have not been systematically examined.

The effectiveness and cost-effectiveness of the SLI that were shown in the original clinical trials, translational trials, and computer simulation studies may not hold for the NDPP/MDPP due to using different enrollment criteria, different SLI program delivery methods, and much lower program participation and completion rates.

2. Approach Objectives Component A - Longitudinal Cohort:

The primary objective of Component A is to collect data needed for establishing a longitudinal electronic study cohort for answering the two primary research questions: 1) what are the system and individual level barriers to and facilitators of participation in and completion of NDPP/MDPP and (2) what are the long-term effectiveness and cost-effectiveness of SLI programs as implemented in the NDPP/MDPP, measured in reduction of incidence of type 2 diabetes, and improvements in CVD risk factors and in health related quality of life (HRQoL).

The study participants are those who meet the CDC NDPP or MDPP eligibility criteria.

Applicants will be expected to identify records of eligible individuals who participate (intervention group) and who do not participate (control group) in the NDPP/MDPP. For the first study objective, applicants shall be able to collect information from both intervention and control groups on their basic socioeconomic characteristics, barriers to and facilitators of NDPP/MDPP enrollment, retention, and completion, including but not limited to availability of NDPP/MDPP providers, physician referrals, access to healthy foods and facilities for physical activities such as gyms and other exercise facilities, built environment to support walking/biking, or parks or trails, neighborhood safety including violence, unsafe air or water, and other health and safety risks, distance to NDPP/MDPP providers, availability of transportation to NDPP/MDPP providers if walking and biking are not feasible, internet access, socio-economic and employment status, urban/rural residence, knowledge of NDPP/MDPP programs, and competing obligations – e.g., nightshift worker, dual caregivers (parent + child), social support/network, community cohesion and more. For the second study objective, applicants shall demonstrate the capacity to collect/link individual level data from different entities, i.e., SLI program information from the NDPP/MDPP providers, electronic health records from health care providers, and health care utilizations and cost data from the insurance claims, and to be able to obtain/link these individual-level data for a minimum of 5 years after NDPP/MDPP enrollment or study entry (i.e., data from the NDPP/MDPP providers are not needed for the control group). The intervention cohort shall include NDPP/MDPP delivered either in person, virtually, or a combination of the two.

The longitudinal cohort includes records of all eligible individuals as defined in the NDPP/MDPP and are divided into two groups: the intervention group, which consists of those who participated in the NDPP/MDPP (either completing or not completing the program); the control group, which consists of those who met the NDPP/MDPP enrollment criteria but did not enroll in the program. Information to be collected for the intervention group includes (1) individual medical/health electronic records data, health care utilization and cost data at least two years prior to the NDPP/MDPP enrollment, and 5 years after the enrollment; (2) demographics, and social determinants of health (SDOH) information (About Social Determinants of Health (SDOH) (cdc.gov)), attitude to the SLI program (e.g., perceived benefits and barriers); and (3) information on the specific SLI program a participant received (type of the program, number of sessions attended), cost and payment of the SLI program and, healthy behavioral changes such as changes in diet and physical activities of the participants if such data is available from the NDDP/MDPP providers or other sources. Information needed for the control group is the same as for the intervention group except the SLI program information. Data on health-related quality of life for both intervention and control groups is also expected. Potential data sources are electronic data records or data systems from SLI program providers, electronic health records from participants’ routine healthcare providers, claims data from the health insurance companies, data from devices and/or big data aggregators (i.e., for neighborhood characteristics), additional surveys of the study participants and/or NDPP/MDPP providers. Applicants for Component A are expected to demonstrate ability to collect all data components and to establish partnerships with organizations that processed the data including, but not limited to, data collection companies, community organizations, SLI providers, health care providers, employers, and health care insurance companies. Capacity to include and follow-up individuals’ records from socio-demographic disadvantaged groups is required and is expected to be described in detail.

Establishing a control group is required for Component A. The control group is expected to have a similar health profile as the NDPP/MDPP participants (i.e., eligible but not referred, or referred and not enrolled in NDPP/MDPP). Applicants are expected to describe in detail the data and methods used in establishing the control group and for the follow-up of these individuals’ records.

Each applicant for component A is expected to describe in detail their strategy for identifying and follow-up of the study cohort, data collection method, and analytic approach used for the data analysis. A minimum sample size of 5,000 NDPP/MDPP program enrollees and equal or a greater number of matched controls is required per applicant. Additional information on study sample size will be described in the next section.

Component B - Coordinating Center:

Through Component B, a Coordinating Center will support the research activities of Component A. The main objectives of the coordination center related to support include:

1. Maintain the central data (or aggregate data) repository for the longitudinal cohort; create a common data protocol and mechanisms to secure harmonization of data within the cohort sites and between sites; transmit data and relevant data management reports between the recipients for Component A.

2. Provide expertise and leadership in population-based longitudinal data collection, surveillance, methodology, implementation, and evaluation.

3. Provide expert statistical and other analytic support including development of analytic methods and files for validation of pre-diabetes and diabetes diagnosis.

4. Provide innovative biostatistical expertise and support timely dissemination of study results and estimates of real-life type 2 diabetes incidence among adults participating in SLIs.

Objectives/Outcomes Outcomes:

Component A - Longitudinal Cohort:

The primary outcomes of Component A are: (1) significant barriers to and facilitators of enrollment in and completion of the NDPP/MDPP; and (2) the long term (≥5 years) effectiveness and cost-effectiveness of the NDPP/MDPP. The effectiveness of the NDPP/MDPP is measured in primary and secondary outcomes. The primary outcome is incidence rate of type 2 diabetes.

The secondary health outcomes include CVD risk factors and HRQoL. The cost outcome includes changes in health care services utilization and cost before and after the enrollment of the NDPP/MDPP and cost of the programs. Cost-effectiveness measures include cost per case of diabetes prevented and cost per quality-adjusted life year gained. All outcomes are for overall study population and by age group, sex, race/ethnicity, social-economic category, and eligibility criteria for the NDDP/MDPP (HbA1c, fasting glucose, or OGTT, or diabetes risk score).

A minimum of 5,000 NDPP/MDPP participants and an equal or greater number of matched controls is required for each applicant. The total number of participants includes any SLI delivery mode (in-person, virtual or combination of the two). Including participants from all three delivery modes are preferred. The study population should also be socio-demographically diverse and include those who are socioeconomically disadvantaged. The proportion of socioeconomically disadvantaged and ethnic minority groups included in the study should be equal to or greater than their corresponding proportion of the national population with pre-diabetes.

The funding recipients are expected to:

1. Establish an electronic study cohort of persons who are eligible for NDPP/MDPP to identify barriers and facilitators to participating in or completing the NDPP/MDPP, including but not limited to social determinant factors, availability of NDPP/MDPP providers, physician referrals, access to healthy foods and facilities for physical activities, neighborhood safety, distance to NDPP/MDPP providers, availability of transportation to NDPP/MDPP providers, internet access, socio-economic and employment status, urban/rural residence, knowledge of NDPP/MDPP, and competing obligations – e.g., nightshift worker, dual caregivers (parent + child), social support/network, community cohesion and more.

2. Conduct detailed descriptive and modeling analyses of the electronic cohort population (NDPP/MDPP completers, non-completers, and controls) to identify significant barriers to and facilitators for participating in and completing the NDPP/MDPP.

3. Estimate incidence rate of type 2 diabetes for NDPP/MDPP enrollees (completers and non-completers) and risk of type 2 diabetes relative to controls (eligible but not enrolled).

4. Estimate incidence rate of type 2 diabetes in subgroups by age group, sex, race/ethnicity, social-economic category, and eligibility criteria for the NDDP/MDPP (Hb A1c test, fasting or OGTT test, or diabetes risk score).

5. Estimate trends in diabetes risk factors, including, but not limited to bodyweight, BMI, blood glucose levels, dietary and physical activity behaviors.

6. Estimate trends in CVD risk factors, including, but not limited to, BMI, blood pressure, lipid levels, and smoking status.

7. Estimate the intervention cost of the NDPP/MDPP.

8. Estimate trends in health services utilization and cost at least two years before the follow-up and at least 5 years during the follow-up.

9. Estimate the HRQoL at the baseline and during the follow-up.

10. Assess longitudinal epidemiological associations between NDPP/MDPP enrollment criteria, program delivery mode, compliance with the SLI program, provider characteristics and the above outcomes (type 2 diabetes, CVD risk factors, HRQoL, and heath care utilizations and expenditures) with adequate controls and follow-up time.

11. Estimate the cost-effectiveness of the NDPP/MDPP as measured by cost per case of diabetes prevented and cost per quality-adjusted life year.

12. Estimate the effectiveness and cost-effectiveness of the NDPP/MDPP by type 2 diabetes risk level defined by value of the A1c test, fasting or OGTT test or risk score.

13. Estimate the effectiveness and cost-effectiveness of the NDPP/MDPP by delivery mode.

14. Estimate the effectiveness and cost-effectiveness of the NDPP/MDPP by age group and race/ethnic group.

Target Population Component A - Longitudinal Cohort:

The target population is adults (≥18 years old) in the U.S. at a high risk of developing type 2 diabetes. Applicants’ sites are expected to have access to socio-demographically disadvantaged and diverse populations.

Collaboration/Partnerships

Component A - Longitudinal Cohort:

Applicants are expected to demonstrate ability to collect all electronic data components needed to build the longitudinal electronic study cohort as described above. Applicants are expected to link NDPP/MDPP participant information to their electronic medical records and health insurance /Medicare claims data at least two years before the intervention and five years or more after the intervention so that NDPP/MDPP participants (completers and non-completers) can be followed longitudinally. Applicants are also expected to link electronic medical records, health insurance /Medicare claims data for the control group similar to the intervention group for comparing the two groups. Surveying study participants and/or NDPP/MDPP providers to collect information on barriers to and facilitators of participation and completion of the programs, HRQoL, and programs cost, and sources of payments is anticipated. Accessing individual electronic data for the SLI program each NDPP/MDPP enrollee participated in is also required. Applicants are anticipated to show their abilities to link data from all entities that have different data components. These entities include NDPP/MDPP providers, clinical records from the participants’ health providers, health insurance/Medicare claim data, and individual-level demographic, socio-economic, health, and health behavioral information of the study participants. Data collection methods can be prospective or a combination of retro- and prospective methods. Applicants using either approach are expected to describe their methods in detail.

Applicants are expected to provide evidence of established and well-defined working relationships with organizations and/or outside entities expected to participate in the proposed research.

Applicants are expected to demonstrate partnerships with health care networks or systems to access information on study participants. Applicants are expected to demonstrate experience in working collaboratively with research partners.

Component B - Coordinating Center:

Applicants are expected to collaborate with recipients of component A and other partners to accomplish goals and objectives of the study.

The applicant should demonstrate experience in coordination of multi-center studies, data management and innovative analysis. Applicants should demonstrate experience in working collaboratively with research partners.

Evaluation/Performance Measurement Component A - Longitudinal Cohort:

The applicants are expected to be evaluated based on

1. Ability to collect all longitudinal core data (described below under Research Plan) for the study cohort, including proposed approaches for the data collection, commitment from entities/organizations to contribute the data, experience with working with different partners. Ability and experience to analyze the data collected.

2. Technical approaches to achieve the two study objectives. Justifications for all measures and analytical methods used to assess the barriers to and facilitators of NDPP/MDPP participation and completion, and effectiveness and cost-effectiveness of the SLI program, approaches to identify and validate persons with pre-diabetes and type 2 diabetes and controls for the study, and statistical and economics methods for the data analysis. Strategies and methods used to ensure validity and accuracy of data on race/ethnicity, socioeconomic status of the study population, measures for health services utilization and cost, SLI program cost and health-related quality of life. Methods to collect valid and accurate information on participant’s eligibility at the NDPP/MDPP enrollment, SLI program structure and delivery mode, and participant compliances with the SLI programs.

3. Approaches to reach, enroll, and follow-up socio-demographically disadvantaged and diverse populations.

Emphasis should be on rigorous scientific approaches and methodologies and feasibility of the data collection.

Component B - Coordinating Center:

Applicants for Component B are expected to provide:

1) Evidence of organizational experience and capabilities, including, but not limited to: site support, governance support, and staff training plans; plans to ensure the quality and integrity of collected data; plans to maintain accurate and timely information on the progress of study and site performance;

2) Evidence of staff experience and capabilities, including, but not limited to: demonstration of innovative analytic approaches to evaluating research data; and the qualifications and research experience of the management and analytic team.

3) Evidence of specialized capabilities and experience in large scale network coordination, including, but not limited to, previous experience with design, administration, management, and coordination of multi-site studies.

Translation Plan Applicants for Components A and B are expected to work collaboratively to establish a longitudinal electronic cohort and develop innovative methods for aggregating data and presenting joint analyses that will produce results comparable across sites. Applicants are expected to communicate the findings to the larger scientific and public health communities. The results are expected to be timely communicated through peer reviewed journals, presentations at scientific meetings, and other means. Applicants are expected to engage with public health entities to translate the findings for the state or local communities.

OMB/PRA may apply.

References:

1. Diabetes Prevention Program (DPP) Research Group. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care 2002;25(12):2165‒2171.

2. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403.

3. Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677–1686.

4. Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention: an intent-to-treat analysis of the DPP/DPPOS. Diabetes Care. 2012;35(4):723–730.

5. Diabetes Prevention Program Research Group, Orchard TJ, Temprosa M, et al. Long-term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors: a report from the DPP Outcomes Study. Diabetic Medicine. 2013;30(1):46–55.

6. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. The Lancet Diabetes & Endocrinology 2015;3(11):866–875.

7. Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med.

2001;344(18):1343-1350.

8. Lindström J, Peltonen M, Eriksson JG, Ilanne-Parikka P, Aunola S, Keinänen- Kiukaanniemi S, Uusitupa M, Tuomilehto J; Finnish Diabetes Prevention Study (DPS).

Improved lifestyle and decreased diabetes risk over 13 years: long-term follow-up of the randomised Finnish Diabetes Prevention Study (DPS). Diabetologia. 2013;56(2):284- 293.

9. Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV.

Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997;20(4):537-544.

10. Gong Q, Zhang P, Wang J, Ma J, An Y, Chen Y, Zhang B, Feng X, Li H, Chen X, Cheng YJ, Gregg EW, Hu Y, Bennett PH, Li G; Da Qing Diabetes Prevention Study Group.

Morbidity and mortality after lifestyle intervention for people with impaired glucose tolerance: 30-year results of the Da Qing Diabetes Prevention Outcome Study. Lancet Diabetes Endocrinol. 2019;7(6):452-461.

11. Weber MB, Ranjani H, Staimez LR, Anjana RM, Ali MK, Narayan KM, Mohan V. The Stepwise Approach to Diabetes Prevention: Results From the D-CLIP Randomized Controlled Trial. Diabetes Care. 2016;39(10):1760-1767.

12. Sampson M, Clark A, Bachmann M, Garner N, Irvine L, Howe A, Greaves C, Auckland S, Smith J, Turner J, Rea D, Rayman G, Dhatariya K, John WG, Barton G, Usher R, Ferns C, Pascale M; Norfolk Diabetes Prevention Study (NDPS) Group. Lifestyle Intervention With or Without Lay Volunteers to Prevent Type 2 Diabetes in People With Impaired Fasting Glucose and/or Nondiabetic Hyperglycemia: A Randomized Clinical Trial. JAMA Intern Med. 2021;181(2):168-178.

13. Ali MK, Echouffo-Tcheugui J, Williamson DF. How effective were lifestyle interventions in real-world settings that were modeled on the Diabetes Prevention Program? Health Affairs 31, NO. 1, 2012: 67–75.

14. Ely EK, Gruss SM, Luman ET, Gregg EW, Ali MK, Nhim K, Rolka DB, Albright AL. A National Effort to Prevent Type 2 Diabetes: Participant-Level Evaluation of CDC's National Diabetes Prevention Program. Diabetes Care. 2017;40(10):1331-1341.

15. Cannon MJ, Masalovich S, Ng BP, Soler RE, Jabrah R, Ely EK, Smith BD. Retention Among Participants in the National Diabetes Prevention Program Lifestyle Change Program, 2012-2017. Diabetes Care. 2020 Sep;43(9):2042-2049.

3. Funding Strategy N/A

Section II. Award Information Funding Instrument Type:

CA (Cooperative Agreement) A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed:

New - An application that is submitted for funding for the first time. Includes multiple submission attempts within the same round.

Estimated Total Funding:

$16,000,000 The estimated total funding (direct and indirect) for the 5-year period of performance, September 1, 2022 to August 31, 2027, is $16,000,000. It is anticipated that 6 awards will be made under this NOFO RFA-DP-22-001.

Funding for the first 12-month (including both direct and indirect costs):

Component A: (up to 5 awards) $570,000 per award Component B: (1 award) $350,000

Awards issued under this NOFO are contingent on the availability of funds and submission of a sufficient number of meritorious applications.

Anticipated Number of Awards:

Award Ceiling:

For Component A:

Award ceiling: $570,000 Award floor: $200,000 For Component B:

Award ceiling: $350,000 Award floor $200,000

Awards issued under this NOFO are contingent on the availability of funds and submission of a sufficient number of meritorious applications.

Award Ceiling:

$900,000 Per Budget Period

Award Floor:

$200,000 Per Project Period

Total Period of Performance Length:

5 year(s)

Throughout the Period of Performance, CDC's commitment to continuation of awards will depend on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and CDC’s determination that continued funding is in the best interest of the Federal government.

HHS/CDC grants policies as described in the HHS Grants Policy Statement (https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf) will apply to the applications submitted and awards made in response to this NOFO.

If you are successful and receive a Notice of Award, in accepting the award, you agree that the award and any activities thereunder are subject to all provisions of 45 CFR Part 75, currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category:

99 (Unrestricted (i.e., open to any type of entity above), subject to any clarification in text field entitled "Additional Information on Eligibility")

00 (State governments)

01 (County governments)

02 (City or township governments)

04 (Special district governments)

05 (Independent school districts)

06 (Public and State controlled institutions of higher education)

07 (Native American tribal governments (Federally recognized))

08 (Public housing authorities/Indian housing authorities)

11 (Native American tribal organizations (other than Federally recognized tribal governments))

12 (Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education)

13 (Nonprofits without 501(c)(3) status with the IRS, other than institutions of higher education)

20 (Private institutions of higher education)

22 (For profit organizations other than small businesses)

23 (Small businesses)

25 (Others (see text field entitled "Additional Information on Eligibility" for clarification))

Additional Eligibility Category:

The following types of Higher Education Institutions are always encouraged to apply for CDC 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

Nonprofits (Other than Institutions of Higher Education):

Nonprofits (Other than Institutions of Higher Education)

Governments:

Eligible Agencies of the Federal Government

U.S. Territory or Possession

Other:

Faith-based or Community-based Organizations

Regional Organizations

Bona Fide Agents: A Bona Fide Agent is an agency/organization identified by the state as eligible to submit an application under the state eligibility in lieu of a state application. If applying as a bona fide agent of a state or local government, a legal, binding agreement from the state or local government as documentation of the status is required. Attach with "Other Attachment Forms."

Federally Funded Research and Development Centers (FFRDCs): FFRDCs are operated, managed, and/or administered by a university or consortium of universities, other not-for-profit or nonprofit organization, or an industrial firm, as an autonomous organization or as an identifiable separate operating unit of a parent organization. A FFRDC meets some special long-term research or development need which cannot be met as effectively by an agency's existing in-house or contractor resources. FFRDC's enable agencies to use private sector resources to accomplish tasks that are integral to the mission and operation of the sponsoring agency. For more information on FFRDCs, go to https://gov.ecfr.io/cgi-bin/searchECFR.

2. Foreign Organizations Foreign Organizations are not eligible to apply.

Foreign components of U.S. Organizations are not eligible to apply.

For this announcement, applicants may not include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Additional Information on Eligibility For an applicant to be even considered they must be responsive to the following.

Component A - Longitudinal Cohort:

Applicants must provide evidence of being able to access electronic records for building a cohort of individuals meeting eligibility criteria for the NDPP/MDPP (both participated in the NDPP/MDPP and not participated but eligible for the NDPP/MDPP program), individual program participation information of the NDPP/MDPP participants, medical records and health services utilization and cost data of all study participants.

A minimum number of 5,000 NDPP/MDPP program enrollees and equal or a greater number of matched controls is required per applicant.

If the application is incomplete or non-responsive to the special eligibility requirements listed in this…