dd14-001 amendment ii 02 25 14.pdf

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Rev. 10/2012

Amendment II made on (02/25/2014)

Link changed on page 30 Section IV. Application and Submission Information, All instructions in the SF424 (R&R) Application Guide. Form C should be used for the application package.

(http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_Adobe_VerC.pdf)

An amendment has been made to change application due date from March 7, 2014 to March 12, 2014. Revision made on page 5, Key dates.

Amendment I made on February 19, 2014:

Questions and Answers (Attachment 1), pages 61-65

Table of Contents Part 1. Overview Information

Key Dates

Required Application Instructions

Executive Summary

Part 2. Full Text

Section I. Funding Opportunity Announcement Description

Statutory Authority

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

Section IV. Application and Submission Information

2. Content and Form of Application Submission

3. Letter of Intent

4. Required and Optional Components

5. PHS 398 Research Plan Component

6. Appendix

7. Page Limitations

8. Format for Attachments

9. Submission Dates and Times

10. Intergovernmental Review (E.O. 12372)

11. Funding Restrictions

12. Other Submission Requirements and Information http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_Adobe_VerC.pdf

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Section V. Application Review Information

1. Criteria

4. Review and Selection Process

5. Anticipated Announcement and Award Dates

Section VI. Award Administration Information

1. Award Notices

2. CDC Administrative Requirements

5. Reporting

Section VII. Agency Contacts

Section VIII. Other Information

Part 1. Overview Information

Participating Organization(s)

Centers for Disease Control and Prevention (CDC)

Components of Participating Organizations

National Center on Birth Defects and Developmental Disabilities

(NCBDDD)

Division of Human Development and Disability (DHDD)

Funding Opportunity Announcement (FOA) Title

Surveillance and Research of Muscular Dystrophies and Neuromuscular Disorders

Activity Code Applications in response to this FOA will be funded using U01 activity code

Funding Opportunity Announcement Type

New http://www.cdc.gov/ http://grants.nih.gov/grants/funding/ac_search_results.htm?text_curr=U01&Search_Type=Activity&Search.x=16&Search.y=3

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Funding Opportunity Announcement Number

RFA-DD-14-001

Catalog of Federal Domestics Assistance (CFDA) Number(s)

93.315

Category of Funding Activity

Health

FOA Purpose This funding opportunity announcement (FOA) will support:

1. Conducting population-based surveillance, longitudinal follow-up, and public health research for muscular dystrophies and neuromuscular disorder(s) using methods based on those from the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): 1) to develop estimates for prevalence, survival, healthcare service use and costs, disparities in access to care (by proximity to source of care, race/ethnicity, and socioeconomic status (SES)), and 2) to determine associations between specific clinical treatments and specific outcomes for specific types of muscular dystrophy (MD) and neuromuscular disorders, and 3) to support public health and clinical practice for prevention of morbidities and their progression among persons with muscular dystrophy and neuromuscular disorders

2. Expanding the number of surveillance site(s) to increase the demographic, racial, and ethnic diversity of the MD surveillance system

3. Sharing data with stakeholders seeking to improve health and access to care of people living with these conditions

4. Evaluating, modifying, and documenting the methodology and infrastructure of the surveillance system

5. Conducting pilot studies that investigate specific MD

CDC Research 4 knowledge gaps and sharing results with participants and stakeholders

This FOA has four components to achieve the purposes of the program. Components A and B consist of the core activities.

Component A - core (existing MD surveillance and research programs) consists of using methods based on those from MD STARnet and lessons learned from previous MD surveillance systems to conduct surveillance and longitudinal follow-up for muscular dystrophies and neuromuscular disorder(s); maintaining current and building new key partnerships; analyzing data to produce findings useful for public health practice; disseminating results to stakeholders using data collected from current and previous MD surveillance programs; and evaluating, modifying, and documenting the surveillance methods and infrastructure.

Component B - core (new MD surveillance and research programs) consists of building a system using methods based on those from MD STARnet to conduct surveillance and longitudinal follow-up for muscular dystrophies and neuromuscular disorder(s) in a population with a large minority group (i.e. African Americans, Hispanics, Asians);

building new key partnerships; analyzing data to produce findings useful for public health practice; disseminating data to stakeholders; and evaluating, modifying, and documenting the surveillance methods and infrastructure.

Component C consists of the data coordinating center and abstractor training and quality assurance/control that support the core activities.

Component D consists of additional muscular dystrophy research studies in which applicants design a study to address a knowledge gap in MD and share data with study participants and MD stakeholders.

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Key Dates

Publication Date

To receive notification of any changes to RFA-DD-14-001, 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 February 7, 2014

Application Due Date March 12, 2014, by 11:59 PM U.S. Eastern Time.

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

HHS/CDC grant submission procedures do not provide a period of time beyond the application due date 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 April 2014

Secondary Review June 2014

Estimated Start Date September 2014

Expiration Date March 13, 2014

Due Dates for E.O. 12372 Executive Order 12372 does not apply to this program.

http://www.grants.gov/

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Required Application Instructions It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise in this FOA. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

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

Executive Summary

Purpose. Using methods based on those from the Muscular Dystrophy Surveillance Tracking and

Research Network (MD STARnet), this funding opportunity announcement (FOA) will support:

1. Conducting population-based surveillance, longitudinal follow-up, and public health research for muscular dystrophies and neuromuscular disorder(s): 1) to develop estimates for prevalence, survival, healthcare service use and costs, disparities in access to care (by proximity to source of care, race/ethnicity, and SES), and 2) to determine associations between specific clinical treatments and specific outcomes for specific types of MD and neuromuscular disorders, and 3) to support public health and clinical practice for prevention of morbidities and their progression among persons with muscular dystrophy and neuromuscular disorders

2. Expanding the number of surveillance site(s) to increase the demographic, racial, and ethnic diversity in the current MD surveillance system

3. Sharing data with stakeholders seeking to improve health and access to care of people living with these conditions

4. Evaluating, modifying, and documenting the methodology and infrastructure of the surveillance system

5. Conducting pilot studies that investigate specific MD knowledge gaps and sharing results with participants and stakeholders

This FOA has four components to achieve the purpose of the program. Components A and B consist of the core activities. Component A - core (existing MD surveillance and research programs) consists of using methods based on those from MD STARnet and http://grants.nih.gov/grants/guide/url_redirect.htm?id=12000

CDC Research 7 lessons learned from previous MD surveillance systems to conduct surveillance and longitudinal follow-up for muscular dystrophies and neuromuscular disorder(s);

maintaining current and building new key partnerships; analyzing data to produce findings useful for public health practice; disseminating results to stakeholders using data collected from current and previous MD surveillance programs; and evaluating, modifying, and documenting the surveillance methods and infrastructure. Component

B - core (new MD surveillance and research programs) consists of building a system using methods based on those from MD STARnet to conduct surveillance and longitudinal follow-up for muscular dystrophies and neuromuscular disorder(s) in a population with a large minority group (i.e. African Americans, Hispanics, Asians);

building new key partnerships; analyzing data to produce findings useful for public health practice; disseminating data to stakeholders; and evaluating, modifying, and documenting the surveillance methods and infrastructure. Component C consists of the data coordinating center (DCC) and abstractor training and quality assurance/control that support the core activities. Component D consists of additional muscular dystrophy research studies in which applicants design a study to address a knowledge gap in MD and share data with study participants and MD stakeholders.

(Note: The methodology for component D studies will not be known until applications have been submitted. 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.)

Mechanism of Support. This funding opportunity will use the cooperative agreement funding mechanism (CDC U-01).

Funds Available and Anticipated Number of Awards. Total funding available for this cooperative agreement is expected to be $15,500,000 over the five-year project period.

Component A: It is anticipated that up to five awards will be made to five recipients for up to $500,000 each in FY 2014. Component B: It is anticipated that up to two awards will be made to two recipients for up to $450,000 each in FY 2014. Component C –

Enhanced Activities/DCC: It is anticipated that one award will be made to a single recipient for up to $250,000 in FY 2014. Component C – Enhanced Activities/Abstractor training and QA/QC: It is anticipated that one award will be made to a single recipient for up to $100,000 in FY 2014. Component D: It is anticipated that up to three awards

(range $75,000 to $125,000 each) will be made to three recipients in FY 2014. Awards issued under this FOA are contingent upon availability of funds and a sufficient number of meritorious applications. Because the nature and scope of the proposed activities and 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

CDC Research 8 awards will depend upon the number, quality, duration and cost of the applications received.

Budget and Project Period. The estimated total funding (direct and indirect) for the first year (12 month budget period) is $3,100,000. The total funding available for the entire project period will be $15,500,000. The project period for components A, B and C will run from September 1, 2014 to August 31, 2019. The project period for component D will range in length from 1 to 3 years based on the scope of the research project(s) proposed.

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 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 contain more than one PI, however, the first PI listed will be the “contact PI” for all correspondence.

Number of Applications. Only one application per institution (normally identified by having a unique DUNS Number) per component is allowed for this FOA. Applicants must submit separate applications if applying to more than one Component. All eligible applicants for Component A or B may also apply for one or both of the Component C -enhanced activities and/or Component D – muscular dystrophy research studies. To apply for component C and/or D, eligible applicants must apply for Component A or B.

Application Type. New (type 1) Special Date(s). CDC will conduct one conference call for prospective applicants. This session will provide information about the FOA and will answer questions pertinent to preparing applications in response to this FOA.

Conference Call Details:

Date: January 16, 2014 at 1:00 p.m. (EST)

Call-in Number: 1-877-316-1834

Participant Pass Code: 95920706

Application Materials. See Section IV.1 for application materials.

Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (770) 488-2783.

http://grants.nih.gov/grants/guide/pa-files/PAR-11-022.html#SectionIV http://grants.nih.gov/grants/guide/pa-files/PAR-11-022.html#SectionIII1A http://grants.nih.gov/grants/guide/pa-files/PAR-11-022.html#SectionIV1

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Part 2. Full Text

Section I. Funding Opportunity Announcement 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 (MD) are a group of rare inherited disorders characterized by progressive 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 clinic-based populations, population-based epidemiological studies are needed to more accurately estimate prevalence and mortality, and describe access to care and treatments received by individuals with MD. Epidemiological data allow for the establishment and evaluation of policy, health services, and health outcomes among people affected by muscular dystrophies.

To obtain epidemiological 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/Becker muscular dystrophy (DBMD), the most common type of muscular dystrophy 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 DBMD1. During that time, up to six sites (Arizona, Colorado, Georgia, Hawaii, Iowa, Western New York State) participated in surveillance of DBMD. Data from this surveillance system have being disseminated through various mechanisms including peer-reviewed journals, presentations at professional and advocacy group meetings, newsletters, and webinars. In 2011, the number of sites was reduced to four and surveillance was expanded to include all types of MD to test the ability of the existing network to conduct surveillance for other MDs.

Data collection is currently underway, but preliminary data show that the MD STARnet infrastructure can be used to identify and collect epidemiological and clinical data on people with other types of MD and could be a platform for conducting surveillance for other rare disorders.

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While MD STARnet is an established network for obtaining population-based data on people with MD, collecting data through abstraction of medical records is resource intensive. Two additional projects based in South Carolina were funded by CDC to determine whether linked administrative databases, combined with other data sources could be a viable approach to carry out surveillance for MD and other rare disorders. The goals of these projects include identifying existing local, regional, and national data sources, gaps and deficiencies in these sources, and developing and executing a plan to integrate all major data sources into a workable single surveillance system for rare conditions. One of the projects includes a collaboration among the state health departments of South Carolina, Colorado and Kansas to build a three-state surveillance system for MD, spina bifida, and fragile X syndrome and to determine the range of differences between these states in accessing linked administrative data and the ability to conduct surveillance for rare disorders. The data thus far shows that access to linked administrative data varies widely among states: some states can access linked administrative data sets to examine care and services for people affected by MD, spina bifida, and fragile X syndrome, but other states have limited to no access to this type of data.

Projects funded under this announcement will modify the current MD STARnet protocol considering lessons learned from both MD STARnet and the rare disorders surveillance projects in South Carolina to establish one multi-site population-based surveillance system for muscular dystrophies and neuromuscular disorders. Neuromuscular disorders such as Pompe disease and spinal muscular atrophy are also rare conditions for which epidemiological data is lacking.

Pompe disease was recently recommended for addition to the Recommended Uniform Screening Panel by the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children2. If the Secretary approves the committee’s recommendation and States add Pompe disease to their newborn screening panels, conducting surveillance for Pompe disease would allow for long-term follow-up and enable comparisons in outcomes between newly diagnosed newborns and those clinically diagnosed. Piloting long-term follow-up for newly diagnosed infants could be a model that is extended to Duchenne muscular dystrophy if and when this condition is recommended for addition to state newborn screening panels. Piloting surveillance for neuromuscular disorders should not require significant resources beyond those needed to conduct surveillance for MD as individuals with both types of conditions are typically treated at the same clinical sources and can be found by ICD code in administrative data sets.

MD STARnet data gathered from across existing sites provides valuable information on the impact of MD on affected individuals and their families; however, more data is needed to fully investigate the impact of having MD among members of minority groups (i.e. African Americans, Asians, and Hispanics) as data is lacking on these populations. As a result, new surveillance sites with large populations of these minority groups are encouraged to apply.

The goal of the projects funded under this announcement is to conduct population-based surveillance, longitudinal follow-up, and research for muscular dystrophies and neuromuscular disorders by combining administrative data and data abstracted from medical records.

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Surveillance results will be shared with state and local government agencies, patient advocacy groups, clinicians and other partners seeking to improve health and access to care of people living with these conditions. Scientific activities to be conducted under this FOA include: 1) developing estimates for prevalence, survival, healthcare service use and costs, disparities in access to care (by proximity to source of care, race/ethnicity, and SES), and impact of specific clinical treatments on specific outcomes for specific types of MD and neuromuscular disorders;

2) determining whether methods and infrastructure for conducting surveillance for MDs can be successfully used to conduct surveillance for neuromuscular disorders; and 3) defining the most efficient and effective methods from MD STARnet and the SC surveillance projects to conduct population-based surveillance for muscular dystrophy and neuromuscular disorders.

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 RFA 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: (Developmental) Reduce the proportion of people with disabilities who report delays in receiving primary and periodic preventive care due to specific barriers

The goals and objectives of this funding opportunity announcement (FOA) are consistent with the missions of NCBDDD and DHDD:

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

Disabilities:

Improve 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.

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Public Health Impact

The muscular dystrophy and neuromuscular disorders surveillance system could serve as a model for conducting rare disease surveillance and could be expanded to include more rare conditions. Long-term follow-up of newborns diagnosed with Pompe disease could be a model for comparing the health of newborns diagnosed with the condition with those diagnosed clinically. This could lead to a better understanding of the impact of these diseases over the life course and enable development of targeted public health interventions that may have a major impact on the health and economy of the affected individuals and families. Surveillance and research data could be used to address and improve policies that benefit people affected by muscular dystrophy and other rare diseases. Advocacy groups, public health practitioners, and clinicians could use data to determine where resources and care are most needed and determine appropriate interventions to improve clinical care or access to clinical care. Researchers could use data to identify trends and gaps where further research is needed. Other neuromuscular diseases and potentially other rare diseases could be added to the surveillance system to make the system more cost-effective and more broadly applicable to a larger population of individuals with rare diseases.

2. Approach

This FOA has four components to achieve the purpose of the program:

Component A - core (existing MD surveillance and research programs)

Component B - core (new MD surveillance and research programs)

Component C – enhanced activities (data coordinating center)

Component C – enhanced activities (abstractor training and quality assurance/control)

Component D – muscular dystrophy research studies

In applying for the core components, applicants may only apply to either A or B. All eligible applicants for Component A or B may also apply for one or both of the Component C -enhanced activities and/or Component D – muscular dystrophy research studies. To apply for component C and/or D, eligible applicants must apply for Component A or B.

Objectives/Outcomes

Component A (existing muscular dystrophy surveillance programs) – Core activities:

1. Using methods based on those from the MD STARnet, conduct population-based, longitudinal surveillance, follow-up and research for all muscular dystrophies by accessing administrative data and medical records.

a. Address the following research questions and develop additional public health and clinical research questions to be answered by analyzing the data.

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i. Characterize the prevalence, natural history, healthcare service use and costs, and disparities in access to care (by proximity to source of care and demographic factors), of people with MDs and identify demographic, behavioral, and psycho-social factors that are associated with disease progression and survival.

ii. Assess whether specific treatments, interventions, or changes in healthcare use are associated with disease progression and survival;

identify demographic, behavioral, and psycho-social factors that modify the effects of treatments, interventions, and health care use on disease progression and survival; and quantify the effects while accounting for disease progression.

b. Collaborate with other component A and B grantees and CDC to modify the current MD STARnet protocol, incorporating lessons learned from MD STARnet and other CDC-funded surveillance programs. As needed, modify protocol over the duration of the project to document changes in methods.

i. Determine the data variables to be collected to be able to answer the specified research questions. Variables chosen should be those reliably collected from medical records and administrative data.

ii. Describe case definitions, cohorts, data sources, procedures for case ascertainment, data collection, and data management.

iii. Propose cohorts for each MD type to follow longitudinally to answer research questions. The cohorts followed should be determined by the data available and the age of onset and progression of the specific type of MD (Example: following individuals with DBMD born between 1990 and 2010 because sites can easily access medical record and administrative data on these individuals and DBMD affects a younger population). Funded sites and CDC will determine the age groups to be followed.

iv. Collaborate with CDC to plan up to two in-person Principal Investigator meetings in Years 2 through 5 of the project.

c. Contribute to a pooled data set by sending individual level data with limited identifiers to the data coordinating center. All funded sites and CDC will have access to the pooled data set.

2. Pilot longitudinal surveillance for one or more neuromuscular disorders.

a. Propose neuromuscular disorders to be piloted; selected disorders may include Pompe disease, spinal muscular atrophy, or other neuromuscular disorders. Individuals with these disorders are those also being treated at MDA and neurology clinics. For those conditions that are being screened for in the newborn period, individuals could be identified through collaboration with newborn screening programs. The final determination of the disease(s) to be piloted will be made by the steering committee composed of PIs from each awarded site and CDC.

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b. In collaboration with CDC and other grantees, plan and implement collection of data on people with the selected neuromuscular disorder(s) to determine prevalence, survival, healthcare service use and costs, disparities in access to care (by proximity to sources of care and demographic factors), and effect of specific treatments on outcomes.

3. Build new and maintain existing relationships with muscular dystrophy and other neuromuscular disease partners and stakeholders to enhance and promote surveillance efforts.

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

b. Collaborate and coordinate across state agencies to enhance case ascertainment and data collection activities. (Examples of assistance by states include enabling access to administrative data and data from birth defects and other surveillance systems, and assisting in making MD a reportable condition.)

4. Collaborate with CDC and other component A and B grantees to develop and implement a communications plan to disseminate surveillance and research results to advocacy groups, people affected by MD, public health practitioners, policy makers, and clinicians/researchers seeking to improve access to services and care.

a. Continue to analyze and disseminate previously collected MD surveillance data.

5. Collaborate with CDC and other component A and B grantees to develop and implement an evaluation plan for the multi-site surveillance system.

a. The evaluation should include assessment of: 1) the availability, validity, and completeness of each data source used for case ascertainment and longitudinal follow-up; 2) the feasibility of linking individual records across the data sources with the highest data quality; 3) logistics of data collection;

4) data quality including whether or not the analysis of the data collected will be able to answer the research questions; and 5) the utility of the information for public health practice.

b. As the evaluation is implemented and assessment identifies issues or areas where surveillance methods or data quality could be improved, sites will be expected to make adjustments that will increase the quality of surveillance methods and data.

Component B (new muscular dystrophy surveillance program)– Core activities:

1. Using methods based on those from the MD STARnet1, build a system to conduct population-based, longitudinal surveillance, follow-up and research for all muscular dystrophies by accessing administrative data and medical records. Contribute to the diversity of the current MD surveillance system by conducting surveillance in a population of at least 3 million people that includes a large group of one or more of

CDC Research 15 the following minorities: African Americans, Asians, Hispanics. The population should be of sufficient size to be able to address the specific objectives listed below.

a. Address the following research questions and develop additional public health and clinical research questions to be answered by analyzing the data.

i. Characterize the prevalence, natural history, healthcare service use and costs, and disparities in access to care (by proximity to source of care and demographic factors), of people with MDs and identify demographic, behavioral, and psycho-social factors that are associated with disease progression and survival.

ii. Assess whether specific treatments, interventions, or changes in healthcare use are associated with disease progression and survival;

identify demographic, behavioral, and psycho-social factors that modify the effects of treatments, interventions, and health care use on disease progression and survival; and quantify the effects while accounting for disease progression.

b. Collaborate with other component A and B grantees and CDC to modify the current MD STARnet protocol, incorporating lessons learned from MD STARnet and other CDC-funded MD surveillance programs. As needed, modify protocol over the duration of the project to document changes in methods.

i. Determine the data variables to be collected to be able to answer the specified research questions. Variables chosen should be those reliably collected from medical records and administrative data.

ii. Describe case definitions, cohorts, data sources, procedures for case ascertainment, data collection, and data management.

iii. Propose cohorts for each MD type to follow longitudinally to answer research questions. The cohorts followed should be determined by the data available and the age of onset and progression of the specific type of MD (Example: following individuals with DBMD born between 1990 and 2010 because sites can easily access medical record and administrative data on these individuals and DBMD affects a younger population). Funded sites and CDC will determine the age groups to be followed.

iv. Collaborate with CDC to plan up to two in-person Principal Investigator meetings in Years 2 through 5 of the project.

c. Contribute to a pooled data set by sending individual level data with limited identifiers to the data coordinating center. All funded sites and CDC will have access to the pooled data set.

2. Pilot longitudinal surveillance for at least one other neuromuscular disorder.

a. Propose neuromuscular disorders to be piloted; selected disorders may include Pompe disease, spinal muscular atrophy, or other neuromuscular disorders. Individuals with these disorders are those also being treated at MDA or neurology clinics. For those conditions that are being screened for in

CDC Research 16 the newborn period, individuals could be identified through collaboration with newborn screening programs. The final determination of the disease(s) to be piloted will be made by the steering committee composed of PIs from each awarded site and CDC.

b. In collaboration with CDC and other grantees, plan and implement collection of data on people with the selected neuromuscular disorder(s) to determine prevalence, survival, healthcare service use and costs, disparities in access to care (by proximity to sources of care and demographics), and effect of specific treatments on outcomes.

3. Build new and maintain existing relationships with muscular dystrophy and other neuromuscular disease partners and stakeholders to enhance and promote surveillance efforts.

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

b. Collaborate and coordinate across state agencies to enhance case ascertainment and data collection activities. (Examples of assistance by states include enabling access to administrative data and data from birth defects and other surveillance systems, and assisting in making MD a reportable condition).

4. Collaborate with CDC and other component A and B grantees to develop and implement a communications plan to disseminate surveillance and research results to advocacy groups, people affected by MD, public health practitioners, policy makers, clinicians/researchers seeking to improve access to services and care.

5. Collaborate with CDC and other component A and B grantees to develop and implement an evaluation plan for the multi-site surveillance system.

a. The evaluation should include assessment of: 1) the availability, validity, and completeness of each data source used for case ascertainment and longitudinal follow-up; 2) the feasibility of linking individual records across the data sources with the highest data quality; 3) logistics of data collection;

4) data quality including whether or not the analysis of the data collected will be able to answer the research questions; and 5) the utility of the information for public health practice.

b. As the evaluation is implemented and assessment identifies issues or areas where surveillance methods or data quality could be improved, sites will be expected to make adjustments that will increase the quality of surveillance and data.

Component C: Enhanced Activities: In addition to the above core activities, sites can apply and receive funding to conduct one or more of the following activities to support the conduct of surveillance across all sites and the overall surveillance system:

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Data Coordinating Center (DCC):

1. Develop and maintain software applications, databases, and related documentation that enable data collection and analysis of surveillance data for MD and the selected neuromuscular disorder(s).

2. Manage the pooling and cleaning of site-specific data; and disseminate the pooled data for the multi-site surveillance system.

3. Distribute applications, databases, and software required for abstraction, clinical review, and data analysis to component A and B grantees and provide support to sites in using them.

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

5. Participate in planning and implementing the Component A/B evaluation plan.

Abstractor training and quality assurance and control activities:

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

2. Provide ongoing training to abstractors to improve standardization of data collection from medical records.

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

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

5. Participate in planning and implementing the Component A/B evaluation plan.

Component D: Muscular Dystrophy Research Studies: In addition to the above core and enhanced activities, sites can apply and receive funding to design and implement a research study to:

1. Identify an important gap in the public health or clinical literature on the population or subgroups of people with MD that cannot be addressed by using surveillance data (e.g., data about service needs, quality of life, or a clinical aspect of the disease not reliably recorded in medical records).

2. Propose an innovative pilot study that would be conducted in your site to collect and analyze data to address the knowledge gap and to provide findings from the study back to the MD population.

3. Develop and finalize pilot study and project protocol(s), establishing a realistic timeline that does not exceed the 3-year project period. Submit to committee composed of CDC and other grantees for review and comment and subsequently to institutional review board for approval(s) of project protocol.

4. Conduct pilot study and present status of study to CDC and grantee committee.

5. Communicate results through peer-reviewed publication and other methods to share data with families involved in the study and other MD stakeholders.

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(Note: The methodology for the studies will not be known until applications have been submitted. 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.)

Example timeline for components A, B, C:

Year 1:

1. Establish new and maintain existing partnerships with local, state, and national partners and stakeholders

2. Finalize agreements to be able to conduct surveillance for MDs.

3. Modify methods and protocol for conducting longitudinal surveillance on all MDs.

4. Develop, test, and distribute software and databases for data collection.

5. Train abstractors and other staff on new procedures and methods.

6. Participate in committee to plan evaluation of conducting surveillance for MD and other rare disorders.

7. Participate in developing a communications plan and begin implementation.

8. Pilot longitudinal surveillance for MDs.

Year 2:

1. Conduct longitudinal surveillance for MDs.

2. Continue to follow communication plan.

3. Begin assessment of surveillance system as part of evaluation plan and make changes to system as needed.

4. In collaboration with CDC and grantees, consider and decide on additional neuromuscular disorder(s) to be piloted.

5. Modify methods for MD surveillance for piloting surveillance for selected neuromuscular disorder(s).

6. Modify/develop software and databases for data collection for neuromuscular disorder(s).

7. Train abstractors and other staff in surveillance for neuromuscular disorder(s).

Year 3:

1. Create pooled data set for MDs.

2. Pilot surveillance for additional neuromuscular disorders(s), make necessary changes in methods, software, abstractor training, and other activities as needed after initial evaluation.

3. Continue surveillance for neuromuscular disorder(s).

4. Continue surveillance for MDs including follow-up abstraction.

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5. Continue following evaluation and communication plans.

Year 4:

1. Create first pooled data set for neuromuscular disorder(s).

2. Continue surveillance for MD and neuromuscular disorder(s).

3. Continue following evaluation, modifying systems as needed to increase efficiency and data quality and utility.

4. Continue following communications plan.

Year 5:

1. Continue surveillance for MD and neuromuscular disorder(s).

2. Continue following evaluation, modifying systems as needed to increase efficiency and data quality and utility.

3. Continue following communications plan.

4. Create pooled data sets for MD and neuromuscular disorder(s).

Target population The target populations for all components are people with any type of muscular dystrophy residing in the surveillance sites. People with the selected neuromuscular disorder(s) who reside in the surveillance sites will also be target populations for components A, B, and C during the piloting of surveillance for neuromuscular disorders.

The Component B sites should contribute to the diversity of the MD surveillance system by including large target populations of specific minority groups (African Americans, Asians, or Hispanics).

Collaboration/Partnerships

Components A and B:

The applicant is expected to use existing or establish new partnerships. These partnerships include advocacy groups and clinicians who treat patients with MD and neuromuscular disorders to promote surveillance and research efforts with the populations they serve and to disseminate surveillance information to people with MD and neuromuscular disorders. Letters of support from these groups should be provided in the appendix of the application. Applicants will also need to form strong partnerships with their state to facilitate access to linked administrative data, enable MD and selected neuromuscular disorder(s) to become reportable conditions, 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.

Agreements or letters of support for the ability to access and link data should be provided in the appendix. Applicants will also need to partner with clinics and hospitals to conduct medical record abstraction and explain the types of relationships that have

CDC Research 20 been or they are planning to establish. Applicants who are awarded funds under this cooperative agreement are expected to collaborate with other grantees and CDC under this award.

Component C:

The applicants for the enhanced activities will be expected to collaborate with other grantees and CDC. The data coordinating center will be responsible for providing software, databases, and relevant documentation and support of these applications to all sites to enable data collection, pooling, and analysis of data. The applicant awarded abstractor training and quality assurance and control activities will work with abstractors and investigators in all sites to ensure that the activities are successfully conducted.

Component D:

The applicant(s) should consider partnering with national, regional, and/or local MD advocacy groups in promoting participation in the research study and in disseminating results of the study including sharing of results with participants.

Evaluation/Performance measurement

For Components A, B, and C, the applicant will be required to participate in a committee composed of CDC and grantee staff to determine an overall evaluation plan and to participate in the activities of the plan throughout the life of the cooperative agreement. The evaluation plan will be designed to include periodic assessment of 1) logistics of data collection, 2) completeness of ascertaining people with MD and selected neuromuscular disorders including the ability to following them longitudinally,

3) data quality and the readiness of the data for analyses to answer the research questions, and 4) the utility of the information for public health practice. The applicant should indicate in their application how they will participate as active members of the committee in planning the evaluation component and in all evaluation activities specified by the plan.

Component D:

The proposed pilot study will be submitted to a committee composed of CDC and grantees prior to implementation. The following will be presented orally to the committee with a written summary provided: 1) literature review, rationale for proposed investigation, anticipated benefits of the completed investigation, involvement of stakeholders in promoting participation of study participants; 2) proposed methods, anticipated challenges, potential approaches to overcoming them and effect of the challenges to conducting the study, timetable for the research; 3) the approach for communicating results back to study participants, interpretation and implications for public health practice. The pilot study will be presented again to the Committee when interim results are available and when the study is final. A

CDC Research 21 manuscript, suitable for publication, should be developed. For each step of the research, the applicant will be required to respond to the Committee’s comments by modifying the research methods or explaining why modification is not possible.

Translation plan

For components A and B, the applicant will be required to collaborate with CDC and other grantees in developing and implementing a communications/translation plan to ensure dissemination of surveillance data to MD and neuromuscular disorders stakeholders. Examples of dissemination include a report or methods paper describing and evaluating MD and neuromuscular disease surveillance, peer-reviewed publications;

webinars, newsletters, website content, plain language key findings summaries and talking points from peer-reviewed publications, and social media. Grantees will be expected to engage in communications activities specified by the plan throughout the life of the cooperative agreement. These activities are expected to include communication tactics implemented by both the grantee alone, and by the grantee in collaboration with CDC and other grantees.

For component D, the applicant will be expected to disseminate results back to study participants and more broadly to other MD partners and stakeholders.

References:

1Miller 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.

2http://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/nominateconditi on/reviews/pompereport2013.pdf

Section II. Award Information

Funding Mechanism Applications in response to this FOA will be funded using the U01 mechanism.

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.

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Application Types Allowed

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

Funds Available and Anticipated Number of Awards

Total estimated funding (direct and indirect costs) for the first year (12 month budget period) is $3,100,000. Estimated total funding for the entire project is $15,500,000.

Component A: Up to $500,000 each for up to five awards Component B: Up to $450,000 each for up to two awards Component C: Data Coordinating Center: Up to $250,000 - one award Component C: Abstractor training and quality assurance/control:

Up to $100,000 – one award Component D: Average award size will range from $75,000 - $125,000 with up to three awards

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

Ceiling and Floor of Individual Award Range

The ceiling amounts for the first 12 month budget period are:

Component A: An applicant may…