RFA-DD-19-002 FINAL.pdf

Centers for Disease Control

National Center on Birth Defects and Developmental Disabilities Extramural Research Program

Office

The Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)

RFA-DD-19-002

Application Due Date: 02/13/2019

The Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)

RFA-DD-19-002

TABLE OF CONTENTS

Part 1. Overview Information Key Dates Required Application Instructions Executive Summary

Part 2. Full Text 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

Part 1. Overview Information Participating Organization(s) Centers for Disease Control Components of Participating Organizations National Center on Birth Defects and Developmental Disabilities Extramural Research Program Office (NCBDDD ERPO) National Center on Birth Defects and Developmental Disabilities (NCBDDD) Notice of Funding Opportunity (NOFO) Title The Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) Activity Code U01

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

RFA-DD-19-002

Assistance Listings (CFDA) Number(s) 93.315 Category of Funding Activity:

Health NOFO Purpose The purpose of this NOFO is to better understand the public health and clinical impacts of living with muscular dystrophies (MDs) by conducting longitudinal, population-based surveillance and research of eligible MDs (Duchenne MD, Becker MD, myotonic dystrophy, facioscapulohumeral MD, limb-girdle MD, congenital MD, Emery-Dreifuss MD, oculopharyngeal MD, and distal MD).

Key Dates Publication Date: To receive notification of any changes to RFA-DD-19-002, 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: 01/14/2019

Application Due Date: 02/13/2019

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. Applications must be submitted using the Application Submission System & https://www.grants.gov

Interface for Submission Tracking (ASSIST) module which is a web-based service used for the preparation and submission of grant applications to CDC through Grants.gov. ASSIST provides the ability for applicants to prepare their applications online, and offers the applicant additional capabilities including the ability to preview the application image, validate the application against required business rules, and prepopulate data from an applicant organization's records, therefore identifying issues earlier in the application submission process.

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: 04/10/2019

Secondary Review: 05/20/2019

Estimated Start Date: 09/01/2019

Expiration Date: 02/14/2019 Due Dates for E.O. 12372: Executive Order 12372 does not apply to this program.

Required Application Instructions

**ELECTRONIC APPLICATION SUBMISSION VIA ASSIST IS PREFERRED**

It is recommended that applicants use ASSIST for the electronic preparation and submission of applications through Grants.gov to CDC. ASSIST is an alternative method to prepare and submit applications, and provides many features to facilitate the application submission process which improves data quality (e.g., pre-population of organization data, pre-submission validation of business rules, and preview of the application image used for review). Use of the Grants.gov downloadable Adobe application packages and submission process will still be supported.

It is critical that applicants follow the instructions in the SF 424 (R&R) 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.

Note: The Research Strategy component of the Research Plan is limited to 25 pages.

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

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348 (See Part 2, Section IV, 7. Page Limitations).

http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf

Executive Summary Purpose. The purpose of this NOFO is to better understand the public health and clinical impacts of living with muscular dystrophies (MDs) by conducting longitudinal, population-based surveillance and research of eligible MDs (Duchenne MD, Becker MD, myotonic dystrophy, facioscapulohumeral MD, limb-girdle MD, congenital MD, Emery-Dreifuss MD, oculopharyngeal MD, and distal MD).

This NOFO has five components to achieve the purpose of the program:

Component A – Core-Current: Current MD STARnet sites will continue to conduct surveillance for eligible MDs, collect clinical data on existing cohorts, and conduct research studies on surveillance populations. Applicants must be a current MD STARnet site to apply for Component A.

Component B – Core-New: New MD STARnet sites will build a program to conduct MD surveillance, identify and collect data on eligible MD populations, and conduct research studies on surveillance populations. Applicants proposing a new MD STARnet site may apply for Component B. Component B applicants should contribute to the diversity of the MD surveillance population by including large target populations of specific minority groups (e.g. non-Hispanic Blacks, Asians, and Hispanics).

Component C – Enhanced-Dissemination: Analysis of MD STARnet data and dissemination of results through publications in peer-reviewed journals and presentations at stakeholder meetings. Only Component A applicants are eligible to apply for Component C.

Component D – Enhanced-Data Coordinating Center: Data coordinating center (DCC) that supports activities involving data collection, quality improvement, cleaning, pooling, and release for the network. Component A and B applicants are eligible to apply for Component D.

Component E – Enhanced-Abstractor: Center that conducts abstractor training and data quality activities for the network. Only Component A applicants are eligible to apply for Component E.

Mechanism of Support. Cooperative Agreement Funds Available and Anticipated Number of Awards. Component A: It is anticipated that up to six awards will be made to up to six recipients for up to $375,000 each in FY 2019. Component B: It is anticipated that up to two awards will be made to up to two recipients for up to $350,000 each in FY 2019. Component C: It is anticipated that up to five awards will be made to up to five recipients for up to $80,000 each in FY 2019. Component D: It is anticipated that one award will be made to a single recipient for up to $250,000 in FY 2019. Component E: It is anticipated that one award will be made to a single recipient for up to $80,000 in FY 2019. Awards issued under this NOFO are contingent upon availability of funds and a sufficient number of meritorious applications. Because the nature and scope of the proposed research will vary from application to application, it is also anticipated that the size and duration of each award may also vary. The total amount awarded and the number of awards will depend upon the number, quality, duration and cost of the applications received.

Budget and Project Period. The estimated total funding for all components (direct and indirect) for the first budget period, 9/1/2019 – 8/31/2020, is $3,250,000. The estimated total funding for all components (direct and indirect) for the entire project period, 9/1/2019 – 8/31/2024, is $16,250,000.

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

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. NOTE:

CDC does not make awards to individuals directly. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply.

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

Number of Applications. Only one application per institution (normally identified by having a unique DUNS Number) per component is allowed for this NOFO. Applicants must submit separate applications if applying to more than one Component. All eligible applicants for Component A can also apply for Component C, D, or E. To apply for component C, D, or E, eligible applicants must apply for Component A. To apply for Component D, eligible applicants must apply for Component B.

Application Type. New Special Date(s). CDC will conduct one conference call for prospective applicants on

December 14, 2018 from 2:00 pm - 3:30 pm, EST. The conference call number is 1-855- 644-0229 and Conference ID: 5069266. This session will provide information about the NOFO and will answer questions pertinent to preparing applications in response to this

NOFO.

Application Materials. See Section IV.1 for application materials. Please note that Form D is to be used when downloading the application package. http://grants.nih.gov /grants/how-to-apply-application-guide/forms-d/general-forms-d.pdf%20

Hearing Impaired. Telecommunications for the hearing impaired are available at:

TTY: 1-888-232-6348.

Part 2. Full Text Section I. Funding Opportunity Description

Statutory Authority This program is authorized under Section 301(a) and 317C of the Public Health Service Act, [42 U.S.C. Section 241(a)).and 247-4], as amended.

1. Background and Purpose In the U.S. population, approximately 7,000 rare diseases affect an estimated 25 million people.

Many of these conditions have severe, lifelong health effects which usually lead to premature disability and even death. Muscular dystrophies (MDs) are a group of rare inherited disorders http://www.cdc.gov/od/pgo/funding/grants/additional_req.shtm#SectionIV http://era.nih.gov/commons/index.cfm#SectionIII1A http://grants.nih.gov/grants/ElectronicReceipt/submit_app.htm#SectionIV1 http://grants.nih.gov/grants/how-to-apply-application-guide/forms-d/general-forms-d.pdf%20 http://grants.nih.gov/grants/how-to-apply-application-guide/forms-d/general-forms-d.pdf%20 characterized by progressive and irreversible muscle weakness and wasting. The nine major types of MD (Duchenne, Becker, myotonic dystrophy, congenital, limb girdle, Emory-Dreifuss, facioscapulohumeral, distal, and oculopharyngeal) vary by age of onset, muscle groups affected, genes involved, severity, and progression of disease. Although MDs have been studied in numerous clinic-based groups, population-based epidemiologic studies are needed to more accurately estimate prevalence, morbidity, and mortality, and to describe the variability in access to care and treatments received among individuals with MD. Epidemiological data also support the establishment and evaluation of policies, health care services, and health outcomes among people affected by MD.

To obtain epidemiologic data, surveillance for muscular dystrophies started in 2002 with the development of the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) after passage of the MD CARE Act of 2001, which authorized CDC to award grants and cooperative agreements to public or nonprofit entities for a national surveillance program for muscular dystrophies. From 2002 through 2011, the goal of MD STARnet was to identify and collect information on all people with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), the most common types of MD in children, to determine prevalence, types of care received, factors that affect outcomes, and the needs and quality of life of patients and families affected by these MDs[1]. During that time, up to six sites (i.e. award recipients) participated in surveillance of DMD and BMD. In 2011, the number of sites was reduced to four and surveillance was expanded to include a total of nine types of MD to test the ability of the existing network to conduct surveillance for other MDs. Pilot data showed that the MD STARnet infrastructure could be used to identify and collect epidemiologic and clinical data on people with other types of MD (myotonic dystrophy (DM), facioscapulohumeral MD (FSHD), limb-girdle MD (LGMD), congenital MD (CMD), oculopharyngeal MD (OPMD), Emery-Dreifuss MD (EDMD), and distal MD)[2]. Building on the pilot, in 2014, three of the original sites and three new sites were awarded funds to conduct population-based surveillance for nine MDs (DMD, BMD, DM, FSHD, LGMD, CMD, OPMD, EDMD, and distal MD). The focus of the past five years has been to establish three new MD STARnet sites, modify protocols and eligibility criteria for each of the nine MDs, expand data collection to include more extensive clinical data on all MDs, and publish and disseminate results of data collected through previous funding cycles (on primarily DMD/BMD).

The purpose of this NOFO is to better understand the public health and clinical impacts of living with MD by conducting longitudinal, population-based surveillance and research of eligible MDs (DMD, BMD, DM, FSHD, LGMD, CMD, EDMD, OPMD, and distal MD). The current cycle will focus on identifying eligible MD cases, conducting longitudinal follow-up and research, analyzing data, and publishing and disseminating the results. Current MD STARnet sites will collect data to estimate prevalence and survival and additional clinical data on existing MD cohorts. New MD STARnet sites will focus on identifying eligible MD cases and collecting data to estimate prevalence, survival and track key clinical indicators.

Identification of cases through population-based surveillance will enable existing and new sites to conduct research on these populations. This information is expected to advance understanding of diagnosed prevalence, disease progression and survival; clinical care and interventions and their alignment with recommended care; disparities in access to care; the association of treatment with outcomes, and the impact of MD on the lives of affected individuals and their families.

The following objectives address the purpose of the NOFO:

1. Conduct longitudinal, population-based surveillance and follow-up on individuals with eligible muscular dystrophies.

a. For current MD STARnet sites:

Eligibility criteria will be expanded and basic demographic, clinical data, and vital records information will be collected for DM, FSHD, LGMD, CMD, EDMD, and distal MD to enable better estimation of clinically diagnosed prevalence and survival. For DM, FSHD, LGMD, CMD, EDMD, and distal MD, sites will also continue to collect clinical information for those cases with definitive diagnoses and/or family history to better understand disease progression, care and clinical interventions and their alignment with recommended care, disparities in access to care, and association of clinical treatment on outcomes.

DMD/BMD cohorts will continue to be followed to determine changes over time in prevalence and survival, and to further describe disease progression, care and clinical interventions and their alignment with the DMD care considerations, disparities in access to care, and association of clinical treatment on outcomes.

b. New MD STARnet sites will use MD STARnet methods to identify eligible MD cases and collect data to determine prevalence, survival, and track key clinical indicators.

c. Current and new MD STARnet sites will determine a method for collecting ICD-10 codes and conduct research to validate implementation of the new codes for DMD/BMD and FSHD.

2. Conduct research with populations identified through surveillance to address knowledge gaps (e.g. quality of life, pregnancy and fertility issues, and burden of care) that cannot be investigated well through surveillance methods.

3. Analyze, publish, and disseminate surveillance and research studies that address knowledge gaps in diagnosed prevalence, disease progression and survival; clinical care and interventions and their alignment with recommended care; disparities in access to care;

the association of clinical treatment with outcomes; and the impact of MD on the lives of affected individuals and their families.

Although new MD STARnet sites added during the last funding cycle have been contributing data on minority populations, more data on these populations are needed to better understand the impact of MD on affected individuals and their families among minority populations (e.g.

non-Hispanic Blacks, Asians, and Hispanics). As a result, potential applicants with large populations of one or more racial/ethnic minority groups are encouraged to apply for Component B.

Healthy People 2020 and other National Strategic Priorities The CDC and NCBDDD are committed to achieving the health promotion and disease prevention objectives of "Healthy People 2020". This NOFO addresses the following “Healthy People 2020” priority areas:

1. Ensure that federal, state, tribal, and local health agencies have the necessary infrastructure to effectively provide essential public health services

PHI-13: Increase the proportion of tribal, state, and local public health agencies that provide or assure comprehensive epidemiology services to support essential public health services

2. Improve access to comprehensive, quality health care services.

AHS-6: Reduce the proportion of individuals who are unable to obtain or delay in obtaining necessary medical care, dental care, or prescription medicines

3. Promote the health and well-being of people with disabilities.

DH-4: Reduce the proportion of adults with disabilities aged 18 years and older who experience delays in receiving primary and periodic preventive care due to specific barriers

The goals and objectives of this NOFO are consistent with the missions of NCBDDD and Division of Human Development and Disability (DHDD):

1. Performance goals for the National Center on Birth Defects and Developmental Disabilities:

Improving the health and well-being of people with disabilities Helping children to develop and reach their full potential Promoting health and well-being among people of all ages with disabilities

2. Priorities of the Division of Human Development and Disability

Improve developmental outcomes of children Reduce disparities in health care access for people with disabilities

Public Health Impact Surveillance and public health research resulting from this NOFO can be used to inform and improve policies that benefit people affected with MD. Analysis of MD STARnet data can identify trends and gaps where further research or intervention is needed. Patient advocacy groups, federal and state agencies, and clinicians can use these new data to determine where resources and care are most needed and determine appropriate interventions to improve clinical care or access to clinical care.

Relevant Work Over the past 12 years, MD STARnet has published data on Duchenne and Becker muscular dystrophies examining prevalence, diagnostic delay, steroid use and trends, growth and other important topics that address the original research objectives [3]. A full list of publications is available on request (see Scientific/Research Contact under Section VII. Agency Contacts).

Under the current award, MD STARnet sites developed a coordinated muscular dystrophy research agenda using literature reviews to determine knowledge gaps. The purpose of the research agenda is to focus data collection and dissemination of results on important knowledge gaps in muscular dystrophy that can be addressed using data from MD STARnet. Key knowledge gaps that are not easily investigated using MD STARnet data collected from medical records and administrative data (e.g. vital records, hospital discharge data) may be considered as topics for surveys or other research methods. This research agenda can be shared upon request (see Scientific/Research Contact under Section VII. Agency Contacts).

2. Approach This NOFO has five components to achieve the purpose of the program:

Component A – Core-Current: Current MD STARnet sites will continue to conduct surveillance for eligible MDs, collect clinical data on existing cohorts, and conduct research studies on surveillance populations. Applicants must be a current MD STARnet site to apply for Component A.

Component B – Core-New: New MD STARnet sites will build a program to conduct MD surveillance, identify and collect data on eligible MD populations, and conduct research studies on surveillance populations. Applicants proposing a new MD STARnet site may apply for Component B. Component B applicants should contribute to the diversity of the MD surveillance population by including large target populations of specific minority groups (e.g. non-Hispanic Blacks, Asians, and Hispanics).

Component C – Enhanced-Dissemination: Analysis of MD STARnet data and dissemination of results through publications in peer-reviewed journals and presentations at stakeholder meetings. Only Component A applicants are eligible to apply for Component C; however, applying for Component C is optional.

Component D – Enhanced-Data Coordinating Center: Data coordinating center (DCC) that supports activities involving data collection, quality improvement, pooling, and release for the network. Component A or B applicants are eligible to apply for Component D.

Component E – Enhanced-Abstractor: Center that conducts abstractor training and data quality activities for the network. Only Component A applicants are eligible to apply for Component E.

A separate application is required for each Component.

Objectives/Outcomes Component A – Core-Current:

1. Continue to conduct longitudinal, population-based surveillance for MD by using existing MD STARnet methods to identify and gather data on individuals with eligible MDs

a. Collaborate with other Component A and B recipients and CDC to refine the variables collected. Reduce the number of variables to those reliably collected from medical records and administrative data (e.g. vital records, hospital discharge data) that can address questions in the research agenda

b. Access clinic and administrative data sources to maximize ascertainment of eligible MD cases and define population-based cohorts that can be recruited for additional research studies through methods such as phone interviews or surveys

c. Conduct new and follow-up abstraction on eligible MD cases

i. Eligible DMD/BMD cases:

a. Date of birth on or after January 1, 2000

b. Residency in a site at any time after January 1, 2000

c. Diagnosis of DMD or BMD

ii. Expand eligibility of the following MD cohorts (DM, FSHD, LGMD, CMD, EDMD, and Distal MD) to better address prevalence and mortality

a. Eligible cases:

i. Health encounter on or after January 1, 2008

ii. Residency in the surveillance area at any time after January 1, 2008

iii. Diagnosis of DM, FSHD, LGMD, CMD, EDMD, or Distal MD

1. For cases without confirmatory diagnosis or family history (possible cases), collect enough data to establish eligibility, case definition, and mortality (causes and age at death). Collect mortality data from medical and vital records (State vital records and National Death Index searches)

2. For cases with confirmatory diagnosis and/or family history (definite or probable cases), abstract additional clinical information

iii. Abstract data from clinical and administrative data sources (e.g. vital records, hospital discharge data) that can be used to address priority topic areas in the MD research agenda (i.e. diagnosed prevalence; disease progression and survival;

clinical care and interventions and their alignment with recommended care;

disparities in access to care; the association of treatment with outcomes; and the impact of MD on the lives of affected individuals and their families)

d. Collect ICD-10 codes on all cases to evaluate how well the new codes for DMD/BMD and FSHD, which were implemented in October 2018, identify cases

e. Clean local data according to protocol, and contribute to a pooled data set by contributing individual level data with limited identifiers to the data coordinating center

f. Participate as co-authors in the development of manuscripts that use MD STARnet data; leading manuscript development is optional

g. Conduct follow-up abstraction for DMD/BMD cohort in year 4 (for MD research and surveillance sites that have data on cases born between 1982-1999)

i. With CDC, refine the variables by abstracting reliability collected clinical variables that can answer research questions defined in the research agenda

ii. Abstract a minimum of five years follow-up data on DMD/BMD cohort of cases born between 1982-1999

iii. Clean and send de-identified, locally collected data to the Data Coordinating Center (DCC)

2. Develop research methods and tools (i.e. surveys, interviews) and conduct research within sites

a. In collaboration with other sites and CDC, determine topic(s) for research using the newly created MD research agenda, and develop research methods and tools. Studies that address topics relevant to more than one MD will be prioritized

b. Conduct research with MD populations identified through surveillance and contribute to a pooled data set by collecting and cleaning individual level data with limited identifiers and sending them to the DCC

i. Note: Applicants should take into account the time required for developing methods and tool(s) and for OMB approval

c. Participate in activities to engage the study population and promote participation in research studies (e.g., periodically disseminating newsletters to potential study participants about research findings)

3. Build new and maintain existing relationships with MD partners and stakeholders to enhance and promote surveillance and research efforts

a. Involve appropriate partners, such as health care organizations/providers, professional clinical societies, patient advocacy groups, and other organizations who serve people with MDs to assist with or promote the collection of data

b. Collaborate and coordinate with state agencies and partner organizations to enhance case ascertainment and data collection activities (e.g. getting access to administrative data and data from birth defects and other surveillance systems to assist with case identification)

c. With assistance from CDC, collaborate with muscular dystrophy registries on data linkages and data sharing agreements to more thoroughly describe the health care and health outcomes of individuals with MD

Component B – Core-New:

1. Conduct longitudinal, population-based surveillance for MD by using existing MD STARnet methods[1,2] to identify and gather data on individuals with eligible MDs

a. Collaborate with other Component A and B recipients and CDC to refine the variables collected. Reduce the number of variables to those reliably collected from medical records and administrative data (e.g. vital records, hospital discharge data) that can address questions in the research agenda

b. Access clinic and administrative data sources to maximize ascertainment of eligible MD cases and define population-based cohorts that can be recruited for additional research studies through methods such as phone interviews or surveys

c. Identify and abstract information on eligible MD cases and collect the data elements sufficient to address prevalence and survival (i.e. data to establish eligibility, case definition (diagnostic data), and mortality (causes and age at death)). For select MDs, collect additional data elements related to key clinical indicators. (The selected MDs for which clinical indicators will be tracked will be determined by CDC and recipient.)

i. Eligible DMD/BMD cases:

1. Date of birth on or after January 1, 2000

2. Residency in a site at any time after January 1, 2000

3. Diagnosis of DMD or BMD

ii. Eligible DM, FSHD, LGMD, CMD, EDMD, OPMD and distal MD cases:

1. Health encounter after January 1, 2008

2. Residency in a site at any time after January 1, 2008

3. Diagnosis of DM, FSHD, LGMD, CMD, EDMD, OPMD or distal MD

d. Collect ICD-10 codes on all cases to evaluate how well the new codes for DMD/BMD and FSHD, which were implemented in October 2018, identify cases

e. Clean local data according to protocol, and contribute to a pooled data set by contributing individual level data with limited identifiers to the DCC

f. Participate as co-authors in the development of manuscripts that use MD STARnet data; leading manuscript development is optional

2. Develop research methods and tools (i.e. surveys, interviews) and conduct research within site

a. In collaboration with other sites and CDC, determine topic(s) for research using MD research agenda, and develop research methods and tools. Studies that address topics relevant to more than one MD will be prioritized

b. Conduct research with MD populations identified through surveillance and contribute to a pooled data set by sending individual level data with limited identifiers to the DCC

i. Note: Applicants should take into account the time required for developing methods and tool(s) and for OMB approval

c. Participate in activities to engage the study population and promote participation in research studies (e.g., periodically disseminating newsletters to potential study participants about research findings)

3. Build new and maintain existing relationships with MD partners and stakeholders to enhance and promote surveillance and research efforts

a. Involve appropriate partners, such as health care organizations/providers, professional clinical societies, patient advocacy groups, and other organizations who serve people with MDs to assist with or promote the collection of data

b. Collaborate and coordinate with state agencies and partner organizations to enhance case ascertainment and data collection activities (e.g. getting access to administrative data and data from birth defects and other surveillance systems to assist with case identification)

c. With assistance from CDC, collaborate with MD registries on data linkages and data sharing agreements to more thoroughly describe the health care and health outcomes of individuals with MD

Component C – Enhanced-Dissemination:

1. Analyze surveillance data and disseminate research results through peer-reviewed publications and presentations to target audiences using data from the 2014 – 2019 funding cycle

a. Use the coordinated research agenda for the different MDs (currently under development), analyze and publish results addressing gaps in knowledge identified as high priority

b. Publish at least 5 papers in peer-reviewed journals for the total period of funding

c. Present results of data analyses at least 5 times at national conferences, professional societies or other meetings that include target audiences (i.e., clinicians, industry representatives, families and individuals with MD, scientists and researchers, and/or public health professionals) for the total period of funding

d. Conduct secondary analysis for at least three research projects led by other sites or

CDC

e. Participate in analyses, abstracts, and manuscripts led by other MD sites or CDC investigators that require epidemiologic, clinical, analytical, and other expertise available in the site

Component D – Enhanced-DCC:

1. Develop, modify, and/or maintain customized off the shelf (COTS) software applications (e.g. data cleaning, clinical review), databases, and related documentation (e.g.

data manager manual, codebooks for data sets) that enable data collection and analysis of surveillance and research data for MD

2. Distribute applications, databases, and COTS software required for abstraction, clinical review, and data analysis to Component A and B recipients (software should be customizable off the shelf products that other recipients can easily obtain and support)

3. Provide end-user technical assistance to sites (e.g. data managers, abstractors, clinical reviewers) in using applications, databases and software via communication such as conference calls, and calls and e-mails with sites. Travel to new sites to provide additional support, if necessary

4. Perform extensive data cleaning efforts along with guiding and supporting local sites in data cleaning activities. Complete and document data cleaning methods, procedures, and timelines for completion

5. Work with data analysts from all sites to standardize variables

6. Manage the pooling of multiple site-specific data sets and release analytic data sets to CDC and other sites

7. Create, modify, and update all calculated variables determined by the coordinating and/or data sharing committees and provide detailed methodology/documentation for each.

New calculated variables may be suggested or initially developed by other sites in conducting analyses for manuscripts; however the creation, modification and updating of the calculated variables will solely be the responsibility of the DCC

8. Create and maintain detailed records (codebooks, survey instruments, and other materials) on data collection methodology for surveillance and other research activities (i.e., surveys or interviews)

9. In codebooks for each MD, identify and flag variables that have changed since the previous data collections (i.e. V8, DMD/BMD (DOB 200+, DMD/BMD legacy, new data collections). Create cross-walks between datasets

10. Maintain or contribute to a shared web portal or website housing relevant documents and files to assist sites in surveillance and research activities

11. Provide technical assistance to sites and participating in workgroups, committees, and in-person meetings

12. Participate in activities required by the federal government including the Security Assessment and Authorization (SA&A) process [formerly know as the Certification and Accreditation (C&A) process] from the Office of the Chief Information Security Officer (OCISO) and production of restricted use data sets with accompanying documentation

Component E – Enhanced-Abstractor:

1. Train and certify abstractors in the standardized collection of data from medical records.

Travel to sites may be necessary to train new abstractors

2. Provide ongoing training to abstractors to maintain the standardization of data collection from medical records. Conduct conference calls and in-person trainings as needed

3. Create and implement a plan to periodically re-sample a portion of all abstracted records to assess inter-abstractor reliability

4. Provide technical assistance as needed through participation in committees, workgroups, in-person meetings and direct communication with sites

OMB/PRA approval will be required for research studies (described in Components A and B objective 2). CDC and recipients will identify and design the Components A and B research studies. Studies that collect data on 10 or more people are required to have OMB approval unless one of several exemptions apply. Data will not be collected without the Office of

Management and Budget’s (OMB) approval. CDC will lead and submit the application for OMB approval.

References:

[1]Miller LA, Romitti PA, Cunniff C et al. The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): surveillance methodology. Birth Defects Res A Clin Mol Teratol. 2006 Nov;76(11):793-7.

[2] Do T, Street, N, Donnelly J et al. Muscular Dystrophy Surveillance, Tracking, and Research Network pilot: Population-based surveillance of major muscular dystrophies at four U.S. sites, 2007-2011. Birth Defects Res. 2018 Aug 2. doi: 10.1002/bdr2.1371.

[3] Sahay K, Smith T, Conway KM et al. A Review of MD STARnet's Research Contributions to Pediatric-Onset Dystrophinopathy in the United States; 2002-2017. J Child Neurol. 2018 Oct 22: doi: 10.1177/0883073818801704. [Epub ahead of print]

Target Population The target populations for all components are individuals with muscular dystrophies (DMD, BMD, DM, FSHD, LGMD, CMD, EDMD, OPMD and distal MD) who meet eligibility criteria.

Applicants for Component B sites are expected to contribute to the racial and ethnic diversity of the MD surveillance population by including relatively large populations of specific minority groups (e.g., non-Hispanic Blacks, Asians, or Hispanics).

Collaboration/Partnerships Component A:

Recipient is expected to maintain existing partnerships and establish new partnerships as needed. These partnerships include patient advocacy groups and clinicians who treat patients with MD to promote surveillance and research efforts with the populations they serve and to disseminate surveillance information to individuals with MD and their families. Recipient will maintain or build partnerships with their state health department or other state agencies to facilitate access to administrative data and to communicate information gathered from surveillance that can be useful to states in tracking their patient populations and informing changes in policy and services. Recipient will partner with clinics and hospitals to conduct medical record abstraction and describe the types of relationships that currently exist or they plan to establish. CDC is pursuing collaborations with registries to establish linkages and data use agreements to more thoroughly describe the health care and health outcomes for individuals with MD. Recipient is expected to work with CDC and registries to achieve this goal. Recipient is also expected to collaborate with other recipients and CDC under this award.

Component B:

Recipient is expected to maintain existing partnerships and build new partnerships as needed, with particular emphasis on minority populations. These partnerships include patient advocacy groups and clinicians who treat patients with MD to promote surveillance and research efforts with the populations they serve and to disseminate surveillance information to individuals with

MD and their families. Letters of support from potential partners should be provided in the appendix of the application. Recipient must already have or plan to form strong partnerships with relevant other state health department organizational units or state agencies and/or their state health department that could facilitate access to administrative data, support efforts to designate MD as a reportable condition in their state (if not already), use aggregate surveillance information to track health and care received, and inform policy and interventions. Agreements or letters of support for the ability to access and link data should be provided in the appendix.

Recipient will partner with clinics and hospitals to conduct medical record abstraction and describe the types of relationships that currently exist or that they plan to establish. CDC is pursuing collaborations with registries to establish linkages and data use agreements to more thoroughly describe the health care and health outcomes for individuals with MD. Recipient is expected to work with CDC and registries to achieve this goal. Recipient is also expected to collaborate with other recipients and CDC under this award.

Component C:

Recipient will be expected to lead and collaborate with other MD STARnet investigators, CDC, and outside investigators on analysis and dissemination of the results of surveillance and research activities to stakeholders.

Components D:

Recipient will be expected to collaborate with other recipients and CDC. The DCC will be responsible for providing COTS software, databases, and relevant documentation and support of these applications for all sites. Recipient must be able to collect and pool, MD STARnet data that is collected by individual sites.

Component E:

Recipient for the abstractor training and data quality activities is expected to collaborate with other recipients and CDC. The recipient will work with abstractors and investigators in all sites to ensure that the abstraction activities are successfully conducted.

Evaluation/Performance Measurement For Components A and B, recipients are expected to use clinical data and administrative data (e.g. vital records, hospital discharge data) to ascertain all eligible MD cases and to collect the longitudinal data needed to describe the population of people with MD. For surveillance, recipient should attempt to identify all cases of eligible MDs residing within their surveillance catchment areas . Sites will be evaluated by comparing the number of cases collected by site with the expected number of cases based on existing prevalence estimates. Before the beginning of data collection at the start of the funding period, a workgroup composed of CDC and representatives from sites will review the variables to be collected to determine those that are most reliable, previously used, and necessary to answer the research questions identified in the research agenda, to modify and streamline the database. Data subsequently collected should be periodically evaluated for missing entries, quality, and ability to answer priority research questions through periodic analyses and presentations at Principal Investigators’ (PI) meetings.

The Component C recipient will analyze and publish at least 5 peer-reviewed manuscripts and give 5 presentations at professional society meetings on high priority topic areas from the MD research agenda during the funding period. Recipient will also be expected to participate in projects led by other investigators and CDC including conducting secondary analysis for three projects.

The Component D recipient will be evaluated on the usability of the COTS software, the readiness and quality of the pooled data sets, the clarity of the data documentation.

The Component E recipient will be evaluated on the deliverables such as certifying all abstractors, reducing inter-rater variability and identifying areas where more training is needed.

Translation Plan For Component C, the recipient will be required to collaborate with CDC and other recipients to ensure results of MD surveillance and research activities are publicly available to stakeholders (e.g. patient advocacy groups, federal and state agencies, clinicians, and researchers). Recipient and CDC are expected to follow the MD research agenda (currently under development) to address priority topics on knowledge gaps in MD. Broadly, topics included in the research agenda are diagnosed prevalence, disease progression and survival, clinical care, interventions and their alignment with recommended care, disparities in access to care, association of clinical treatment with outcomes, and the impact of MD on the lives of affected individuals and their families. Component A and C recipients will be expected to participate as co-authors in manuscripts.

Section II. Award Information Funding Instrument Type: 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: $16,250,000 The estimated total funding for all components (direct and indirect) for the first budget period, 9/1/2019 – 8/31/2020, is $3,250,000:

Component A: The estimated total funding (direct and indirect) for the first budget period is up to $375,000 each in FY 2019. Award Floor amount is $0 and Award Ceiling amount is $375,000.

Component B: The estimated total funding (direct and indirect) for the first budget period is up to $350,000 each in FY 2019. Award Floor amount is $0 and Award Ceiling amount is $350,000.

Component C: The estimated total funding (direct and indirect) for the first budget period is up to $80,000 each in FY 2019. Award Floor amount is $0 and Award Ceiling amount is $80,000.

Component D: The estimated total funding (direct and indirect) for the first budget period is up to $250,000 in FY 2019. Award Floor amount is $0 and Award Ceiling amount is $250,000.

Component E: The estimated total funding (direct and indirect) for the first budget period is up to $80,000 in FY 2019. Award Floor amount is $0 and Award Ceiling amount is $80,000.

The estimated total funding for all components (direct and indirect) for the entire project period, 9/1/2019 – 8/31/2024, is $16,250,000.

Anticipated Number of Awards: 15 Component A: It is anticipated that up to six awards will be made to up to six recipients.

Component B: It is anticipated that up to two awards will be made to up to two recipients.

Component C: It is anticipated that up to five awards will be made to up to five recipients.

Component D: It is anticipated that one award will be made to a single recipient.

Component E: It is anticipated that one award will be made to a single recipient.

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

Award Ceiling: $375,000 Per Budget Period Award Floor: $0 Per Budget 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 (http://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.

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category: State governments http://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf

County governments City or township governments Special district governments Independent school districts Public and State controlled institutions of higher education Native American tribal governments (Federally recognized) Public housing authorities/Indian housing authorities Native American tribal organizations (other than Federally recognized tribal governments) Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education Nonprofits without 501(c)(3) status with the IRS, other than institutions of higher education Private institutions of higher education For profit organizations other than small businesses Small businesses Others (see text field entitled "Additional Information on Eligibility" for clarification) Unrestricted (i.e., open to any type of entity above), subject to any clarification in text field entitled "Additional Information on Eligibility"

Additional Eligibility Category:

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. Special Eligibility Requirements For an applicant to be considered they must be responsive to the information here.

Component A – Core-Current:

Applicants must document current funding under RFA DD-14-001 Surveillance and Research of Muscular Dystrophies and Neuromuscular Disorders.

Component B – Core-New:

Applicants must propose a study site that should be a specific geographic area with a population of at least 3 million people including a large minority population (e.g.

African American, Asian, or Hispanic).

Component C – Enhanced-Dissemination:

Applicants must submit an application for Component A to apply for Component C.

To be funded for Component C, the applicant must also be funded for Component A.

Applicants should document that they have applied for Component A.

Component D – Enhanced-DCC:

Applicants must submit an application for Component A or B to apply for Component D.

To be funded for Component D, the applicant must also be funded for Component A or B.

Applicants should document that they have applied for Component A or B.

Applicants must submit an application for Component A to apply for Component E.

To be funded for Component E, the applicant must also be funded for Component A.

Applicants should document that they have applied for Component A.

If your application is incomplete or non-responsive to the special eligibility requirements listed in this section, it will not enter the review process.

4. Justification for Less than Maximum Competition N/A

5. Responsiveness Component A – Core-Existing:

Applicants must provide a statement that the applicant institution is currently funded under DD-14-001 Surveillance and Research of Muscular Dystrophies and Neuromuscular Disorders and provide cooperative agreement number.

Component B – Core-New:

Applicant must show evidence that their proposed…