DD15-003 NOFO.pdf

Centers for Disease Control and Prevention

National Center on Birth Defects and Developmental Disabilities Extramural Research Program

Office

Using Longitudinal Data to Characterize The Natural History of Fragile X Syndrome to

Improve Service

RFA-DD-15-003

Application Due Date: 02/20/2020

Using Longitudinal Data to Characterize The Natural History of Fragile X Syndrome to

Improve Service

RFA-DD-15-003

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 and Prevention 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) Funding Opportunity Announcement (FOA) Title Using Longitudinal Data to Characterize The Natural History of Fragile X Syndrome to Improve Service Activity Code Amendment 2 - made on December 30, 2019.

This supplemental funding opportunity will provide FY20 funds to existing recipients to maximize the value of activities undertaken in accordance with CDC-RFA-DD-15-003, the activities supported with this supplemental funding will extend the project period for Component A and B for one additional year.

See Section VIII. Other Information -Appendix A

AMENDMENT 1 made on February 10, 015.

U01

Funding Opportunity Announcement Type Reissue of CDC-RFA-DD-15-003 Funding Opportunity Announcement Number

RFA-DD-15-003

Catalog of Federal Domestic Assistance (CFDA) Number(s) 93.315 Category of Funding Activity:

Health FOA Purpose The purpose of this FOA is to contribute to the understanding of the natural history of fragile X syndrome (FXS) across the lifespan, explore effective strategies to increase participation in the longitudinal database for minority, underserved, and adults living with FXS, and test approaches to measure cognitive and behavioral function in the FXS population.

Component A The purpose of Component A is to coordinate and expand the FORWARD longitudinal database to describe the natural history of FXS across the life span and characterize the impact of interventions and treatments on both health outcomes and quality of life.

Component B The purpose of Component B is to support a Data Coordinating Center to manage the receipt, processing, and analysis of patient, caregiver, clinician, and laboratory reported data from clinics participating in the longitudinal database and other data sources.

Component C The purposes of Component C are to enhance participation in the longitudinal database;

develop, implement, and evaluate a plan to increase participation of minority and underserved populations in the longitudinal database; and test approaches to measure cognitive and behavioral function in the FXS population.

Key Dates Publication Date: To receive notification of any changes to RFA-DD-15-003, 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: 01/29/2020

Application Due Date: 02/20/2020

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: 04/06/2020 The 04/06/2020 date listed above is an approximate date for this supplemental funding opportunity.

Secondary Review: 04/06/2020

Estimated Start Date: 09/01/2020 Estimated Start Date for this supplemental funding opportunity: September 1, 2020.

Expiration Date: 02/21/2020 Due Dates for E.O. 12372: Executive Order 12372 does not apply to this program.

Required Application Instructions It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide http://www.grants.gov http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf 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. The purpose of this FOA is to contribute to the understanding of the natural history of fragile X syndrome (FXS) across the lifespan, explore effective strategies to increase participation in the longitudinal database for minority, underserved, and adults living with FXS, and test approaches to measure cognitive and behavioral function in the FXS population.

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

Funds Available and Anticipated Number of Awards. Component A: Total funding is expected to be $1,750,000 (direct and indirect) over the five year project period ($350,000/year). It is anticipated that 1 award will be made to a single recipient for up to $350,000 in FY 2015. Component B: Total funding is expected to be $1,000,000 (direct and indirect) over the five year project period ($200,000/year). It is anticipated that 1 award of up to $200,000 will be made in FY 2015. Component C: Total funding is expected to be $1,500,000 (direct and indirect) over the five year project ($300,000/year). It is anticipated that up to 3 awards of up to $100,000 each will be made in FY 2015.

Budget and Project Period. Component A: The estimated total funding (direct and indirect) for the first year (12 month budget period from September 1, 2015 to August 31, 2016) will be up to $350,000. The total funding available for the project period will be approximately $1,750,000. The project period will run from September 1, 2015 to August 31, 2020. Component B: The estimated total funding (direct and indirect) for the first year (12 month budget period from September 1, 2015 to August 31, 2016) will be up to $200,000. The total funding available for the project period will be approximately $1,000,000. The project period will run from September 1, 2015 to August 31, 2020. Component C: The estimated total funding (direct and indirect) for the first year (12 month budget period from September 1, 2015 to August 31, 2016) will be up to $300,000. The total funding available for the project period will be approximately $1,500,000. The project period for Components A, B and C will run from September 1, 2015 to August 31, 2020.

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 must designate a PI. Applications may designate co- PIs, however, the first PI listed will be the designated PI and official “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. Applicants can apply for more than one component. If applying for more than one component, a separate application for each component is required.

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.

o Conference Call Details:

o Date: January 15, 2015 from 1:00 - 2:00 pm (EST) o Call-in Number: 1-855-644-0229Toll Free o Participant Pass Code: 7457938

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

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

TTY: (770) 488-2783.

Part 2. Full Text Section I. Funding Opportunity Description

Statutory Authority This program is authorized under Sections 301 and 317C of the Public Health Service Act, (42 USC Sections 241 and 247b-4), as amended.

1. Background and Purpose Fragile X syndrome (FXS) is the most common known inherited cause of intellectual disability (ID). FXS affects both males and females. However, females can have milder symptoms than males. The exact number of people who have FXS is unknown, but it has been estimated that about 1 in 4,000 - 5,000 males and about 1 in 6,000 – 8,000 females are born with the disorder.

People who have FXS show a range of intellectual disability and may also experience emotional, behavioral, sensory, and/or social difficulties.

Over the past two decades, scientists have made advancements in understanding the genetics of FXS: it is a genetic disorder caused by a CGG trinucleotide repeat mutation in the fragile X http://grants.nih.gov/grants/guide/pa-files/PAR-11-022.html#SectionIV1 mental retardation 1 (FMR1) gene. However, we are just beginning to understand how this complex condition affects individuals and their families. Some parents spend years taking their child to different doctors before getting a diagnosis of FXS. After the diagnosis, they still may struggle with the behavioral and communication challenges or co-occurring conditions that can come with FXS. The more we know about this population across the lifespan, both from a clinical perspective and a parent/caregiver perspective, the better we can design services and care that will improve the lives of those affected.

To date, limited data are available to describe the prevalence of co-occurring conditions in the FXS population (such as Autism, ADHD, anxiety, depression, and seizures) and the spectrum of interventions used to treat symptoms. Data are limited with regard to determining if these interventions improve short-or long-term health and wellness outcomes among people with fragile X syndrome. Further, research aimed at understanding unmet needs and challenges faced by individuals who have FXS could also benefit the broader population of individuals living with intellectual and developmental disabilities. CDC has funded two pilot studies to determine the feasibility of collecting data needed to expand our understanding of FXS.

The first pilot study (2008-2011) tested the infrastructure required to carry out multi-site research in FXS. Results of this study demonstrated that working with The Fragile X Clinical and Research Consortium (FXCRC) was an effective way to reach clinics and demonstrated that facilitated research across multiple FXS specialty clinics could be successfully conducted. The second pilot study (2011-2015) is currently testing the ability of this infrastructure to collect and manage longitudinal data. FXCRC launched the Fragile X Online Registry With Accessible Research Database (FORWARD), and is working with FXS specialty clinics across the country to contribute data on individuals diagnosed with FXS, ages 0-24 years of age. The FORWARD Database has thus far demonstrated that longitudinal data can be successfully collected on participants.

The next FOA will build on this work by expanding it in two ways: 1) collecting additional longitudinal data on participants already enrolled, and 2) enrolling new participants with a focus on minority and underserved populations and the adult FXS population (>24 years of age). The expansion of the longitudinal database will provide a data resource that clinicians and researchers can use to address clinical care and public health research questions. This could include questions such as: what are the most common co-occurring conditions across the life span? How often do they occur in the FXS population? What types of interventions and treatments are used to address symptomology? What are the service needs of the adult fragile X population?

In May 2014, CDC gathered FXS stakeholders to discuss gaps in public health knowledge about FXS, identified through a structured literature review. Working from a summary of the latest FXS scientific literature, CDC identified six topic areas where public health research and programs can contribute knowledge about this complex condition: 1) epidemiology, 2) early identification and screening, 3) impact on individuals and families, 4) FXS across the lifespan,

5) co-occurring conditions, and 6) interventions and outcome measures. Researchers, clinicians, behavior and education specialists, patient advocates, and families had an opportunity to discuss challenges and strategies for addressing gaps in each of these six areas. This FOA will address gaps identified through this process in five of the six topic areas.

This FOA will support the epidemiologic collection of data that will support a more robust and inclusive description of the FXS population (e.g. gender, age, race, ethnicity, and socio-economic factors). With regard to impact on individuals and families, this FOA supports the continued collection of longitudinal data that can provide a data resource for answering research questions related to how FXS is impacting individuals and families. In relation to topics 4 and 5 listed above, it is imperative to think about the transitions individuals living with FXS navigate throughout their lifespan. Little is known about the health and social issues adults with FXS face and there are very limited data on aging with FXS. Work undertaken through this FOA can begin to shed light on the transition out of school, employment issues, daily living and functional skills of adults living with FXS, and guardianship of adults living with FXS. The research supported by this FOA can further describe conditions that occur more frequently in FXS patients (e.g., anxiety, ADHD, seizures, depression, and autism) and provide insight into the issues that come with these co-occurring conditions. Testing different ways to measure cognitive or behavioral function and assessing applicability to the FXS population will also result from work undertaken as part of this FOA.

The intent of this FOA is to support research that will contribute to: a more robust description of the FXS population, an informed understanding of the natural history of FXS across the lifespan, the impact of treatments and interventions on health outcomes and quality of life, approaches to measuring cognitive and behavioral status in FXS patients, and assessing the impact of treatments and interventions. This FOA builds upon knowledge gleaned through the two pilot studies and uses the lessons learned to collect important longitudinal data that allows for continued public health research in the FXS population. Analyses could generate information to guide parents and health professionals to the best services and outcomes possible, as well as inspire future research aimed at furthering improvements in health and wellness. To achieve this, longitudinal data needs to be collected on individuals already enrolled in the database and new enrollees, in particular adults living with FXS and participants from diverse backgrounds.

To accomplish the intent of the FOA, there are three separate components:

Component A – Coordination of the Longitudinal Database The purpose of Component A is to coordinate efforts to expand the FORWARD longitudinal database in order to describe the natural history of FXS across the life span and characterize the impact of interventions and treatments on both health outcomes and quality of life.

Component A will expand on the FORWARD longitudinal database in two ways: 1) collect additional data points on individuals already enrolled and 2) enroll new study participants, with a focus on minority and underserved populations and the adult fragile X population (> 24 years of age). New questions directed at the adult FXS population will be developed and piloted.

Component B – Data Coordinating Center The purpose of Component B is to support a Data Coordinating Center to manage the receipt, processing, and analysis of patient, parent, clinician, and laboratory reported data from clinics participating in the longitudinal database and other sources.

Component C – Enhanced Participation of Fragile X Specialty Clinics The purpose of Component C is to enhance participation in the longitudinal database; develop, implement, and evaluate a plan to increase participation of minority and underserved populations in the longitudinal database; and test approaches to measure changes in cognitive function or behavior.

Applicants can apply for more than one component. If applying for more than one component, a separate application for each component must be submitted.

Healthy People 2020 and other National Strategic Priorities The National Center on Birth Defects and Developmental Disabilities (NCBDDD) of CDC within HHS is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2020" and to measuring program performance as stipulated by the Government Performance and Review Act (GPRA). This FOA addresses Healthy People 2020 Goal: Improve health-related quality of life and well-being for all individuals.

This FOA will contribute to this Healthy People 2020 goal with regard to the FXS population.

Collecting and analyzing longitudinal data can assist researchers and clinicians in answering clinical care and public health research questions. This can facilitate the identification of important therapeutic, behavioral and educational interventions and provide essential information to assist health care and allied professionals in providing better care, with the long-term goal of improving health outcomes and quality of life across the lifespan.

Public Health Impact FXS is a lifelong condition and in order to address the long-term goal of improving health outcomes and quality of life, gaps in knowledge about the health status of people living with FXS and interventions that may or may not be effective need to be filled. Little is currently known about which interventions and treatments yield the best outcomes. To date, research efforts have primarily focused on children, therefore not much is known about the health status and social wellbeing of adults living with FXS - where they seek specialized care, how aging influences what services are used and needed, and whether caregiver and guardianship challenges change. In addition to collecting longitudinal data on individuals 24 years of age or younger, this project will begin to collect data on individuals over 24 years of age as well. This can provide a much needed epidemiologic profile of the adult FXS population for the first time, leading to interventions and services that can then be developed. Additionally, efforts to include minority and underserved populations will create a more inclusive description of the FXS clinic-based population and provide preliminary data that can be used to investigate if there are differences between subgroups of the population that may be related to health disparities.

Relevant Work This work will build on two pilot studies. The first pilot study (2008-2011) tested the infrastructure required to carry out multi-site research in FXS; the Fragile X Clinical and Research Consortium (FXCRC) successfully facilitated research across multiple FXS specialty clinics. The second pilot study (2011-2015) is testing whether it is feasible and effective to collect and manage longitudinal data. During the second pilot study, the grantee has worked with FXS specialty clinics across the country, in collaboration with the FXCRC, to contribute data on individuals diagnosed with FXS ages 0-24 years of age. Data are currently being collected through the Fragile X Online Registry With Accessible Research Database (FORWARD). Data for the Registry and Database are provided by 24 participating clinics, each with IRB approval, using structured clinician and parent-report forms and standardized parent-report instruments on behavior and communication (i.e. SRS, SCQ, ABC-C). More information can be found at www.fxcrc.org.

2. Approach This work should build on previous efforts to develop and implement the FORWARD Registry and Database as well as address gaps in knowledge identified by a structured literature review and input from stakeholders and FXS experts. This FOA will support expansion of the FORWARD database to include adults living with FXS and encourage participation of underserved and minority populations. To address the need to understand more about the adult FXS population the approach shall include, but is not limited to, developing and piloting the collection of variables specific to adult individuals living with FXS (e.g. clinical, occupational, familial, and social service needs, as well as guardianship and caregiver issues).

This FOA is comprised of three separate components aimed at collecting and analyzing data that can provide a robust description of the FXS population, an informed understanding of the natural history of FXS across the lifespan, an analysis of the impact of treatments and interventions on health outcomes and quality of life, and improved approaches to measuring cognitive and behavioral status in FXS patients.

Objectives/Outcomes Component A – Coordination of the Longitudinal Database: Outcomes Component A will utilize a national coordinator to support and coordinate data collection activities across fragile X specialty clinics and facilitate the expansion of the longitudinal database to include adults living with FXS. The national coordinator may collaborate with the Fragile X Clinical Research Consortium (FXCRC) to facilitate access to study participants from the specialty clinics. The national coordinator will collaborate with the Data Coordinating Center to ensure timely and accurate data collection.

Component A – Coordination of the Longitudinal Database: Objectives http://www.fxcrc.org/

Using the data collection tools of the FORWARD Registry and Database, expand on longitudinal data by collecting four additional data points on at least 150 individuals with fragile X syndrome already enrolled in the longitudinal database; three additional data points on at least 175 enrollees; and two additional data points on at least 225 enrollees; and enroll at least 450 new participants (all ages) with fragile X syndrome into the database.

Develop and pilot questions to obtain new data specific to the adult FXS population – clinical and social services used and needed across the lifespan as well as possible occupational, familial, sociocultural, and guardianship factors that need to be addressed along with other caregiver needs.

Collaborate with clinicians and researchers from the sites participating in the longitudinal database, the PIs of Components B and C, and CDC representatives to identify important clinical care and public health research questions and utilize data from the longitudinal database to address them.

Collaborate with the PIs of Components B and C and CDC representatives to establish and implement guidelines and processes for data analysis and publications.

Participate in a Steering Committee that is intended to encourage collaboration across components of this FOA and provide the necessary expertise and oversight to ensure successful completion of Components A, B, and C. Members of the Steering Committee will be comprised of PIs, or co-PIs, from each awarded site from Components A, B, and C and CDC staff. The Steering Committee may consider adding non-voting liaisons from patient oriented organizations, including but not limited to, the National Fragile X Foundation and FRAXA Research Foundation. Addition of non-voting members must be unanimously approved by the designated Steering Committee members described above.

Develop a sustainability plan for the maintenance and support of the longitudinal database beyond the completion of this FOA.

Component B – Data Coordinating Center: Outcomes Component B will utilize a Data Coordinating Center to build on the existing longitudinal database to maintain and manage data collected by participating clinics.

Component B – Data Coordinating Center: Objectives

Build on the existing longitudinal database to provide a data management and analysis center for receipt, processing, and analysis of patient, parent, clinician, and laboratory reported data from the participating clinics or other data sources.

Conduct ongoing quality control/quality assurance to maintain high quality data Create at least one, but no more than two, clean de-identified datasets each year to be used for analysis.

Issue a “data dictionary” or “documentation of data” to accompany each dataset.

Collaborate with the PI of Components A and C and CDC representatives to establish and implement guidelines and processes for data analysis and publications.

Work with clinicians and researchers participating in the longitudinal database to conduct analyses and publish findings.

Participate in a Steering Committee that is intended to encourage collaboration across components of this FOA and provide the necessary expertise and oversight to ensure successful completion of Components A, B, and C. Members of the Steering Committee will be comprised of PIs, or co-PIs, from each awarded site from Components A, B, and C and CDC staff. The Steering Committee may consider adding non-voting liaisons from patient oriented organizations, including but not limited to, the National Fragile X Foundation and FRAXA Research Foundation. Addition of non-voting members must be unanimously approved by the designated Steering Committee members described above.

Collaborate with clinicians and researchers to conduct analyses using established cleaned datasets.

Component C – Enhanced Participation of Fragile X Specialty Clinics: Outcomes Component C will engage FXS specialty clinics in the data collection process for the longitudinal database. These clinics will collaborate with the CDC to develop, implement, and evaluate a plan to increase the participation of minority and underserved populations in the longitudinal database and share the results with other fragile X specialty clinics; this may be done by collaborating with the FXCRC. The clinics will use data collected on participants in the longitudinal database to test different ways to measure cognitive and behavioral function and assess if these measures can be used to measure changes in cognitive or behavioral function in this population.

Component C – Enhanced Participation of Fragile X Specialty Clinics: Objectives

Participate in the longitudinal database – proactively approach at least 85% of currently enrolled participants for follow-up data and approach at least 85% of those not enrolled (all ages) to obtain complete baseline data. This shall include, but is not limited to, developing and implementing a system to track patient participation in FORWARD, identifying patients that have not been offered participation in FORWARD and offering participation at their next visit, documenting patients that have declined participation, alerting clinic staff when enrolled participants are eligible for annual follow-up data, and notifying participants they are due for collection of follow-up data.

Select approach for enhanced participation and/or enhanced measurement – choose one or both.

o Enhanced participation (minority and underserved populations) Increase participation in the longitudinal database among minority and underrepresented populations and measure the increases in recruitment and enrollment among these populations.

AND/OR

Enhanced measurement (outcome measures) o Identify and test the reliability, validity, and utility of one or more selected cognitive or behavior measures.

o Implement the selected measure(s) at least annually for five years and if applicable, compare the performance with one of the standardized parent-report instruments on behavior and communication currently being collected as part of the FORWARD database: SRS, SCQ, ABC-C.

Collaborate with the recipients of Components A and B to develop and implement an analysis plan for utilizing data from the longitudinal database.

o Address clinical care and public health research questions. Examples include a description of the FXS population and subgroups of the population, identifying risk factors for co-occurring conditions, describing interventions and treatments being used and the impact on health and wellness outcomes.

o Examine approaches selected to enhance participation and/or measurement.

Upon completion of enhancement activities, explore stratified analysis by race/ethnicity/socio-demographics or utilize the piloted outcome measure in an analysis.

Participate in a Steering Committee that is intended to encourage collaboration across components of this FOA and provide the necessary expertise and oversight to ensure successful completion of Components A, B, and C. Members of the Steering Committee will be comprised of PIs, or co-PIs, from each awarded site from Components A, B, and C and CDC staff. The Steering Committee may consider adding non-voting liaisons from patient oriented organizations, including but not limited to, the National Fragile X Foundation and FRAXA Research Foundation. Addition of non-voting members must be unanimously approved by the designated Steering Committee members described above.

Target Population The target populations for this FOA are individuals diagnosed with fragile X syndrome, all ages, currently attending a fragile X specialty clinic and those not attending a FXS specialty clinic but who meet the criteria to be attending; fragile X specialty clinics; other clinics that see FXS cases; and fragile X clinicians and researchers. For Component C, the specific target population is fragile X specialty clinics with an annual expected patient base of at least 30 individuals with full mutation fragile X syndrome of all ages, with an emphasis on individuals with FXS from minority and underserved populations.

Collaboration/Partnerships Recipients of each of the components are expected to collaborate with one another, the fragile X specialty clinics (this may include collaboration with the Fragile X Clinical and Research Consortium), and the CDC to accomplish the study goals and objectives. The awardee of Component A will be expected to also collaborate with fragile X organizations such as, but not limited to, The National Fragile X Foundation and FRAXA Research Foundation.

Evaluation/Performance Measurement

Recipients of Components A and B are expected to participate in the planning and implementation of Program and Process Evaluation of the longitudinal database in collaboration with CDC. Recipients of Component C, depending on the area of focus, are expected to participate in the planning and implementation of evaluating the utility of identified measures for use in individuals living with FXS or evaluating recruitment strategies targeted at minority and underserved populations.

Translation Plan Applicants are expected to disseminate findings through peer-reviewed journals, presentations at professional conferences, oral and written communication with the FXS population, and other mechanisms.

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:

Revision (formerly Competing Supplement) - Request for additional funds for a current award to expand the scope of work. Applicants should contact the awarding agency for advice on submitting any revision/supplement application.

Estimated Total Funding: $550,000 The estimated total funding for Components A, B, and C of this FOA is expected to be up to $4,250,000 (direct and indirect) over a five year project period.

Component A: Total funding is expected to be up to $1,750,000 (direct and indirect) over the five year project period ($350,000/year). It is anticipated that 1 award will be made to a single recipient for up to $350,000 in FY 2015.

Component B: Total funding is expected to be up to $1,000,000 (direct and indirect) over the five year project period ($200,000/year). It is anticipated that 1 award of up to $200,000 will be made in FY 2015.

Component C: Total funding is expected to be up to $1,500,000 (direct and indirect) over the five year project ($300,000/year). It is anticipated that up to three awards up to $100,000 each will be made in FY 2015.

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

Anticipated Number of Awards: 2 The ceiling of the award for Component A will be $350,000 (including direct and indirect costs). This ceiling is for the first 12-month project period. The range of funding is $0 - $350,000.

The ceiling of the award for Component B will be $200,000 (including direct and indirect costs). This ceiling is for the first 12-month project period. The range of funding is $0 - $200,000.

The ceiling of the award for Component C will be $100,000 (including direct and indirect costs). This ceiling is for the first 12-month project period. The range of funding for up to three awards is $0 - $100,000.

Applications with budget requests greater than the ceiling will be considered non-responsive and will not be reviewed.

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

Award Ceiling: $350,000 Per Project Period Award Floor: $0 Per Project Period Total Project Period Length: 1 year(s)

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

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

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category: State governments

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) https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf

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

Additional Eligibility Category:

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

Hispanic-serving Institutions Historically Black Colleges and

Universities (HBCUs) Tribally Controlled Colleges and

Universities (TCCUs) Alaska Native and Native Hawaiian

Serving Institutions

Nonprofits Other Than Institutions of Higher Education:

Nonprofits (Other than Institutions of

Higher Education)

Governments:

Eligible Agencies of the Federal

Government U.S. Territory or Possession

Other:

Native American tribal organizations

(other than Federally recognized tribal governments)

Faith-based or Community-based Organizations

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

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

4. Justification for Less than Maximum Competition Not applicable

5. Responsiveness To be considered responsive to this announcement, applicants may not request funding above the ceiling amount of $350,000 for Component A, $200,000 for Component B, or $100,000 for Component C for Year 1 (includes both direct and indirect costs).

Component C Applicants must provide a table or figure with 1) the number and basic demographic information (age, gender, race, ethnicity) for the FXS patients seen in the clinic for the past three years, demonstrating greater than or equal to 30 fragile X syndrome patients (all ages) per year; and 2) an estimate of the number of FXS patients the clinic expects to serve each year between 2015 ? 2020.

Electronically submitted applications must be submitted no later than 5:00 p.m., ET, on the listed application due date.

Applicants should present this responsiveness information for Component C in Appendix A of their application. Incomplete applications, applications submitted after 5:00 PM on the listed application due date or non-responsive applications with budgets that exceed the ceiling of the award will not be entered into the review process.

6. Required Registrations Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

(Foreign entities only): Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: https://eportal.nspa.nato.

int/AC135Public/Docs/US%20Instructions%2 0for%20NSPA%20NCAGE.pdf

System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, https://www.sam.gov/portal/SAM/#1.

Grants.gov eRA Commons

All applicant organizations must register with Grants.gov. Please visit www.Grants.gov at least 30 days prior to submitting your application to familiarize yourself with the registration and submission processes. The “one-time” registration process will take three to five days to complete. However, it is best to start the registration process at least two weeks prior to application submission.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization. All registrations must be successfully completed and active before the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

7. Universal Identifier Requirements and System for Award Management (SAM) All applicant organizations must obtain a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number is a nine-digit number assigned by Dun and Bradstreet Information Services. An AOR should be consulted to determine the appropriate https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf https://www.sam.gov/portal/SAM/%231 https://www.Grants.gov https://public.era.nih.gov/commons/public/login.do?TYPE=33554433&REALMOID=06-1edb031f-46c7-44b3-b803-60b537de74d2&GUID=&SMAUTHREASON=0&METHOD=GET&SMAGENTNAME=-SM-938PYmoLVb4VrDeXo04LZUDVDvc%2b3899ByInEAjuSUvWNIGfB2zRpWiCivYGCogG&TARGET=-SM-http%3a%2f%2fpublic%2eera%2enih%2egov%2fcommons https://www.Grants.gov number. If the organization does not have a DUNS number, an AOR should complete the US D&B D-U-N-S Number Request Web Form or contact Dun and Bradstreet by telephone directly at 1-866-705-5711 (toll-free) to obtain one. A DUNS number will be provided immediately by telephone at no charge. Note this is an organizational number. Individual Program Directors/Principal Investigators do not need to register for a DUNS number.

Additionally, all applicant organizations must register in the System for Award Management (SAM). Organizations must maintain the registration with current information at all times during which it has an application under consideration for funding by CDC and, if an award is made, until a final financial report is submitted or the final payment is received, whichever is later. SAM is the primary registrant database for the Federal government and is the repository into which an entity must provide information required for the conduct of business as a recipient. Additional information about registration procedures may be found at the SAM internet site at https://www.sam.gov/index.html.

If an award is granted, the recipient organization must notify potential sub-recipients that no organization may receive a subaward under the grant unless the organization has provided its DUNS number to the recipient organization.

8. Eligible Individuals (Project Director/Principal Investigator) in Organizations/Institutions Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for HHS/CDC support.

9. Cost Sharing This FOA does not require cost sharing as defined in the HHS Grants Policy Statement (http:// www.hhs.gov/ asfr/ ogapa/ aboutog/ hhsgps107.pdf).

10. Number of Applications As defined in the HHS Grants Policy Statement,(https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf), applications received in response to the same Notice of Funding Opportunity generally are scored individually and then ranked with other applications under peer review in their order of relative programmatic, technical, or scientific merit. HHS/CDC will not accept any application in response to this NOFO that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Section IV. Application and Submission Information

1. Address to Request Application Package Applicants must download the SF424 (R&R) application package associated with this funding opportunity from www.Grants.gov.

If access to the Internet is not available or if the applicant encounters difficulty accessing the http://fedgov.dnb.com/webform http://fedgov.dnb.com/webform https://www.sam.gov/index.html http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf https://www.Grants.gov forms on-line, contact the HHS/CDC Office of Grants Services (OGS) Technical Information Management Section (TIMS) staff at (770) 488-2700 or ogstims@cdc.gov for further instructions. Hours: Monday - Friday, 7am – 4:30pm U.S. Eastern Time. CDC Telecommunications for the hearing impaired or disabled is available at: TTY 1-888-232-6348.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/ 424/SF424_RR_Guide_General_VerC.pdf), except where instructed in this Funding Opportunity Announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow the instructions in the SF 424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

In conjunction with the SF424 (R&R) components, CDC grants applicants should also complete and submit additional components titled “PHS398.” Note the PHS398 should include assurances and certifications, additional data required by the agency for a complete application.

While these are not identical to the PHS398 application form pages, the PHS398 reference is used to distinguish these additional data requirements from the data collected in the SF424 (R&R) components. A complete application to CDC will include SF424 (R&R) and PHS398 components. These forms can be downloaded from http://grants.nih.gov/grants/forms.htm

3. Letter of Intent Due Date for Letter of Intent: 01/29/2020 Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows CIO staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

Name of the Applicant Descriptive title of proposed research (identify the component you are applying to) Name, address, and telephone number of the PD(s)/PI(s) Names of other key personnel Participating institutions Number and title of this funding opportunity

The letter of intent should be sent to:

National Center for Chronic Disease and Health Promotion (NCCDPHP) and NCBDDD Extramural Research Program Operations and Services (ERPOS) Marcella Law mailto:pgotim@cdc.gov http://grants.nih.gov/grants/forms.htm

Scientific Program Official Extramural Research Program Operations and Services Centers for Disease Control and Prevention 4770 Buford Highway, NE M/S F-80 Atlanta, GA 30341 Telephone: (770)-488-5416 Email: mah7@cdc.gov

4. Required and Optional Components A complete application has many components, both required and optional. The forms package associated with this NOFO in Grants.gov includes all applicable components for this NOFO, required and optional.

5. PHS 398 Research Plan Component The SF424 (R&R) Application Guide includes instructions for applicants to complete a PHS 398 Research Plan that consists of 16 components. Not all 16 components of the Research Plan apply to all Funding Opportunity Announcements (FOAs). Specifically, some of the following 16 components are for Resubmissions or Revisions only. See Part I, Section 5.5 of the SF 424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf) for additional information. Please attach applicable sections of the following Research Plan components as directed in Part 2, Section 1 (Funding Opportunity Announcement Description).

Follow the page limits stated in the SF 424 unless otherwise specified in the FOA. As applicable to and specified in the FOA, the application should include the bolded headers in this section and should address activities to be conducted over the course of the entire project, including but not limited to:

1. Introduction to Application (for Resubmission and Revision ONLY) - provide a clear description about the purpose of the proposed research and how it addresses the specific requirements of the FOA.

2. Specific Aims – state the problem the proposed research addresses and how it will result in public health impact and improvements in population health.

3. Research Strategy – the research strategy should be organized under 3 headings:

Signific…